Mar 2009

PNN Quarterly File—First Quarter 2009

PNN Pharmacotherapy Line
Jan. 5, 2009 * Vol. 16, No. 1
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Jan. 3 issue of Lancet (2009; 372).
First- v. Second-Generation Antipsychotics: Second-generation (atypical) antipsychotics are a heterogenous class of medications that differ in many of their properties, concludes a meta-analysis of 150 studies comparing these agents with first-generation agents (pp. 31–41). Among 21,533 participants in the mostly short-term trials, the investigators noted these trends: ìFour of [the second-generation] drugs were better than first-generation antipsychotic drugs for overall efficacy, with small to medium effect sizes (amisulpride −0.31 [95% CI −0.44 to −0.19, p < 0.0001], clozapine −0.52 [−0.75 to −0.29, p < 0.0001], olanzapine −0.28 [−0.38 to −0.18, p < 0.0001], and risperidone −0.13 [−0.22 to −0.05, p = 0.002]). The other second-generation drugs were not more efficacious than the first-generation drugs, even for negative symptoms. Therefore efficacy on negative symptoms cannot be a core component of atypicality. Second-generation antipsychotic drugs induced fewer extrapyramidal side-effects than did haloperidol (even at low doses). Only a few have been shown to induce fewer extrapyramidal side-effects than low-potency first-generation antipsychotic drugs. With the exception of aripiprazole and ziprasidone, second-generation antipsychotic drugs induced more weight gain, in various degrees, than did haloperidol but not than low-potency first-generation drugs. The second-generation drugs also differed in their sedating properties. We did not note any consistent effects of moderator variables, such as industry sponsorship, comparator dose, or prophylactic antiparkinsonian medication.î (S. Leucht, Stefan.Leucht@lrz.tum.de)

>>>NEJM Highlights
Source:
Jan. 1 issue of the New England Journal of Medicine (2009; 360).
Osteoclasts with Long-Term Bisphosphonate Therapy: Long-term alendronate treatment among healthy postmenopausal women is associated with an increase in the number of osteoclasts, including ìdistinctive giant, hypernucleated, detached osteoclasts that are undergoing protracted apoptosis,î researchers report (pp. 53–62). Examining 51 bone-biopsy specimens obtained at the conclusion of a 3-year trial in which patients took alendronate or placebo for varying lengths of time, the authors found: ìThe number of osteoclasts was increased by a factor of 2.6 in patients receiving 10 mg of alendronate per day for 3 years as compared with the placebo group (P < 0.01). Moreover, the number of osteoclasts increased as the cumulative dose of the drug increased (r = 0.50, P < 0.001). Twenty-seven percent of these osteoclasts were giant cells with pyknotic nuclei that were adjacent to superficial resorption cavities. Furthermore, giant, hypernucleated, detached osteoclasts with 20 to 40 nuclei were found after alendronate treatment had been discontinued for 1 year. Of these large cells, 20 to 37% were apoptotic, according to both their morphologic features and positive findings from in situ end labeling.î (R. S. Weinstein, weinsteinroberts@uams.edu)

>>>PNN NewsWatch
* Following up on an FDA warning from earlier in December (see PNN, Dec. 3), Celgene has issued a Dear Healthcare Professional letter describing a controlled clinical study that suggests that tinzaparin (Innohep) may increase the risk for death, compared with unfractionated heparin, when used to treat elderly patients with renal insufficiency. Clinicians should consider alternatives to tinzaparin when treating these patients for deep-vein thrombosis with or without pulmonary embolism, the company advises.

>>>PNN JournalWatch
* Intensive Glycemic Control and the Prevention of Cardiovascular Events: Implications of the ACCORD, ADVANCE, and VA Diabetes Trials: A Position Statement of the American Diabetes Association and a Scientific Statement of the American College of Cardiology Foundation and the American Heart Association, in Diabetes Care, 2009; 32: 187–92. (M. S. Kirkman, skirkman@diabetes.org)
* Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy. A Consensus Statement of the American Diabetes Association and the European Association for the Study of Diabetes, in
Diabetes Care, 2009; 32: 193–203. (D. M. Nathan, dnathan@partners.org)
* Inhaled Corticosteroids and Asthma Control in Children: Assessing Impairment and Risk, in
Pediatrics, 2009; 123: 353–66. (G. Rachelefsky)

