Mar 2010

PNN Quarterly File—First Quarter 2010

PNN Pharmacotherapy Line
Jan. 4, 2010 * Vol. 17, No. 1
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Jan. 2 issue of Lancet (2010; 375).
Immune Responses After A/H1N1 Influenza Vaccine: Two randomized controlled Phase II trials support use of one dose of the 2009 A/H1N1 influenza vaccine in adults and the elderly, but study results show that two doses are likely needed in children younger than 9 years, a conclusion different from that reported in JAMA study 2 weeks ago (see PNN, Dec. 23) (pp. 41–8). The dose-ranging studies, conducted in the U.S., showed these outcomes based on hemagglutination antibody responses measured at 21 days: “410 of 423 children and 724 of 750 adults given an active vaccine, and 50 of 51 children and 95 of 99 adults given placebo were assessed for immunogenicity on day 21. After active vaccination, 45 of 101 (45%; 95% CI 35–55) to 47 of 94 (50%; 40–61) infants aged 6–35 months, 75 of 109 (69%; 59–77) to 80 of 106 (75%; 66–83) 3–9-year-old children, 134 of 141 (95%; 90–98) to 144 of 144 (100%; 98–100) of 18–64-year-old adults, and 93 of 100 (93%; 86—96) to 93 of 98 (95%; 89–98) elderly adults were seroprotected (proportion with titres ≥1:40). No vaccine-related serious adverse events occurred. Injection-site and systemic reactions were reported by up to about 50% of every age and vaccine group, with no noticeable differences between vaccine and placebo groups.” (M. Denis, martine.denis@sanofipasteur.com)
Safety & Immunogenicity of A/H1N1 Influenza Vaccine: Two additional research articles explore the safety and immunogenicity of 2009 A/H1N1 influenza vaccine.
One study shows that the pandemic vaccine can be safely administered with the seasonal influenza vaccine (
pp. 49–55). Data from two Hungarian centers show the following safety and immunogenicity trends: “Two participants receiving the pandemic vaccine only (group 1) and one receiving pandemic and seasonal vaccines (group 2) were lost to follow-up. Participants in both groups developed antibody responses against the pandemic influenza A H1N1 virus (group 1: seroconversion for adults 74.3%, 95% CI 64.6–82.4 and for elderly people 61.3%, 49.1–72.4; group 2: 76.8%, 67.2–84.7 and 81.8%, 71.4–89.7, respectively). Single doses of 6 mcg fulfilled European Union and US licensing criteria for interpandemic and pandemic influenza vaccines. Simultaneously, participants in group 2 developed the immune responses needed for licensing for all three seasonal strains in the seasonal vaccine for the 2009–10 season. All adverse events were rare, mild, and transient; the most frequent were pain at injection site (eight cases in group 1 vs 18 in group 2) and fatigue for 1–2 days after vaccination (three vs five cases).” (Z. Vajo, zoltanvajo@gmail.com)
Among 12,691 children and adults in China vaccinated with single dose of split-virion nonadjuvanted A/H1N1 influenza vaccine, one dose with 7.5 mcg hemagglutinin was effective in those aged 12 years or older, but two doses would likely be needed in children aged 3–12 years of age (
pp. 56–66). The study also tested whole-virion formulations with aluminum hydroxide adjuvant and doses of 15 and 30 mcg. The authors report: “The seroprotection rate 21 days after the first dose of vaccine ranged from 69.5% (95% CI 65.9–72.8) for the 7.5 mcg adjuvant split-virion formulation to 92.8% (91.9–93.6) for the 30 mcg non-adjuvant split-virion formulation. The seroprotection rate was 86.5% (796 of 920; 84.1–88.7) in recipients of one dose of the 7.5 mcg non-adjuvant split-virion vaccine compared with 9.8% (140 of 1,432; 8.3–11.4) in recipients of placebo (p < 0.0001). One dose of the 7.5 mcg non-adjuvant split-virion vaccine induced seroprotection in 178 of 232 children (aged 3 years to <12 years; 76.7%, 70.7–82.0), 211 of 218 adolescents (12 years to <18 years; 96.8%, 93.5–98.7), 289 of 323 adults (18–60 years; 89.5%, 85.6–92.6), and 118 of 147 adults older than 60 years (80.3%, 72.9–86.4), meeting the European Union’s licensure criteria for seroprotection in all age-groups. In children, a second dose of the 7.5 mcg formulation increased the seroprotection rate to 97.7% (215 of 220, 94.8–99.3).” (Y. Wang, wangyu@chinacdc.cn)

>>>PNN JournalWatch
* Executive Summary: Standards of Medical Care in Diabetes—2010, in Diabetes Care, 2010; 33 suppl 1: S4–10.
* Activated Protein C for Sepsis, in
New England Journal of Medicine, 2009; 361: 2646–52. (H. Gerlach, herwig.gerlach@vivantes.de)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 5, 2010 * Vol. 17, No. 2
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Jan. 5 issue of the Annals of Internal Medicine (2010; 152).
Risk of Diabetes After Smoking Cessation: Short-term risks of developing type 2 diabetes are actually increased when patients stop smoking, making it important for clinicians to implement diabetes-education and early-detection strategies during this time period, researchers report (pp. 10–7). In the ARIC (Atherosclerosis Risk in Communities) study, 10,892 middle-aged adults who did not have diabetes in 1987–89 had these outcomes based on fasting glucose assays through 1998 and self-report of diagnosis or use of antidiabetic medications through 2004: “During 9 years of follow-up, 1,254 adults developed type 2 diabetes. Compared with adults who never smoked, the adjusted hazard ratio of incident diabetes in the highest tertile of pack–years was 1.42 (95% CI, 1.20 to 1.67). In the first 3 years of follow-up, 380 adults quit smoking. After adjustment for age, race, sex, education, adiposity, physical activity, lipid levels, blood pressure, and ARIC Study center, compared with adults who never smoked, the hazard ratios of diabetes among former smokers, new quitters, and continuing smokers were 1.22 (CI, 0.99 to 1.50), 1.73 (CI, 1.19 to 2.53), and 1.31 (CI, 1.04 to 1.65), respectively. Further adjustment for weight change and leukocyte count attenuated these risks substantially. In an analysis of long-term risk after quitting, the highest risk occurred in the first 3 years (hazard ratio, 1.91 [CI, 1.19 to 3.05]), then gradually decreased to 0 at 12 years.” (H-C Yeh, hyeh1@jhmi.edu)
Antiretroviral Adherence & Health Care Costs: Among South African patients with HIV infection, those with high antiretroviral therapy adherence had significantly lower direct health care costs (pp. 18–25). The 6,833 patients in the cohort study began ART in 2000–06, and their monthly direct health care costs and pharmacy claim adherence rates, expressed as a percentage and categorized by quartiles, showed these patterns: “Total mean monthly costs were $370 (SD, $644). Mean monthly costs of ART were $32 (SD, $18); hospitalizations, $151 (SD, $436); consultations, $76 (SD, $66); investigations, $37 (SD, $50); and non-ART medications, $53 (SD, $180). Total mean monthly costs ranged from $313 (SD, $598) for quartile 4 to $376 (SD, $657) for quartile 1. Hospitalization costs increased from 29% to 51% of total costs as adherence decreased. In the [generalized linear model] 2-step model, moving from adherence quartile 1 to quartile 2, 3, or 4 increased the probability of having nonzero total monthly costs by 0.078, 0.15, and 0.21 percentage point, respectively (P < 0.001). For patients with nonzero costs, increasing adherence from quartile 1 to quartile 2, 3, or 4 decreased total monthly costs by $70, $133, and $192, respectively (P < 0.001). Moving from adherence quartiles 1 to 4 had the highest decrease in net overall median monthly health care costs (–$85 [interquartile range, –$116 to –$41]).” (J. B. Nachega, jnachega@hsph.harvard.edu)
Editorialists write that it makes sense to “spend more to save more” (
pp. 54–6): “Nachega and colleagues tell us that it makes sense to invest in improving adherence even when resources are scarce. We suggest that resources should be directed at both the community and patient levels. In addition, we believe these findings define the need for novel—albeit expensive—real-time monitoring and intervention to both improve outcomes and potentially reduce health care costs.” (D. R. Bangsberg, david_bangsberg@harvard.edu)
2010 Adult Immunization Schedule: Commenting on the new recommended adult immunization schedule from the Advisory Committee on Immunization Practices (pp. 36–9), editorialists provide useful advice that can be applied by immunizing pharmacists and those serving as preceptors of pharmacy students, residents, and fellows (pp. 59–60): “For too many years, vaccines have been viewed as routine only for children and travelers. Our challenge is to change this perception and to make immunizations integral to each encounter for physicians that care for adults in primary and specialty care settings. The importance of immunization cannot be overemphasized; it should be imparted directly to our patients, as well as to students and residents early in their training, as an essential component of the comprehensive care of adults in ambulatory and inpatient settings.” (R. H. Hopkins Jr., hopkinsroberth@uams.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 6, 2010 * Vol. 17, No. 3
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 6 issue of JAMA (2010; 303).
Disease-Dependent Antidepressant Drug Effects: For patients with depression, the magnitude of benefits derived from antidepressant drug therapy is proportional to the severity of symptoms, according to a patient-level meta-analysis (pp. 47–53). Data on 718 patients in six studies that used the Hamilton Depression Rating Scale (HDRS) in assessing baseline severity of depression showed: “Medication vs placebo differences varied substantially as a function of baseline severity. Among patients with HDRS scores below 23, Cohen d effect sizes for the difference between medication and placebo were estimated to be less than 0.20 (a standard definition of a small effect). Estimates of the magnitude of the superiority of medication over placebo increased with increases in baseline depression severity and crossed the threshold defined by the National Institute for Clinical Excellence for a clinically significant difference at a baseline HDRS score of 25.” (J. C. Fournier, jcf@sas.upenn.edu)

>>>Pediatrics Highlights
Source:
Jan. issue of Pediatrics (2010; 125).
2010 Pediatric Immunization Schedules: New childhood and adolescent immunization schedules reflect changes for vaccines licensed by FDA (pp. 195–6). The three schedules—for patients aged 0–6 years, aged 7–18 years, or in need of catch-up vaccine—include reference to a single dose of the A/H1N1 influenza vaccine; revaccination with meningococcal conjugate vaccine for children who remain at increased risk for meningococcal disease; use of combination vaccines, including advice on the administration of the final dose of inactivated poliovirus vaccine; and use of the bivalent human papillomavirus vaccine in females and the quadrivalent papillomavirus product in males. (AAP Committee on Infectious Diseases)
Alternative Venues for Adolescent Immunizations: Teenagers enrolled in Medicaid programs often do not have annual preventive-care visits, and researchers write that this means that administration of immunizations in alternative settings should be considered for some subpopulations of adolescents (pp. 43–9). Analysis of outpatient claims data for 2001–05 in Michigan showed these patterns for annual health-maintenance examinations (HMEs): “Of the 718,847 adolescents included in the study, <50% had 1 HME visit within any 2-year time period, and substantially fewer (<15%) had annual HMEs. In contrast, at least 75% of the adolescents had 1 problem-focused visit in any given 2-year period, and approximately half had participated in at least 2 problem-focused visits. Problem-focused, but not HME, visit utilization was significantly associated with gender, with girls increasing, but boys decreasing, visit utilization as they aged.” (A. F. Dempsey)
Vitamin D Supplements During Prolonged Breastfeeding: In a practice-based research network, only a few infants breastfed for more than 6 months received needed vitamin D supplementation, researchers report (pp. 105–11). Surveys of pediatricians and parents with children 6–24 months of age showed the following: “Among 44 responding pediatricians, 36.4% indicated that they recommended vitamin D supplementation for all breastfed infants. A total of 2,364 surveys were completed on age-eligible children; 1,140 infants were breastfed for at least 6 months with little or no formula supplementation. The rate of vitamin D use for these infants was 15.9%. Use of vitamin D was significantly associated with parental agreement that their child’s pediatrician recommended supplementation (odds ratio [OR]: 7.8), and that vitamins are unnecessary because breast milk has all needed nutrition (OR: 0.12). Among parents of predominantly breastfed infants who indicated that their child’s doctor recommended vitamin D, 44.6% gave the supplementation to their child. Conversely, 67% of parents agreed that breast milk has all needed nutrition, and only 3% of these parents gave vitamin D to their children.” (J. A. Taylor)

>>>PNN NewsWatch
* An unusual Tylenol recall generated coverage in the lay media over the holidays. FDA said a moldy, musty, or mildew-like odor in all lots of Tylenol Arthritis Pain Caplets in 100-count bottles was caused by presence of a chemical, 2,4,6-tribromoanisole, that came from wooden pallets on which the products were stored.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 7, 2010 * Vol. 17, No. 4
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 7 issue of the New England Journal of Medicine (2010; 362).
Preventing Surgical-Site Infections in S. aureus Carriers: Identifying and decolonizing nasal carriers of Staphylococcus aureus can lead to lower rates of surgical-site infections caused by the pathogen, a research study shows (pp. 9–17). Rapid screening with polymerase chain reaction assays and treatment of carriers with mupirocin nasal ointment and chlorhexidine soap produced these outcomes in a randomized controlled trial: “From October 2005 through June 2007, a total of 6,771 patients were screened on admission. A total of 1,270 nasal swabs from 1,251 patients were positive for S. aureus. We enrolled 917 of these patients in the intention-to-treat analysis, of whom 808 (88.1%) underwent a surgical procedure. All the S. aureus strains identified on PCR assay were susceptible to methicillin and mupirocin. The rate of S. aureus infection was 3.4% (17 of 504 patients) in the mupirocin–chlorhexidine group, as compared with 7.7% (32 of 413 patients) in the placebo group (relative risk of infection, 0.42; 95% confidence interval [CI], 0.23 to 0.75). The effect of mupirocin–chlorhexidine treatment was most pronounced for deep surgical-site infections (relative risk, 0.21; 95% CI, 0.07 to 0.62). There was no significant difference in all-cause in-hospital mortality between the two groups. The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocin–chlorhexidine group (P = 0.005).” (L. G. M. Bode, l.bode@erasmusmc.nl)
Commenting on this and another study that compared chlorhexidine–alcohol and povidone–iodine as surgical scrubs (
pp. 18–26; R. O. Darouiche, rdarouiche@aol.com), an editorialist makes recommendations for preventing postoperative infections (pp. 75–7): “The weight of evidence suggests that chlorhexidine–alcohol should replace povidone–iodine as the standard for preoperative surgical scrubs. The use of intranasal mupirocin and chlorhexidine baths for carriers of S. aureus who have been identified preoperatively by means of a real-time polymerase-chain-reaction assay could be reserved primarily for patients who are undergoing cardiac surgery, all patients receiving an implant, and all immunosuppressed surgical candidates. Currently, the incremental value of preoperative baths with chlorhexidine alone for all surgical patients is unclear, but this relatively straightforward procedure could be examined critically in future studies. In the meantime, the data reported in these two studies offer remarkably safer strategies for all patients who require surgery.” (R. P. Wenzel)
Genes for Asthma: A study of genomes of patients with asthma has associated changes in a specific enzyme with occurrence of asthma (pp. 36–44). Included in the genomewide study were 793 North American children of European ancestry with persistent asthma and 1,988 matched controls (the discovery set) and an independent cohort of 917 persons of European ancestry with asthma and 1,546 matched controls (the replication set). The researchers also looked for an association between 20 single-nucleotide polymorphisms (SNPs) at chromosome 1q31 and asthma in 1,667 North American children of African ancestry with asthma and 2,045 ancestrally matched controls. Results showed: “In our meta-analysis of all samples from persons of European ancestry, we observed an association, with genomewide significance, between asthma and SNPs at the previously reported locus on 17q21 and an additional eight SNPs at a novel locus on 1q31. The SNP most strongly associated with asthma was rs2786098 (P = 8.55x10–9). We observed replication of the association of asthma with SNP rs2786098 in the independent series of persons of European ancestry (combined P = 9.3x10–11). The alternative allele of each of the eight SNPs on chromosome 1q31 was strongly associated with asthma in the children of African ancestry (P = 1.6x10–13 for the comparison across all samples). The 1q31 locus contains DENND1B, a gene that is expressed by natural killer cells and dendritic cells and that encodes a protein that interacts with the tumor necrosis factor alpha receptor.” (H. Hakonarson, hakonarson@email.chop.edu)

>>>PNN NewsWatch
* The Medication Exposure in Pregnancy Risk Evaluation Program is a new FDA effort to study the effects of prescription medications when used during pregnancy.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 8, 2010 * Vol. 17, No. 5
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Jan. issue of Diabetes Care (2010; 33).
Need for Metformin Treatment of Prediabetes: One in 12 American adults “has a combination of prediabetes and risk factors [that] may justify consideration of metformin treatment for diabetes prevention,” write authors of a study that analyzed data on 1,581 participants in the Screening for Impaired Glucose Tolerance (SIGT), 2,014 patients in the Third National Health and Nutrition Examination Survey (NHANES III), and 1,111 participants in the National Health and Nutrition Examination Survey 2005–2006 (NHANES 2005–2006) (pp. 49–54). Using the ADA’s criteria for consideration of metformin therapy (impaired fasting glucose [IFG], impaired glucose tolerance [IGT], and risk factors for diabetes), the investigators found: “Isolated IFG, isolated IGT, and IFG and IGT were found in 18.0, 7.2, and 8.2% of SIGT; 22.3, 6.4, and 9.4% of NHANES III; and 21.8, 5.0, and 9.0% of NHANES 2005–2006 subjects, respectively. In SIGT, NHANES III, and NHANES 2005–2006, criteria for metformin consideration were met in 99, 96, and 96% of those with IFG and IGT; 31, 29, and 28% of all those with IFG; and 53, 57, and 62% of all those with IGT (8.1, 9.1, and 8.7% of all subjects), respectively.” (M. K. Rhee, mrhee@emory.edu)
Safety of Insulin Glargine in Pregnancy: Therapeutic doses of insulin glargine are not likely to cross the placenta when used in pregnant women, researchers report (pp. 29–33). Using placentae obtained following elective cesarean sections, investigators tested maternal and fetal circuits ex vivo using therapeutic (150 pmol/L) and supratherapeutic (150, 225, 300 nmol/L) concentrations of insulin glargine, with these results: “Results from perfusions carried out at therapeutic concentrations (150 pmol/l) of insulin glargine showed no detectable insulin glargine in the fetal circuit. After perfusion with very high insulin glargine concentrations of 150, 225, and 300 nmol/l, the rate of transfer remained low at 0.079 ± 0.01, 0.14, and 0.064 pmol · min−1 · g tissue−1, respectively.” (G. Koren, gkoren@sickkids.ca)

>>>Pharmacotherapy Report
Source:
Jan. issue of Pharmacotherapy (2010; 30).
Genotypic Risk of Potassium Excursions with Spironolactone: In patients with heart failure who have the NR3C2 215G allele or possible elevated aldosterone concentrations (as evidenced by requirement for high diuretic doses), potassium concentrations should be monitored with “particular caution” during spironolactone therapy, a 62-patient study shows (pp. 1–9). In two adult heart failure clinics, these differences were noted among those whose serum potassium concentrations increased with spironolactone by more than 0.5 meq/L (n = 15) and 47 other patients: “Patients with a greater potassium level elevation had a higher mean ± SD aldosterone concentration (178 ± 92 vs 102 ± 57 pg/ml, p = 0.007) and NR3C2 215G allele frequency (50% vs 22%, p < 0.01). Aldosterone concentrations positively correlated with diuretic dose (r = 0.313, p = 0.014) and negatively correlated with serum potassium level (r = −0.319, p = 0.012). On regression analysis, factors predictive of potassium level increases greater than 0.5 mEq/L with spironolactone were aldosterone level greater than 150 pg/ml (odds ratio [OR] 30, 95% confidence interval [CI] 3.2–287] and NR3C2 215G carrier status (OR 17, 95% CI 1.6–167).” (L. H. Cavallari, humma@uic.edu)
Immunogenicity to New Influenza Antigens in Heart Failure: Reduced but adequate T-cell responses were noted in patients with congestive heart failure during immunization with the 2006–07 trivalent inactivated influenza vaccine, with significantly lower response to the novel A/H3N2 antigen being used for the first time (pp. 10–6). Measurement of antibody titers using a hemagglutination inhibition assay at times 0, 2–4 weeks, and 3–4 months showed these results: “Median T-cell–mediated immune responses to A/H3N2 were less vigorous in patients with CHF than in control subjects (62.5 vs 87.5 µm, unadjusted p = 0.031, age-adjusted p = 0.006). Median responses to A/H1N1 were not significantly different between the groups (56.3 vs 75 µm, p = 0.11). Median responses to B type were also similar between the groups (62.5 vs 75 µm, p = 0.47). All participants mounted an antibody response to the influenza vaccine.” (O. Vardeny)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 11, 2010 * Vol. 17, No. 6
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2010; 340).
Hypoglycemia & Mortality: In one of two early-release papers from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, an increased risk of death was found in 10,194 patients with type 2 diabetes regardless of whether they were managed with intensive glycemic control strategies or usual care (b4909). The data from the study, whose intensive-control arm was stopped early, show a lower risk of death among those who had one or more hypoglycemic episode, making it unlikely that symptomatic, severe hypoglycemia caused the difference in mortality that led to the study arm to be terminated. Intensive control was aimed at achieving glycosylated hemoglobin levels below 6%; standard glucose control sought to achieve A1C levels of 7.0–7.9%. Results showed the following: “Unadjusted annual mortality among patients in the intensive glucose control arm was 2.8% in those who had one or more episodes of hypoglycaemia requiring any assistance compared with 1.2% for those with no episodes (53 deaths per 1,924 person years and 201 deaths per 16m315 person years, respectively; adjusted hazard ratio (HR) 1.41, 95% CI 1.03 to 1.93). A similar pattern was seen among participants in the standard glucose control arm (3.7% (21 deaths per 564 person years) v 1.0% (176 deaths per 17,297 person years); adjusted HR 2.30, 95% CI 1.46 to 3.65). On the other hand, among participants with at least one hypoglycaemic episode requiring any assistance, a non-significantly lower risk of death was seen in those in the intensive arm compared with those in the standard arm (adjusted HR 0.74, 95% 0.46 to 1.23). A significantly lower risk was observed in the intensive arm compared with the standard arm in participants who had experienced at least one hypoglycaemic episode requiring medical assistance (adjusted HR 0.55, 95% CI 0.31 to 0.99). Of the 451 deaths that occurred in ACCORD up to the time when the intensive treatment arm was closed, one death was adjudicated as definitely related to hypoglycaemia.” (D. E. Bonds, bondsde@nhlbi.nih.gov)
Glycemic Control & Severe Hypoglycemia: In the second ACCORD report, patients at greatest risk of hypoglycemia were those with overall poorer glycemic control, irrespective of their assigned study group (b5444). “Identification of baseline subgroups with increased risk for severe hypoglycaemia can provide guidance to clinicians attempting to modify patient therapy on the basis of individual risk,” the investigators conclude. (M. E. Miller, mmiller@wfubmc.edu)

Lancet Highlights
Source:
Jan. 9 issue of Lancet (2010; 375).
Antiretroviral Therapy Monitoring Patterns: Clinically driven monitoring (CDM) of antiretroviral therapy was used safely in an open noninferiority trial in Africa, but data suggest a role for routine ART monitoring starting in the second year to detect the need for second-line agents, researchers report (pp. 123–31). Laboratory and clinical monitoring (LCM) is often used as-needed in resource-poor countries, and investigators studied its effects in a trial of more than 3,300 patients: “5-year survival was 87% (95% CI 85–88) in the CDM group and 90% (88–91) in the LCM group, and 122 (7%) and 112 (7%) participants, respectively, were lost to follow-up over median 4.9 years’ follow-up. 459 (28%) participants receiving CDM versus 356 (21%) LCM had a new WHO stage 4 event or died (6.94 [95% CI 6.33–7.60] vs 5.24 [4.72–5.81] per 100 person–years; absolute difference 1.70 per 100 person–years [0.87–2.54]; HR 1.31 [1.14–1.51]; p =0 .0001). Differences in disease progression occurred from the third year on ART, whereas higher rates of switch to second-line treatment occurred in LCM from the second year. 283 (17%) participants receiving CDM versus 260 (16%) LCM had a new serious adverse event (HR 1.12 [0.94–1.32]; p = 0.19), with anaemia the most common (76 vs 61 cases).” (DART Trial Team)

>>>PNN JournalWatch
* Diagnosis and Management of Vitamin D Deficiency, in BMJ, 2010; 340: b5664. (S. H. S. Pearce, s.h.s.pearce@ncl.ac.uk)
* Recent Insights into Atopic Dermatitis and Implications for Management of Infectious Complications, in
Journal of Allergy and Clinical Immunology, 2010; 125: 4–13. (M. Boguniewicz, boguniewiczm@njhealth.org)
* Specialists/Subspecialists and the Patient-Centered Medical Home, in
Chest, 2010; 137: 200–4. (N. Kirschner, nkirschner@acponline.org)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 12, 2010 * Vol. 17, No. 7
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Jan. 11 issue of the Archives of Internal Medicine (2010; 170).
Improving Prescription Drug Warnings: Replacing traditionally worded prescription drug warning labels with simple, explicit language improves patients’ understanding, according to a study of 500 adult patients (pp. 50–6). Those who viewed three types of warning labels (currently used warning labels [standard; e.g., “For external use only”], warnings written in plain language [simplified text; e.g., “Use only on your skin”], and plain language plus icons [simplified text + icon]) said what they thought the labels meant during a structured cognitive interview. A panel categorized the responses: “Overall rates of correct interpretation of drug warnings varied among standard, simplified text, and simplified text + icon labels (80.3%, 90.6%, and 92.1%, respectively; P < .001). Warnings with simplified text and simplified text + icons were more likely to be correctly interpreted compared with standard labels (simplified text–adjusted odds ratio [AOR] = 2.64; 95% confidence interval [CI], 2.00–3.49; simplified text + icons–AOR = 3.26; 95% CI, 2.46–4.32). Patients’ ability to correctly interpret labels was not significantly different with the inclusion of icons (simplified text + icons–AOR = 1.23; 95% CI, 0.90–1.67; P = .20). Low literacy was also an independent predictor of misinterpretation (AOR, 0.65; 95% CI, 0.44–0.94). Patients with marginal and low literacy were better able to correctly interpret warning labels with simplified text + icons compared with labels with simplified text only (marginal literacy–AOR = 2.59; 95% CI, 1.24–5.44; P = .01; low literacy–AOR = 3.22; 95% CI, 1.39–7.50; P = .006).” (M. S. Wolf, mswolf@northwestern.edu)
Treatment Modification in HIV: Among patients with HIV infection beginning combination antiretroviral therapy (CART) in 2005–08, drug toxicity was a common reason for later therapy modification, but toxicity did not affect treatment success, researchers from the Swiss HIV Cohort Study report (pp. 57–65). Concluding that “close monitoring and management of adverse effects and drug–drug interactions are crucial for the durability of CART,” the investigators report these trends among study participants: “The total rate of treatment modification was 41.5 (95% confidence interval [CI], 37.6–45.8) per 100 person–years. Of these, switches or discontinuations because of drug toxicity occurred at a rate of 22.4 (95% CI, 19.5–25.6) per 100 person–years. The most frequent toxic effects were gastrointestinal tract intolerance (28.9%), hypersensitivity (18.3%), central nervous system adverse events (17.3%), and hepatic events (11.5%). In the multivariate analysis, combined zidovudine and lamivudine (hazard ratio [HR], 2.71 [95% CI, 1.95–3.83]; P < .001), nevirapine (1.95 [1.01–3.81]; P = .050), comedication for an opportunistic infection (2.24 [1.19–4.21]; P = .01), advanced age (1.21 [1.03–1.40] per 10-year increase; P = .02), female sex (1.68 [1.14–2.48]; P = .009), nonwhite ethnicity (1.71 [1.18–2.47]; P = .005), higher baseline CD4 cell count (1.19 [1.10–1.28] per 100/mcL increase; P < .001), and HIV-RNA of more than 5.0 log10 copies/mL (1.47 [1.10–1.97]; P = .009) were associated with higher rates of treatment modification. Almost 90% of individuals with treatment-limiting toxic effects were switched to a new regimen, and 85% achieved virologic suppression to less than 50 copies/mL at 12 months compared with 87% of those continuing CART (P = .56).” (M. Battegay, mbattegay@uhbs.ch)
An editorialist describes challenges in adverse effects of HIV drugs, viral resistance, awareness of infection, and ongoing HIV transmission (
pp. 6–8; M. H. Katz, mitch.katz@sfdph.org).