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 © 2009, 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, 2009 * Vol. 16, No. 2
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from and Jan. 6 issue of the Annals of Internal Medicine (2009; 150).
Management of Hepatitis B: Appropriate use of the seven FDA-approved agents for hepatitis B infection is detailed in a statement issued by an NIH consensus development conference (early release). The panel, while concluding that no concrete recommendations can be made regarding a particular therapeutic course, provided these insights into the available agents: ìEach category of treatment, interferons or nucleoside or nucleotide analogues, has unique advantages and risks associated with administration of the drug. An advantage of interferon is that it is given for a defined course (16 to 48 weeks) and is not associated with the development of antiviral resistance. The use of interferon requires subcutaneous injection and is associated with systemic side effects, such as headache, nausea, flu-like symptoms, depression, and some hematologic abnormalities. Nucleoside and nucleotide analogues are administered orally, are associated with more profound HBV DNA suppression than interferon, and may be safely used in previous nonresponders to interferon therapy. However, if prematurely discontinued, these drugs are associated with resurgence of HBV DNA levels or reactivation of hepatitis. In addition, long-term use of these drugs is compromised by the development of resistance. Several of the nucleoside and nucleotide analogues are associated with renal toxicity, myopathy (muscle weakness or pain), and mitochondrial toxicity.î (www.consensus.nih.gov; 888-644-2667)
Antiviral Therapy of Chronic Hepatitis B: In a systematic review conducted in conjunction with the above-mentioned NIH consensus development conference, authors provide these evaluation of available randomized controlled trials (early release): ìIn 16 RCTs (4,431 patients), drug treatment did not improve clinical outcomes of chronic hepatitis B infection, but the trials were underpowered. In 60 RCTs that examined intermediate outcomes, no single treatment improved all intermediate outcomes. Low-quality evidence suggested HBsAg clearance after interferon-2b (2 RCTs; 211 patients). Moderate-quality evidence suggested ALT normalization at follow-up after treatment with adefovir (2 RCTs; 600 patients) and HBeAg loss with lamivudine (2 RCTs; 318 patients). With interferon-2b, moderate-quality evidence suggested HBeAg loss (3 RCTs; 351 patients), seroconversion (2 RCTs; 304 patients), and ALT normalization (2 RCTs; 131 patients). Pegylated interferon-2a versus lamivudine improved HBeAg seroconversion (1 RCT; 814 patients) and ALT normalization (2 RCTs; 905 patients) off treatment. Pegylated interferon-2a combined with lamivudine versus lamivudine improved HBeAg loss (1 RCT; 543 patients) and ALT normalization (2 RCTs; 905 patients). Adverse events during antiretroviral therapy occurred in more than 50% of patients but were not associated with increased treatment discontinuation. However, most studies excluded patients with hepatic or renal insufficiency or other serious comorbid conditions.î (T. A. Shamliyan, shaml005@umn.edu)
Statin Use & Risk for Keratinocyte Carcinoma: Long-term statin use is not associated with development of keratinocyte carcinoma, according to results of the Veterans Affairs Topical Tretinoin Chemoprevention Trial, which compared topical tretinoin 0.1% with placebo vehicle (pp. 9–18). Among 1,037 participants in the trial who were using a statin at randomization, researchers observed: ì37% used a statin at randomization (n = 397) for a median duration of at least 900 days over a median follow-up of 3.5 years. In the propensity score–matched analysis, statin use at randomization was not associated with keratinocyte carcinoma (rate ratio, 0.92 [95% CI, 0.73 to 1.16]), a finding that was consistent with the estimates derived from the Cox proportional hazards regression (rate ratio, 0.84 [CI, 0.70 to 1.02]).î (D. D. Dore, david.dore@i3drugsafety.com)

>>>PNN NewsWatch
* Indicated for treatment of hypotrichosis of the eyelashes, bimatoprost ophthalmic solution 0.03% (Latisse, Allergan) has been approved for marketing by FDA. The solution is applied with a sterile, single-use-per-eye applicator to the base of the eyelashes to make them longer, thicker, and darker, the company noted in a news release.

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 © 2009, 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, 2009 * Vol. 16, No. 3
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 7 issue of JAMA (2009; 301).
Deep Brain Stimulation for Advanced Parkinson Disease: Compared with best medical therapy for advanced Parkinson disease, deep brain stimulation was more effective for improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, researchers report, but the new technology produced a greater number of serious adverse events (pp. 63–73). Surgeons used the deep brain stimulation system (Kinetra, Medtronic) to insert leads into the subthalamic nucleus (n = 60) or globus pallidus (n = 61). Compared with best medical therapy provided to 134 patients by movement disorder neurologists, the surgical intervention produced these results: ìPatients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7–5.4 h/d]; P < .001). Motor function improved significantly (P < .001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores (P < .001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P < .001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage.î (F. M. Weaver, Frances.Weaver@va.gov)
The adverse events occurring in the surgical group are just one of several areas of uncertainty regarding neurostimulation, writes an editorialist (
pp. 104–5): ìThe present results showing similar efficacy and tolerability of deep brain stimulation in younger and older patients must be replicated because it is at variance with some other reports demonstrating lower rates of operative and postoperative complications in younger patients. Postoperative long-term outcomes have been published up to 5 years postoperatively but longer-lasting observations are certainly needed. Moreover, the relative advantages of the 2 deep brain stimulation targets remain undefined.î (G. Deuschl, g.deuschl@neurologie.uni-kiel.de)
The ìOtherî Medical Home: The Medical Home initiative, now in pilot testing through the Medicare Payment Advisory Commission, ìironically fails to emphasize the complex chronically ill patient’s actual home,î writes the author of a commentary (pp. 97–9): ìThis represents a failure to recognize the profile of the highest-risk beneficiaries driving much of the high Medicare costs—that is those with 4 or more chronic conditions and activity limitations whose homes and bodies are filled with the latest equipment, devices, and drugs, but often without the accessible, personal, holistic, and integrated care they need to take advantage of these interventions in ways that improve their overall well-being. These highly vulnerable Medicare beneficiaries often cannot access office-based medical practices because of their functional limitations. Even if these patients could readily get there, many physician practices are high volume and not well positioned to deliver or coordinate the type of time-intensive multidisciplinary care that can improve outcomes for these patients. This shortcoming more reflects a financing system that undervalues generalist physicians and other primary care clinicians than a failure of the physicians and practices themselves.Ö
ìA promising way to strengthen and broaden the Medical Home initiative for high-risk Medicare beneficiaries may be to make their actual homes the central venue of primary health care. This could be accomplished through another reform agenda that specifically empowers family caregivers, home health and hospice nurses, social workers, therapists, and personal care aides. This agenda places primary care physicians, advanced practice nurses, and physician assistants as partners and advisors to ongoing multidisciplinary care teams in the patient’s home.î (S. H. Landers,
landers@ccf.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 © 2009, 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, 2009 * Vol. 16, No. 4
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 8 issue of the New England Journal of Medicine (2009; 360).
Glucose Control & Vascular Complications in Type 2 Diabetes: Among 1,791 veterans with poorly controlled diabetes, long-term intensive glucose control had no significant effect on rates of major cardiovascular events, death, or microvascular complications, according to an analysis from the Veterans Affairs Diabetes Trial (VADT) (pp. 129–39). At study entry, patients had been diagnosed with the disease for a mean of 11.5 years, and 40% had prior cardiovascular events. Randomization to intensive glucose control with a goal of reducing the glycated hemoglobin level by 1.5 percentage points or standard care produced these results over a median of 5.6 years of follow-up: ìMedian glycated hemoglobin levels were 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group. The primary outcome occurred in 264 patients in the standard-therapy group and 235 patients in the intensive-therapy group (hazard ratio in the intensive-therapy group, 0.88; 95% confidence interval [CI], 0.74 to 1.05; P = 0.14). There was no significant difference between the two groups in any component of the primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95% CI, 0.81 to 1.42; P = 0.62). No differences between the two groups were observed for microvascular complications. The rates of adverse events, predominantly hypoglycemia, were 17.6% in the standard-therapy group and 24.1% in the intensive-therapy group.î (W. Duckworth, william.duckworth@va.gov)
Medication-Induced Gingival Hypertrophy: Clinical images of phenytoin-induced gingival hypertrophy are presented along with a brief summary of the case of a 30-year-old man who had been taking the drug for more than 20 years (e2). ìExamination of a mucosal-biopsy specimen showed proliferation of fibroblasts and an increased number of collagen fibers, as well as glycosaminoglycans,î the authors write. ìWith time, such gingival overgrowth may develop in patients taking phenytoin, a condition that may be exacerbated by poor oral hygiene. Severe overgrowth may lead to impairment in gingival function, requiring surgical excision of the excessive tissue. In the case of this patient, treatment of the gingival overgrowth was declined.î (D-S Yu, lyb80@catholic.ac.kr)
Neurontin Marketing Practices: Charging that the legacy of Neurontin (gabapentin) is ìmarketing through misinformation and manipulation,î authors of a Perspective article use court documents to provide a retrospective piece that notes (pp. 103–6): ìWe have learned that pharmaceutical marketing can be comprehensive, strategic, well financed, disguised as ‘education’ and ‘research’ influential, and very effective. Promotion of Neurontin was neither discrete, compartmentalized, nor readily apparent; instead, it was intercalated in nearly every aspect of physicians’ professional lives, from the accoutrements of practice to lectures, professional meetings, and publications. Although some pharmaceutical marketing may be less opaque, deceptive, and manipulative, evidence indicates that drug promotion can corrupt the science, teaching, and practice of medicine.î
The writers conclude: ìThese cases substantiate the emerging conviction that ‘drastic action is essential’ to preserve the integrity of medical science and practice and to justify public trust. We believe that such action should include the routine placement of legally discovered documents in the public domain, the study of such documents to inform strategies for minimizing abuses, the establishment of penalties that eliminate the profit to be gained through illegal marketing, and the independent public funding of peer-reviewed pharmaceutical research through a National Institute for Pharmaceutical Research that might be funded by a tax on all drug sales.
ìWill our profession soon feel compelled to advocate for such actions to preserve our integrity, our social contract, and ultimately our privileges? Neurontin’s most important legacy may be promoting our discussion of these issues and perhaps pushing us beyond the tipping point to action.î (C. S. Landefeld)