>>>PNN NewsWatch
* Tocilizumab (Actemra, Genentech) has been approved by FDA for treatment of adults with moderate to severe rheumatoid arthritis who have not adequately responded to or cannot tolerate drugs in other approved classes. The agent, which blocks interleukin-6, was associated with a number of serious adverse effects (elevated liver enzymes and low-density lipoprotein levels, hypertension, gastrointestinal perforations) during clinical trials, and thus it should be reserved for second- or third-line treatment of RA. FDA is requiring a postmarketing clinical trial to evaluate the long-term safety of tocilizumab, Risk Evaluation and Mitigation Strategy, communication plan for physicians, and MedGuide for patients.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 13, 2010 * Vol. 17, No. 8
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 13 issue of JAMA (2010; 303).
U.S. Biomedical Research Funding: In 2003–08, growth in all-source funding of biomedical research in the U.S. declined from double-digit growth of the prior decade and then shrank by 2% (pp. 137–43). Looking at government, private, and industry sources and FDA approvals from 1993 through 2007, the investigators determined: “Biomedical research funding increased from $75.5 billion in 2003 to $101.1 billion in 2007. In 2008, funding from the National Institutes of Health and industry totaled $88.8 billion. In 2007, funding from these sources, adjusted for inflation, was $90.2 billion. Adjusted for inflation, funding from 2003 to 2007 increased by 14%, for a compound annual growth rate of 3.4%. By comparison, funding from 1994 to 2003 increased at an annual rate of 7.8% (P < .001). In 2007, industry (58%) was the largest funder, followed by the federal government (33%). Modest increase in funding was not accompanied by an increase in approvals for drugs or devices. In 2007, the United States spent an estimated 4.5% of its total health expenditures on biomedical research and 0.1% on health services research.” (E. R. Dorsey, ray.dorsey@ctcc.rochester.edu)
An editorialist notes the need for a more balanced approach to biomedical research funding (
pp. 170–1): “National research policy should address not only funding of adequate, stable, and productive biomedical research but also adequate funding of research that addresses interventions designed to improve the delivery of a broad range of health services at an affordable cost. New drugs, biologics, and devices are needed to prevent and alleviate disease-related morbidity and extend the productive lives of individuals having a multitude of disorders for which there is no effective treatment. Productivity of research aimed at improving these outcomes deserves ongoing emphasis. Balancing funding for investigative efforts across the entire spectrum of health care needs also deserves the highest level of attention.” (T. F. Boat, thomas.boat@cchmc.org)
Screening for Breast Cancer: Commenting on the controversial 2009 breast cancer screening recommendations from the U.S. Preventive Services Task Force (pp. 162–3; S. H. Woolf, swoolf@vcu.edu) and three related commentaries (pp. 164–5, L. M. Schwartz, lisa.schwartz@dartmouth.edu; pp. 166–7, A. M. Murphy, amurphy2@jhmi.edu; pp. 168–9, W. A. Berg, wendieberg@gmail.com), JAMA editors make these observations in an editorial (pp. 172–3): “Physicians and patients should continue to rely on unbiased, rigorous, objective evaluation of the available evidence for recommendations about screening for breast cancer and other clinical interventions. Perhaps now more than ever—especially with the current debates about health system reform and health care funding, with the media providing instant if not always completely accurate health news, and with the importance of preventing the politicization of biological science—independent panels such as the USPSTF and the Institute of Medicine committees are essential to provide objective appraisals, reports, and guidelines without concern about special interests, politics, or ideology or fear of repercussions for seeking the truth in providing evidence-based recommendations. In issuing the 2009 recommendation statement, the USPSTF has fulfilled its mandate to provide guidance and evidence that will help physicians and patients make informed, individualized decisions about screening for breast cancer.” (C. D. DeAngelis, cathy.deangelis@jama-archives.org)

>>>Circulation Report
Source:
Jan. 5/12 issue of Circulation (2010; 121).
Costs of Prasugrel v. Clopidogrel: A cost-effectiveness analysis shows that prasugrel is “an economically attractive” alternative to clopidogrel in patients awaiting planned percutaneous coronary interventions for up to 15 months (pp. 71–9). Assessing data from the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) from the perspective of the U.S. health care system, investigators found mean total costs to be lower by $221 per patient and life expectancy gains of 0.102 years over an average of 14.7 months, compared with clopidogrel. (E. M. Mahoney, emahoney1@saint-lukes.org)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 14, 2010 * Vol. 17, No. 9
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 14 issue of the New England Journal of Medicine (2010; 362).
Morphine Use & Development of Posttraumatic Stress Disorder: Patients who receive morphine during trauma care develop posttraumatic stress disorder less often, according to a study of U.S. military personnel with serious nonbrain injuries (pp. 110–7). These results were noted: “Among the 696 patients studied, 243 received a diagnosis of PTSD and 453 did not. The use of morphine during early resuscitation and trauma care was significantly associated with a lower risk of PTSD after injury. Among the patients in whom PTSD developed, 61% received morphine; among those in whom PTSD did not develop, 76% received morphine (odds ratio, 0.47; P < 0.001). This association remained significant after adjustment for injury severity, age, mechanism of injury, status with respect to amputation, and selected injury-related clinical factors.” (T. L. Holbrook, troy@epi-soar.com)
An editorialist explores the implications of this study in trauma management (
pp. 168–70): “What about persons with minor injuries or no injuries in the aftermath of major trauma who do not need morphine to attenuate physical pain? It is possible that the routine administration of morphine could protect them from subsequent PTSD, but it is unlikely that this could become acceptable in clinical practice. This disorder is understood to develop from Pavlovian fear conditioning in which the adrenergic activation of the amygdala during the traumatic event facilitates encoding of traumatic memories. Indeed, microinjections of norepinephrine into the amygdala in rats can enhance fear conditioning, and this response can be blocked by propranolol. Adrenergic activation can also be blocked by morphine operating at mu-opioid receptors located both in the amygdala and the locus ceruleus (which houses most of the brain’s adrenergic neurons). Presynaptic inhibitory 2-noradrenergic receptors operate synergistically with opiate mu-opioid receptors and also blunt adrenergic activation in both the amygdala and the locus ceruleus.” (M. J. Friedman)
Ustekinumab for Psoriasis: Among 903 patients with moderate-to-severe psoriasis, ustekinumab 45–90 mg was superior to that of high-dose etanercept in a 12-week trial (pp. 118–28). Ustekinumab, an inhibitor of interleukins 12 and 23, was administered subcutaneously at weeks 0 and 4, while etanercept 50 mg was administered subcutaneously twice weekly. Looking at the proportion of patients with 75% or more improvement in the psoriasis area-and-severity index (PASI) at week 12, the investigators found: “There was at least 75% improvement in the PASI at week 12 in 67.5% of patients who received 45 mg of ustekinumab and 73.8% of patients who received 90 mg, as compared with 56.8% of those who received etanercept (P = 0.01 and P < 0.001, respectively). Similarly, 65.1% of patients who received 45 mg of ustekinumab and 70.6% of patients who received 90 mg of ustekinumab had cleared or minimal disease according to the physician’s global assessment, as compared with 49.0% of those who received etanercept (P < 0.001 for both comparisons). Among patients who did not have a response to etanercept, 48.9% had at least 75% improvement in the PASI within 12 weeks after crossover to ustekinumab. One or more adverse events occurred through week 12 in 66.0% of patients who received 45 mg of ustekinumab and 69.2% of patients who received 90 mg of ustekinumab and in 70.0% who received etanercept; 1.9%, 1.2%, and 1.2%, respectively, had serious adverse events. Safety patterns were similar before and after crossover from etanercept to ustekinumab.” (C. E. M. Griffiths, christopher.griffiths@manchester.ac.uk)
Measuring Health Care: After discussing the poor performance of the U.S. health care system in a variety of commonly cited worldwide rankings, Perspective authors provide this post-health care reform scenario (pp. 98–9): “Within the United States, there are dramatic variations among regions and racial or ethnic groups in the rates of death from preventable causes. While aiming to provide solutions to the problems of incomplete insurance coverage and inefficiency of care delivery, health care reformers have given insufficient attention to the design, funding, and evaluation of interventions that are tailored to local realities and address preventable causes of death.” (C. J. L. Murray)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 15, 2010 * Vol. 17, No. 10
Providing news and information about medications and their proper use

>>>Allergy/Immunology Report
Source:
Jan. issue of the Journal of Allergy and Clinical Immunology (2010; 125).
Advances in Pediatric Asthma: An annual review reports progress in gaining control of childhood asthma (pp. 69–78): “New National Asthma Education and Prevention Program asthma guidelines were released in 2007, with a particular emphasis on asthma control. Now that we have worked with the principals of the guidelines for 2 years, new insights are reported on how to implement the guidelines into clinical practice. This year’s report will focus on gaps in management that need to be addressed, including health disparities, methods to improve asthma management through opportunities available in school-based asthma programs, and more information on the development of asthma in childhood. This information brings us closer to the point of managing children with controllable asthma and understanding reasons why asthma is not controlled in the remaining children. If we can close these gaps through better communication, improvements in the health care system, and new insights into treatment, we will move closer to better methods to intervene early in the course of the disease and induce clinical remission as quickly as possible in most children.” (S. J. Szefler, szeflers@njhealth.org)
Sublingual Grass Allergy Immunotherapy: Patients receiving sublingual tablets containing grass allergy immunotherapy showed consistent clinical and immunologic improvements during 3 years’ treatment and for 1 year thereafter, researchers report (pp. 131–8.e7). In a Phase III trial, 257 adults with moderate-to-severe grass pollen–induced rhinoconjunctivitis showed these changes in efficacy and immunologic end points: “Significant improvements in efficacy were consistently shown during 3 years’ treatment. One year after treatment, the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores (26%, P < .001) and medication scores (29%, P = .022) when compared with placebo. This level was similar to the efficacy observed during the 3-year treatment period. The differences in percentages of symptom- and medication-free days were significant during and 1 year after treatment. The active group also reported sustained and significant improvements in quality of life. Sustained clinical benefit was accompanied by immunologic changes. No safety issues were identified.” (S. R. Durham, s.durham@imperial.ac.uk)

>>>Chest Highlights
Source:
Jan. issue of Chest (2010; 137).
Safety of Drug Therapy in COPD: Authors of two studies focus on the cardiovascular safety of ipratropium and tiotropium.
A cohort of U.S. veterans with new diagnoses of chronic obstructive pulmonary disorders in 1999–2002 had an increased risk of cardiovascular events associated with use of ipratropium bromide during the past 6 months (
pp. 13–9). Researchers concluded, “These findings are consistent with previous concerns raised about the cardiovascular safety of ipratropium bromide.” (T. A. Lee, todd.lee@va.gov)
Contrary findings came from the second study, which showed an reduced risk in all-cause deaths, cardiovascular mortality, and cardiovascular events in patients with COPD using tiotropium (
pp. 20–30). The study compiled data from 30 clinical trials of 19,545 patients. Incidence rates with tiotropium were 3.44 per 100 patient–years for all-cause mortality, 2.15 per 100 patient–years for a composite cardiovascular end point, and 0.91 per 100 patient–years for cardiovascular mortality, all significantly lower than with placebo. (B. Celli, bcelli@cchcs.org)

>>>PNN NewsWatch
* Chest and the American College of Chest Physicians celebrate 75 years by naming 75 seminal studies selected from more than 36,000 articles published in the ACCP journal since its inception in 1935. A special print supplement contains the text of the 12 “most important” articles, and the other articles are provided online.
*
Tiotropium use is not associated with greater risk of stroke, myocardial infarction, or death, FDA has concluded after reviewing UPLIFT (Understanding the Potential Long-Term Impacts on Function with Tiotropium) data. The possibility of adverse effects had been reported originally in March 2008.
*
PNN will not be published on Mon., Jan. 18, King Day.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 19, 2010 * Vol. 17, No. 11
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Jan. 19 issue of the Annals of Internal Medicine (2010; 152).
Optimal Statin Therapy: Compared with recommendations of the National Cholesterol Education Program (NCEP) for preventing coronary artery disease (CAD), tailored treatment provides greater benefits to patients with less use of high-dose statins, researchers report (pp. 69–77). Based on a simulated population effects of NCEP’s standard and intensive treat-to-target approaches and tailored treatment based on individuals’ 5-year CAD risk, these calculations were made concerning quality-adjusted life–years (QALYs) from societal and individual perspectives: “Compared with the standard NCEP III approach, the intensive NCEP III approach treated 15 million more persons and saved 570,000 more QALYs over 5 years. The tailored strategy treated a similar number of persons, as did the intensive NCEP III approach, but saved 500,000 more QALYs and treated fewer persons with high-dose statins.” (R. A. Hayward, rhayward@umich.edu)
Atrial Fibrillation with Antihypertensive Drugs: Calcium-channel blockers are not as protective against incident atrial fibrillation as other classes of antihypertensive agents, according to a nested case–control analysis of the U.K. General Practice Research Database (pp. 78–84). Considering 4,661 patients with AF and 18,642 matched controls who were selected from nearly 700,000 patients treated for hypertension, the investigators calculated these risks of AF: “Current exclusive long-term therapy with ACE inhibitors (odds ratio [OR], 0.75 [95% CI, 0.65 to 0.87]), [angiotensin II receptor blockers] (OR, 0.71 [CI, 0.57 to 0.89]), or beta-blockers (OR, 0.78 [CI, 0.67 to 0.92]) was associated with a lower risk for atrial fibrillation than current exclusive therapy with calcium-channel blockers.” (C. R. Meier, meierch@uhbs.ch)
Opioids & Overdose: Patients receiving prescriptions for higher doses of opioids are at greater risk of overdose and should have close supervision, authors who analyzed an HMO database conclude (pp. 85–92). A study of 9,940 persons receiving three or more opioid prescriptions within 90 days for chronic noncancer pain showed the following: “51 opioid-related overdoses were identified, including 6 deaths. Compared with patients receiving 1 to 20 mg/d of opioids (0.2% annual overdose rate), patients receiving 50 to 99 mg/d had a 3.7-fold increase in overdose risk (95% CI, 1.5 to 9.5) and a 0.7% annual overdose rate. Patients receiving 100 mg/d or more had an 8.9-fold increase in overdose risk (CI, 4.0 to 19.7) and a 1.8% annual overdose rate.” (M. Von Korff, vonkorff.m@ghc.org)

>>>Lancet Highlights
Source:
Jan. 16 issue of Lancet (2010; 375).
Misoprostol for Postpartum Bleeding: For stopping excessive postpartum bleeding in oxytocin-treated women with possible uterine atony, sublingual misoprostol is clinically equivalent to intravenous oxytocin, a study shows (pp. 217–23). Among 809 women at five hospitals, these results were noted with misoprostol 800 mcg and oxytocin 40 IU: “Active bleeding was controlled within 20 min after initial treatment for 363 (89%) women given misoprostol and 360 (90%) given oxytocin (relative risk [RR] 0.99, 95% CI 0.95–1.04; crude difference 0.4%, 95% CI –3.9 to 4.6). Additional blood loss of 300 mL or greater after treatment occurred for 139 (34%) women receiving misoprostol and 123 (31%) receiving oxytocin (RR 1.12, 95% CI 0.92–1.37). Shivering (152 [37%] vs 59 [15%]; RR 2.54, 95% CI 1.95–3.32) and fever (88 [22%] vs 59 [15%]; 1.47, 1.09–1.99) were significantly more common with misoprostol than with oxytocin. Six women had hysterectomies and two women died.” (J. Blum, jblum@gynuity.org)
A second paper details the results of misoprostol treatment in women who did not receive oxytocin before delivery, concluding, “In settings in which use of oxytocin is not feasible, misoprostol might be a suitable first-line treatment alternative for post-partum haemorrhage.” (
pp. 210–6; R. Dabash, rdabash@gynuity.org)

>>>PNN JournalWatch
* The Role of Leptin in Human Physiology: Emerging Clinical Applications, in Annals of Internal Medicine, 2010; 152: 93–100. (C. S. Mantzoros, cmantzor@bidmc.harvard.edu)
* The Breast Cancer Alternative Hypothesis: Is There Evidence to Justify Replacing It?, in
Journal of Clinical Oncology, 2010; 28: 366–74. (B. Fisher, fisherb2@upmc.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 20, 2010 * Vol. 17, No. 12
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 20 issue of JAMA (2010; 303).
Obesity & High Body Mass Index—Epidemiologic Transition? Two research articles and an editorial examine the growing waistlines of Americans.
Among U.S. adults, 32.2% of men and 35.5% of women were obese in 2007–08, reflecting a plateau in the epidemic of obesity and overweight evident since the 1970s (
pp. 235–41). Comparing data from the 2007–08 National Health and Nutrition Examination Survey (NHANES) with those from 1999 through 2006, investigators found: “In 2007–2008, the age-adjusted prevalence of obesity was 33.8% (95% confidence interval [CI], 31.6%–36.0%) overall, 32.2% (95% CI, 29.5%–35.0%) among men, and 35.5% (95% CI, 33.2%–37.7%) among women. The corresponding prevalence estimates for overweight and obesity combined (BMI 25) were 68.0% (95% CI, 66.3%–69.8%), 72.3% (95% CI, 70.4%–74.1%), and 64.1% (95% CI, 61.3%–66.9%). Obesity prevalence varied by age group and by racial and ethnic group for both men and women. Over the 10-year period, obesity showed no significant trend among women (adjusted odds ratio [AOR] for 2007–2008 vs 1999–2000, 1.12 [95% CI, 0.89–1.32]). For men, there was a significant linear trend (AOR for 2007–2008 vs 1999–2000, 1.32 [95% CI, 1.12–1.58]); however, the 3 most recent data points did not differ significantly from each other.” (K. M. Flegal, kmf2@cdc.gov)
Other than in the heaviest of young boys, body mass index among American children and adolescents has leveled off, a study shows (
pp. 242–9). Estimates of high BMI among children and adolescents and high weight for recumbent length among infants and toddlers, derived from the National Health and Nutrition Examination Survey 2007–08, showed these patterns during the first years of the 2000s: “In 2007–2008, 9.5% of infants and toddlers (95% confidence interval [CI], 7.3%–11.7%) were at or above the 95th percentile of the weight-for-recumbent-length growth charts. Among children and adolescents aged 2 through 19 years, 11.9% (95% CI, 9.8%–13.9%) were at or above the 97th percentile of the BMI-for-age growth charts; 16.9% (95% CI, 14.1%–19.6%) were at or above the 95th percentile; and 31.7% (95% CI, 29.2%–34.1%) were at or above the 85th percentile of BMI for age. Prevalence estimates differed by age and by race/ethnic group. Trend analyses indicate no significant trend between 1999–2000 and 2007–2008 except at the highest BMI cut point (BMI for age 97th percentile) among all 6- through 19-year-old boys (odds ratio [OR], 1.52; 95% CI, 1.17–2.01) and among non–Hispanic white boys of the same age (OR, 1.87; 95% CI, 1.22–2.94).” (C. L. Ogden, cogden@cdc.gov)
Does our age of inactivity and obesity reflect a fifth epidemiologic transition? An editorialist, reflecting on these two studies, thinks so (
pp. 275–6): “Given the risk of obesity-related major health problems, a massive public health campaign to raise awareness about the effects of overweight and obesity is necessary. Such campaigns have been successful in communicating the dangers of smoking, hypertension, and dyslipidemia; educating physicians, other clinicians, and the public has yielded significant returns. Major research initiatives are needed to identify better management and treatment options. The longer the delay in taking aggressive action, the higher the likelihood that the significant progress achieved in decreasing chronic disease rates during the last 40 years will be negated, possibly even with a decrease in life expectancy.” (J. M. Gaziano)
Marine Omega-3 Fatty Acids & Aging: Over a 5-year period in 608 patients with coronary artery disease, changes in a key marker of aging were reduced with higher blood levels of marine omega-3 fatty acids, researchers report (pp. 250–7). Telomere shortening, described in the study as an “emerging marker of biological age,” occurred at faster rates in the those in the lowest quartile of omega-3 levels, while such changes occurred most slowly in the highest quartile. (R. Farzaneh-Far, rfarzanehfar@medicine.ucsf.edu)

>>>PNN NewsWatch
* Nobody saw this one coming. With yesterday’s Republican capture of liberal icon Ted Kennedy’s Massachusetts Senate seat, Democrats are thrown into disarray as they try to wrap up work on health care reform. As described in an article posted on APhA’s pharmacist.com, their options are limited and fraught with political danger.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 21, 2010 * Vol. 17, No. 13
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 21 issue of and early-release articles from the New England Journal of Medicine (2010; 362).
Monoclonal Antibodies Against C. difficile Toxins: Adding two neutralizing monoclonal antibodies to antibiotic therapy can reduce the incidence of Clostridium difficile infection, according to a 200-patient trial (pp. 197–205). Patients were being treated with metronidazole or vancomycin when they had symptomatic C. difficile infections. Addition of the fully human monoclonal antibodies against C. difficile A (CDA1) and B (CDB1) to antibiotic therapy produced these outcomes during 84 days of administration: “Among the 200 patients who were enrolled (101 in the antibody group and 99 in the placebo group), the rate of recurrence of C. difficile infection was lower among patients treated with monoclonal antibodies (7% vs. 25%; 95% confidence interval, 7 to 29; P < 0.001). The recurrence rates among patients with the epidemic BI/NAP1/027 strain were 8% for the antibody group and 32% for the placebo group (P = 0.06); among patients with more than one previous episode of C. difficile infection, recurrence rates were 7% and 38%, respectively (P = 0.006). The mean duration of the initial hospitalization for inpatients did not differ significantly between the antibody and placebo groups (9.5 and 9.4 days, respectively). At least one serious adverse event was reported by 18 patients in the antibody group and by 28 patients in the placebo group (P = 0.09).” (D. C. Molrine, deborah.molrine@umassmed.edu)
The possibility provided by passive immunization with monoclonal antibodies is a welcome tool in the fight against problematic pathogens, an editorialist writes (
pp. 264–5): “Passive immunization with monoclonal antibodies may reduce the rate of recurrence in groups of patients who are likely to have a reduced response to active immunization at a critical time in their illness. Studies are needed to determine whether monoclonal antibodies are useful as adjunctive therapy in patients with severe or fulminant C. difficile infection or whether there is a role for prophylactic passive immunization of patients at high risk for infections associated with health care settings. It is unlikely that monoclonal antibodies will be used for primary treatment, but they may allow a reduction in the number of days of standard antibiotic therapy for C. difficile infection. These novel approaches to breaking the cycle of C. difficile infection, along with continued attention to appropriate antibiotic use and infection prevention and control, offer hope in the battle against this increasingly prevalent and difficult-to-manage disease.” (L. Kyne)
Cause of Lethal Skeletal Dysplasia: The cause of a rare human skeletal dysplasia, achondrogenesis type 1A, is a mutation that results in changes to a Golgi microtubule protein, researchers report (pp. 206–16). Based on mouse and human data, the study concludes, “[Golgi microtubule-associated protein 210] is required for the efficient glycosylation and cellular transport of multiple proteins. The identification of a mutation affecting GMAP-210 in mice, and then in humans, as the cause of a lethal skeletal dysplasia underscores the value of screening for abnormal phenotypes in model organisms and identifying the causative mutations.” (M. L. Warman, matthew.warman@childrens.harvard.edu)
Oral Drugs for Multiple Sclerosis: Two orally administered drugs are effective for treating relapsing multiple sclerosis, according to three research studies released in advance of print.
Fingolimod reduced the rates of relapse and disability progression in a 24-month trial (
10.1056/NEJMoa0909494; L. Kappos, lkappos@uhbs.ch) and was more effective than intramuscular interferon beta-1a in the second study, which lasted 1 year (10.1056/NEJMoa0907839; J. A. Cohen, cohenj@ccf.org).
A 96-week trial demonstrated efficacy of oral cladribine in patients with relapsing MS (
10.1056/NEJMoa0902533). Compared with placebo, both of two doses of cladribine significantly lowered annualized rates of relapse, produced higher relapse-free rate, lowered risk of 3-month sustained progression of disability, and reduced brain lesion counts. Adverse effects of the drug included lymphocytopenia in one-fifth to one-third of patients and herpes zoster in small numbers of patients. (G. Giovannoni, g.giovannoni@qmul.ac.uk)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 22, 2010 * Vol. 17, No. 14
Providing news and information about medications and their proper use

>>>JAPhA Highlights
Source:
Jan/Feb issue of the Journal of the American Pharmacists Association (2010; 50).
Pharmacy-Based Immunization Services: Pharmacies that have been offering immunization services since before 2003 (“sustainers&rdquoWinking more frequently have year-round services, administer vaccine in more settings, provide vaccinations to adolescents, and have more trained pharmacists than do “new adopters” (pp. 52–61). In a mixed-mode survey of pharmacies in Washington State, these trends were evident in 2003, 2004, and 2006–07: “A total of 37 sustainers and 27 new adopters met the inclusion criteria. The majority of independent and supermarket pharmacies were sustainers, whereas the majority of chain and mass merchant pharmacies were new adopters. In-house services offered by sustainers were broader in service accessibility and scope and involved a greater number of pharmacists trained in immunization delivery than services offered by new adopters in the same year. Further, when comparing sustainers’ in-house services offered in 2003 and 2006, the 2006 services were expanded to provide year-round services, involved a greater number of settings, included services to adolescents, and involved a greater number of trained pharmacists.” (S. C. Westrick, westrsc@auburn.edu)
Financial Analysis of MTM: A community pharmacy barely broke even on its medication therapy management services, according to a retrospective financial analysis (pp. 62–6). In 2006–07, these MTM workload and income and expense figures were recorded: “103 initial and 88 follow-up MTM visits were conducted during a 16-month time period. The total cost for these services to the pharmacy was $11,191.72. Total revenue from these services was $11,195.00; therefore, the pharmacy experienced a net financial gain of $3.28. Sensitivity analyses were conducted, revealing the net gain/loss to the pharmacy if a student pharmacist was used and the net gain/loss if the pharmacist needed extra training to provide the services. Using a student pharmacist resulted in a net gain of $6,308.48, while extra training for the pharmacist resulted in a net loss of $1,602.72.” (W. R. Doucette, mailto:william-doucette@uiowa.edu)
Physician Views of Pharmacist-Provided MTM: In three focus groups of 23 Pennsylvania physicians, a need for much education about pharmacist-provided medication therapy management services was evident (pp. 67–71): “Participants identified common medication issues in their practices: nonadherence, adverse effects, drug interactions, medication costs, and incomplete patient understanding of the medication regimen. Receipt of a complete patient medication list was reported as the greatest potential benefit of MTM. Participants believed that physicians would be better suited as MTM providers than pharmacists. Concerns identified were the mechanism of pharmacist payment, reimbursement of time spent by physicians to coordinate care, and the training/preparation of the pharmacist. The need for a trusting relationship between a patient’s primary care physician and the pharmacists providing MTM was identified.” (S. H. McGrath, stephanie.harriman@gmail.com)

>>>Geriatrics Highlights
Source:
Jan. Journal of the American Geriatrics Society (2010; 58).
CAM Use & Antihypertensive Medication Adherence: Among blacks, use of complementary and alternative medicines was associated poor adherence to antihypertensive drugs in a study of more than 2,000 older patients in a managed care organization (pp. 54–61). The researchers found these results: “The mean age of participants was 75.0 ± 5.6, 30.7% were black, 26.5% used CAM, and 14.1% had low antihypertensive medication adherence. In managing blood pressure, 30.5% of black and 24.7% of white participants had used CAM in the last year (P = .005), and 18.4% of black and 12.3% of white participants reported low adherence to antihypertensive medication (<.001). After multivariable adjustment for sociodemographic information, depressive symptoms, and reduction in antihypertensive medications because of cost, the prevalence ratios of low antihypertensive medication adherence associated with CAM use were 1.56 (95% confidence interval (CI) = 1.14–2.15; P = .006) in blacks and 0.95 (95% CI=0.70–1.29; P = .73) in whites (P value for interaction = .07).” (M. Krousel–Wood, mawood@ochsner.org)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 25, 2010 * Vol. 17, No. 15
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Jan. 23 issue of Lancet (2010; 375).
Ticagrelor for ACS: For management of acute coronary syndromes in patients who will undergo early revascularization, ticagrelor proved a better choice than clopidogrel in the PLATO (Planned Invasive Strategy for Acute Coronary Syndromes) study (pp. 283–93). Of 18,624 patients hospitalized for ACS and admitted to the trial, 13,408 were to receive an early invasive strategy. Ticagrelor or clopidogrel were administered to these patients using loading doses and maintenance doses for 6–12 months, with these results: “The primary composite endpoint occurred in fewer patients in the ticagrelor group than in the clopidogrel group (569 [event rate at 360 days 9.0%] vs 668 [10.7%], hazard ratio 0.84, 95% CI 0.75–0.94; p = 0.0025). There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding (691 [11.6%] vs 689 [11.5%], 0.99 [0.89–1.10]; p = 0.8803) or severe bleeding, as defined according to the Global Use of Strategies To Open occluded coronary arteries, (198 [3.2%] vs 185 [2.9%], 0.91 [0.74–1.12]; p = 0.3785).” (C. P. Cannon, cpcannon@partners.org)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2010; 340).
Prediagnosis Vitamin D Levels & Colon Cancer: A large observational study finds a significant, inverse relationship between prediagnostic circulating vitamin D concentrations and risk of colorectal cancer (b5500). The study, conducted within the EPIC trial of 520,000 patients in 10 western European countries, compared 25-hydroxy-vitamin D levels in 1,248 patients with incident colorectal cancer against those of an equal number of matched controls, with these results: “5-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0–75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0–49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0–99.9 nmol/l: 0.88 (0.68 to 1.13); 100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P < 0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity = 0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation.” (M. Jenab, Jenab@iarc.fr)
Smoking Cessation After Lung Cancer Diagnosis: Prognostic outcomes are improved if patients diagnosed with early-stage lung cancer stop smoking, report researchers who conducted a meta-analysis of 10 studies (b5569): “Continued smoking was associated with a significantly increased risk of all cause mortality (hazard ratio 2.94, 95% confidence interval 1.15 to 7.54) and recurrence (1.86, 1.01 to 3.41) in early stage non–small cell lung cancer and of all cause mortality (1.86, 1.33 to 2.59), development of a second primary tumour (4.31, 1.09 to 16.98), and recurrence (1.26, 1.06 to 1.50) in limited stage small cell lung cancer. No study contained data on the effect of quitting smoking on cancer specific mortality or on development of a second primary tumour in non–small cell lung cancer. Life table modelling on the basis of these data estimated 33% five year survival in 65 year old patients with early stage non–small cell lung cancer who continued to smoke compared with 70% in those who quit smoking. In limited stage small cell lung cancer, an estimated 29% of continuing smokers would survive for five years compared with 63% of quitters on the basis of the data from this review.” (A. Parsons, a.c.parsons@bham.ac.uk)

>>>PNN JournalWatch
* Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America, in Clinical Infectious Diseases, 2010; 50: 291–322. (J. R. Perfect, perfe001@mc.duke.edu)
* Glucose, Obesity, Metabolic Syndrome, and Diabetes: Relevance to Incidence of Heart Failure, in
Journal of the American College of Cardiology, 2010; 55: 283–93. (G. C. Fonarow, gfonarow@mednet.ucla.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 26, 2010 * Vol. 17, No. 16
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Jan. 25 issue of the Archives of Internal Medicine (2010; 170).
Obesity Complications & Treatment: Three research articles and an editorial discuss obesity.
Exercise and weight loss compliment the benefits of the DASH (Dietary Approaches to Stop Hypertension) diet in patients with overweight/obesity and above-normal blood pressure, according to findings from the ENCORE (Exercise and Nutrition interventions for CardiOvasculaR hEalth) study (
pp. 126–35). Among 144 patients, usual diet, DASH alone, and diet plus DASH produced these outcomes: “Clinic-measured BP was reduced by 16.1/9.9 mm Hg (DASH plus weight management); 11.2/7.5 mm (DASH alone); and 3.4/3.8 mm (usual diet controls) (P < .001). A similar pattern was observed for ambulatory BP (P < .05). Greater improvement was noted for DASH plus weight management compared with DASH alone for pulse wave velocity, baroreflex sensitivity, and left ventricular mass (all P < .05).” (J. A. Blumenthal, Blume003@mc.duke.edu)
In comparison with orlistat plus a low-fat diet, a low-carbohydrate, ketogenic diet performed well in a study of 146 veterans being seen at primary care VA clinics (
pp. 136–45). Both interventions produced similar amounts of weight loss over 48 weeks among the overweight and obese patients, who had a mean age of 52 years and mean body mass index of 39.3 kg/sq m. Serum lipids and glycemic parameters were also statistically similar, but the low-carbohydrate, ketogenic diet provided greater reduction in blood pressure. (W. S. Yancy Jr., yancy006@mc.duke.edu)
In the Louisiana Obese Subjects Study (LOSS), personnel in primary care practices (PCPs) learned and effectively implemented medical-management strategies for extreme obesity, researchers report (
pp. 146–54). The 2-year “pragmatic clinical trial” compared usual care with intensive medical intervention with a 900-kcal liquid diet for 12 weeks or less, group behavioral counseling, structured diet, and choice of pharmacotherapy with sibutramine, orlistat, or diethylpropion. During year 2 of the intervention, intensive management produced 20% or greater weight loss in 7% of participants, compared with 1% of those receiving usual care. A loss of 5% was recorded in 31% of the intensive group and 9% of usual-care patients. (D. H. Ryan, ryandh@pbrc.edu)
Reviewing these and other studies, an editorialist writes that “health care reform and training is needed to allow [primary care] physicians to tackle the obesity crisis.” (
pp. 121–3; R. F. Kushner, rkushner@northwestern.edu)
Drug Safety—Any Progress? In a short invited commentary, a writer opines that few of the drug-safety recommendations of the Institute of Medicine have been implemented (p. 202). Implementation of clinicaltrials.gov has helped, the author notes, but Phase IV trials continue to be underfunded by industry—if they are conducted at all. (Russell V. Luepker, luepker@epi.umn.edu)

>>>PNN NewsWatch
* Pre-existing cardiovascular disease is now a contraindication to use of sibutramine (Meridia, Abbott), FDA has announced. Data indicate that patients with histories of cardiovascular disease taking the drug are at increased risk of myocardial infarction and stroke, the agency said. Revised product labeling states that sibutramine should not be used in patients with uncontrolled hypertension with readings above 145/90 mm Hg or with histories of coronary artery disease, stroke or transient ischemic attack, cardiac arrhythmias, congestive heart failure, or peripheral arterial disease.
* Consumers should be on alert for
counterfeit versions of Alli 60 mg capsules (120-count refill pack) being sold over the Internet, particularly at online auction sites, FDA says. People may be taking the product may be receiving 3 times the usual daily dose (twice the recommended maximum dose) of sibutramine if they are following the dosing directions for Alli. The counterfeit product looks very similar to Alli. It can be identified by a missing lot code on the outer cardboard packaging; an expiration date that includes a month, day, and year (instead of the just the month and year); a plain foil for the inner safety seal without any words on it; and capsules with powder rather than the small white pellets found in Alli.
* FDA has approved
dalfampridine (Ampyra, Elan) for oral treatment for multiple sclerosis and liraglutide (Victoza, Novo Nordisk) for treating type 2 diabetes in adults.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 27, 2010 * Vol. 17, No. 17
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 27 issue of JAMA (2010; 303).
Management of Paroxysmal Atrial Fibrillation: Patients with paroxysmal atrial fibrillation who have not responded to at least one antiarrhythmic drug are best managed with catheter ablation, investigators conclude based on a comparison with continued drug therapy (pp. 333–40). In an unblinded, Bayesian-designed study of 167 patients at 19 hospitals who had at least three episodes of AF within 6 months before randomization, catheter ablation or antiarrhythmic drug therapy (ADT) produced these results: “At the end of the 9-month effectiveness evaluation period, 66% of patients in the catheter ablation group remained free from protocol-defined treatment failure compared with 16% of patients treated with ADT. The hazard ratio of catheter ablation to ADT was 0.30 (95% confidence interval, 0.19-0.47; P < .001). Major 30-day treatment-related adverse events occurred in 5 of 57 patients (8.8%) treated with ADT and 5 of 103 patients (4.9%) treated with catheter ablation. Mean quality of life scores improved significantly in patients treated by catheter ablation compared with ADT at 3 months; improvement was maintained during the course of the study.” (D. J. Wilber, dwilber@lumc.edu)
Management of Septic Shock: Among 509 adult patients with septic shock who were being managed with corticosteroid therapy, neither intensive insulin therapy or addition of oral fludrocortisone provided clinical benefits, the Corticosteroids and Intensive Insulin Therapy for Septic Shock (COIITSS) trial shows (pp. 341–8). Patients, receiving intravenous hydrocortisone for multiple organ dysfunction while in 11 French intensive-care units, received either continuous insulin infusion or conventional insulin therapy for glucocorticoid-induced hyperglycemia plus either hydrocortisone alone or hydrocortisone and fludrocortisone, with these results: “Of the 255 patients treated with intensive insulin, 117 (45.9%), and 109 of 254 (42.9%) treated with conventional insulin therapy died (relative risk [RR], 1.07; 95% confidence interval [CI], 0.88–1.30; P = .50). Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia (<40 mg/dL) than those in the conventional-treatment group, with a difference in mean number of episodes per patient of 0.15 (95% CI, 0.02–0.28; P = .003). At hospital discharge, 105 of 245 patients treated with fludrocortisone (42.9%) died and 121 of 264 (45.8%) in the control group died (RR, 0.94; 95% CI, 0.77–1.14; P = .50).” (D. Annane, djillali.annane@rpc.aphp.fr)
An editorialist asks whether glucocorticoid-induced hyperglycemia should be treated in patients with septic shock (
pp. 365–6): “[This] situation seems, on the surface, somewhat hopeless: the COITTSS trial investigators executed a difficult multicenter trial in very complex, seriously ill patients, and yet clinicians can only conclude from their efforts that there is still uncertainty about how to do things differently. Another conclusion might be that often the only robust evidence that clinicians can use comes from megatrials, the very execution of which could be plagued by ongoing changes in usual-care practices. Yet, syndromes such as septic shock continue to portend a grave threat to life, the provision of ICU care for these patients is exceedingly costly, and a lack of adequately robust evidence on how best to provide that care is a glaring deficiency. Rather than tolerate a climate of clinical uncertainty, it seems imperative for funding agencies and researchers invested in care of critically ill patients to conduct adequately powered trials, even if these trials might be far larger than those of the past. To ensure that such studies can be completed in a timely fashion, the cooperation of national and international trials groups, and their funding sources, will likely be necessary. Precedents for large-scale international cooperation exist in oncology and cardiology. Given the huge global burden of conditions such as septic shock, which causes hundreds of thousands of deaths in the United States alone each year, such international collaboration should and must be achievable.” (G. Van den Berghe, greet.vandenberghe@med.kuleuven.be)

>>>PNN NewsWatch
* FDA has announced a Class I recall of Exel/Exelint Huber needles and infusion sets. The agency also approved a Roxane oral morphine sulfate solution that had previously been sold unapproved.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 28, 2010 * Vol. 17, No. 18
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 28 issue of the New England Journal of Medicine (2010; 362).
Effects of Rotavirus Vaccine in Developing Countries: Two research studies and an editorial explore effects of rotavirus vaccine.
Incidence of severe rotavirus gastroenteritis among infants in South Africa and Malawi was significantly lower in babies who received rotavirus vaccine, compared with placebo (
pp. 289–98). The live oral vaccine in two- or three-dose series or placebo was administered to infants, with these results: “Of the 4,417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group.” (N. A. Cunliffe, n.a.cunliffe@liv.ac.uk)
Diarrhea-related deaths were reduced by rotavirus vaccination in a study conducted in Mexico (
pp. 299–305). Mortality data in 2003–09 among those 5 or younger showed: “By December 2007, an estimated 74% of children who were 11 months of age or younger had received one dose of rotavirus vaccine. In 2008, there were 1,118 diarrhea-related deaths among children younger than 5 years of age, a reduction of 675 from the annual median of 1793 deaths during the 2003–2006 period. Diarrhea-related mortality fell from an annual median of 18.1 deaths per 100,000 children at baseline to 11.8 per 100,000 children in 2008 (rate reduction, 35%; 95% confidence interval [CI], 29 to 39; P < 0.001). Among infants who were 11 months of age or younger, diarrhea-related mortality fell from 61.5 deaths per 100,000 children at baseline to 36.0 per 100,000 children in 2008 (rate reduction, 41%; 95% CI, 36 to 47; P < 0.001). As compared with baseline, diarrhea-related mortality was 29% lower for children between the ages of 12 and 23 months, few of whom were age-eligible for vaccination. Mortality among unvaccinated children between the ages of 24 and 59 months was not significantly reduced. The reduction in the number of diarrhea-related deaths persisted through two full rotavirus seasons (2008 and 2009).” (M. Patel, mpatel@cdc.gov)
The currently marketed rotavirus vaccines provide efficacy with a good safety profile, an editorialist writes (
pp. 358–60): “In the 10-year period since RotaShield was withdrawn from the market, more than 5 million children have died from rotavirus disease. Thus, current vaccines should be widely used now, while trials of other vaccine candidates are continued in various populations and mechanisms to improve vaccine efficacy are investigated. Since rotavirus is only one of many pathogens that cause diarrhea, the use of rotavirus vaccine will need to be supplemented by other preventive and treatment strategies to reduce the high mortality from diarrheal diseases. Unfortunately, the coverage for known effective interventions, such as oral rehydration therapy, in parts of Africa and South Asia is less than 35%.” (M. Santosham)

>>>PNN NewsWatch
* Patients with moderate or severe hepatic impairment have increased exposure to bortezomib (Velcade, Takeda), FDA says. Product labeling has been updated to suggest dosage adjustment of the multiple-myeloma agent in such patients.
* Steve Jobs and Barack Obama, iconic figures of our times, were on stage yesterday at two highly anticipated events. Jobs introduced
Apple’s iPad, claiming that it creates a new category of devices positioned between laptop computers and smartphones. Not all analysts agreed with that leap, but the device’s use of iPhone apps and WiFi technology holds promise for medical applications similar to those in use already at Ohio State University. Obama’s first State of the Union address delivered little in terms of insights into Democrats’ plan for the health care reform desert in which they find themselves. Buried 25 minutes into his speech, the HCR passage simply called on Democrats to persevere with the legislation that is, or was, so close to passage.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Jan. 29, 2010 * Vol. 17, No. 19
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Feb. issue of Diabetes Care (2010; 33).
Incretin-Based Therapies: A review of incretin-based therapies concludes that glucagon-like peptide-1 (GLP-1) agents have a favorable risk–benefit profile (pp. 428–33). Surveying antidiabetic drugs, the authors note: “Although the number of patients with type 2 diabetes that successfully achieve target levels of A1C is steadily improving, a substantial number of subjects continue to fall short of acceptable treatment goals, leaving them at high risk for development of diabetes-associated complications. More importantly, a large number of subjects with type 2 diabetes fail to achieve target values for glucose, lipids, and blood pressure, with only 12.2% of patients meeting target values despite recent improvements in therapeutic agents targeting hyperglycemia, dyslipidemia, and hypertension. The development of multiple new agents for the treatment of type 2 diabetes has broadened the options for patient-specific therapy. However, no currently available agents exhibit the ideal profile of exceptional glucose-lowering efficacy to safely achieve target levels of glycemia in a broad range of patients.” (D. J. Drucker, d.drucker@utoronto.ca)
Responding to this favorable evaluation of incretin-based therapies, editorialists write (
pp. 453–5): “History has taught us that enthusiasm for new classes of drugs, heavily promoted by the pharmaceutical companies that market them, can obscure the caution that should be exercised when the long-term consequences are unknown. Of perhaps greatest concern in the case of the GLP-1–based drugs, including GLP-1 agonists and dipeptidyl peptidase-4 inhibitors, is preliminary evidence to suggest the potential risks of asymptomatic chronic pancreatitis and, with time, pancreatic cancer.” (P. Butler, pbutler@mednet.ucla.edu)
Skipping Insulin Injections: Among American adults with type 1 or 2 diabetes, the omission of insulin injections was more common when injections interfered with daily activities, produced pain, or were needed in embarrassing situations, researchers report (pp. 240–5). An Internet-based survey showed the following: “Intentional insulin omission was reported by more than half of respondents; regular omission was reported by 20%. Significant independent risk factors for insulin omission were younger age, lower income and higher education, type 2 diabetes, not following a healthy diet, taking more daily injections, interference of injections with daily activities, and injection pain and embarrassment. Risk factors differed between type 1 and type 2 diabetic patients, with diet nonadherence more prominent in type 1 diabetes and age, education, income, pain, and embarrassment more prominent in type 2 diabetes.” (M. Peyrot, mpeyrot@loyola.edu)
Use, Kinetics of U-500 Regular Insulin: Experiences in patients requiring more than 200 units of regular insulin per day and A1C levels exceeding 8.0% who used U-500 formulations of regular insulin are reported along with insulin levels obtained in fasting subjects given the product (pp. 281–3): “U-500 regular insulin doses were adjusted using the same approach as for adjusting NPH insulin doses. Mean values at baseline and at minimum A1C levels were, respectively, A1C 9.9 and 7.1%, 3.2 and 3.3 units/kg, and weight 98.6 and 102.8 kg. Pharmacokinetically, insulin concentrations rose briskly by 30 min and remained elevated for at least 7 h.” (M. B. Davidson, mayerdavidson@cdrewu.edu)
Aspirin for Primary Prevention: All-cause and cardiovascular mortality may be lower in patients with type 2 diabetes who use aspirin for primary prevention, with greater effects in men and those aged 65 or older (pp. 317–21). The longitudinal Fremantle Diabetes Study reports these outcomes for 651 patients with no prior cardiovascular disease at study admission: “There were 160 deaths (24.6%) during follow-up, with 70 (43.8%) due to CVD. In Kaplan–Meier survival analysis, there was no difference in either CVD or all-cause mortality in aspirin users versus nonusers (P = 0.52 and 0.94, respectively, by log-rank test). After adjustment for significant variables in the most parsimonious Cox models, regular aspirin use at baseline independently predicted reduced CVD and all-cause mortality (hazard ratio [HR] 0.30 [95% CI 0.09–0.95] and 0.53 [0.28–0.98[, respectively; P ≤ 0.044). In subgroup analyses, aspirin use was independently associated with reduced all-cause mortality in those aged ≥65 years and men.” (T. M. E. Davis, tdavis@cyllene.uwa.edu.au)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 1, 2010 * Vol. 17, No. 20
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Early-release article from and Jan. 30 issue of Lancet (2010; 375).
Ulipristal for Emergency Contraception: Compared with levonorgestrel, ulipristal may provide a more effective contraceptive for use between 72 and 120 hours after intercourse, researchers report (doi: 10.1016/S0140-6736). Single oral doses of ulipristal acetate 30 mg or levonorgestrel 1.5 mg produced these results: “In the efficacy-evaluable population, 1,696 women received emergency contraception within 72 h of sexual intercourse (ulipristal acetate, n = 844; levonorgestrel, n = 852). There were 15 pregnancies in the ulipristal acetate group (1.8%, 95% CI 1.0–3.0) and 22 in the levonorgestrel group (2.6%, 1.7–3.9; odds ratio [OR] 0.68, 95% CI 0.35–1.31). In 203 women who received emergency contraception between 72 h and 120 h after sexual intercourse, there were three pregnancies, all of which were in the levonorgestrel group. The most frequent adverse event was headache (ulipristal acetate, 213 events [19.3%] in 1,104 women; levonorgestrel, 211 events [18.9%] in 1,117 women). Two serious adverse events were judged possibly related to use of emergency contraception; a case of dizziness in the ulipristal acetate group and a molar pregnancy in the levonorgestrel group. In the meta-analysis (0–72 h), there were 22 (1.4%) pregnancies in 1,617 women in the ulipristal acetate group and 35 (2.2%) in 1,625 women in the levonorgestrel group (OR 0.58, 0.33–0.99; p = 0.046).” (A. F. Glasier, Anna.Glasier@nhslothian.scot.nhs.uk)
Trastuzumab in Breast Cancer: Event-free survival, survival, and clinical and pathological tumor responses were all improved when trastuzumab was added to neoadjuvant chemotherapy in women with HER2-positive locally advanced or inflammatory breast cancer, according to results from the NOAH trial (pp. 377–84). The 1-year trial showed these patterns in 235 patients and a parallel cohort of 99 patients with HER2-negative disease: “Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer (3-year event-free survival, 71% [95% CI 61–78; n = 36 events] with trastuzumab, vs 56% [46–65; n = 51 events] without; hazard ratio 0.59 [95% CI 0.38–0.90]; p = 0.013). Trastuzumab was well tolerated and, despite concurrent administration with doxorubicin, only two patients (2%) developed symptomatic cardiac failure. Both responded to cardiac drugs.” (L. Gianni, luca.gianni@istitutotumori.mi.it)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2010; 340).
Risk of MI, Stroke with Antihypertensives: Calling for a large trial of second-line antihypertensive drug regimens, researchers report higher rates of myocardial infarction in patients with hypertension being treated with diuretics plus calcium-channel blockers (c103). Data from the Group Health Cooperative show these patterns for 353 cases (patients aged 30–79 years, being treated for hypertension with drugs, and having a first fatal or nonfatal MI or stroke in 1989–2005) and 952 controls (other patients with pharmacologically treated hypertension): “Compared with users of diuretics plus beta-blockers, users of diuretics plus calcium channel blockers had an increased risk of myocardial infarction (adjusted odds ratio (OR) 1.98, 95% confidence interval 1.37 to 2.87) but not of stroke (OR 1.02, 95% CI 0.63 to 1.64). The risks of myocardial infarction and stroke in users of diuretics plus angiotensin converting enzyme inhibitors or angiotensin receptor blockers were slightly but not significantly lower than in users of diuretics plus beta-blockers (myocardial infarction: OR 0.76, 95% CI 0.52 to 1.11; stroke: OR 0.71, 95% CI 0.46 to 1.10).” (B. M. Psaty, psaty@u.washington.edu)

>>>PNN NewsWatch
* FDA has issued warnings about liver toxicities with didanosine (Videx, Bristol-Myers Squibb) and weight gain and hyperlipidemia in adolescents treated for psychiatric disorders with olanzapine (Zyprexa, Lilly).

>>>PNN JournalWatch
* Cardiovascular Disease in Type 2 Diabetes from Population to Man to Mechanisms: The Kelly West Award Lecture 2008, in Diabetes Care, 2010; 33: 442–9. (M. Laakso, markku.laakso@kuh.fi)
* Understanding the Genetic Basis for Adverse Drug Effects: The Calcineurin Inhibitors, in
Pharmacotherapy, 2010; 30: 195–209. (G. J. Burckart, gilbert.burckart@fda.hhs.gov)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 2, 2010 * Vol. 17, No. 21
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Feb. 2 issue of the Annals of Internal Medicine (2010; 152).
NSAIDs for Postoperative Pericardial Effusion: The NSAID diclofenac had no effect on size of effusions or late cardiac tamponade among 196 high-risk patients who had undergone cardiac surgery, a report shows (pp. 137–43). Those included in the study had moderate to large persistent pericardial effusion more than 7 days after surgery. Diclofenac 50 mg or placebo twice daily for 14 days had these effects: “The initial mean pericardial effusion grade was 2.58 (SD, 0.73) for the placebo group and 2.75 (SD, 0.81) for the diclofenac group. The 2 groups showed similar mean decreases from baseline after treatment (−1.08 grades [SD, 1.20] for the placebo group vs. −1.36 (SD, 1.25) for the diclofenac group). The mean difference between groups was −0.28 grade (95% CI, −0.63 to 0.06 grade; P = 0.105). Eleven cases of late cardiac tamponade occurred in the placebo group and 9 in the diclofenac group (P = 0.64). These differences persisted after adjustment for grade of pericardial effusion at baseline, treatment site, and type of surgery.” (P. Meurin, philippemeurin@hotmail.com)
Extended-Duration Transdermal Nicotine Therapy: Among 568 adult smokers, extending use of transdermal nicotine patches from 8 to 24 weeks after the quit day can increase confirmed abstinence, reduce smoking lapses, and increase recovery after lapses, researchers report (pp. 144–51). Participants used Nicoderm CQ 21 mg for 8 or 24 weeks. Results showed: “At week 24, extended therapy produced higher rates of point-prevalence abstinence (31.6% vs. 20.3%; odds ratio, 1.81 [95% CI, 1.23 to 2.66]; P = 0.002), prolonged abstinence (41.5% vs. 26.9%; odds ratio, 1.97 [CI, 1.38 to 2.82]; P = 0.001), and continuous abstinence (19.2% vs. 12.6%; odds ratio, 1.64 [CI, 1.04 to 2.60]; P = 0.032) versus standard therapy. Extended therapy reduced the risk for lapse (hazard ratio, 0.77 [CI, 0.63 to 0.95]; P = 0.013) and increased the chances of recovery from lapses (hazard ratio, 1.47 [CI, 1.17 to 1.84]; P = 0.001). Time to relapse was slower with extended versus standard therapy (hazard ratio, 0.50 [CI, 0.35 to 0.73]; P < 0.001). At week 52, extended therapy produced higher quit rates for prolonged abstinence only (P = 0.027). No differences in side effects and adverse events between groups were found at the extended-treatment assessment.” (R. A. Schnoll, schnoll@mail.med.upenn.edu)
IVIG for Complex Regional Pain Syndrome: Symptoms of long-standing complex regional pain syndrome can be relieved by low doses of intravenous immunoglobulin, according to a 13-patient trial (pp. 152–8). Using a crossover design, researchers tested IVIG 0.5 g/kg and normal saline, with these results at 6–19 days after initial treatment: “13 eligible participants were randomly assigned between November 2005 and May 2008; 12 completed the trial. The average pain intensity was 1.55 units lower after IVIG treatment than after saline (95% CI, 1.29 to 1.82; P < 0.001). In 3 patients, pain intensity after IVIG was less than after saline by 50% or more. No serious adverse reactions were reported.” (A. Goebel, andreasgoebel@rocketmail.com)
Treatment of Fibrotic Diseases: Drug therapy plays an important role in management of fibrotic diseases such as systemic sclerosis and pulmonary, liver, and kidney fibrosis, authors of a review article write (pp. 159–66): “Delineation of the central role of transforming growth factor-beta (TGF-beta) and identification of the specific cellular receptors, kinases, and other mediators involved in the fibrotic process have provided a sound basis for development of effective therapies. The inhibition of signaling pathways activated by TGF-beta represents a novel therapeutic approach for the fibrotic disorders. One of these TGF-beta pathways results in the activation of the nonreceptor tyrosine kinase cellular Abelson (c-Abl), and c-Abl inhibitors, including imatinib mesylate, diminishing the fibrogenic effects of TGF-beta. Thus, recently acquired basic knowledge about the pathogenesis of the fibrotic process has enabled the development of novel therapeutic agents capable of modifying the deleterious effects of the fibrotic diseases.” (S. A. Jimenez, sergio.jimenez@jefferson.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 3, 2010 * Vol. 17, No. 22
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Feb. 3 issue of JAMA (2010; 303).
DVT Risk After Negative Compression Ultrasound: Anticoagulation may not be needed in patients who have negative whole-leg compression ultrasounds conducted because of suspected deep-vein thrombosis, according to a systematic review and meta-analysis (pp. 438–45). Literature from 1970 through late 2009 showed the following: “Seven studies were included totaling 4,731 patients with negative whole-leg CUS examinations who did not receive anticoagulation. Of these, up to 647 patients (13.7%) had active cancer and up to 725 patients (15.3%) recently underwent a major surgery. Most participants were identified from an ambulatory setting. Venous thromboembolism or suspected venous thromboembolism–related death occurred in 34 patients (0.7%), including 11 patients with distal DVT (32.4%); 7 patients with proximal DVT (20.6%); 7 patients with nonfatal pulmonary emboli (20.6%); and 9 patients (26.5%) who died, possibly related to venous thromboembolism. Using a random-effects model with inverse variance weighting, the combined venous thromboembolism event rate at 3 months was 0.57% (95% confidence interval, 0.25%–0.89%).” (S. M. Stevens, Scott.StevensMD@imail.org)
An editorialist expounds on the difficulty of matching the results of broad meta-analyses to specific situations in patient care (
pp. 454–5): “To be most useful, evidence from clinical research studies must relate to a specific clinical context by more explicitly addressing variations in those clinical contexts that are relevant to individual patients. Generalizing the findings related to a diagnostic test or treatment regimen beyond the specific context from which a study was performed is fraught with danger. For instance, based on the [above] meta-analysis…, clinicians may infer that not initiating anticoagulation treatment after a negative CUS result in some surgical or ambulatory patients at low risk of having VTE may be appropriate; however, that inference may not may not be true for hospitalized patients or those with cancer. Greater detail about individual patient scenarios is necessary to facilitate better application of the study results to individual patients. One helpful approach may be for reports of meta-analyses to include, in detail, the inclusion and exclusion criteria for patients enrolled in the original studies.” (E. H. Livingston, edward.livingston@utsouthwestern.edu)

>>>Pharmacotherapy Report
Source:
Feb. issue of Pharmacotherapy (2010; 30).
Reconsidering ‘an Aspirin a Day’: For preventing cardiovascular prevention, aspirin is not a universally safe drug that should be recommended to all patients, editorialists write (pp. 115–8): “Clinicians must emphasize the importance of proven cardiovascular disease risk-reduction strategies to at-risk patients. In the absence of further studies, universal prescription of aspirin for adults is unwarranted and stands in stark contrast to the potential benefits achieved by narrowing the treatment gap for both blood pressure and LDL level control.” (M. J. Krantz, mori.krantz@cpcmed.org)

>>>PNN NewsWatch
* FDA yesterday announced approval of collagenase clostridium histolyticum (Xiaflex, Auxilium Pharmaceuticals) as the first drug to treat Dupuytren’s contracture. The biologic drug breaks down collagen in the hand, helping patients with the progressive disease to straighten and properly use their fingers. Xiaflex is injected directly into the collagen cord of the hand and should be administered only by a health care professional experienced with injections of the hand, because tendon ruptures may occur. In clinical trials, 44%–64% of those receiving the product had successful outcomes, compared with 5%–7% of those given placebo. The most common adverse reactions in patients treated with Xiaflex were fluid build up, swelling, bleeding, and pain in the injected area. Although no serious allergic reactions have been observed, such a response would not be unexpected because this foreign protein could prompt an immune system reaction.
* A key publication linking childhood
vaccine administration with autism has been fully retracted by The Lancet. The 12-patient study, by Wakefield et al. and published in 1998, led many parents to refuse vaccinations for their children.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 4, 2010 * Vol. 17, No. 23
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 4 issue of the New England Journal of Medicine (2010; 362).
Oral Drugs for Multiple Sclerosis: Three studies on oral treatments of multiple sclerosis released in advance of print publication (see PNN, Jan. 21) are in today’s issue. An editorialist writing about oral fingolimod (pp. 387–401 and 402–15) and cladribine (pp. 416–26) asks whether these agents represent a sea change or incremental progress in treatment of MS (pp. 456–8): “The studies in this issue of the Journal provide a new horizon for patients with relapsing–remitting multiple sclerosis and a welcome increase in the range of treatment options. Although current therapies remain very effective, particularly when they are administered early, and have well-defined side-effect profiles, oral therapies further support a change in treatment approach to directly prevent immune-mediated injury. This approach will probably be followed until the next step in the therapeutic advance occurs, but such a change in strategy highlights the final question: What are the long-term goals of this new phase of therapy? The question will not be fully answered until the underlying cause of multiple sclerosis is better understood, but the lack of a definable end point remains a contentious issue for clinicians and health care funders alike. Time will determine the long-term effectiveness of these treatments in delaying the development of irreversible disability, and as ongoing, real-life experiments, they will contribute to our understanding of this enigmatic disease.” (W. M. Carroll)
Acyclovir & HIV-1 Transmission: Despite significant reductions in plasma HIV-1 levels and genital herpetic lesions, daily acyclovir use in dually infected patients did not reduce transmission of HIV-1, researchers report (pp. 427–39). Couples in which only one partner was infected with HIV-1 and herpes simplex virus type 2 were studied for the effects of suppressive doses of acyclovir (400 mg orally twice daily). Results showed: “A total of 3,408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person–years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P = 0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log10 copies per milliliter (95% CI, 0.22 to 0.29; P < 0.001) and the occurrence of HSV-2–positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P < 0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed.” (C. Celum)
Comparative Effectiveness & Clinical Practice: In a Sounding Board article, authors discuss the impact of the $1.1 billion in stimulus money being spent on comparative effectiveness research and relate that concept to cost-effectiveness studies (pp. 460–5). “Getting to the win–win balance” is a difficult but necessary chore if society is to achieve lower costs and better outcomes, the authors note, adding: “At some point, however, we will have to confront the problem of cost-effectiveness at the level of the patient. The limitless pipeline of effective clinical strategies—biologic drugs (e.g., etanercept for rheumatoid arthritis, imatinib for chronic myelogenous leukemia, and trastuzumab for breast cancer), enhanced imaging tests, and personalized medicine—offers improved outcomes, but the costs of development and production are often very high. Even if all hospitals, medical practices, and health plans became efficient in the sense that they adopted all interventions that are more cost-effective than anything they currently do, they would still have to draw the line on expenditures somewhere. There are trade-offs—reallocating resources from cost-ineffective treatments for late-stage pancreatic cancer to cost-effective treatments for diabetes may improve health outcomes in the aggregate but not for patients with late-stage pancreatic cancer.” (M. C. Weinstein)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 5, 2010 * Vol. 17, No. 24
Providing news and information about medications and their proper use

>>>Psychiatry Highlights
Source:
Feb. issue of the American Journal of Psychiatry (2010; 167).
Suicide in Patients with HIV: Suicide rates among patients with HIV infection declined after introduction of highly active antiretroviral therapy, but they remain above those for the general population, researchers report (pp. 143–50). Longitudinal data from the Swiss HIV Cohort Study and the Swiss National Cohort revealed these patterns: “From 1988 to 2008, 15,275 patients were followed in the Swiss HIV Cohort Study for a median duration of 4.7 years. Of these, 150 died by suicide (rate 158.4 per 100,000 person–years). In men, standardized mortality ratios declined from 13.7 (95% CI = 11.0–17.0) in the pre-HAART era to 3.5 (95% CI = 2.5–4.8) in the late HAART era. In women, ratios declined from 11.6 (95% CI = 6.4–20.9) to 5.7 (95% CI = 3.2–10.3). In both periods, suicide rates tended to be higher in older patients, in men, in injection drug users, and in patients with advanced clinical stage of HIV illness. An increase in CD4 cell counts was associated with a reduced risk of suicide.” (O. Keiser, keiser@ispm.unibe.ch">okeiser@ispm.unibe.ch)
An editorialist makes these recommendations for care of patients with HIV (pp. 117–9): “Physicians should routinely screen HIV-positive persons for comorbid psychiatric disorders and explicitly assess suicidal ideation, plan, and intent. In HIV specialty clinics that use electronic medical records, brief structured assessments with clinical reminders could be implemented to ensure that patients are routinely screened. In addition to routine screening, data from the Swiss HIV Cohort Study also highlight the need for innovative interventions that promote access to and utilization of mental health treatment. Among HIV-positive individuals who died by suicide in the ART era, more than one-fifth of those with a mental health diagnosis were not receiving any psychiatric treatment (2). Providing mental health and substance abuse treatment on-site in HIV specialty clinics can remove barriers to accessing care and assist with engaging patients who axe ambivalent about seeking psychiatric treatment. Addressing structural barriers to psychiatric screening and referral could promote an integrated approach to HIV specialty care that has the potential to more effectively meet the needs of HIV-positive persons.” (A. W. Carrico, adam.carrico@ucsf.edu)
Oral v. Depot Olanzapine: In a head-to-head comparison, oral and depot olanzapine produced similar clinical outcomes over a 24-week period, except for the occurrence of injection-related adverse events in the depot group (pp. 181–9). Patients were stabilized on oral olanzapine before random assignment to low, medium or high doses of injectable olanzapine, a very low reference dose of the drug, or their stabilized oral dose, with these results: “At 24 weeks, the majority of oral olanzapine-treated patients (93%), as well as most olanzapine long-acting injection-treated patients receiving high (95%), medium (90%), low (84%), and very low doses (69%), remained exacerbation free, with the therapeutic 4-week regimen (medium dose) and pooled 2-week regimen (low and high doses) demonstrating efficacy similar to that of oral olanzapine as well as to each other. The three standard long-acting doses were superior to the very low reference dose based on time to exacerbation. Incidence of weight gain ≥7% of baseline was 21% for oral olanzapine compared with 21%, 15%, 16%, and 8% for the high, medium, low, and very low olanzapine long-acting treatment groups, respectively. No clinically significant differences were observed between the long-acting injection and oral olanzapine groups in general safety parameters. Few injection-site reactions occurred (3%). Two patients experienced sedation and delirium consistent with olanzapine overdose following possible accidental intravascular injection.” (J. M. Kane, psychiatry@lij.edu)
An editorialist suggests (
pp. 125–6). “When a depot formulation is contemplated, both the patient and the physician should have had experience with the oral formulation. Most efficacy difference between drugs occurs in the first month, and about 50% of the weight gain occurs in the first few months. Consequently, the experience with the oral formulation should guide drug choice for depot formulation, especially when a depot formulation has to be instituted because of the patient’s nonadherence or frequent relapse, where there is evidence that change to a depot medication does decrease relapses.” (J. M. Davis, jdavis@psych.uic.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 8, 2010 * Vol. 17, No. 25
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2010; 340).
Cost of UTI Management: A variety of assessment and treatment methods for urinary tract infections are evaluated in a cost-effectiveness study, with authors concluding that use of dipstick testing and targeted antibiotics are more likely to be cost-effective when the value of saving a day of moderately bad symptoms is £10 (US$15.60) or more (c346). During a randomized controlled trial of 309 nonpregnant adult women with suspected UTIs, the investigators randomly assigned participants to these five strategies: empirical antibiotics, empirical delayed (by 48 hours) antibiotics, or targeted antibiotics based on either a high symptom score (two or more of urine cloudiness, smell, nocturia, dysuria), dipstick results (nitrite or leukocytes and blood), or receipt of a positive result on midstream urine analysis. Results of cost-effectiveness analysis of the data showed: “Management with targeted antibiotics with midstream urine analysis was more costly over the period of one month. Costs for the midstream urine analysis and dipstick management groups were £37 and £35, respectively; these compared with £31 for immediate antibiotics. Cost effectiveness acceptability curves suggested that if avoiding a day of moderately bad symptoms was valued at less than £10, then immediate antibiotics is likely to be the most cost effective strategy. For values over £10, targeted antibiotics with dipstick testing becomes the most cost effective strategy, though because of the uncertainty we can never be more than 70% certain that this strategy truly is the most cost effective.” (D. Turner, dturner@soton.ac.uk)
Mortality Risk with Venlafaxine: Risk of sudden cardiac death or near death was not elevated in patients taking venlafaxine, compared with those on other antidepressants, in a large, population-based study (c249). Data from the U.K. General Practice Research Database showed the following: “207,384 participants were followed-up for an average of 3.3 years. There were 568 cases of sudden cardiac death or near death, which were matched to 14,812 controls. The adjusted odds ratio of sudden cardiac death or near death associated with venlafaxine use was 0.66 (95% confidence interval 0.38 to 1.14) relative to fluoxetine use, whereas compared with citalopram it was 0.89 (0.50 to 1.60) and with dosulepin 0.83 (0.46 to 1.52).” (S. Suissa, samy.suissa@mcgill.ca)

>>>Lancet Highlights
Source:
Feb. 6 issue of Lancet (2010; 375).
Procalcitonin-Guided Antibiotic Therapy: For nonsurgical patients with suspected bacterial infections, antibiotic therapy guided by serum levels of procalcitonin was noninferior to usual care, report researchers who add that the strategy could reduce unnecessary antibiotic use and thereby decrease microbial resistance (pp. 463–74). Procalcitonin is not normally present in human sera; when it is, that is an indicator of active bacterial infection. In an open-label trial, patients received either antibiotics started and stopped based on predetermined procalcitonin levels or a control group in which physicians prescribed antibiotics according to current guidelines. Results showed: “Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21.2% [65/307] vs 20.4% [64/314]; absolute difference 0.8%, 90% CI −4.6 to 6.2) and day 60 (30.0% [92/307] vs 26.1% [82/314]; 3.8%, −2.1 to 9.7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14.3 days [SD 9.1] vs 11.6 days [SD 8.2]; absolute difference 2.7 days, 95% CI 1.4 to 4.1, p < 0.0001).” (M. Wolff, michel.wolff@bch.aphp.fr)

>>>PNN JournalWatch
* Effectiveness of Weight Management Interventions in Children: A Targeted Systematic Review for the USPSTF, in Pediatrics, 2010; 125: e396–418. (E. P. Whitlock)
* Smoking Cessation, in
Chest, 2010; 137: 428–35. (M. A. Chandler, mikechan62@hotmail.com)
* Defining and Setting National Goals for Cardiovascular Health Promotion and Disease Reduction: The American Heart Association’s Strategic Impact Goal Through 2020 and Beyond, in
Circulation, 2010; 121: 586–613. (D. M. Lloyd-Jones)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 9, 2010 * Vol. 17, No. 26
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Feb. 8 issue of the Archives of Internal Medicine (2010; 170).
Selenium Toxicity from Dietary Supplement: An outbreak of cases of selenium toxicity was investigated by public health officials, who found that the source was a contaminated dietary supplement (pp. 256–61). To support their conclusion that the outbreak could have been prevented through application of drug laws to dietary supplements, the authors cite these findings from their research: “The source of the outbreak was identified as a liquid dietary supplement that contained 200 times the labeled concentration of selenium. Of 201 cases identified in 10 states, 1 person was hospitalized. The median estimated dose of selenium consumed was 41,749 µg/d (recommended dietary allowance is 55 µg/d). Frequently reported symptoms included diarrhea (78%), fatigue (75%), hair loss (72%), joint pain (70%), nail discoloration or brittleness (61%), and nausea (58%). Symptoms persisting 90 days or longer included fingernail discoloration and loss (52%), fatigue (35%), and hair loss (29%). The mean initial serum selenium concentration of 8 patients was 751 µg/L (reference range, ≤125 µg/L). The mean initial urine selenium concentration of 7 patients was 166 µg/24 h (reference range, ≤55 µg/24 h).” (T. F. Jones, Tim.F.Jones@tn.gov)
An editorialist is critical of the Dietary Supplement Health and Education Act, which allows marketing of products without evidence of efficacy and safety (
pp. 261–3): “The last decade and a half has been fraught with significant controversy surrounding the DSHEA. With few exceptions, definitive evidence for the efficacy of dietary supplements for the treatment or prevention of any disease has been lacking, while reports of adverse effects continue to surface. Despite their widespread use, Americans are no healthier than they were in 1994 and health expenditures continue to rise. The fact that most patients do not experience adverse events from their supplement use should not be solely sufficient to justify their promotion without premarket evaluation. The time has come for lawmakers to re-evaluate the DSHEA.” (B. H. Ashar, bashar1@jhmi.edu)
Treating Low Back Pain: Release of an Australian guideline on treatment of low back pain (LBP) had little impact on inappropriate prescribing and management of that condition by the country’s general practitioners, according to results of an evaluation of data from the Bettering the Evaluation and Care of Health (BEACH) study (pp. 271–7). Patterns in the years before and after the 2004 release of the guideline showed these patterns: “Although guidelines discourage the use of imaging, over one-quarter of patients were referred for imaging. Guidelines recommend that initial care should focus on advice and simple analgesics, yet only 20.5% and 17.7% of patients received these treatments, respectively. Instead, the analgesics provided were typically nonsteroidal anti-inflammatory drugs (37.4%) and opioids (19.6%). This pattern of care was the same in the periods before and after the release of the local guideline.” (C. M. Williams, cwilliams@george.org.au)

>>>PNN NewsWatch
* The risk of progressive multifocal leukoencephalopathy (PML) increases with the number of natalizumab (Tysabri; Biogen Idec, Elan) infusions received, FDA announced on Friday. This new safety information, based on reports of 31 confirmed cases of PML received by the FDA as of January 21, will be added to the Tysabri drug label and patient Medication Guide. In addition, information about Immune Reconstitution Inflammatory Syndrome (IRIS) in patients who have developed PML and subsequently discontinued natalizumab has also been added to the drug label. IRIS is a rare condition characterized by a severe inflammatory response that can occur during or following immune system recovery, causing an unexpected decline in a patient’s condition after return of immune function.
* To help health professionals address consumer questions about yesterday’s approval of
rosuvastatin (Crestor, AstraZeneca) for primary prevention of cardiovascular disease, FDA posted a question-and-answer page about the CRESTOR and JUPITER trials. Those studies provided the data on which the new approval was based. The new indication marks the first time rosuvastatin has been approved for use in people with normal LDL cholesterol levels and no clinically evident heart disease.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 10, 2010 * Vol. 17, No. 27
Providing news and information about medications and their proper use

>>>Cardiology Highlights
Source:
Feb. 8 issue of the Journal of the American College of Cardiology (2010; 55).
Enoxaparin Monitoring Before PCI: In a study from France, a bedside test was deemed “fast and reliable” for monitoring the anticoagulation status of patients on enoxaparin who were about to undergo percutaneous coronary interventions (pp. 617–25). The Hemochron Jr. Hemonox (International Technidyne Corp.) tests for anti-Xa activity. It was assessed in the study, which compared baseline (T1) and 10-minute (T2; samples taken 10 minutes after IV enoxaparin administration) whole blood Hemonox clotting times with plasma chromogenic anti-Xa activity levels. Results showed: “Median values were 0.1 IU/ml (interquartile range [IQR]: 0.1 to 0.1 IU/ml) and 0.87 IU/ml (IQR: 0.74 to 1.03 IU/ml) for anti-Xa; 74 s (IQR: 70 to 81 s) and 143 s (IQR: 114 to 206 s) for Hemonox CT; and 44 s (IQR: 39 to 50 s) and 72 s (IQR: 58 to 93 s) for aPTT at T1 and T2, respectively. When using Hemonox CT to discriminate patients with anti-Xa level <0.5 IU/ml, the area under the receiver operating characteristic curve was 0.95 ± 0.01 (95% confidence interval [CI]: 0.93 to 0.97) versus 0.89 ± 0.01 (95% CI: 0.86 to 0.92) for aPTT. The threshold value of 120 s was associated with a 94.9% (95% CI: 91.1% to 97.4%) sensitivity and a 73.3% (95% CI: 67.6% to 78.5%) specificity to detect patients with inadequate anti-Xa level (<0.5 IU/ml) and positive predictive and negative predictive values of 73.9% (95% CI: 68.7% to 79.0%) and 94.78% (95% CI: 91.8% to 97.8%), respectively.” (G. Montalescot, gilles.montalescot@psl.aphp.fr)

>>>Circulation Highlights
Source:
Feb. 9 issue of Circulation (2010; 121).
Kidney Function, Albuminuria, & Cardiovascular Events in HIV: In patients with HIV infection, kidney function and albuminuria can be used to stratify individual risks of cardiovascular disease, a VA study shows (pp. 651–8). In a national sample of 17,264 patients with HIV who had incident CVD, these patterns were observed in a longitudinal analysis of estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 sq m and albuminuria ≥300 mg/dL: “After multivariable adjustment, eGFR levels 45 to 59, 30 to 44, and <30 mL/min per 1.73 sq m were associated with hazard ratios for incident CVD of 1.46 (95% confidence interval, 1.15 to 1.86), 2.03 (1.47 to 2.82), and 1.99 (1.46 to 2.70) compared with eGFR ≥60 mL/min per 1.73 sq m. Similarly, albuminuria levels 30, 100, and ≥300 mg/dL had hazard ratios for CVD of 1.28 (1.09 to 1.51), 1.48 (1.15 to 1.90), and 1.71 (1.30 to 2.27) compared with absent albuminuria. The associations between eGFR and albuminuria with heart failure were larger in magnitude and followed the same trends.” (A. I. Choi, andy.choi@ucsf.edu)

>>>Nephrology Highlights
Source:
Feb. issue of the American Journal of Kidney Diseases (2010; 55).
Tubular Toxicity with Sirolimus: Used for immunosuppression in recipients of kidney transplants, sirolimus may not be the nephrotoxic-free drug commonly assumed, according to a study that compared the agent with cyclosporine (pp. 335–43). Instead, evidence of “de novo low-grade glomerular proteinuria, increased excretion of markers associated with tubular damage, and evidence of tubular damage on kidney biopsy” was found in patients in an open-label trial in Basel, Switzerland, between 2001 and 2004: “There were 63 patients randomly assigned to cyclosporine-based regimens, and 64, to sirolimus-based regimens. Kidney function was similar in both groups, whereas levels of markers associated with glomerular damage (albumin, 19.5 vs 8.96 mg/mmol creatinine; P < 0.001; transferrin, 13.1 vs 5.7 mg/mmol creatinine; P < 0.001) and those associated with tubular damage (alpha-1-microglobulin, 11 vs 7.6 mg/mmol creatinine; P = 0.004; retinol-binding protein, 19.6 vs 9.6 mg/mmol creatinine; P = 0.002) were higher beginning at day 7 in patients randomly assigned to sirolimus therapy, with similar findings through day 90. Glucosuria incidence was higher in patients randomly assigned to sirolimus therapy beginning by day 30 (65% vs 30% on day 30; P = 0.002; 51% vs 22% on day 90; P < 0.001). On histologic examination, the overall severity of tubular lesions was significantly higher in patients randomly assigned to sirolimus therapy.” (M. Dickenmann, mdickenmann@uhbs.ch)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 11, 2010 * Vol. 17, No. 28
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 11 issue of the New England Journal of Medicine (2010; 362).
Cardiovascular Risk Factors in Children: In a cohort of American Indian children, obesity, glucose intolerance, and hypertension but not increased cholesterol levels were predictors of premature death, researchers report (pp. 485–93). The children, born between 1945 and 1984 and without diabetes when they were examined at a mean age of 11.3 years, showed these patterns in body mass index, other risk factors, and outcomes: “There were 166 deaths from endogenous causes (3.4% of the cohort) during a median follow-up period of 23.9 years. Rates of death from endogenous causes among children in the highest quartile of BMI were more than double those among children in the lowest BMI quartile (incidence-rate ratio, 2.30; 95% confidence interval [CI], 1.46 to 3.62). Rates of death from endogenous causes among children in the highest quartile of glucose intolerance were 73% higher than those among children in the lowest quartile (incidence-rate ratio, 1.73; 95% CI, 1.09 to 2.74). No significant associations were seen between rates of death from endogenous or external causes and childhood cholesterol levels or systolic or diastolic blood-pressure levels on a continuous scale, although childhood hypertension was significantly associated with premature death from endogenous causes (incidence-rate ratio, 1.57; 95% CI, 1.10 to 2.24).” (P. W. Franks, paul.franks@medicin.umu.se)
Because of the availability of drug therapy, pediatricians are more likely to treat hypertension and hypercholesterolemia in children, an editorialist notes, but he adds that these factors did not “track into adulthood as persistently as obesity and impaired glucose tolerance” (
pp. 548–50): “The dilemma raised by epidemiologic data—that interventions that are targeted to youths need to be extraordinarily sustainable to pay off later in life—requires us to revisit the common sources of the epidemics of obesity and diabetes. Fortunately, there is active discussion about what the most promising interventions are. Schools, families, and social groups are all potential targets.” (E. W. Gregg)
Amphotericin B for Visceral Leishmaniasis: In an open-label study of 412 patients with visceral leishmaniasis, single-dose liposomal amphotericin B 10 mg/kg was not inferior to but was less expensive than 15 courses of amphotericin B deoxycholate 1 mg/kg over a 29-day period (pp. 504–12). Results showed: “A total of 410 patients—304 of 304 patients (100%) in the liposomal-therapy group and 106 of 108 patients (98%) in the conventional-therapy group—had apparent cure responses at day 30. Cure rates at 6 months were similar in the two groups: 95.7% (95% confidence interval [CI], 93.4 to 97.9) in the liposomal-therapy group and 96.3% (95% CI, 92.6 to 99.9) in the conventional-therapy group. Adverse events in the liposomal-therapy group were infusion-related fever or rigors (in 40%) and increased anemia or thrombocytopenia (in 2%); such events in the conventional-therapy group were fever or rigors (in 64%), increased anemia (in 19%), and hypokalemia (in 2%). Nephrotoxicity or hepatotoxicity developed in no more than 1% of patients in each group.” (S. Sundar, drshyamsundar@hotmail.com)
Cyclophilin B in Osteogenesis Imperfecta: Extensive studies of two siblings with osteogenesis imperfecta show a lack of production of cyclophilin B (CyPB), one of the components of the collagen prolyl 3--hydroxylation complex (pp. 521–8). Data on the boy and girl led researchers to conclude: “These unexpected data open fundamental questions concerning the function of the 3-hydroxylation modification, the role of CyPB in the complex, and the identity of the major collagen isomerase. It is tempting to speculate that FKBP65, another PPIase that resides in the endoplasmic reticulum and binds to collagen, may be the major isomerase or that FKBP65 and CyPB have redundant functions. FKBP65 is partially inhibited by both cyclosporine and FK506, both of which delay collagen folding. To date, all probands with normal type I collagen folding have an intact [collagen prolyl 3--hydroxylation] complex and normal alpha-1(I)Pro986 hydroxylation. Perhaps 3-hydroxylation triggers a conformational change of the collagen substrate or 3-hydroxylation complex that facilitates binding of FKBP65.” (J. C. Marini, idoc@helix.nih.gov">oidoc@helix.nih.gov)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 12, 2010 * Vol. 17, No. 29
Providing news and information about medications and their proper use

>>>Rheumatology Report
Source:
Feb. issue of Arthritis & Rheumatism (2010; 62).
Estrogenic Effects Not Same as Antirheumatic Action: No improvement in symptoms and signs of rheumatoid arthritis was observed in patients receiving the selective estrogen-alpha agonist Org 37663, a finding that refutes ideas that sex hormones play a role in RA pathogenesis or clinical expression (pp. 351–8). In a 10-week study, postmenopausal women with RA received Org 37663 or placebo, with methotrexate or sulfasalazine, with these results: “Org 37663 induced a clear biologic, estrogenic response in several organ systems, including a dose-related increase in levels of sex hormone binding globulin. However, the [Disease Activity Score in 28 joints] decreased similarly for all treatment groups including placebo, indicating lack of clinical efficacy of Org 37663 in this trial.” (A. M. M. Miltenburg, a.miltenburg@spcorp.com)
Methotrexate Levels Not Linked to Efficacy, Safety: In contrast to previous studies showing a relationship between drug concentrations of methotrexate polyglutamate (MTXGlu) and drug efficacy, data from 192 patients on oral MTX showed no relationship between erythrocyte drug levels and reduced disease activity (pp. 359–68). The current report is consistent with past literature in that none of the studies have been able to associate adverse drug effects with drug concentrations. Investigators analyzed red blood cell concentrations of MTXGlun, where n is the number of glutamate groups, and made these observations: “The MTX dosage was significantly higher in patients in whom the swollen joint count and [Disease Activity Score in 28 joints] were higher. The MTXGlu4, MTXGlu5, MTXGlu3-5, and MTXGlu1-5 concentrations were significantly higher in patients with high disease activity. After correction for age, the estimated glomerular filtration rate, and the MTX dosage, the association remained significant for MTXGlu5. RBC folate concentrations were significantly higher in the group with high disease activity. There was no association between any MTXGlun concentration and adverse effects.” (L. K. Stamp, lisa.stamp@cdhb.govt.nz)

>>>Allergy/Immunology Report
Source:
Feb. issue of the Journal of Allergy and Clinical Immunology (2010; 125).
Pharmacogenomics in Asthma: A review article on pharmacogenomics covers principles of investigation in the field, possible approaches to applying the information to patients with asthma, and potential uses and impediments (pp. 295–302). The authors conclude: “All of the different genetic approaches (ie, candidate gene, family-based, pathway, and [genome-wide association study] approaches) will identify increasing numbers of associations between genetic variants and interindividual responses to therapeutic interventions. With appropriate validation (currently and yet to be undertaken) and adequate informatics support, these associations will allow us to choose among asthma therapies most likely to produce intended outcomes and to minimize unintended side effects. Such validation will need to include confirmation of associations in multiple cohorts and explication of the genetic background of the populations in which the associations have been verified. In many cases the associations will require prospective confirmation. As the information becomes available, we will approach our goal of using the right medications for the right patient.” (E. Israel, eisrael@partners.org)
Personalized medicine is the future for patients with asthma, writes an editorialist (
pp. 305–6): “Although the prevalence of asthma continues to increase and the number of hospitalizations on a per capita basis has not decreased since 1980, we know much about this very complex disorder and have more options for achieving control of asthma. The scientific basis for use of avoidance measures, pharmacotherapy, immunotherapy, and an immunomodulator is established. Future studies should help clarify how to achieve effective control, decrease hospitalizations and legitimate emergency department care, and reduce fatalities while identifying the good or essentially nonresponders to medications. We are at the dawn of more precise use of treatments for patients with asthma.” (P. A. Greenberger, p-greenberger@northwestern.edu)

>>>PNN NewsWatch
* PNN will not be published on Mon., Feb. 15, Presidents Day.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 16, 2010 * Vol. 17, No. 30
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Feb. 16 issue of the Annals of Internal Medicine (2010; 152).
Fishy Odor of Metformin: The oral antidiabetic drug metformin has a commonly recognized fishy odor that has not previously been discussed in the literature, researchers report (pp. 267–8). After examining case files for two patients reporting a “dead fish” or “fishy” odor associated with the immediate release formulation of metformin, researchers searched medical literature for other documented cases. Although reaction to the odor of metformin had not been reported in medical literature, hundreds of postings to message boards on the Internet noted the peculiar odor of the drug. In addition, an informal survey of pharmacists found that metformin was easily identified by its smell, which was described as “fishy” or “like old locker-room sweat socks.” The authors believe that the adverse reaction to metformin’s odor may not be published because patients may report that the drug makes them nauseous, but they may not distinguish this as a visceral reaction to the smell of the medication. Physicians should consider inquiring more closely about revulsion to the odor of the medication when patients stop taking it, the authors write, adding that a trial of a film-coated, extended release formulation may be a reasonable approach in such cases. (A. L. Pelletier)
Effects of Pipe, Cigar Smoking: Tobacco smoking is tobacco smoking, whether it’s done with cigarettes, pipes, or cigars, a study shows (pp. 201–10). In MESA (Multi-Ethnic Study of Atherosclerosis), increased urine cotinine levels and risk of airflow obstruction and decreased lung function were found among cigar and pipe smokers, including those who had never smoked cigarettes. (R. G. Barr, rgb9@columbia.edu)
CHD Risk with Estrogens/Progestins After Menopause: Exploring the possibility that estrogen plus progestin therapy might decrease risk of coronary heart disease in the years after menopause, researchers instead found increased CHD risk for the first 2 years of therapy and possible increases for up to 6 years (pp. 211–7). The effects were present regardless of whether fewer or more than 10 years had passed since menopause, the researchers report: “Compared with no use of hormone therapy, the hazard ratio for continuous use of estrogen plus progestin therapy was 2.36 (95% CI, 1.55 to 3.62) for the first 2 years and 1.69 (CI, 0.98 to 2.89) for the first 8 years. For women within 10 years after menopause, the hazard ratios were 1.29 (CI, 0.52 to 3.18) for the first 2 years and 0.64 (CI, 0.21 to 1.99) for the first 8 years, and the CHD-free survival curves for continuous use and no use of estrogen plus progestin crossed at about 6 years (CI, 2 years to 10 years).” (S. D. Toh, darrentoh@post.harvard.edu)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2010; 340).
Prophylactic Antibiotics for Burns: While methodologic quality of 17 trials testing use of systemic prophylactic antibiotics in burn patients is weak, a beneficial effect was identified in a systematic review and meta-analysis (c241): “Trials that assessed systemic antibiotic prophylaxis given for 4–14 days after admission showed a significant reduction in all cause mortality (risk ratio 0.54, 95% confidence interval 0.34 to 0.87, five trials). The corresponding number needed to treat was 8 (5 to 33), with a control event rate of 26%. Perioperative non-absorbable or topical antibiotics alone did not significantly affect mortality. There was a reduction in pneumonia with systemic prophylaxis and a reduction in wound infections with perioperative prophylaxis. Staphylococcus aureus infection or colonisation was reduced with anti-staphylococcal antibiotics. In three trials, resistance to the antibiotic used for prophylaxis significantly increased (rate ratio 2.84, 1.38 to 5.83). The overall methodological quality of the trials was poor.” (M. Paul, paulm@post.tau.ac.il)

>>>PNN JournalWatch
* Liver Disease in Pregnancy, in Lancet, 2010; 375: 594–605. (M. A. Heneghan, michael.heneghan@kch.nhs.uk)
* State of Research in Pediatric Gastroenterology, Hepatology, and Nutrition: 2010 and Beyond, in
Gastroenterology, 2010; 138: 411–16.e2. (W. A. Walker)
* Do Differences in Pegylation of Interferon Alfa Matter [editorial]?, in
Gastroenterology, 2010; 138: 34–6. (S. Zeuzem, Zeuzem@em.uni-frankfurt.de)
* Adenosine Triphosphate: A Multifaceted Chemical Signal in the Nervous System, in
Neurology, 2010; 74: 601–7. (E. E. Benarroch)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 17, 2010 * Vol. 17, No. 31
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Feb. 17 issue of JAMA (2010; 303).
Chronic Diseases of Childhood: In addition to obesity, numerous other chronic conditions have become common among pediatric patients, a study shows, including learning disabilities, ADHD, other behavioral and learning problems; asthma, allergies, and other respiratory disorders; epilepsy, blood disorders, immune deficiency, heart trouble, and other major condition; chronic ear problems and infections; and physical impairments such as difficulty in hearing or seeing and orthopedic impairments (pp. 623–30). Assessing 5,000 children in the National Longitudinal Survey of Youth–Child Cohort who were aged 2–8 in 1988 (cohort 1), 1994 (cohort 2), and 2000 (cohort 3), the investigators report these findings regarding the ensuing 6 years of the patients’ lives: “The end-study prevalence of any chronic health condition was 12.8% (95% confidence interval [CI], 11.2%–14.5%) for cohort 1 in 1994, 25.1% (95% CI, 22.7%–27.6%) for cohort 2 in 2000, and 26.6% (95% CI, 23.5%–29.9%) for cohort 3 in 2006. There was substantial turnover in chronic conditions: 7.4% (95% CI, 6.5%–8.3%) of participants in all cohorts had a chronic condition at the beginning of the study that persisted to the end, 9.3% (95% CI, 8.3%–10.3%) reported conditions at the beginning that resolved within 6 years, and 13.4% (95% CI, 12.3%–14.6%) had new conditions that arose during the 6-year study period. The prevalence of having a chronic condition during any part of the 6-year study period was highest for cohort 3 (51.5%; 95% CI, 47.3%–55.0%), and there were higher rates among male (adjusted odds ratio [AOR], 1.24; 95% CI, 1.07–1.42), Hispanic (AOR, 1.36; 95% CI, 1.11–1.67), and black (AOR, 1.60; 95% CI, 1.35–1.90) youth.” (J. Van Cleave, jvancleave@partners.org)
These changes in childhood diseases are important, editorialists note, as many carry over into adult conditions (
pp. 665–6): “The epidemiologic shift, signified by the increasing number of children with obesity, ADHD, asthma, and other less severe chronic conditions, seems to be associated with a shift in the social ecology of childhood. This changing ecology includes exposures to higher levels of toxic stress, increasing rates of absent parents, more sedentary and less active lifestyles, more television and multimedia use, and the ingestion of high-caloric and high-fat diets. A combination of developmental plasticity and developmental reserves can enable children to be functionally resilient under optimal circumstances. Yet the same adverse childhood experiences that can contribute to the onset of childhood illness can also affect stress-sensitive physiologic systems (nervous, endocrine/metabolic, immune), predisposing the same individuals to develop age-related diseases as adults. This suggests that well-designed prevention strategies initiated in childhood could be a ‘two-for,’ preventing childhood chronic conditions as well as the adult chronic conditions that are likely to emerge in years to come.” (N. Halfon, nhalfon@ucla.edu)
Genomic Markers & Heart Disease: Single-nucleotide polymorphisms (SNPs) in an intergenic region of chromosome 9p21 can be associated with heart disease, authors of a meta-analysis report, but the specific conditions varied by age at disease onset and associations were weak (pp. 648–56). The report states: “Forty-seven distinct data sets from the 22 articles were analyzed, including 35,872 cases and 95,837 controls. The summary OR for heart disease among individuals with 2 vs 1 at-risk alleles was 1.25 (95% confidence interval [CI], 1.21–1.29), with low to moderate heterogeneity. Age at disease diagnosis was a significant covariate, with ORs of 1.35 (95% CI, 1.30–1.40) for age 55 years or younger and 1.21 (95% CI, 1.16–1.25) for age 75 years or younger. For a 65-year-old man, the 10-year heart disease risk for 2 vs 1 at-risk alleles would be 13.2% vs 11%. For a 40-year-old woman, the 10-year heart disease risk for 2 vs 1 at-risk alleles would be 2.4% vs 2.0%. Nearly identical but inverse results were found when comparing 1 vs 0 at-risk alleles. Three studies showed net reclassification indexes ranging from –0.1% to 4.8%.” (G. E. Palomaki, gpalomaki@ipmms.org)

>>>PNN NewsWatch
* CNN is running a segment on the Ohio pharmacist jailed for involuntary manslaughter following the medication error–related death of a 2-year-old patient.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 18, 2010 * Vol. 17, No. 32
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 18 issue of the New England Journal of Medicine (2010; 362).
Potential Cardiovascular Impact of Salt Reductions: With the American diet high in salt—largely because of processed foods—researchers find that substantial reductions in cardiovascular events and therefore medical costs would be possible if intake were reduced by about half a teaspoonful each day (pp. 590–9). Advocating adoption of a 3-g/d reduction (1,200 mg of sodium) as a public health goal, the investigators report these populationwide results based on the Coronary Heart Disease Policy Model: “Reducing dietary salt by 3 g per day is projected to reduce the annual number of new cases of CHD by 60,000 to 120,000, stroke by 32,000 to 66,000, and myocardial infarction by 54,000 to 99,000 and to reduce the annual number of deaths from any cause by 44,000 to 92,000. All segments of the population would benefit, with blacks benefiting proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. The cardiovascular benefits of reduced salt intake are on par with the benefits of population-wide reductions in tobacco use, obesity, and cholesterol levels. A regulatory intervention designed to achieve a reduction in salt intake of 3 g per day would save 194,000 to 392,000 quality-adjusted life–years and $10 billion to $24 billion in health care costs annually. Such an intervention would be cost-saving even if only a modest reduction of 1 g per day were achieved gradually between 2010 and 2019 and would be more cost-effective than using medications to lower blood pressure in all persons with hypertension.” (K. Bibbins-Domingo)
Editorialists explain that daily salt intake approaches 12 and 8 g/d for most American men and women, respectively. After noting that a 3-g reduction in salt intake would not even bring most Americans’ daily intake down to the recommended upper limit of 5.8 g/d (and would come nowhere near the 3.8 g/d goal that applies to 69% of Americans), they outline these options (
pp. 650–2): “In broad terms, there are two complementary strategies that could be used to lower salt intake: a public health approach, in which food manufacturers reduce levels of salt in processed and prepared foods, and an individual approach, which relies on each person to select and prepare foods with little or no salt. Given that approximately 75% of dietary salt comes from processed foods, the individual approach is probably impractical. Since 1969, the United States has implemented several individual-level initiatives targeting sodium reduction, yet per capita salt consumption appears to be increasing or is at best unchanged. A public health approach is needed. A number of countries, including the United Kingdom, Finland, and Ireland, have implemented aggressive public health programs to reduce salt intake. Monitoring efforts to determine the level of success of these programs are ongoing. Concomitantly, several U.S. manufacturers are reducing the salt content of certain foods (e.g., soups, cereals, and breads), but other manufacturers are increasing the salt levels in their products. For example, the addition of salt to poultry, meats, and fish appears to be occurring on a massive scale.” (L. J. Appel)
Prophylactic Platelet Transfusions: Mixed results come from a study designed to identify appropriate doses of platelets to use prophylactically in patients undergoing hematopoietic stem-cell transplantation (pp. 600–13). Low, medium, and high doses of platelets were administered on mornings when 1,272 patients had platelet counts of 10,000 per cu mm or lower, and about 70% in each group reached a primary end point of grade 2 or higher bleeding. The median number of platelets infused was lower for the low-dose group, but that group required significantly more transfusions. “The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups,” the authors write. “Bleeding occurred on 25% of the study days on which morning platelet counts were 5,000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6,000 to 80,000 per cubic millimeter (P < 0.001).” (S. J. Slichter, sjslichter@psbc.org)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 19, 2010 * Vol. 17, No. 33
Providing news and information about medications and their proper use

>>>Infectious Disease Report
Source:
Mar. 15 issue of Clinical Infectious Diseases (2010; 50).
Gender Differences in Travel-Associated Morbidity: When traveling internationally, men and women do not have the same risks for the infectious pathogens they may encounter or for other diseases, a study shows (pp. 826–32). Preventive travel medicine and future travel medicine research should address these divergent patterns, the authors write. Compared with men, women were at greater risk of acute or chronic diarrhea, irritable bowel syndrome, upper respiratory tract infection, urinary tract infection, psychological stressors, oral and dental conditions, and adverse reactions to medications. Men more commonly had febrile illnesses; vector-borne diseases such as malaria, leishmaniasis, and rickettsioses; sexually transmitted diseases; and noninfectious conditions such as cardiovascular conditions, acute mountain sickness, and frostbite. (P. Schlagenhauf, pat@ifspm.unizh.ch)

>>>Oncology Highlights
Source:
Feb. issue of the Journal of Clinical Oncology (2010; 28).
Risedronate Prevention of Bone Loss from Aromatase Inhibitors: In patients with early breast cancer who receive adjuvant anastrozole, osteoporosis can be prevented or treated with risedronate, researchers report (pp. 967–75). Study participants were all postmenopausal women with hormone receptor–positive early breast cancer, and those at highest risk of osteoporosis received risedronate 35 mg/wk orally. Medium-risk patients were randomized in double-blind fashion to risedronate or placebo, while low-risk patients received only the aromatase inhibitor. Results at 24 months showed significant increases in lumbar spine and total hip bone mineral density in treated medium-risk patients and all high-risk patients. Low-risk patients had significantly lower BMD in the lumbar spine and numerically lower values for total hip. (C. Van Poznak, cvanpoz@umich.edu)

>>>PNN NewsWatch
* FDA has approved rituximab (Rituxan, Genentech) for the additional indication of treatment of patients with chronic lymphocytic leukemia who are beginning chemotherapy for the first time and for those who have not responded to other cancer drugs for CLL. It is the third agent approved recently for CLL, joining second-line agent ofatumumab (Arzerra, GlaxoSmithKline) and first-line drug bendamustine (Treanda, Cephalon).
*
Long-acting beta-agonists (LABAs) should never be used alone in patients with asthma, FDA said yesterday. The agency went so far as to recommend that only combination products be used to enhance adherence in pediatric and adolescent patients whose asthma requires an LABA in addition to an inhaled corticosteroid. A Risk Management and Evaluation Strategy (REMS) will be required for LABAs. The REMS will focus on education of health professionals and written information to be provided to patients with asthma when they receive their prescribed LABAs. FDA said that the new recommendations do not apply to those chronic obstructive pulmonary disease.
* In two safety-related warnings this week, FDA cautioned of confusion about the intended use of
Maalox Total Relief and said that it will require a REMS for erythropoiesis-stimulating agents. The packaging for Maalox Total Relief is very similar to that for Maalox Advanced Maximum or Regular Strength, marketed as antacids. But the products are not interchangeable, as Maalox Total Relief contains bismuth salicylate and is intended for use in upset stomach and diarrhea. Use of the Total Relief product in patients with histories of gastrointestinal ulcer disease or a bleeding disorder is not appropriate, FDA said, as bismuth salicylate can cause adverse effects similar to those of aspirin. FDA has provided a cautionary poster, Avoiding Maalox Mix-Ups, as a PDF file that health professionals can print and post or send to patients by e-mail. Novartis has agreed to rename Maalox Total Relief in September to eliminate the confusion caused by this use of a common OTC brand name on products with different indications. The ESA REMS, being implemented through Amgen’s ESA APPRISE Oncology Program, will require hospitals and health professionals to enroll and complete training before they can prescribe and dispense the ESAs erythropoietin and darbepoetin.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 22, 2010 * Vol. 17, No. 34
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Feb. 20 issue of Lancet (2010; 375).
Combination Immunotherapy in Renal Cell Carcinoma: Identification of suitable candidates is the key to use of combination immunotherapy in patients with metastatic renal cell carcinoma, investigators conclude based on findings that some—but not all—patients have remissions of “clinically relevant length” with multiple drug therapy (pp. 641–8). In the MRC RE04/EORTC GU 30012 trial, 1,006 treatment-naive patients received either interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil, with these overall results: “Median follow-up was 37.2 months (24.8–52.3). Median overall survival was 18.8 months (17.0–23.2) for patients receiving interferon alfa-2a versus 18.6 months (16.5–20.6) for those receiving combination therapy. Overall survival did not differ between the two groups (hazard ratio 1.05 [95% CI 0.90–1.21], p = 0.55; absolute difference 0.3% (–5.1 to 5.6) at 1 year and 2.7% (–8.2 to 2.9) at 3 years). Serious adverse events were reported in 113 (23%) patients receiving interferon alfa-2a and 131 (26%) of those receiving combined treatment.” (M. E. Gore, Martin.Gore@rmh.nhs.uk)
Venous Thromboembolism in Inflammatory Bowel Disease: Trials of primary prophylaxis in patients with inflammatory bowel disease are warranted based on results of a cohort study, researchers report (pp. 657–63). Using data from the U.K. General Practice Research Database from 1987 through mid-2001, investigators find: “13,756 patients with inflammatory bowel disease and 71,672 matched controls were included in the analysis, and of these 139 patients and 165 controls developed venous thromboembolism. Overall, patients with inflammatory bowel disease had a higher risk of venous thromboembolism than did controls (hazard ratio 3.4, 95% CI 2.7–4.3; p < 0.0001; absolute risk 2.6 per 1,000 per person–years). At the time of a flare, however, this increase in risk was much more prominent (8.4, 5.5–12.8; p < 0.0001; 9.0 per 1,000 person–years). This relative risk at the time of a flare was higher during non-hospitalised periods (15.8, 9.8–25.5; p < 0.0001; 6.4 per 1,000 person–years) than during hospitalised periods (3.2, 1.7–6.3; p = 0.0006; 37.5 per 1,000 person–years).” (M. J. Grainge, matthew.grainge@nottingham.ac.uk)

>>>PNN NewsWatch
* Focusing on actions taken by FDA and GlaxoSmithKline with regard to the adverse cardiovascular risks of rosiglitazone (Avandia), Chairman Max Baucus (MT) and Ranking Member Chuck Grassley (IA) of the Senate Finance Committee demanded explanations from FDA Commissioner Margaret A. Hamburg, MD, in a letter sent last Thursday and released on Saturday. “After reading these documents, we would like to know what steps the FDA has taken to protect patients in the TIDE trial, and why this trial is allowed to continue,” the Senators wrote. “We would also like to know if the Office for Human Research Protection (OHRP) was notified about the safety concerns of the TIDE trial identified by the FDA. Further, we were alarmed to learn that the warnings from these safety officers do not appear to be addressed in the consent form that was handed out to patients that were enrolled in the study.” The Senators gave FDA 2 weeks to respond to its 2-year investigation, which relied on more than 250,000 pages of documents. GSK issued a news release rejecting the Committee’s conclusions, which it said “are based on analyses that are not consistent with the rigorous scientific evidence supporting the safety of the drug.”

>>>PNN JournalWatch
* An Approach to the Evaluation and Management of Syncope in Adults, in BMJ, 2010; c880. (S. W. Parry, swparry@hotmail.com)
* Biological, Clinical, and Ethical Advances of Placebo Effects, in
Lancet, 2010; 375: 686–95. (D. G. Finniss, dfinniss@med.usyd.edu.au)
* Clinical Implications of Genotypic Resistance to the Newer Antiretroviral Drugs in HIV-1–Infected Patients with Virological Failure, in
Clinical Infectious Diseases, 2010; 50: 872–81. (J. M. Llibre, jmllibre@flsida.org)
* Hospitalizations and Deaths Among Adults with Cardiovascular Disease Who Underuse Medications Because of Cost: A Longitudinal Analysis, in
Medical Care, 2010; 48: 87–94. (M. Heisler)
* Chronic Conditions Account for Rise in Medicare Spending from 1987 to 2006, in
Health Affairs, 2010; 10.1377/hlthaff.2009.0474. (K. E. Thorpe, kthorpe@sph.emory.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 23, 2010 * Vol. 17, No. 35
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Feb. 23 issue of the Archives of Internal Medicine (2010; 170).
Hospitals Balancing Costs, Outcomes: Examining quality and cost of hospital care, researchers found mixed results (pp. 340–6). In a study of U.S. hospitals discharging Medicare patients for congestive heart failure or pneumonia in 2006, investigators found these associations: “Compared with hospitals in the lowest-cost quartile for CHF care, hospitals in the highest-cost quartile had higher quality-of-care scores (89.9% vs 85.5%) and lower mortality for CHF (9.8% vs 10.8%) (P < .001 for both). For pneumonia, the converse was true. Compared with low-cost hospitals, high-cost hospitals had lower quality-of-care scores (85.7% vs 86.6%, P = .002) and higher mortality for pneumonia (11.7% vs 10.9%, P < .001). Low-cost hospitals had similar or slightly higher 30-day readmission rates compared with high-cost hospitals (24.7% vs 22.0%, P < .001 for CHF and 17.9% vs 17.3%, P = .20 for pneumonia). Nevertheless, patients initially seen in low-cost hospitals incurred lower 6-month inpatient cost of care compared with patients initially seen in hospitals with the highest cost of care ($12 715 vs $18 411 for CHF and $10 143 vs $15 138 for pneumonia, P < .001 for both).” (L. M. Chen, lenac@umich.edu)
Can we decrease hospital costs while maintaining quality, an editorialist asks (
pp. 317–8): “To increase progress on lowering hospital costs without harming quality, we need more comparative effectiveness studies—specifically, studies that show that 2 interventions of different costs are of equal value. While it is a cliché to end a commentary calling for more research, a focus on equivalence studies would actually be a paradigm shift. Overwhelmingly, biomedical research is designed to prove that one treatment is superior to another, often with a focus on statistical significance rather than clinical importance. Fortunately, the American Recovery and Reinvestment Act has dedicated $1.1 billion of stimulus funds to perform comparative effectiveness research. This research is critical to increasing quality of care at the same time as we decrease cost, so that we can afford to expand health care coverage for the uninsured.” (M. H. Katz, mitch.katz@sfdph.org)
Reminders for Influenza Vaccination: Reminders for influenza vaccinations are used infrequently in the U.S., survey results show (pp. 390–2). Based on nationally representative responses from 5,105 adults in March and April 2009, investigators determined: “Only approximately 1 in 4 US adults reported receipt of a vaccination reminder during the 2008–2009 vaccination season, despite their well-documented effectiveness in improving immunization rates. Thus, our results highlight the large potential of more widespread use of vaccination reminders to increase influenza vaccine uptake. Moreover, the relatively low share of adults receiving vaccination reminders from health care providers and the limited variation of reminder receipt by health risk factors suggest that primary care providers could make better use of patients’ medical records in order to effectively target influenza immunizations according to need.” (J. Maurer, jmaurer@rand.org)
Industry Support Not Good But Accepted: In a survey, 72% of 236 directors of internal medicine residency programs indicated that pharmaceutical industry support is “not desirable,” but 56% of respondents accept the funds (pp. 356–62): “Residency programs were less likely to receive pharmaceutical support when the program director held the opinion that industry support was not acceptable (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.02–0.22). Programs located in the southern United States were more likely to accept pharmaceutical support (OR, 8.45; 95% CI, 1.95–36.57). The American Board of Internal Medicine pass rate was inversely associated with acceptance of industry support: each 1% decrease in the pass rate was associated with a 21% increase in the odds of accepting industry support (OR, 1.21; 95% CI, 1.07–1.36).” (F. S. McDonald)

>>>PNN NewsWatch
* The health care reform proposal released by the White House yesterday addresses some pharmacy issues, the Part D donut hole and generics in particular, but medication therapy management and workforce issues seem to have fallen out. Details in the proposal are sketchy, however, ASHP reports.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 24, 2010 * Vol. 17, No. 36
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Feb. 24 issue of JAMA (2010; 303).
Work Hours of Physicians: Physicians are working less and being paid less, a research study shows (pp. 747–53). “After remaining stable through the early 1990s, mean hours worked per week decreased by 7.2% between 1996 and 2008 among all physicians (from 54.9 hours per week in 1996–1998 to 51.0 hours per week in 2006–2008; 95% confidence interval [CI], 5.3%–9.0%; P < .001),” investigators reported based on 1976–2008 data from the U.S. Census Bureau Current Population Survey. “Excluding resident physicians, whose hours decreased by 9.8% (95% CI, 5.8%–13.7%; P < .001) in the last decade due to duty hour limits imposed in 2003, nonresident physician hours decreased by 5.7% (95% CI, 3.8%–7.7%; P < .001). The decrease in hours was largest for nonresident physicians younger than 45 years (7.4%; 95% CI, 4.7%–10.2%; P < .001) and working outside of the hospital (6.4%; 95% CI, 4.1%–8.7%; P < .001), and the decrease was smallest for those aged 45 years or older (3.7%; 95% CI, 1.0%–6.5%; P = .008) and working in the hospital (4.0%; 95% CI, 0.4%–7.6%; P = .03). After adjusting for inflation, mean physician fees decreased nationwide by 25% between 1995 and 2006, coincident with the decrease in physician hours. In 2001, mean physician hours were less than 49 hours per week in metropolitan areas with the lowest physician fees, whereas physician hours remained more than 52 hours per week elsewhere (P < .001 for difference).” (D. O. Staiger, doug.staiger@dartmouth.edu)
Front Food Labels: The First Amendment notwithstanding, FDA needs to enforce stricter standards for nutrition and health claims made on the front-of-package food labels, argues the author of a commentary (pp. 771–2). “If health claims are allowed on food packages, they should be regulated more strictly according to rigorous, evidence-based national standards,” the write explains. “Because such standards are inevitably arbitrary and subject to manipulation, consideration should be given to an outright ban on all front-of-package claims. Doing so would aid educational efforts to encourage the public to eat whole or minimally processed foods and to read the ingredient lists on processed foods. In addition, the Nutritional Facts Panel should be revised and updated to facilitate informed dietary choice and minimize the possibility of marketing manipulation. Presently, consumers may greatly underestimate the calories in a 20-oz bottle of sugared beverage, for example, because the Nutrition Facts pertain to a serving size of 8 oz.” (D. S. Ludwig, david.ludwig@childrens.harvard.edu)

>>>PNN NewsWatch
* FDA said yesterday it is reviewing data about prolongation of QT and PR intervals when saquinavir is used with ritonavir. While the agency analyzes available data, it recommends that the drug combination not be used in patients already taking medications known to cause QT interval prolongation—including Class IA (such as quinidine,) or Class III (such as amiodarone) antiarrhythmic drugs—or in patients with a history of QT interval prolongation.
* In a safety announcement issued on Monday,
FDA responded to the Senate Finance Committee report (see PNN, Feb. 22) on rosiglitazone (Avandia, GlaxoSmithKline). FDA said that it is reviewing data from the RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes) trial, patients should talk with health professionals about the risks of taking the drug and read the MedGuide that is dispensed with each rosiglitazone prescription, and health professionals should use the agent in accordance with the FDA-approved product labeling.
* A boxed warning has been added to the labeling of
deferasirox (Exjade), Novartis Oncology and FDA announced last week. The iron-overload treatment may cause serious adverse effects, the labeling notes, including potentially fatal renal impairment, including failure; hepatic impairment, including failure; and gastrointestinal hemorrhage. These reactions were more frequently observed in patients with advanced age, high risk myelodysplastic syndromes, underlying renal or hepatic impairment or low platelet counts. Serum creatinine, creatinine clearance, and serum transaminases and bilirubin should monitored closely in patients on deferasirox therapy, as recommended in product labeling, FDA said.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 25, 2010 * Vol. 17, No. 37
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 25 issue of the New England Journal of Medicine (2010; 362).
Lasofoxifene for Postmenopausal Osteoporosis: Risks of nonvertebral and vertebral fractures, estrogen-receptor–positive breast cancer, coronary heart disease, and stroke were reduced by lasofoxifene therapy among 8,556 women with low bone mineral densities after menopause, but with an increased risk of venous thromboembolic events (pp. 686–96). Doses of 0.5 mg/day of this investigational selective estrogen-receptor modulator produced these outcomes over 5 years: “Lasofoxifene at a dose of 0.5 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (13.1 cases vs. 22.4 cases per 1,000 person–years; hazard ratio, 0.58; 95% confidence interval [CI], 0.47 to 0.70), nonvertebral fracture (18.7 vs. 24.5 cases per 1,000 person–years; hazard ratio, 0.76; 95% CI, 0.64 to 0.91), ER-positive breast cancer (0.3 vs. 1.7 cases per 1,000 person–years; hazard ratio, 0.19; 95% CI, 0.07 to 0.56), coronary heart disease events (5.1 vs. 7.5 cases per 1,000 person–years; hazard ratio, 0.68; 95% CI, 0.50 to 0.93), and stroke (2.5 vs. 3.9 cases per 1,000 person–years; hazard ratio, 0.64; 95% CI, 0.41 to 0.99). Lasofoxifene at a dose of 0.25 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (16.0 vs. 22.4 cases per 1,000 person–years; hazard ratio, 0.69; 95% CI, 0.57 to 0.83) and stroke (2.4 vs. 3.9 cases per 1,000 person–years; hazard ratio, 0.61; 95% CI, 0.39 to 0.96) Both the lower and higher doses, as compared with placebo, were associated with an increase in venous thromboembolic events (3.8 and 2.9 cases vs. 1.4 cases per 1,000 person–years; hazard ratios, 2.67 [95% CI, 1.55 to 4.58] and 2.06 [95% CI, 1.17 to 3.60], respectively). Endometrial cancer occurred in three women in the placebo group, two women in the lower-dose lasofoxifene group, and two women in the higher-dose lasofoxifene group. Rates of death per 1,000 person–years were 5.1 in the placebo group, 7.0 in the lower-dose lasofoxifene group, and 5.7 in the higher-dose lasofoxifene group.” (S. R. Cummings, scummings@sfcc-cpmc.net)
Starting Antiretroviral Drugs During TB Therapy: In 642 patients coinfected with HIV and tuberculosis, initiation of antiretroviral therapy during treatment for TB significantly improved survival, researchers report (pp. 697–706). The data, from South Africa, supports integration of TB and HIV services, the authors conclude, adding these study results: “This analysis compares data from the sequential-therapy group and the combined integrated-therapy groups up to September 1, 2008, when the data and safety monitoring committee recommended that all patients receive integrated antiretroviral therapy. There was a reduction in the rate of death among the 429 patients in the combined integrated-therapy groups (5.4 deaths per 100 person–years, or 25 deaths), as compared with the 213 patients in the sequential-therapy group (12.1 per 100 person–years, or 27 deaths); a relative reduction of 56% (hazard ratio in the combined integrated-therapy groups, 0.44; 95% confidence interval, 0.25 to 0.79; P = 0.003). Mortality was lower in the combined integrated-therapy groups in all CD4+ count strata. Rates of adverse events during follow-up were similar in the two study groups.” (S. A. Karim, caprisa@ukzn.ac.za)

>>>PNN NewsWatch
* Annual influenza vaccination of all Americans 6 months of age and older is being recommended by the CDC’s Advisory Committee on Immunization Practices, according to media reports. If yesterday’s vote of the panel is confirmed in the final plans for 2010–11, the proportion of the U.S. population for whom influenza vaccine is recommended would expand from 85% to near universal. ACIP continues to meet in Atlanta today with these topics on its agenda: National Vaccine Plan, meningococcal vaccine, ongoing mumps outbreaks in the northeastern U.S., rotavirus vaccines, vaccine supply, and Evidence-Based Recommendations Work Group.
* The
World Health Organization last week voted to include the A/H1N1 (2009) influenza strain in the vaccine prepared for use in the Northern Hemisphere in 2010–11. The other two recommended strains are A/H3N2 and B Brisbane.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Feb. 26, 2010 * Vol. 17, No. 38
Providing news and information about medications and their proper use

>>>Pharmacotherapy Reports
Source:
Mar. issue of Pharmacotherapy (2010; 30).
Effects on Blood Pressure of Pharmacist Deintervention: Cessation of a physician–pharmacist collaboration in management of patients with hypertension resulted in a deterioration of blood pressure control over the ensuing 18 months, a study shows (pp. 228–35). The intervention lasted for 9 months, after which patients returned to usual care. Blood pressures measured at 9, 18, and 27 months showed these patterns: “At baseline, mean ± SD systolic blood pressure was 152.5 ± 9.5 and 150.1 ± 9.6 mm Hg in the intervention and control groups, respectively (p = 0.22). At 9 months, systolic blood pressure decreased to 124.5 ± 10.7 and 132.0 ± 15.1 mm Hg (p = 0.0038 between groups), and blood pressure was controlled in 78.5% and 48.7% (p = 0.0017) of patients in the intervention and control groups, respectively. By 18 months, systolic blood pressure had deteriorated to 131.0 ± 12.2 and 143.3 ± 17.5 mm Hg (p < 0.001), and blood pressure control rates decreased to 53.9% and 30.8% (p = 0.02). By 27 months, systolic blood pressure was 131.3 ± 13.0 and 141.2 ± 15.8 mm Hg (p = 0.0008), and blood pressure control was 55.4% and 35.9% (p = 0.05).” (B. L. Carter, barry-carter@uiowa.edu)
“In the current climate of health care reform and the medical home model, we need to find better and more efficient ways to care for patients with chronic diseases,” an editorialist writes (
pp. 221–3). “Maybe even more important, we need to raise the value assigned to preventing or at least delaying the onset of chronic disease. Dr. Carter and his colleagues are to be congratulated for adjusting the barometer that judges the total value of pharmacist intervention.” (J. G. Gums, jgums@ufl.edu)
Monitoring Vitamin D Concentrations: Measurement of serum vitamin D concentrations is not yet of sufficient value to guide treatment of osteoporosis, according to authors of a review article (pp. 254–64): “Current vitamin D assays yield varying results, making it challenging for clinicians to interpret results from clinical trials and apply them directly to patients and their specific serum level data. Fracture risk is not easily assessable clinically, with no clear relationship between vitamin D concentrations and bone mineral density. The existing primary literature shows no clear relationship between vitamin D concentrations and fracture risk; target concentrations are not well established. Although the pharmacokinetic parameters of vitamin D are unpredictable and vitamin D supplementation is frequently lifelong, results of a vitamin D assay are unlikely to make a significant difference in the clinical decision-making process (i.e., provide more information than clinical judgment alone).” (M. H. H. Ensom)

>>>PNN NewsWatch
* Prevnar 13 (Wyeth), a pneumococcal 13-valent conjugate vaccine for infants and young children ages 6 weeks through 5 years, has been licensed by FDA for prevention of invasive pneumococcal disease (IPD) and otitis media. Prevnar 13 replaces 7-valent Prevnar, adding coverage against additional strains of Streptococcus pneumoniae. Effectiveness of the new product was evaluated through immunologic responses to vaccinations, with Prevnar 13 yielding similar levels of antibodies as Prevnar. In nearly 8,000 infants and young children included in a safety evaluation, adverse reactions to Prevnar 13 were similar to those of Prevnar: pain, redness and swelling at the injection site, irritability, decreased appetite and fever. Postmarketing studies will include continued monitoring for reduction in IPD and otitis media, as well as continued evaluation of safety. The vaccine is administered in a four-dose schedule given at 2, 4, 6, and 12–15 months of age. It is available in single-dose, prefilled syringes.
* Yesterday’s
health care summit did little to break the political logjam, most observers agree. Lecturing Members of Congress earned the President a “Professor Obama” moniker in a front-page article of today’s Washington Post, which pointed out, “Obama controlled the microphone and the clock, and he used both skillfully to limit the Republicans’ time, to rebut their arguments and to always have the last word.” Whether the effort created any negotiable points or lacking that, enough leverage for Democrats to proceed using parliamentary and procedural maneuvers that would avoid the need for the 60-vote super majority in the Senate remains to be seen.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 1, 2010 * Vol. 17, No. 39
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Feb. 27 issue of Lancet (2010; 375).
Statins & Diabetes: Despite a slightly increased risk of diabetes among patients taking statins, the agents should continue to be used as recommended in those with moderate or high cardiovascular risk or existing cardiovascular disease, authors of a collaborative meta-analysis conclude (pp. 735–42): “We identified 13 statin trials with 91,140 participants, of whom 4,278 (2,226 assigned statins and 2,052 assigned control treatment) developed diabetes during a mean of 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR] 1.09; 95% CI 1.02–1.17), with little heterogeneity (I2 = 11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body-mass index nor change in LDL-cholesterol concentrations accounted for residual variation in risk. Treatment of 255 (95% CI 150–852) patients with statins for 4 years resulted in one extra case of diabetes.” (N. Sattar, nsattar@clinmed.gla.ac.uk)
Closed-Loop Insulin Delivery in Type 1 Diabetes: Nocturnal hypoglycemia could be reduced among patients with type 1 diabetes if closed-loop insulin delivery systems were used instead of standard continuous subcutaneous insulin infusions, researchers report (pp. 743–51). In three randomized controlled trials, glucose-guided closed-loop insulin delivery was compared with conventional systems after rapidly and slowly absorbed meals (7 patients) and after exercise (10 patients). Patients were studied during 33 closed-loop and 21 continuous infusion nights. Percentages of time patients were in normal or hypoglycemic ranges appeared to be similar among the groups. But a secondary analysis of pooled data showed “increased time in the target range (60% [51–88] vs 40% [18–61]; p = 0.0022) and reduced time for which glucose concentrations were 3.90 mmol/L or lower (2.1% (0.0–10.0) vs 4.1% (0.0–42.0); p = 0.0304).” The authors added, “No events with plasma glucose concentration lower than 3.0 mmol/L were recorded during closed-loop delivery, compared with nine events during standard treatment.” (R. Hovorka, rh347@cam.ac.uk)

>>>Diabetes Highlights
Source:
March issue of Diabetes Care (2010; 33).
Genetic Marker for Statin Efficacy: Presence of a mutation in the tumor necrosis factor–alpha gene appears to predict which patients will respond to the LDL cholesterol–lowering effects of statins, according to a study of 322 patients in Japan (pp. 463–6). The locus involved is the TNF-alpha gene promoter region, where a C-857T polymorphism was associated with resistance to LDL-lowering effects of statins. (J. Satoh, jsatoh@iwate-med.ac.jp)

>>>PNN NewsWatch
* Velaglucerase alfa for injection (VPRIV, Shire) has been approved by FDA for long-term treatment of type 1 Gaucher disease in pediatric and adult patients. The product provides replacement therapy for those with this common form of Gaucher disease. It is an alternative to imiglucerase (Cerezyme, Genzyme), which is currently in short supply. Efficacy of velaglucerase alfa was assessed in three clinical studies in a total of 99 patients with type 1 Gaucher disease, some of whom were not currently being treated for this condition and others who had been taking imiglucerase immediately before that. Each study met its primary endpoint, Shire reports. The most common adverse reactions to this product have been allergic reactions; other adverse reactions with velaglucerase are headache, dizziness, abdominal pain, back pain, joint pain, nausea, fatigue/weakness, fever, and prolongation of activated partial thromboplastin time.

>>>PNN JournalWatch
* Age Related Macular Degeneration, in BMJ, 2010; 340: c981. (U. Chakravarthy, u.chakravarthy@qub.ac.uk)
* International Association of Diabetes and Pregnancy Study Groups Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy, in
Diabetes Care, 2010; 33: 676–82. (B. E. Metzger, bem@northwestern.edu)
* Disordered Eating Behavior in Individuals with Diabetes: Importance of Context, Evaluation, and Classification, in
Diabetes Care, 2010; 33: 683–9. (D. Young–Hyman, dyounghyman@mcg.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 2, 2010 * Vol. 17, No. 40
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from and Mar. 2 issue of the Annals of Internal Medicine (2010; 152).
Population Strategies for Decreasing Sodium Intake: Similar to articles published recently in the New England Journal of Medicine (see PNN, Feb. 18), authors report that population-based interventions designed to reduce sodium intake could substantially reduce stroke and myocardial infarction incidence as well as save billions of dollars in medical expenses (early release). A Markov model was used to analyze data from several sources to determine effects of population-based interventions on cost, quality-adjusted life–years, and cardiovascular events. The model assumed adults aged 40–85 years, a lifetime horizon, and a societal perspective. Results showed: “Collaboration with industry that decreases mean population sodium intake by 9.5% averts 513,885 strokes and 480,358 MIs over the lifetime of adults aged 40 to 85 years who are alive today compared with the status quo, increasing QALYs by 2.1 million and saving $32.1 billion in medical costs. A tax on sodium that decreases population sodium intake by 6% increases QALYs by 1.3 million and saves $22.4 billion over the same period.” (C. Smith-Spangler, smith-spangler@stanford.edu)
Editorialists point to successes in other countries in sodium reduction (
early release): “In 2003, the United Kingdom introduced a voluntary strategy to decrease the sodium content of processed and packaged food, which has resulted in reductions of 20% to 30% in most processed food sold in stores. New sodium reduction targets in the United Kingdom are being established and are expected to lead to a total 40% reduction in population sodium intake by 2012. Japan and Finland have also implemented effective salt reduction programs; Ireland, Australia, and Canada have recently begun similar initiatives, and many other countries have committed to reducing sodium intake at the population level.” (T. R. Frieden)
Vitamin D & Cardiometabolic Outcomes: Vitamin D, increasingly recognized for a variety of health benefits that go beyond those traditionally associated with what has been considered adequate intake of the nutrient, may or may not help when it comes to prevention of cardiovascular events and diabetes, researchers report (pp. 307–14). A systematic review identified these patterns in 13 observational studies and 18 trials: “Three of 6 analyses (from 4 different cohorts) reported a lower incident diabetes risk in the highest versus the lowest vitamin D status groups. Eight trials found no effect of vitamin D supplementation on glycemia or incident diabetes. In meta-analysis of 3 cohorts, lower 25-hydroxyvitamin D concentration was associated with incident hypertension (relative risk, 1.8 [95% CI, 1.3 to 2.4]). In meta-analyses of 10 trials, supplementation nonsignificantly reduced systolic blood pressure (weighted mean difference, −1.9 mm Hg [CI, −4.2 to 0.4 mm Hg]) and did not affect diastolic blood pressure (weighted mean difference, −0.1 mm Hg [CI, −0.7 to 0.5 mm Hg]). Lower 25-hydroxyvitamin D concentration was associated with incident cardiovascular disease in 5 of 7 analyses (6 cohorts). Four trials found no effect of supplementation on cardiovascular outcomes.” (E. M. Balk, ebalk@tuftsmedicalcenter.org)
Cardiovascular Events & Vitamin D, Calcium Supplementation: Vitamin D supplements, administered in moderate to high doses, may reduce patients’ risk of cardiovascular disease, while calcium supplementation has little effect, according to a second systematic review published in this issue (pp. 315–23): “Five prospective studies of patients receiving dialysis and 1 study involving a general population showed consistent reductions in cardiovascular disease (CVD) mortality among adults who received vitamin D supplements. Four prospective studies of initially healthy persons found no differences in incidence of CVD between calcium supplement recipients and nonrecipients. Results of secondary analyses in 8 randomized trials showed a slight but statistically nonsignificant reduction in CVD risk (pooled relative risk, 0.90 [95% CI, 0.77 to 1.05]) with vitamin D supplementation at moderate to high doses (approximately 1,000 IU/d) but not with calcium supplementation (pooled relative risk, 1.14 [CI, 0.92 to 1.41]), or a combination of vitamin D and calcium supplementation (pooled relative risk, 1.04 [CI, 0.92 to 1.18]) compared with placebo.” (L. Wang, luwang@rics.bwh.harvard.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 3, 2010 * Vol. 17, No. 41
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 3 issue of JAMA (2010; 303).
Aspirin for Primary Prevention After Brachial Screening: In a population of patients without clinical cardiovascular disease, low-dose aspirin therapy in those with low ankle brachial index scores failed to reduce vascular events significantly, compared with placebo (pp. 841–8). In the Aspirin for Asymptomatic Atherosclerosis trial, 28,980 Scottish patients aged 50–75 years were screened using ABI. Those with low ABI were admitted to the trial, which provided once-daily enteric-coated aspirin 100 mg or placebo. Results showed the following based on a primary (composite of initial fatal or nonfatal coronary event or stroke or revascularization) and two secondary (primary end point events or angina, intermittent claudication, or transient ischemic attack; and all-cause mortality) end points: “After a mean (SD) follow-up of 8.2 (1.6) years, 357 participants had a primary end point event (13.5 per 1,000 person–years, 95% confidence interval [CI], 12.2–15.0). No statistically significant difference was found between groups (13.7 events per 1,000 person–years in the aspirin group vs 13.3 in the placebo group; hazard ratio [HR], 1.03; 95% CI, 0.84–1.27). A vascular event comprising the secondary end point occurred in 578 participants (22.8 per 1,000 person–years; 95% CI, 21.0–24.8) and no statistically significant difference between groups (22.8 events per 1,000 person–years in the aspirin group vs 22.9 in the placebo group; HR, 1.00; 95% CI, 0.85–1.17). There was no significant difference in all-cause mortality between groups (176 vs 186 deaths, respectively; HR, 0.95; 95% CI, 0.77–1.16). An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants (2.5 per 1,000 person–years) in the aspirin group and 20 (1.5 per 1,000 person–years) in the placebo group (HR, 1.71; 95% CI, 0.99–2.97).” (F. G. R. Fowkes, gerry.fowkes@ed.ac.uk)
After noting that “aspirin appears to have marginal benefits for reducing initial cardiovascular events when used for patients without clinically evident [cardiovascular disease],” an editorialist writes (
pp. 880–2): “Future study of aspirin for CVD prevention will require novel designs. Instead of concentrating on identifying individuals’ overall risk for CVD (such as age, hypertension, diabetes, ABI), the individual patient’s nascent platelet reactivity could be considered as an inclusion criteria. Because individuals with increased platelet activity are at greater cardiovascular risk, and because aspirin decreases platelet activity, perhaps measuring platelet activity in individuals without CVD may help to identify a high-risk group that would benefit from preventive aspirin therapy. Only adequately powered trials would provide the answer.” (J. S. Berger, jeffrey.berger@nyumc.org)
Innovations in Health Care: The refocusing of the national health care reform debate into a narrowly focused health insurance bill means that the transformation needed in medicine must come from other sources, the author of a commentary writes (pp. 874–5). Perhaps change could come through health care innovation zones (HIZs), proposed by Allyson Schwartz (D–PA) in HR 3664, the authors suggest: “The goal of HIZs is to demonstrate that coordination of the full spectrum of care for a defined geographic population under multiple payment systems would improve quality while controlling costs. However, often contradictory federal and state regulations stand in the way of meaningful health systems innovation. To achieve care coordination, HIZs would have to be granted focused ‘safe harbor’ protections from counterproductive antitrust and self-referral regulations, as well as be given broad-based payment-waiver authority for its Medicare reimbursement. These regulatory reforms would not only improve outcomes for Medicare patients, but may also include patients having other insurance (eg, Medicaid, private payers, and their own self-insured employees) under the same payment approaches and delivery system redesign.” (D. G. Kirch, dgkirch@aamc.org)
Testing Drugs for Influenza: The opportunity to study the efficacy and safety of medications used in treatment of influenza is “slipping away,” authors of a commentary maintain (pp. 878–9). The A/H1N1 influenza pandemic provided an excellent opportunity to gain clinical knowledge about the neuraminidase inhibitors, especially the largely untested peramivir that is being used under emergency FDA authorization, the group notes. (A. Meyerhoff, ameyerh1@jhmi.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 4, 2010 * Vol. 17, No. 42
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 4 issue of the New England Journal of Medicine (2010; 362).
Dopamine v. Norepinephrine in Shock: Norepinephrine was as effective and safer than dopamine in a trial of 1,679 patients with shock (pp. 779–89). Used as first-line vasopressor therapy, the two agents produced these outcomes over the 28 days after randomization: “There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P = 0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P < 0.001). A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1,044 patients with septic shock or the 263 with hypovolemic shock (P = 0.03 for cardiogenic shock, P = 0.19 for septic shock, and P = 0.84 for hypovolemic shock, in Kaplan–Meier analyses).” (D. De Backer, ddebacke@ulb.ac.be)
This study refutes several presumptions regarding norepinephrine when used for treating shock, an editorialist writes (
pp. 841–3): “Historically, there is a widespread clinical perception that the use of norepinephrine in patients with shock may increase the risk of death. As shown in the study by De Backer et al., shock from any cause carries a high risk of death, and vasopressors are temporizing agents that are administered until the underlying cause has been treated or the shock has resolved. The results of the study by De Backer et al. should also put an end to the outdated view that the use of norepinephrine increases the risk of death.” (J. H. Levy)
Treatment of Childhood Absence Epilepsy: Two older drugs—ethosuximide and valproic acid—were more effective than the more recently marketed lamotrigine when used for treatment of 453 children with childhood absence epilepsy, researchers report (pp. 790–9). The investigators added that ethosuximide had fewer adverse effects on attention, as noted in these results: “After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar (53% and 58%, respectively; odds ratio with valproic acid vs. ethosuximide, 1.26; 95% confidence interval [CI], 0.80 to 1.98; P = 0.35) and were higher than the rate for lamotrigine (29%; odds ratio with ethosuximide vs. lamotrigine, 2.66; 95% CI, 1.65 to 4.28; odds ratio with valproic acid vs. lamotrigine, 3.34; 95% CI, 2.06 to 5.42; P < 0.001 for both comparisons). There were no significant differences among the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide (in 49% of the children vs. 33%; odds ratio, 1.95; 95% CI, 1.12 to 3.41; P = 0.03).” (T. A. Glauser, tracy.glauser@cchmc.org)
Innovation in Health Care: The Center for Medicare and Medicaid Innovation (CMI), proposed in the health care reform legislation that Pres. Obama is trying to revive, is a needed element in the Centers for Medicare & Medicaid Services, authors write (pp. 772–4). “Regardless of the fate of national health care reform, Congress should try to enact some of the many good proposals developed over the past year that have bipartisan support,” the article states. “Successful innovation is essential to the long-term sustainability of Medicare and Medicaid. The CMI would cost relatively little in the context of the overall CMS budget, but if it were successful, the long-term effect on the U.S. health care system could be priceless.” (R. Mechanic)

>>>PNN NewsWatch
* The first generic tamsulosin hydrochloride capsules (IMPAX Laboratories) have been approved by FDA for treatment of benign prostatic hyperplasia.
* Women now make up 46% of practicing pharmacists, and 37% of this population is now older than 55 years, according to data out this week from the Pharmacy Manpower Project. The
2009 National Pharmacist Workforce Survey, available on the AACP website, also reports that nearly one-fourth of pharmacists, both men and women, are working parttime (23% in 2009, compared with 20% and 16% in 2004 and 2000, respectively).

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 5, 2010 * Vol. 17, No. 43
Providing news and information about medications and their proper use

>>>Pediatrics Highlights
Source:
Mar. issue of Pediatrics (2010; 125).
Patient-Held Vaccination Records: Having parents and caregivers keep a copy of children’s vaccination records is associated with increased immunization rates, a study shows (e467–72). The easily implemented strategy was assessed by examining the public-use files of the 2004–06 National Immunization Survey and determining what factors predicted children being up-to-date (UTD) on vaccinations: “Overall, 80.8% of children were UTD, and 40.8% of children had vaccination records. Children with vaccination records were more likely to be UTD (83.9% vs 78.6%; P < .0001). The largest effects associated with vaccination records were seen for children with multiple providers, comparing with and without a vaccination record (82.8% vs 71.9%; P < .0001), those with low maternal education, (81.6% vs 72.9%; P < .0001), and those with 4 children in the household, (76% vs 69.6%; P < .004). Logistic regression predicting UTD status and controlling for race/ethnicity, maternal education, poverty level, language, number of children in the home, and number of vaccine providers revealed the vaccination record to be associated with a 62% increase in the odds of UTD status (odds ratio: 1.62 [95% confidence interval: 1.49–1.77]).” (J. T. McElligott)
Fetal Exposure to Antidepressants: Children of mothers who used antidepressants during the second or third trimesters of pregnancy have developmental delays during the first 19 months of life, according to data from the Danish National Birth Cohort (e600–8). Among eligible pregnant women, 415 used antidepressants, 489 had depression with no medical treatment, and 81,042 had no depression or use of psychotropic medications. Results showed: “Children with second- or third-trimester exposure to antidepressants were able to sit 15.9 days (95% confidence interval [CI]: 6.8–25.0) and to walk 28.9 days (95% CI: 15.0–42.7) later than children of women not exposed to antidepressants but still were within the normal range of development. Fewer children with second- or third-trimester exposure to antidepressants were able to sit without support at 6 months of age (odds ratio: 2.1 [95% CI: 1.23–3.60]), and fewer were able to occupy themselves at 19 months of age (odds ratio: 2.1 [95% CI: 1.09–4.02]). None of the other milestones measured showed statistically significant associations with antidepressant exposure.” (L. H. Pedersen)

>>>Psychiatry Highlights
Source:
Mar. issue of the American Journal of Psychiatry (2010; 167).
Initial Combination Antidepressant Therapy: A study adds to the “growing body of evidence” that initial treatment of depression with two drugs can double the likelihood of remission (pp. 281–8). A total of 105 patients with major depressive disorder received fluoxetine 20 mg/day or mirtazapine 30 mg/day in combination with fluoxetine 20 mg/day, venlafaxine 225 mg/day (titrated in 14 days), or bupropion 150 mg/day for 6 weeks. Scores on the Hamilton Depression Rating Scale showed these changes: “The overall dropout rate was 15%, without notable differences among the four groups. Compared with fluoxetine monotherapy, all three combination groups had significantly greater improvements on the HAM-D. Remission rates (defined as a HAM-D score of 7 or less) were 25% for fluoxetine, 52% for mirtazapine plus fluoxetine, 58% for mirtazapine plus venlafaxine, and 46% for mirtazapine plus bupropion. Among patients who had a marked response, double-blind discontinuation of one agent produced a relapse in about 40% of cases.” (P. Blier)
Modafinil in Chronic Cocaine Users: Morning modafinil can help abstinent cocaine users attain normal sleep patterns, investigators report (pp. 331–40). Nocturnal sleep, sleep architecture, and daytime sleepiness were improved with modafinil. (P. T. Morgan)

>>>PNN NewsWatch
* Dexilant will soon be the new trade name for Takeda’s dexlansoprazole, replacing Kapidex and thereby avoiding confusion with Casodex (bicalutamide) and Kadian (morphine sulfate), FDA announced yesterday. Reports of dispensing errors since Kapidex was introduced last January led to the action, the agency said. The name change for this proton-pump inhibitor is slated for late April. Takeda is fielding professional and consumer questions about the name change on its toll-free number, 877-TAKEDA-7.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 8, 2010 * Vol. 17, No. 44
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 6 issue of Lancet (2010; 375).
Thromboprophylaxis After Knee Replacement: Orally administered apixaban offers an equally safe and effective alternative to subcutaneous enoxaparin in patients who have undergone knee replacement surgery, according to findings from the ADVANCE-2 trial (pp. 807–15). Apixaban 2.5 mg twice daily was started 24 hours after wound closure, while enoxaparin therapy began 12 hours before surgery. Both treatments were continued for 10–14 days. Results showed these effects on a primary outcome of composite of asymptomatic and symptomatic deep vein thrombosis, nonfatal pulmonary embolism, and all-cause death during treatment: “1,973 of 3,057 patients allocated to treatment (1,528 apixaban, 1,529 enoxaparin) were eligible for primary efficacy analysis. The primary outcome was reported in 147 (15%) of 976 apixaban patients and 243 (24%) of 997 enoxaparin patients (relative risk 0.62 [95% CI 0.51–0.74]; p < 0.0001; absolute risk reduction 9.3% [5.8–12.7]). Major or clinically relevant non-major bleeding occurred in 53 (4%) of 1,501 patients receiving apixaban and 72 (5%) of 1,508 treated with enoxaparin (p = 0.09).” (M. R. Lassen, mirula@noh.regionh.dk)
Acyclovir in Dually Infected Patients: Among 3,381 heterosexual people dually infected with herpes simplex virus type 2 and HIV-1, acyclovir therapy reduced the risk of progression of the retrovirus, researchers report (pp. 824–33). At multiple sites in southern and eastern Africa, patients received either acyclovir 400 mg orally twice daily or placebo, with these results based on a primary composite endpoint of first occurrence of CD4 cell counts of fewer than 200 cells per µL, antiretroviral therapy initiation, or nontrauma-related death: “At enrolment, the median CD4 cell count was 462 cells per µL and median HIV-1 plasma RNA was 4.1 log10 copies per µL. Aciclovir reduced risk of HIV-1 disease progression by 16%; 284 participants assigned aciclovir versus 324 assigned placebo reached the primary endpoint (hazard ratio [HR] 0.84, 95% CI 0.71–0.98, p = 0.03). In those with CD4 counts ≥350 cells per µL, aciclovir delayed risk of CD4 cell counts falling to <350 cells per µL by 19% (0.81, 0.71–0.93, p = 0.002).” (J. R. Lingappa, lingappa@u.washington.edu)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2010; 340).
Miscarriage Risk with Bivalent HPV Vaccine: No increased risk of miscarriage was associated with receipt of three doses of bivalent human papillomavirus 16/18 VLP vaccine with AS04 adjuvant, compared with hepatitis A vaccine as a control, in a study conducted on several continents (c712). Over 6 months, 3,599 pregnancies were analyzed in 26,130 women who participated in the study, with these results: “The estimated rate of miscarriage was 11.5% in pregnancies in women in the HPV arm and 10.2% in the control arm. The one sided P value for the primary analysis was 0.16; thus, overall, there was no significant increase in miscarriage among women assigned to the HPV vaccine arm. In secondary descriptive analyses, miscarriage rates were 14.7% in the HPV vaccine arm and 9.1% in the control arm in pregnancies that began within three months after nearest vaccination.” (S. Wacholder, WacholdS@mail.nih.gov)
Parent-Initiated Prednisolone for Acute Asthma: Benefits of a short course of oral prednisolone 1 mg/kg/day initiated by parents of children with acute asthma—including reduced asthma symptoms, health resource use, and school absenteeism—must be balanced against potential adverse effects, researchers report (c843). The 230-patient study showed a 15% reduction in episodes treated with prednisolone than in those treated with placebo, 16% reduction in the night-time symptom score, 46% reduction in risk of health resource use, and an average of 0.4 days fewer absences from school. (P. J. Vuillermin, peterv@barwonhealth.org.au)

>>>PNN JournalWatch
* A Review of the Effects of Prenatal Cocaine Exposure Among School-Aged Children , in Pediatrics, 2010; 125: 566–73. (J. P. Ackerman)
* Cystic Fibrosis and Transition to Adult Medical Care, in
Pediatrics, 2010; 125: 566–73. (L. K. Tuchman)
* Prenatal Infection and Schizophrenia: A Review of Epidemiologic and Translational Studies, in
American Journal of Psychiatry, 2010; 167: 261–80. (A. S. Brown)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 9, 2010 * Vol. 17, No. 45
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release article from and Mar. 8 issue of the Archives of Internal Medicine (2010; 170).
Triple-Class Antiretroviral Drug Failure: While rates of virologic failure of antiretroviral drug therapy using the three original drug classes is low, the need for long-term treatment means that newer drugs are likely to be needed to maintain viral suppression, an analysis shows (pp. 410–9). Within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study, researchers looked at triple-class virologic failure (TCVF) in patients who started antiretroviral therapy (ART) with a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r) from 1998 onward: “Of 45,937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980 developed TCVF (2.1%). By 5 and 9 years after starting ART, an estimated 3.4% (95% confidence interval [CI], 3.1%–3.6%) and 8.6% (95% CI, 7.5%–9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF.” (R. Lodwick, r.lodwick@ucl.ac.uk)
Food Prices & Dietary Choices: Taxing foods associated with weight gain and other adverse health outcomes may not be a bad idea, based on findings of a 20-year longitudinal study that shows higher actual milk prices but lower costs for sodas and pizza (pp. 420–6). The authors provide this summary and analysis of their findings: “Our results provide stronger evidence to support the potential health benefits of taxing selected foods and beverages. We report that an increase in the price of soda and pizza is associated with a significant decrease in daily energy intake from these foods. Price increases in soda and pizza were also associated with significant declines in overall daily energy intake, lower weight, and lower [homeostatic model assessment insulin resistance] scores over the 20-year study period. Furthermore, we report declines in the real (inflation-adjusted) prices of soda and away-from-home foods (foods that are commonly associated with increased caloric consumption and adverse health outcomes).” (B. M. Popkin, popkin@unc.edu)
Alcohol Consumption & Weight Gain in Women: Compared with nondrinkers, those with light to moderate alcohol intake had less weight gain and less overweight/obesity during 12.9 years of follow-up of 19,220 women, researchers report (pp. 453–61). Study participants had normal body mass index at 38.9 years when they enrolled in the study. These changes in BMI were noted during the study: “There was an inverse association between amount of alcohol consumed at baseline and weight gained during 12.9 years of follow-up. A total of 7,942 (41.3%) initially normal-weight women became overweight or obese (BMI ≥25) and 732 (3.8%) became obese (BMI ≥30). After adjusting for age, baseline BMI, smoking status, nonalcohol energy intake, physical activity level, and other lifestyle and dietary factors, the relative risks of becoming overweight or obese across total alcohol intake of 0, more than 0 to less than 5, 5 to less than 15, 15 to less than 30, and 30 g/d or more were 1.00, 0.96, 0.86, 0.70, and 0.73, respectively (P for trend <.001). The corresponding relative risks of becoming obese were 1.00, 0.75, 0.43, 0.39, and 0.29 (P for trend <.001). The associations were similar by subgroups of age, smoking status, physical activity level, and baseline BMI.” (L. Wang, luwang@rics.bwh.harvard.edu)
President Obama’s Physical Examination: Commenting on use of electron-beam computed tomography to scan for coronary calcium and a virtual colonoscopy during President Obama’s recent physical examination, an editorialist writes (doi:10.1001/archinternmed.2010.81): “Mr Obama appears to have been administered 2 cutting edge, expensive diagnostic tests that exposed him to a radiation risk while likely providing no benefit to his care.… It is unlikely that Mr Obama will have a dispute with his insurance company over the costs of the tests performed at his physical examination, whether or not they were necessary, but it is a certainty that we all will have great disputes over the spiraling costs of health care for the rest of us.” (R. F. Redberg, redberg@medicine.ucsf.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 10, 2010 * Vol. 17, No. 46
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 10 issue of JAMA (2010; 303).
Herd Immunity with Influenza Vaccine: In rural Canadian communities, vaccination of children and adolescents with inactivated influenza vaccine protected unvaccinated residents against infection, a study shows (pp. 943–50). In 49 tightly knit Hutterite colonies, 947 healthy children and adolescents aged 36 months to 15 years received either influenza or hepatitis A vaccine, while 2,326 community members did not receive vaccine. Results showed influenza infections, which were confirmed using reverse transcriptase polymerase chain reaction (RT-PCR) assays: “The mean rate of study vaccine coverage among eligible participants was 83% (range, 53%–100%) for the influenza vaccine colonies and 79% (range, 50%–100%) for the hepatitis A vaccine colonies. Among nonrecipients, 39 of 1,271 (3.1%) in the influenza vaccine colonies and 80 of 1,055 (7.6%) in the hepatitis A vaccine colonies had influenza illness confirmed by RT-PCR, for a protective effectiveness of 61% (95% confidence interval [CI], 8%–83%; P = .03). Among all study participants (those who were and those who were not vaccinated), 80 of 1,773 (4.5%) in the influenza vaccine colonies and 159 of 1,500 (10.6%) in the hepatitis A vaccine colonies had influenza illness confirmed by RT-PCR for an overall protective effectiveness of 59% (95% CI, 5%–82%; P = .04). No serious vaccine adverse events were observed.” (M. Loeb, loebm@mcmaster.ca)
Need for More Drug-Comparison Studies: Comparative-effectiveness (CE) research is sorely lacking in drug studies, an analysis of high-profile medicine and internal medicine journals indicates (pp. 951–8). Looking at all randomized trials, observational studies, and meta-analyses involving medications published in six journals between June 1, 2008, and Sept. 30, 2009, researchers found: “We identified 328 studies evaluating medications, 104 of which were CE studies. Among the CE studies, 45 (43%; 95% confidence interval [CI], 34%–53%) compared different medications, 11 (11%; 95% CI, 5%–18%) compared medications with nonpharmacologic interventions, 32 (31%; 95% CI, 22%–41%) compared different pharmacologic strategies, and 16 (15%; 95% CI, 9%–24%) compared different medication dosing schedules. Twenty (19%; 95% CI, 12%–28%) CE studies focused on safety and 2 (2%; 95% CI, 0%–7%) included cost-effectiveness analyses. Comparative effectiveness studies were less likely than non-CE studies to have been exclusively commercially funded: 13% (95% CI, 8%–22%) vs 45% (95% CI, 38%–52%), respectively (P < .001). In total, 90 (87%; 95% CI, 78%–92%) of the CE studies received noncommercial funding, including 66 that received government funding (63%; 95% CI, 53%–73%). Of 212 randomized trials, 97 (46%; 95% CI, 39%–63%) used an active comparator; the rest used an inactive control. Active-comparator trials were less likely than trials with inactive controls to report positive results: 44% (95% CI, 33%–55%) vs 66% (95% CI, 57%–75%), respectively (P = .002).” (M. Hochman, mhochman@usc.edu)
People v. Systems in Medication Errors: Shifting from a “culture of blame” to a “culture of safety” is a difficult process, editorialists write in assessing progress since the 1999 To Err Is Human report (pp. 977–8): “In the wake of an error-related adverse event, great care should be taken to avoid giving the physician the sense that he or she is on trial for a crime. If not, there is the potential for losing good physicians—literally by their dropping out of practice or figuratively by their merely surviving—physicians whose only fault is being human. In evaluating a physician following an error, especially an error that causes harm, the focus should be on 3 crucial questions: (1) Was the standard of care met, including adherence to crucial policies and guidelines? (2) Is the physician willing to incorporate lessons learned into future practice? and (3) Is the physician committed to maintaining his or her relationship with the patient and participating in a full disclosure of events?” (C. M. Pettker, christian.pettker@yale.edu)

>>>PNN NewsWatch
* Fox Insurance Company no longer can provide Medicare Part D services to Medicare patients, following yesterday’s termination by its contract by CMS, pharmacist.com reports. The 123,000 patients previously covered by the PDP have been reassigned to another plan and have until May 1 to pick their own plan.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 11, 2010 * Vol. 17, No. 47
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 12 issue of the New England Journal of Medicine (2010; 362).
Oral Ivermectin for Difficult-to-Treat Head Lice: Compared with topically applied malathion, oral ivermectin was better for eliminating difficult-to-treat head lice in a 15-day study (pp. 896–905). Patients, all at least 2 years of age and 15 kg in weight and infested with live lice not eradicated by topical insecticide applied 2–6 weeks before enrollment, received oral ivermectin 400 mcg/kg or topical 0.5% malathion lotion on days 1 and 8, with these results: “A total of 812 patients from 376 households were randomly assigned to receive either ivermectin or malathion. In the intention-to-treat population, 95.2% of patients receiving ivermectin were lice-free on day 15, as compared with 85.0% of those receiving malathion (absolute difference, 10.2 percentage points; 95% confidence interval [CI], 4.6 to 15.7; P < 0.001). In the per-protocol population, 97.1% of patients in the ivermectin group were lice-free on day 15, as compared with 89.8% of those in the malathion group (absolute difference, 7.3 percentage points; 95% CI, 2.8 to 11.8; P = 0.002). There were no significant differences in the frequencies of adverse events between the two treatment groups.” (O. Chosidow, livier.chosidow@hmn.aphp.fr">olivier.chosidow@hmn.aphp.fr)
Eprotirome in Statin-Treated Dyslipidemia: The thyroid hormone analogue eprotirome provided additional decreases in levels of atherogenic lipoproteins in a group of patients receiving statins, researchers report (pp. 906–16). In 189 adults being treated with simvastatin or atorvastatin, serum LDL cholesterol levels were monitored before and during eprotirome therapy: “The addition of placebo or eprotirome at a dose of 25, 50, or 100 mcg daily to statin treatment for 12 weeks reduced the mean level of serum LDL cholesterol from 141 mg per deciliter (3.6 mmol per liter) to 127, 113, 99, and 94 mg per deciliter (3.3, 2.9, 2.6, and 2.4 mmol per liter), respectively, (mean reduction from baseline, 7%, 22%, 28%, and 32%). Similar reductions were seen in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Eprotirome therapy was not associated with adverse effects on the heart or bone. No change in levels of serum thyrotropin or triiodothyronine was detected, although the thyroxine level decreased in patients receiving eprotirome.” (B. Angelin, bo.angelin@ki.se)
Patient Impressions of Drug Safety: More information provided by patients should be considered in evaluating drug safety, the author of a Perspective article writes (pp. 865–9): “The limitations of current safety-reporting mechanisms are well documented and have led the FDA to develop its recently announced Safe Use Initiative to reduce preventable harm from medicines. Patient self-reporting offers one solution that would enhance the capture of subjective elements of safety information. Given the clinical and scientific value of patient-reported adverse symptom events as well as the feasibility of collecting this information, one can make an ethical argument that patients are entitled to know the impressions of their peers—and that scientists, regulators, and clinicians should have access to those impressions when evaluating drugs. Such a change would lend all of us extra confidence when we reach into the medicine cabinet.” (E. Basch)

>>>PNN NewsWatch
* FDA has approved onabotulinumtoxin A (Botox, Allergan) for treatment of spasticity in the flexor muscles of the elbow, wrist, and fingers in adults. These conditions are common with progression of multiple sclerosis or after stroke or traumatic brain injury. In patients treated with Botox for these indications, common adverse effects are nausea, fatigue, bronchitis, muscle weakness, and pain in the arms. FDA emphasized that Botox has not been shown to be safe and effective treatment for other upper limb muscles, spasticity in the legs, or for treatment of fixed contracture and that treatment with Botox is not intended to substitute for physical therapy or other rehabilitative care.
* No clear connection is evident between use of
bisphosphonates and atypical subtrochanteric femur fractures, FDA said yesterday. The agency added that it is working closely with outside experts, including members of the American Society of Bone and Mineral Research Subtrochanteric Femoral Fracture Task Force, to gather additional information that may provide more insight into these fractures of the femur just below the hip joint.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 12, 2010 * Vol. 17, No. 48
Providing news and information about medications and their proper use

>>>JAPhA Highlights
Source:
Mar/Apr issue of the Journal of the American Pharmacists Association, a theme issue on public health (2010; 50).
Pharmacists’ Role in Public Health: Those seeking to improve public health in the United States increasingly recognize the value of pharmacists, editorialists write in introducing the theme issue (pp. 128–30): “Healthy People 2020, which was being finalized at the time of this writing, identifies several health goals for the United States, such as attaining high-quality, longer lives free of preventable health threats and conditions, achieving health equity, creating environments that promote good health, and promoting quality of life across all life stages. Healthy People 2020 explicitly recognizes that pharmacists have direct access to patients and play an important role in prevention and appropriate treatment. Pharmacists, who seek to ensure appropriate medication use, can assist in achieving these national health goals.” (K. B. Farris, karen-farris@uiowa.edu)
Vaccination Programs of California Pharmacists: Adult and adolescent vaccinations are readily available at California pharmacies, a 2006–07 survey shows (pp. 134–9). A key informant telephone and written survey of eight state-level coordinator corporate liaisons to chain pharmacies’ immunization programs shows the following: “All eight chains provided immunization services to adults; four chains also vaccinated adolescents. More than 1,000 California pharmacists employed at chain pharmacies have been trained to vaccinate; more than 500 locations participate with evening, weekend, and walk-in hours. Influenza and pneumococcal vaccines were the most common vaccines administered. Other vaccines were used less frequently. Respondents expressed interest in partnering with public health to improve record sharing, build awareness, receive vaccine news updates, and explore other activities.” (T. Pilisuk)
Syringe Availability for Injection Drug Users: In New York City, pharmacies and syringe-exchange programs are reaching different populations of injection-drug users, a study shows, but neither is serving the needs of some highly marginalized IDUs, particularly blacks and infrequent injectors (pp. 140–7). Investigators used random street-intercept sampling in 36 socioeconomically disadvantaged neighborhoods to find these patterns regarding syringe availability to IDUs: “Compared with IDUs using other syringe sources, those primarily using [syringe-exchange programs] were less likely to be black (adjusted odds ratio 0.26 [95% CI 0.11–0.57]), more likely to inject daily (3.32 [1.58–6.98]), and more likely to inject with a new syringe (2.68 [1.30–5.54]). Compared with IDUs using other syringe sources, those primarily using pharmacies were less likely to be black (0.39 [0.17–0.90]).” (C. M Fuller, cfuller@nyam.org)
Integrated Pharmacist Training for Emergency Preparedness: Experiences at Washington State U. and in Spokane, WA, with emergency preparedness are related by authors who offered this advice into how colleges of pharmacy can integrate such training of student pharmacists, faculty, and practicing pharmacists (pp. 158–64): “Colleges and schools of pharmacy can take a lead in preparing student pharmacists for this role by incorporating emergency preparedness training into curricula. Community pharmacists can develop their knowledge and skills in emergency preparedness through individualized continuing education plans and integration into community teams through volunteerism. Partnerships developed with local public health and emergency response agencies provide opportunities for pharmacists to become integral members of planning and response teams. Training exercises provide opportunities to test preparedness plans and provide professional education and experience. Actual emergency response activities demonstrate the value of the pharmacist as an important member of the emergency response team.” (L. J. Woodard, woodard@wsu.edu)

>>>PNN NewsWatch
* APhA2010 convenes today in Washington, DC. Some 7,000 pharmacists, students pharmacists, pharmacy technicians, industry representatives, and others are expected to attend. The APhA House of Delegates, meeting today and on Monday, will take up policies on pharmacogenomics and personalized medicine, e-prescribing standards, and personal health records.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 15, 2010 * Vol. 17, No. 49
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 13 issue of Lancet (2010; 375).
Effects on Stroke of Antihypertensive Drug Classes: Differences in risk of stroke between classes of antihypertensive drugs may not relate to the agents’ effects on systolic blood pressures, according to a systematic review and meta-analysis of data from 389 clinical trials (pp. 906–15). In trials with active comparators, investigators found more interindividual variation in SBP with ACE inhibitors, angiotensin II receptor blockers, and beta-blockers. Less variation occurred with calcium-channel blockers and nonloop diuretics. Placebo-controlled trials showed that calcium-channel blockers produced the greatest reduction in SBP. Results were similar in parallel group and crossover trials. Based on their findings, the authors conclude, “Drug-class effects on interindividual variation in blood pressure can account for differences in effects of antihypertensive drugs on risk of stroke independently of effects on mean SBP.” (P. M. Rothwell, peter.rothwell@clneuro.ox.ac.uk)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2010; 340).
Mortality with OC Use: Women who have used oral contraceptives have lower mortality than nonusers, according to a study of 46,112 patients who were observed for up to 39 years, researchers report (c927). Based on nearly 400,000 woman–years of observation among never users and more than 800,000 woman–years of ever users, the investigators found: “1,747 deaths occurred in never users of oral contraception and 2,864 in ever users. Compared with never users, ever users of oral contraception had a significantly lower rate of death from any cause (adjusted relative risk 0.88, 95% confidence interval 0.82 to 0.93). They also had significantly lower rates of death from all cancers; large bowel/rectum, uterine body, and ovarian cancer; main gynaecological cancers combined; all circulatory disease; ischaemic heart disease; and all other diseases. They had higher rates of violent deaths. No association between overall mortality and duration of oral contraceptive use was observed, although some disease specific relations were apparent. An increased relative risk of death from any cause between ever users and never users was observed in women aged under 45 years who had stopped using oral contraceptives 5–9 years previously but not in those with more distant use. The estimated absolute reduction in all cause mortality among ever users of oral contraception was 52 per 100,000 woman years. (P Hannaford, p.hannaford@abdn.ac.uk)
Vitamin A, BCG Vaccination, & Neonatal Weights: Among neonates who were given BCG vaccine on an early or usual late schedule, vitamin A supplementation was of no benefit and might have been harmful to girls, a study shows (c1101). The babies were all less than 2.5 kg at birth, and they received either vitamin A 25,000 IU or placebo and either early or usual late BCG vaccine. Data were reported as mortality rate ratios (MRRs) at 12 months and also after being combined with data on normal birth weight infants in a separate study, as follows: “No interaction was observed between vitamin A supplementation and BCG vaccine allocation (P = 0.73). Vitamin A supplementation at birth was not significantly associated with mortality: the MRR of vitamin A supplementation compared with placebo, controlled for randomisation to ‘early BCG’ versus ‘no early BCG’ was 1.08 (95% CI 0.79 to 1.47). Stratification by sex revealed a significant interaction between vitamin A supplementation and sex (P = 0.046), the MRR of vitamin A supplementation being 0.74 (95% CI 0.45 to 1.22) in boys and 1.42 (95% CI 0.94 to 2.15) in girls. When these data were combined with data from a complementary trial among normal birthweight neonates in Guinea-Bissau, the combined estimate of the effect of neonatal vitamin A supplementation on mortality was 1.08 (95% CI 0.87 to 1.33); 0.80 (95% CI 0.58 to 1.10) in boys and 1.41 (95% CI 1.04 to 1.90) in girls (P = 0.01 for interaction between neonatal vitamin A and sex).” (C. S. Benn, cb@ssi.dk)

>>>PNN JournalWatch
* American College of Chest Physicians Consensus Statement on the Management of Dyspnea in Patients with Advanced Lung or Heart Disease, in Chest, 2010; 137: 674–91. (D. A. Mahler, onald.A.Mahler@Hitchcock.org">Donald.A.Mahler@Hitchcock.org)
* Health Information Technology: A New World for Pharmacy, in
Journal of the American Pharmacists Association, 2010; 50: e20–34. (L. Webster)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 16, 2010 * Vol. 17, No. 50
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Mar. 16 issue of the Annals of Internal Medicine (2010; 152).
Clopidogrel–PPI Use: Reduced hospitalizations for gastroduodenal bleeding were evident while patients with serious coronary heart disease were taking both proton pump inhibitors and clopidogrel, an analysis of Tennessee Medicaid data shows (pp. 337–45). In a retrospective cohort study, data on 20,596 patients, including 7,593 who were taking a PPI and clopidogrel, showed a possibly increased risk of serious cardiovascular disease in those on the controversial drug combination: “Pantoprazole and omeprazole accounted for 62% and 9% of concurrent PPI use, respectively. Adjusted incidence of hospitalization for gastroduodenal bleeding in concurrent PPI users was 50% lower than that in nonusers (hazard ratio, 0.50 [95% CI, 0.39 to 0.65]). For patients at highest risk for bleeding, PPI use was associated with an absolute reduction of 28.5 (CI, 11.7 to 36.9) hospitalizations for gastroduodenal bleeding per 1000 person-years. The hazard ratio associated with concurrent PPI use for risk for serious cardiovascular disease was 0.99 (CI, 0.82 to 1.19) for the entire cohort and 1.01 (CI, 0.76 to 1.34) for the subgroup of patients who had percutaneous coronary interventions with stenting during the qualifying hospitalization.” (W. A. Ray, Wayne.Ray@vanderbilt.edu)
Salsalate & Glycemic Control: Salsalate may offer an alternative for lowering glycosylated hemoglobin and improving glycemic control, a study of the nonacetylated prodrug shows (pp. 346–57). Adult patients with suboptimal glycemic control despite dietary changes, exercise, and oral medications for 8 weeks showed these patterns when given placebo or various doses of salsalate: “Higher proportions of patients in the 3 salsalate treatment groups experienced decreases in HbA1c levels of 0.5% or more from baseline (P = 0.009). Mean HbA1c changes were −0.36% (P = 0.02) at 3.0 g/d, −0.34% (P = 0.02) at 3.5 g/d, and −0.49% (P = 0.001) at 4.0 g/d compared with placebo. Other markers of glycemic control also improved in the 3 salsalate groups, as did circulating triglyceride and adiponectin concentrations. Mild hypoglycemia was more common with salsalate; documented events occurred only in patients taking sulfonylureas. Urine albumin concentrations increased in all salsalate groups compared with placebo. The drug was otherwise well tolerated.” (S. E. Shoelson, steven.shoelson@joslin.harvard.edu)
Drugs v. PCI in Angina: While percutaneous coronary intervention produces greater relief of anginal symptoms than does medical therapy, a meta-analysis shows that contemporary studies show the interventions are equivalent, researchers report (pp. 370–9). This finding may be the result of “greater use of evidence-based medications in contemporary trials,” the authors write, adding these details: “A total of 14 trials, enrolling 7,818 patients, met the inclusion criteria. Although PCI was associated with an overall benefit on angina relief (odds ratio, 1.69 [95% CI, 1.24 to 2.30]), important heterogeneity across trials was observed. The incremental benefit of PCI observed in older trials (odds ratio, 3.38 [CI, 1.89 to 6.04]) was substantially less and possibly absent in recent trials (odds ratio, 1.13 [CI, 0.76 to 1.68]). An inverse relationship between use of evidence-based therapies and the incremental benefit of PCI was observed.” (D. T. Ko, dennis.ko@ices.on.ca)
Pay for Performance & Medical Professionalism: Authors of a review article examine potential conflicts between pay-for-performance models and the tenets of medical professionalism (pp. 366–9): “Lagging quality of care in the U.S. health care system has been a persistent problem and challenge. In the past, medical professionalism and professional certification have served as cornerstones for improving quality in health care. Among newer efforts to improve quality, pay for performance has been proposed to propel better results, but many observers are concerned that pay for performance is at odds with medical professionalism. The authors examine the potential conflicts between pay for performance and medical professionalism and conclude that properly designed pay-for-performance models can support professional objectives.” (A. Qaseem, aqaseem@acponline.org)

>>>PNN NewsWatch
* Health care reform legislation is moving forward in the House, even as Democratic leaders consider a strategy that would avoid the need for members to vote directly on the bill, the Washington Post reports.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 17, 2010 * Vol. 17, No. 51
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 17 JAMA, a theme issue on cancer care (2010; 303).
Age-Related Differences in Chemotherapy Regimens, Adverse Effects: Older patients receive less toxic and shorter chemotherapy regimens for stage III colon cancer than do younger patients, a study shows, and as a result have fewer adverse events (pp. 1037–45). In five geographic areas, this observational study looked at care of patients in five integrated health systems and 15 VA facilities, finding these results: “Of 202 patients aged 75 years and older, 101 (50%) received adjuvant chemotherapy compared with 87% of 473 younger patients (difference, 37%; 95% confidence interval [CI], 30%–45%). Among patients who received adjuvant chemotherapy, 14 patients (14%) aged 75 years and older and 178 younger patients (44%) received a regimen containing oxaliplatin (difference, 30%; 95% CI, 21%–38%). Older patients were less likely to continue treatment, such that by 150 days, 99 patients (40%) aged 65 years and older and 68 younger patients (25%) had discontinued chemotherapy (difference, 15%; 95% CI, 7%–23%). Overall, 162 patients (24%) had at least 1 adverse clinical event, with more events among patients treated with vs without adjuvant chemotherapy (mean, 0.39 vs 0.16; difference, 0.23; 95% CI, 0.11–0.36; P < .001). Among patients receiving adjuvant chemotherapy, adjusted rates of late clinical adverse events were lower for patients 75 years and older (mean, 0.28) vs for younger patients (0.35 for ages 18–54 years, 0.52 for ages 55–64 years, and 0.45 for ages 65–74 years; P = .008 for any age effect).” (K. L. Kahn, kahn@rand.org)
Palliative Care in Cancer Centers: While most of U.S. cancer centers have palliative care programs, the scope of services and the degree of integration vary widely, according to a survey conducted in 2009 (pp. 1054–61). Researchers contacted 71 NCI-designated cancer centers and a random sample of 71 non–NCI cancer centers. Results showed: “A total of 142 and 120 surveys were sent to executives and program leaders, with response rates of 71% and 82%, respectively. National Cancer Institute cancer centers were significantly more likely to have a palliative care program (50/51 [98%] vs 39/50 [78%]; P = .002), at least 1 palliative care physician (46/50 [92%] vs 28/38 [74%]; P = .04), an inpatient palliative care consultation team (47/51 [92%] vs 28/50 [56%]; P < .001), and an outpatient palliative care clinic (30/51 [59%] vs 11/50 [22%]; P < .001). Few centers had dedicated palliative care beds (23/101 [23%]) or an institution-operated hospice (37/101 [37%]). The median (interquartile range) reported durations from referral to death were 7 (4-16), 7 (5-10), and 90 (30-120) days for inpatient consultation teams, inpatient units, and outpatient clinics, respectively. Research programs, palliative care fellowships, and mandatory rotations for oncology fellows were uncommon. Executives were supportive of stronger integration and increasing palliative care resources.” (A. Elsayem, aelsayem@mdanderson.org)
Commenting on this and other articles in this theme issue, editorialists point to the pervasiveness of cancers (
pp. 1094–5): “With the current lifetime probability of being diagnosed with invasive cancer estimated at 37% for women and 44% for men,3 virtually all families have had or will have a family member who has been affected with or has succumbed to this complex and dreaded disease.” (P. B. Fontanarosa, phil.fontanarosa@jama-archives.org)
Vitamin B6 & Colorectal Cancer Risk: Higher serum levels of vitamin B6 and its active form, pyridoxal 5’-phosphate (PLP), are associated with significantly lower risk of colorectal cancer, according to authors who conducted a meta-analysis of published literature (pp. 1077–83): “Nine studies on vitamin B6 intake and 4 studies on blood PLP levels were included in the meta-analysis. The pooled RRs of colorectal cancer for the highest vs lowest category of vitamin B6 intake and blood PLP levels were 0.90 (95% CI, 0.75-1.07) and 0.52 (95% CI, 0.38-0.71), respectively. There was heterogeneity among studies of vitamin B6 intake (P = .01) but not among studies of blood PLP levels (P = .95). Omitting 1 study that contributed substantially to the heterogeneity among studies of vitamin B6 intake yielded a pooled RR of 0.80 (95% CI, 0.69-0.92). The risk of colorectal cancer decreased by 49% for every 100-pmol/mL increase (approximately 2 SDs) in blood PLP levels (RR, 0.51; 95% CI, 0.38-0.69).” (S. C. Larsson, susanna.larsson@ki.se)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 18, 2010 * Vol. 17, No. 52
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release articles from and Mar. 18 issue of the New England Journal of Medicine (2010; 362).
Intensive Blood Pressure Control in Diabetes: In one of several papers released in advance of print publication to coincide with presentations at the American College of Cardiology meeting, researchers report that intensive blood pressure control provides little benefit but causes substantial adverse effects in patients with diabetes (10.1056/NEJMoa1001286). In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure trial (ACCORD BP), 4,733 participants with type 2 diabetes received either intensive therapy that targeted an SBP of 120 mm Hg or standard therapy with a target of 140 mm Hg. Based on a primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes, the results showed: “After 1 year, the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the standard-therapy group. The annual rate of the primary outcome was 1.87% in the intensive-therapy group and 2.09% in the standard-therapy group (hazard ratio with intensive therapy, 0.88; 95% confidence interval [CI], 0.73 to 1.06; P = 0.20). The annual rates of death from any cause were 1.28% and 1.19% in the two groups, respectively (hazard ratio, 1.07; 95% CI 0.85 to 1.35; P =0.55). The annual rates of stroke, a prespecified secondary outcome, were 0.32% and 0.53% in the two groups, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01). Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2,362 participants in the intensive-therapy group (3.3%) and 30 of the 2,371 participants in the standard-therapy group (1.3%) (P < 0.001).” (W. C. Cushman, william.cushman@va.gov)
Intensive Lipids Control in Diabetes: Combination lipid therapy using fenofibrate plus simvastatin failed to improve outcomes anymore than simvastatin alone, according to the ACCORD Lipid trial (10.1056/NEJMoa1001282). During a mean follow-up period of 4.7 years, investigators added masked fenofibrate or placebo to open-label simvastatin therapy, with these results on a primary outcome of first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes: “The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P = 0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P = 0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P = 0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P = 0.057 for interaction).” (H. N. Ginsberg, hng1@columbia.edu)
Step-up Asthma Therapy: Regular monitoring and appropriate adjustments are needed for children with asthma, a study of various step-up therapies shows (pp. 975–85). A group of 182 children and adolescents with uncontrolled asthma while on fluticasone were assigned to receive each of three blinded step-up therapies in random sequence over a 16-week period: fluticasone 250 mcg twice daily (ICS step-up) and fluticasone 100 mcg twice daily plus a long-acting beta-agonist 50 mcg twice daily (LABA step-up) or a leukotriene-receptor antagonist 5 mg daily (LTRA step-up). Results showed: “A differential response occurred in 161 of 165 patients who were evaluated (P < 0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P = 0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P = 0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P = 0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P = 0.005).” (R. F. Lemanske, rfl@medicine.wisc.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 19, 2010 * Vol. 17, No. 53
Providing news and information about medications and their proper use

>>>ACC Highlights
In addition to the ACCORD studies mentioned in yesterday’s PNN, numerous other important papers were presented at the Mar. 14–16 annual scientific session of the American College of Cardiology. Other highlights of the Atlanta meeting included the following:
* Patients with diabetes and documented coronary artery disease did worse when they were treated to systolic blood pressures lower than 120 mm Hg, compared with 140 mm Hg, investigators from the
International Verapamil SR-Trandolapril (INVEST) study reported. Rhonda Cooper-DeHoff, PharmD, MS, of the U. Florida, told the group that the “lower is better” assumptions in current guidelines for blood pressure management in patients with diabetes needs to be revisited. The INVEST data support findings of the above-mentioned ACCORD trials and extend those conclusions into patients with established CAD, she added. In the INVEST trial, patients with systolic blood pressures below 115 mm Hg had significantly greater mortality than patients who received usual care, which targeted SBPs of 130–140 mm Hg.
* Once patients on warfarin are routinely genotyped early in therapy, will anticoagulation clinics still be needed? That is a question to consider when one looks at the results of the
Medco-Mayo Warfarin Effectiveness Study (MM-WES). It showed that hospital admissions for any cause could be cut by nearly one-third, as could hospitalizations for either excess bleeding or unwanted blood clotting, simply by testing up front for variations in the CYP2C9 and VKORC1 genes. Presented by Robert S. Epstein, MD, of the Medco Research Inst., the MM-WES data showed that among 896 patients beginning warfarin therapy, genetic testing reduced all-cause hospitalizations by 31% within the first 6 months, compared with a historical control group, and lowered hospitalizations for bleeding or thromboembolism by 29%. Epstein said the reductions in hospitalizations more than compensate for the $250 to $400 cost of the tests, which are currently not covered for Medicare patients by CMS. The need for follow-up monitoring of patients on warfarin is not eliminated but it is simplified through use of the test, co-principal investigator Thomas P. Moyer, PhD, of the Mayo Clinic, told PNN.

>>>PNN NewsWatch
* FDA has approved carglumic acid (Carbaglu, Orphan Europe) for adjunctive therapy in the treatment of acute hyperammonemia and maintenance therapy for treatment of chronic hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase. Neonates with this genetic condition, NAGS deficiency, often develop high levels of ammonia soon after birth. This product was studied in 23 patients with NAGS deficiency who were treated for periods ranging from 6 months to 21 years. Ammonia levels were reduced within 24 hours of carglumic acid administration and normalized within 3 days. Normal ammonia levels continued during long-term treatment with the drug, a synthetic structural analogue of NAGS that activates the first enzyme in the urea cycle, carbamoyl phosphate synthetase I, in liver mitochondria. Adverse effects experienced by those using carglumic acid included vomiting, abdominal pain, fever, tonsillitis, anemia, ear infection, diarrhea, inflammation of the nose and throat, and headache.
* Pharmacy now has policies on pharmacogenomics and personalized medicine, e-prescribing standards, and personal health records, thanks to actions of the
APhA House of Delegates. Meeting in Washington on Mar. 12 and 15, the House also approved new business items on prescription transfer coupons, sale of tobacco in pharmacies, and introductory practice experience programs for student pharmacists. A new business item on an accreditation process for pharmacies was referred to the Board of Trustees. Harold Godwin of Kansas was installed as APhA president for 2010–11, and Brad Tice of Tennessee was chosen as speaker-elect of the House for the coming year.
* A $75 million theft of Lilly products on Mar. 14 in Connecticut is just one of four
recent heists of pharmaceutical cargo, pharmacist.com reports. Since late Jan., Sanofi Aventis products have been stolen in Puerto Rico, H-E-B products were taken in Dallas, and Mead Johnson infant formula was stolen at a Kentucky truck stop.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 22, 2010 * Vol. 17, No. 54
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 20 issue of Lancet (2010; 375).
Mipomersen in Familial Hypercholesterolemia: In patients with homozygous familial hypercholesterolemia, the antisense agent mipomersen is a novel, effective therapy, according to investigators who studied 51 patients with the condition (pp. 998–1006). The agent, which inhibits apolipoprotein B synthesis, was given in subcutaneous doses of 200 mg weekly for 26 weeks. In comparison with placebo, mipomersen produced these results: “Mean concentrations of LDL cholesterol at baseline were 11.4 mmol/L (SD 3.6) in the mipomersen group and 10.4 mmol/L (3.7) in the placebo group. The mean percentage change in LDL cholesterol concentration was significantly greater with mipomersen (–24.7%, 95% CI –31.6 to –17.7) than with placebo (–3.3%, –12.1 to 5.5; p = 0.0003). The most common adverse events were injection-site reactions (26 [76%] patients in mipomersen group vs four [24%] in placebo group). Four (12%) patients in the mipomersen group but none in the placebo group had increases in concentrations of alanine aminotransferase of three times or more the upper limit of normal.” (F. J. Raal, frederick.raal@wits.ac.za)
HIV Prevention in Injection Drug Users: Core prevention services are needed to curb HIV transmission in injection drug users (IDUs), researchers conclude (pp. 1014–28). The literature was searched for data on these interventions: needle and syringe programs (NSPs), opioid substitution therapy (OST) and other drug treatment, HIV testing ,and counseling, antiretroviral therapy (ART), and condom programs. Results showed the following: “By 2009, NSPs had been implemented in 82 countries and OST in 70 countries; both interventions were available in 66 countries. Regional and national coverage varied substantially. Australasia (202 needle–syringes per IDU per year) had by far the greatest rate of needle–syringe distribution; Latin America and the Caribbean (0.3 needle–syringes per IDU per year), Middle East and north Africa (0.5 needle–syringes per IDU per year), and sub-Saharan Africa (0.1 needle—syringes per IDU per year) had the lowest rates. OST coverage varied from less than or equal to one recipient per 100 IDUs in central Asia, Latin America, and sub-Saharan Africa, to very high levels in western Europe (61 recipients per 100 IDUs). The number of IDUs receiving ART varied from less than one per 100 HIV-positive IDUs (Chile, Kenya, Pakistan, Russia, and Uzbekistan) to more than 100 per 100 HIV-positive IDUs in six European countries. Worldwide, an estimated two needle–syringes (range 1–4) were distributed per IDU per month, there were eight recipients (6–12) of OST per 100 IDUs, and four IDUs (range 2–18) received ART per 100 HIV-positive IDUs.” (B. M. Mathers, b.mathers@unsw.edu.au)

>>>PNN NewsWatch
* Medication therapy management and other pharmacy-favorable provisions are included in the historic health care reform bill passed last night by the House of Representatives and sent to President Obama for his signature, pharmacist.com reports. An adjustment in the medication reimbursement formula, one based on average manufacturer price, is included in both the main bill and the smaller reconciliation package that goes to the Senate. Language in the reconciliation bill would also close the doughnut hole in the Medicare Part D benefits package over a 10-year period, beginning with a $250 rebate as patients hit the gap this year.

>>>PNN JournalWatch
* Randomised Controlled Trial of Integrated Care To Reduce Disability from Chronic Low Back Pain in Working and Private Life, in BMJ, 2010; c1035. (J. R. Anema, h.anema@vumc.nl)
* Planning for the Inevitable: Preparing for Epidemic and Pandemic Respiratory Illness in the Shadow of H1N1 Influenza, in
Clinical Infectious Diseases, 2010; 50: 1145–54. (E. L. Daugherty, edaughe2@jhmi.edu)
* Prevention of Diabetic Kidney Disease: Negative Clinical Trials with Renin-Angiotensin System Inhibitors, in
American Journal of Kidney Diseases, 2010; 55: 426–30. (R. G. Nelson, rgnelson@mail.nih.gov)
* Practice Parameter: Treatment of Nonmotor Symptoms of Parkinson Disease, in
Neurology, 2010; 74: 924–31. (American Academy of Neurology, guidelines@aan.com)
* A-Kinase Anchoring Proteins: Getting to the Heart of the Matter, in
Circulation, 2010; 121: 1264–71. (J. D. Scott, scottjdw@uw.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 23, 2010 * Vol. 17, No. 55
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Mar. 22 issue of Archives of Internal Medicine (2010; 170).
QTc Safety of Methadone Isomers: R-methadone is safer than the chiral mixture of this drug in terms of QTc interval changes, researchers report (pp. 529–36). In a crossover study, 39 opioid-dependent patients received the R-methadone isomer for 14 days followed by their original dose of R,S-methadone, with these results: “The Fridericia-corrected QT (QTcF) interval decreased when (R,S)-methadone was replaced by a half-dose of (R)-methadone; the median (interquartile range [IQR]) values were 423 (398–440) milliseconds (ms) and 412 (395–431) ms (P = .06) at days 0 and 14, respectively. Using a univariate mixed-effect linear model, the QTcF value decreased by a mean of –3.9 ms (95% confidence interval [CI], –7.7 to –0.2) per week (P = .04). The QTcF value increased when (R)-methadone was replaced by the initial dose of (R,S)-methadone for 14 days; median (IQR) values were 424 (398–436) ms and 424 (412–443) ms (P = .01) at days 14 and 28, respectively. The univariate model showed that the QTcF value increased by a mean of 4.7 ms (95% CI, 1.3–8.1) per week (P = .006).” (C. B. Eap, Chin.Eap@chuv.ch)
Cost, Value of New Chemotherapy Drugs: With health care reform legislation being signed into law today by President Obama, it is a good time to ask how much expensive new therapies are worth. In an analysis of the costs and benefits of new chemotherapeutic agents, investigators find that the innovative therapies exceed the commonly used “acceptable” value of $50,000 for a quality-adjusted life–year (pp. 537–42). Concluding that “open-ended coverage policies for new chemotherapeutic agents may prove difficult to sustain as costs continue to rise,” the authors provide these data for a sample of 4,665 patients with metastatic colorectal cancer treated with chemotherapy in 1995–2005: “Life expectancy increased by 6.8 months and lifetime costs by $37,100 (2006 dollars). The implied cost per life–year gained is $66,200 (95% confidence interval, $48,100–$84,200). After discounting life–years and costs and adjusting for patients’ health utility and out-of-pocket payments, the cost per quality-adjusted life–year gained is $99,100 (95% confidence interval, $72,300–$125,900).” (D. H. Howard, david.howard@emory.edu)
Smoking Cessation in Weight-Concerned Women: Among 349 women smokers who were concerned about their weight, a combination of cognitive behavioral therapy plus bupropion proved most likely to lead to abstinence during cessation efforts (pp. 543–50). Study participants received either cognitive behavioral therapy for smoking-related weight concerns (CONCERNS) or standard cessation treatment with added discussion of smoking topics but no specific weight focus (STANDARD) plus either bupropion hydrochloride sustained release (B) or placebo (P) for 6 months. Results showed: “Women in the CONCERNS + B group had higher rates of abstinence (34.0%) and longer time to relapse than did those in the STANDARD + B (21%; P = .05) or CONCERNS + P (11.5%; P = .005) groups at 6 months, although rates of prolonged abstinence in the CONCERNS + B and STANDARD + B groups did not differ significantly at 12 months. Abstinence rates and duration did not differ in the STANDARD + B group (21% and 19%) compared with the STANDARD + P group (10% and 7%) at 6 and 12 months, respectively. There were no differences among abstinent women in postcessation weight gain or weight concerns, although STANDARD + B produced greater decreases in nicotine withdrawal and depressive symptoms than did STANDARD + P.” (M. D. Levine, Levinem@upmc.edu)

>>>PNN NewsWatch
* Clinicians should temporarily suspend use of GlaxoSmithKline’s rotavirus vaccine, Rotarix, FDA said yesterday. An independent academic research team has identified DNA from porcine circovirus 1 in samples of Rotarix, and the company and FDA are investigating the source.
* High doses of
simvastatin (80 mg daily) are associated with a greater risk of rhabdomyolysis than those produced by other statins, FDA is cautioning. The agency is reviewing muscle injury with the drug in clinical trials—including SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine)—as well as observational studies, adverse event reports, and prescription-use data.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 24, 2010 * Vol. 17, No. 56
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 24 issue of JAMA (2010; 303).
Socioeconomic Position, Health Behaviors, & Mortality: Health behaviors such as smoking and drinking explain much of the observed excess mortality among those with lower socioeconomic status, according to a report from the British Whitehall II longitudinal cohort study (pp. 1159–66). Since 1985 in London, 10,308 civil servants have been followed. Repeat assessment of their employment grade and health behaviors yielded these observations: “A total of 654 participants died during the follow-up period. In the analyses adjusted for sex and year of birth, those with the lowest socioeconomic position had 1.60 times higher risk of death from all causes than those with the highest socioeconomic position (a rate difference of 1.94/1000 person–years). This association was attenuated by 42% (95% confidence interval [CI], 21%–94%) when health behaviors assessed at baseline were entered into the model and by 72% (95% CI, 42%–154%) when they were entered as time-dependent covariates. The corresponding attenuations were 29% (95% CI, 11%–54%) and 45% (95% CI, 24%–79%) for cardiovascular mortality and 61% (95% CI, 16%–425%) and 94% (95% CI, 35%–595%) for noncancer and noncardiovascular mortality. The difference between the baseline only and repeated assessments of health behaviors was mostly due to an increased explanatory power of diet (from 7% to 17% for all-cause mortality, respectively), physical activity (from 5% to 21% for all-cause mortality), and alcohol consumption (from 3% to 12% for all-cause mortality). The role of smoking, the strongest mediator in these analyses, did not change when using baseline or repeat assessments (from 32% to 35% for all-cause mortality).” (S. Stringhini, silvia.stringhini@inserm.fr)
This article is an important contribution to the debate over status v. behaviors, an editorialist writes (
pp. 1199–200): “The inference that should be drawn from the study by Stringhini et al is that both health behaviors and social and economic determinants of health remain important factors. Moreover, the stress of low relative socioeconomic status vs health behaviors argument should be considered obsolete. Socioeconomic differences exist for almost every major contemporary and historical cause of morbidity and mortality, suggesting the presence of a common pathway. Moreover, plausible evidence suggests that those pathways are traceable to the development of self-regulation and executive function early in life. This concept represents a modernized version of the notion of ‘host resistance’ and now includes early life developmental phenomena. The study by Stringhini and colleagues is not the end of the debate and inquiry involving the relative influence of behavior and socioeconomic factors on health status, but rather may well represent the beginning of a new model for investigation.” (J. R. Dunn, jim.dunn@mcmaster.ca)
Blood Pressure & Mortality in ICU Patients: Those admitted to intensive care units with chest pain and low supine systolic blood pressures have an increased risk of death at 1 year, researchers report (pp. 1167–72). Using data from the RIKS-HIA (Registry of Information and Knowledge About Swedish Heart Intensive Care Admissions), investigators made these calculations about patients in four systolic BP quartiles ranging from less than 128 mm Hg (Q1) to more than 162 mm Hg (Q4): “Mean (SD) follow-up time was 2.47 (1.5) years (range, 1–10 years). One-year mortality rate by Cox proportional hazard model (adjusted for age, sex, smoking, diastolic BP, use of antihypertensive medication at admission and discharge, and use of lipid-lowering and antiplatelet medication at discharge) showed that participants in Q4 had the best prognosis (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.72–0.80, Q4 compared with Q2; corresponding risks for Q1 were HR, 1.46; 95% CI, 1.39–1.52, and for Q3, HR, 0.83; 95% CI, 0.79–0.87). Patients in Q4 had a 21.7% lower absolute risk compared with Q2, patients in Q3 had a 15.2% lower risk than in Q2, and patients in Q1 had a 40.3% higher risk for mortality than in Q2. The worse prognosis in Q2 compared with Q4 was independent of body mass index and previous diagnoses and similar when analysis was restricted to patients with a final diagnosis of angina or myocardial infarction (HR, 0.75; 95% CI, 0.71–0.80, Q4 compared with Q2).” (F. H. Nystrom, fredrik.nystrom@lio.se)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 25, 2010 * Vol. 17, No. 57
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release articles and the Mar. 25 New England Journal of Medicine (2010; 362).
Bisphosphonates & Fractures of the Femur: Data from three randomized controlled trials fail to support assertions that bisphosphonates are associated with atypical fractures of the femur (10.1056/NEJMoa1001086). The Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX) trial, and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial (PFT) provided these insights into drug-related hip and femur fractures, including those below the lesser trochanter and above the distal metaphyseal flare (subtrochanteric and diaphyseal femur fractures): “We reviewed 284 records for hip or femur fractures among 14,195 women in these trials. A total of 12 fractures in 10 patients were classified as occurring in the subtrochanteric or diaphyseal femur, a combined rate of 2.3 per 10,000 patient-years. As compared with placebo, the relative hazard was 1.03 (95% confidence interval [CI], 0.06 to 16.46) for alendronate use in the FIT trial, 1.50 (95% CI, 0.25 to 9.00) for zoledronic acid use in the HORIZON-PFT trial, and 1.33 (95% CI, 0.12 to 14.67) for continued alendronate use in the FLEX trial. Although increases in risk were not significant, confidence intervals were wide.” (D. M. Black, dblack@psg.ucsf.edu)
Patients on bisphosphonates should be re-evaluated in light of these new data, an editorialist writes, but clinicians should not “rush to judgment” (
10.1056/NEJMe1003064): “Although detailed recommendations are beyond the scope of this editorial, it is reasonable to consider drug holidays with careful observation for most patients with osteoporosis who are receiving long-term therapy, particularly those whose bone-turnover markers indicate substantially reduced levels. However, we must also balance evidence of persistent antifracture efficacy after discontinuation with data showing that the use of alendronate for 10 years, as compared with 5 years, was associated with significantly fewer new vertebral fractures and nonvertebral fractures in patients with a bone mineral density T score of –2.5 or below.” (E. Shane)
Rifaximin in Hepatic Encephalopathy: Compared with placebo, rifaximin more effectively maintained remission from hepatic encephalopathy during a 6-month trial (pp. 1071–81). In 299 patients who were already in remission, rifaximin 550 mg twice daily and placebo produced these results: “Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P < 0.001). A breakthrough episode of hepatic encephalopathy occurred in 22.1% of patients in the rifaximin group, as compared with 45.9% of patients in the placebo group. A total of 13.6% of the patients in the rifaximin group had a hospitalization involving hepatic encephalopathy, as compared with 22.6% of patients in the placebo group, for a hazard ratio of 0.50 (95% CI, 0.29 to 0.87; P = 0.01). More than 90% of patients received concomitant lactulose therapy. The incidence of adverse events reported during the study was similar in the two groups, as was the incidence of serious adverse events.” (W. P. Forbes)
Drug Prevention of Recurrent Miscarriage: Aspirin and the low-molecular-weight heparin nadroparin were both ineffective for preventing recurrent miscarriage in 364 women who initially were less than 6 weeks into pregnancy (10.1056/NEJMoa1000641). Previous miscarriages in the participants were unexplained. Live-birth rates in the study were not significantly different among three treatment groups: 54.5% in women receiving aspirin plus nadroparin, 50.8% in the aspirin-only group, and 57.0% in the placebo group.(M. Goddijn, m.goddijn@amc.uva.nl)

>>>PNN NewsWatch
* The Senate is expected to pass the health care reform reconciliation bill this afternoon, the Washington Post reports. Republicans succeeded on Wednesday in finding two minor changes that will necessitate the House to consider the bill again before it can be sent to President Obama for his signature.
* Two additional lots have been added to the list of
Lilly products stolen in a cargo theft from a Connecticut warehouse on Mar. 14, FDA reports.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 26, 2010 * Vol. 17, No. 58
Providing news and information about medications and their proper use

>>>Health Affairs Highlights
Source:
Early-release article from and the March issue of Health Affairs, a theme issue on childhood obesity (2010; 29).
Growing Medical Cost Burden: For a growing number of Americans, direct medical costs consume 10% or more of their family income, according to an analysis of 2001–06 data (10.1377/hlthaff.2009.0493). The burden is not just among the poor and low-income people, the authors report. In fact, the increase in high burden tilted more toward upper-income groups, with increases of 17%, 56%, and 98% among those in below poverty, middle income, and high income groups, respectively. Investigators add: “The results show considerable state-to-state variation associated mainly with differences in family income and, to a lesser extent, out-of-pocket spending for insurance premiums.… Moreover, almost 30 percent of the U.S. population either had a high financial burden of health costs or were uninsured. These facts underscore that escalating health care costs affect all socioeconomic strata, not just the poor.” (P. J. Cunningham, pcunningham@hschange.org)
Making Childhood Obesity the New Tobacco: Authors call for a public health effort to frame childhood obesity in terms used successfully at combatting tobacco use among youth (pp. 388–92): “Overcoming the childhood obesity epidemic will require changes on the scale of a social movement similar to the shift in attitudes and regulations toward smoking and tobacco. Tobacco control became a successful public health movement because of shifts in social norms and because cigarette companies came to be perceived by many as a common enemy. In contrast, obesity advocates have not identified a common threat or mobilized grass-roots change, nor have they identified strategies that resonate across diverse settings and constituencies. Framing obesity as a common threat can lead to consensus regarding the interventions needed to achieve healthier children and communities.” (J. D. Klein, jklein@aap.org)

>>>Medical Care Report
Source:
Apr. issue of Medical Care (2010; 48).
Patient Perspective on Costs in Alcohol Dependence: Cost-effectiveness analyses fail to consider the patient’s willingness to pay, a study reports (pp. 306–13). Among 1,383 patients in the Combined Pharmacotherapies and Behavioral Interventions (COMBINE) trial, these results were recorded about nine alternative alcohol treatment regimens: “The average total patient time devoted to treatment ranged from about 30 hours to 46 hours. Time spent traveling to and from treatment sessions and participation in self-help meetings accounted for the largest portion of patient time costs. The cost-effectiveness results indicate that 6 of the 9 treatments were economically dominated and only 3 treatments are potentially cost-effective depending on patient’s willingness to pay for the considered outcomes: medical management (MM) + placebo, MM + naltrexone, and MM + naltrexone + acamprosate.” (L. J. Dunlap)
Off-Label Pharmaceutical Diffusion: Gabapentin prescriptions for bipolar disorder, an off-label indication, rose from 8 to 387 per 1,000 enrollees between 1994 and 2000, a period of heavy pharmaceutical marketing, a study of Florida Medicaid data shows (pp. 372–9). Following publication of two negative trials in 2000 and discontinuation of marketing efforts, gabapentin use remained fairly high until a prior-approval requirement produced a 45% decline in such prescriptions. (C. A. Fullerton)

>>>PNN NewsWatch
* FDA has approved a new indication for rifaximin (Xifaxan, Salix Pharmaceuticals), prevention of recurrence of overt hepatic encephalopathy. Yesterday’s PNN reported on a New England Journal of Medicine study on use of the agent in patients with this condition.
* The
Senate and the House of Representatives on Thursday approved the health care reform reconciliation bill. Once signed by President Obama, this legislation will complete the reform process. The provisions of this legislation include further adjustments in the AMP, or average manufacturer price, reimbursement formula for medications and a plan for closure of the Medicare Part D doughnut hole. Part D recipients reaching the coverage gap will get a $250 rebate this year. In subsequent years, discounts on manufacturers’ prices will lead to elimination of the gap in 2020.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 29, 2010 * Vol. 17, No. 59
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 27 issue of Lancet (2010; 375).
Drug-Eluting Stents: In the SORT OUT III trial of routine clinical care, the sirolimus-eluting stent was superior to the zotarolimus-eluting stent, researchers report (pp. 1090–9). The single-blind study of adult patients with stable coronary artery disease or acute coronary syndromes and at least one target lesion showed these results based on a primary composite endpoint of major adverse cardiac events within 9 months: “1,162 patients (1,619 lesions) were assigned to receive the zotarolimus-eluting stent, and 1,170 patients (1,611 lesions) to receive the sirolimus-eluting stent. 67 patients (72 lesions) had stent failure, and six patients were lost to follow-up. All randomly assigned patients were included in analyses at 9-month follow-up; 2,200 patients (94%) had completed 18-month follow-up by the time of our assessment. At 9 months, the primary endpoint had occurred in a higher proportion of patients treated with the zotarolimus-eluting stent than in those treated with the sirolimus-eluting stent (72 [6%] vs 34 [3%]; HR 2.15, 95% CI 1.43–3.23; p = 0.0002). At 18-month follow-up, this difference was sustained (113 [10%] vs 53 [5%]; 2.19, 1.58–3.04; p < 0.0001). For patients receiving the zotarolimus-eluting stent and those receiving the sirolimus-eluting stent, all cause-mortality was similar at 9-month follow-up (25 [2%] vs 18 [2%]; 1.40, 0.76–2.56; p = 0.28), but was significantly different at 18-month follow-up (51 [4%] vs 32 [3%]; 1.61, 1.03–2.50; p = 0.035).” (J. F. Lassen, jens.lassen@ki.au.dk)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2010; 340).
Statin Effects on Blood Pressure: In patients whose hypertension is adequately controlled by blood pressure–lowering drugs, addition of statins has no additive effect, according the PHYLLIS trial (c1197). At 13 Italian hospitals, 508 patients with mild hypertension and hypercholesterolemia were randomized to hydrochlorothiazide 25 mg or fosinopril 20 mg once daily with or without the addition of pravastatin 40 mg once daily, with these results: “Both the group receiving antihypertensive treatment without pravastatin (n = 254) (with little change in total cholesterol) and the group receiving antihypertensive treatment with pravastatin (n = 253) (with marked and sustained reduction in total cholesterol and low density lipoprotein cholesterol) had a clear cut sustained reduction in clinic measured systolic and diastolic blood pressure as well as in 24 hour, and day and night, systolic and diastolic blood pressure. Pravastatin performed slightly worse than placebo, and between group differences did not exceed 1.9 (95% confidence interval –0.6 to 4.3, P = 0.13) mm Hg throughout the treatment period. This was also the case when participants who remained on monotherapy with hydrochlorothiazide or fosinopril throughout the study were considered separately.” (G. Mancia, giuseppe.mancia@unimib.it)

>>>PNN JournalWatch
* Incidence of 2009 Pandemic Influenza A H1N1 Infection in England: A Cross-Sectional Serological Study, in Lancet, 2010; 375: 1100–8. (E. Miller, liz.miller@hpa.org.uk)
* Achieving Asthma Control in the Inner City: Do the National Institutes of Health Asthma Guidelines Really Work?, in
Journal of Allergy and Clinical Immunology, 2010; 125: 521–6. (S. J. Szefler, szeflers@njhealth.org)
* Social Stress and Asthma: The Role of Corticosteroid Insensitivity, in
Journal of Allergy and Clinical Immunology, 2010; 125: 550–8. (A. Haczku, haczku@mail.med.upenn.edu)
* Ceftaroline: A New Cephalosporin with Activity Against Resistant Gram-Positive Pathogens, in
Pharmacotherapy, 2010; 30: 375–89. (M. J. Rybak, m.rybak@wayne.edu)
* Role of Combination Therapy in the Treatment of Pulmonary Arterial Hypertension, in
Pharmacotherapy, 2010; 30: 390–404. (T. Abraham)
* Aspirin Intake and Survival After Breast Cancer, in
Journal of Clinical Oncology, 2010; 28: 1467–72. (M. D. Holmes, michelle.holmes@channing.harvard.edu)
* Meeting Expectations of Patients with Cancer: Relationship Between Patient Satisfaction, Depression, and Coping, in
Journal of Clinical Oncology, 2010; 28: 1560–5. (L. Baider, rnlobel@bezeqint.net)
* Autoimmune Diseases in Women with Turner’s Syndrome, in
Arthritis & Rheumatism, 2010; 62: 658–66. (K. T. Jørgensen, ktj@ssi.dk)
* Psychological Consequences of the Wars in Iraq and Afghanistan, theme of an issue of
Journal of Traumatic Stress, 2010; 23. (P. P. Schnurr, paula.schnurr@dartmouth.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 30, 2010 * Vol. 17, No. 60
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Apr. issue of Diabetes Care (2010; 33).
Costs, Consequences of Newer Medications: The high costs of recently marketed antidiabetic drugs are not offset by sufficient gains in quality and quantify of life, a cost-effectiveness analysis shows (pp. 695–700). Adults aged 25–64 were analyzed in a model that used a lifetime analytic horizon and health care system perspective. Use of glyburide, exenatide, and sitagliptin as second-line agents produced these changes in costs and quality-adjusted life–years: “Exenatide and sitagliptin conferred 0.09 and 0.12 additional QALYs, respectively, relative to glyburide as second-line therapy. In base case analysis, exenatide was dominated (cost more and provided fewer QALYs than the next most expensive option), and sitagliptin was associated with an incremental cost-effectiveness ratio of $169,572 per QALY saved. Results were sensitive to assumptions regarding medication costs, side effect duration, and side effect–associated disutilities.” (A. Sinha, sinhaan1@umdnj.edu)
Adverse Events with False Glucose Readings: Used in the presence of interfering sugars, glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) test strips are unsafe, with risks including deaths and severe hypoglycemia, researchers report (pp. 728–9). Review of an FDA adverse events (AEs)database showed the following: “Eighty-two reports were identified: 16 (20%) were associated with death, 46 (56%) with severe hypoglycemia, and 12 (15%) with nonsevere hypoglycemia. In eight reports (10%), the AE was not described. Forty-two events (51%) occurred in the U.S. Although most events occurred in hospitalized patients, at least 14 (17%) occurred in outpatients. Agents most commonly associated with AEs were icodextrin-containing peritoneal dialysate and maltose-containing intravenous immune globulin.” (J. Ellison, jellison@its.jnj.com)
Medication-Induced Diabetes in Children: Medications cause diabetes in some Canadian children, according to a prospective national surveillance study (pp. 786–91). The investigators also found that many children had at least one comorbidity at diabetes diagnosis, supporting recommendations for screening at that time: “From a population of 7.3 million children, 345 cases of non–type 1 diabetes were reported. The observed minimum incidence rates of type 2, medication-induced, and monogenic diabetes were 1.54, 0.4, and 0.2 cases per 100,000 children aged <18 years per year, respectively. On average, children with type 2 diabetes were aged 13.7 years and 8% (19 of 227) presented before 10 years. Ethnic minorities were overrepresented, but 25% (57 of 227) of children with type 2 diabetes were Caucasian. Of children with type 2 diabetes, 95% (206 of 216) were obese and 37% (43 of 115) had at least one comorbidity at diagnosis.” (S. Amed, samed@cw.bc.ca)
Glitazone Prescribing Changes: Rosiglitazone use fell quickly during a period of cautionary scientific publications, advisories, and media exposure, an analysis of U.S. prescribing patterns in 2003–09 shows (pp. 823–5). But pioglitazone prescribing was relatively unaffected, the authors report, despite a class-level FDA advisory: “From 2003 through 2005, glitazone use increased steadily. From February 2005 to January 2007, rosiglitazone use decreased by 16% (95% CI −20 to −11) annually; pioglitazone use increased at an annual rate of 14% (9–18). During a period of Food and Drug Administration (FDA) advisories, rosiglitazone use declined sharply from 0.42 million monthly treatment visits (February 2007) to 0.13 million monthly visits (May 2008). Pioglitazone use remained stable, accounting for ~5.8 million physician visits (77% of all glitazone use) where a treatment was used during the final 12 months of observation.” (G. C. Alexander, galexand@uchicago.edu)
Lacosamide in Diabetic Neuropathy: In patients with painful diabetic neuropathy, lacosamide reduced symptoms and was well tolerated, but a placebo response in the last 4 weeks of the 12-week trial may have prevented the agent from achieving statistically improved scores on a daily Numeric Pain Rating Scale (pp. 839–41). Lacosamide doses of 400 or 600 mg/day were significantly more effective than placebo during a 6-week titration phase, the maintenance 12-week phase, and both phases together. But intraindividual changes in pain ratings failed to reach significance, the authors report. (D. Ziegler, dan.ziegler@ddz.uni-duesseldorf.de)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Mar. 31, 2010 * Vol. 17, No. 61
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Apr. issue of Pharmacotherapy (2010; 30).
Care Models for Anticoagulation: Pharmacist-managed anticoagulation produced significantly better clinical and economic outcomes among patients seen in anticoagulation clinics, compared with nurse-directed and usual care, a study shows (pp. 330–8). In an 8-county New York health system, 996 patients who had been on warfarin therapy for at least 6 months and had 3 or more INR determinations were studied. These results were noted for the three care models: “The pharmacist-managed service yielded the lowest rates of hospitalization and emergency department visits, with hospitalizations reduced by 56% versus nurse-managed service and 61% versus usual care (p < 0.01). Emergency department visits were reduced by 78% in both the nurse-managed and usual care models (p < 0.002). Based on visit rates, the pharmacist-managed service averted $141,277.34 in hospitalization costs and $10,183.76 in emergency department visit costs versus the nurse-managed service and $95,579.08 in hospitalization costs and $5,511.21 in emergency department costs compared with the usual care model.” (K. Rudd, Kelly.Rudd@bassett.org)
Anticoagulation services are entering a new era, an editorialist writes (
pp. 327–9): “In summary, traditional anticoagulation monitoring services will likely be short lived. The anticoagulation clinics of the future will be the ones that will expand to multidisciplinary comprehensive thrombosis programs (both inpatient and outpatient) that will focus on management of the whole spectrum of thrombotic diseases and on coordination of various antithrombotic therapies. These are the services that are also expected to meet current and future safety and quality regulations and requirements. For our profession, this transition presents great opportunities, and we are more than better equipped and should be ready to be at the forefront of these changes.” (E. A. Nutescu, enutescu@uic.edu)
Biologic Agents for Rheumatoid Arthritis: During short-term therapy in patients with rheumatoid arthritis, etanercept and adalimumab were more effective than infliximab, according to a meta-analysis of these anti–tumor necrosis factor-alpha drugs (pp. 339–53). But adalimumab was more effective during long-term therapy, the authors report, noting: these results based on American College of Rheumatology (ACR) 20% improvement criteria (ACR20), 50% improvement criteria (ACR50), and 70% improvement criteria (ACR70): “With short-term treatment (12–30 wks), etanercept demonstrated the highest risk ratios (RRs) for reaching ACR20 and ACR50: 2.94 (95% confidence interval [CI] 2.27–3.81) and 5.28 (95% CI 3.12–8.92), respectively. Adalimumab demonstrated the highest RR for achieving ACR70 (5.36, 95% CI 3.76– 7.64). Over a long-term treatment course (1–3 yrs), adalimumab demonstrated the highest RRs (95% CIs) for these parameters: 1.85 (1.07–3.19), 2.80 (1.16–6.77), and 3.23 (1.37–7.61) for ACR20, ACR50, and ACR70, respectively. No statistically significant differences were noted in the safety of any of the three drugs compared with placebo. Infliximab had the highest RRs for withdrawing from the study due to lack of efficacy (2.05, 95% CI 1.33–3.16) and adverse events (0.41, 95% CI 0.18–0.95).” (C. Januário Correr, cassyano@ufpr.br)

>>>PNN NewsWatch
* Polidocanol injection (Asclera, BioForm Medical) has been approved by FDA for treatment of varicose veins. Polidocanol is approved to close spider veins (less than 1 mm in diameter) and reticular veins (1–3 mm in diameter). The agent acts by damaging the cell lining of blood vessels. This causes the blood vessel to close, and it is eventually replaced by other types of tissue. Common adverse reactions to polidocanol include hematoma, bruising, irritation, discoloration, and pain at the injection site.
* Use of
rosuvastatin in patients without elevated cholesterol levels is the subject of an article in today’s New York Times. Based on results of Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), FDA last month approved an additional indication for the product: primary prevention of cardiovascular disease in men aged 50 and older and women aged 60 and older who have elevated C-reactive protein levels and at least one additional cardiovascular risk factor.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.