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 © 2009, 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. 9, 2009 * Vol. 16, No. 5
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Jan. issue of Pharmacotherapy (2009; 29).
Nocturnal Blood Pressure Measurements: Writing that the ìnighttime blood pressure is the blood pressure,î an editorialist advocates new approaches to the diagnosis of hypertension (pp. 3–6): ìBlood pressure measurement is long overdue for a paradigm shift. Accruing evidence indicates the risk:benefit ratio of hypertension treatment seems most closely defined by blood pressure at night. Clinicians should consider routine incorporation of out-of-office assessments into their practices to obtain this information. Nocturnal blood pressures are most consistently correlated with prediction of cardiovascular risk and provide more close surveillance of safety. For these reasons, evidence clearly points to the fact that nighttime blood pressure is, indeed, the blood pressure.î (M. E. Ernst, michael-ernst@uiowa.edu)
Mycophenolic Acid Kinetics in Lupus Nephritis: When dosing mycophenolic acid, clinicians should be mindful of changes in creatinine clearance and serum albumin levels during the course of lupus nephritis, conclude authors of an 18-patient pharmacokinetic analysis (pp. 7–16). Based on HPLC analysis of 24-hour urine and serum samples, the investigators found: ìTime to maximum concentration was variable (0.5–8 hrs). Mean ± SD fraction of unbound mycophenolic acid was 2.6 ± 1.9%, and oral clearance (Cl/F) was about 2-fold higher (343 ± 200 ml/min) than previously reported. Multiple regression analysis showed that Cl/F of mycophenolic acid was predicted by creatinine clearance and serum albumin level: ln Cl/F = 5.358 + 0.0092 (creatinine clearance) – 0.078 (ranked albumin), R2 = 51.1%, p = 0.0195. Patients with urinary protein excretion of 1 g/day or higher had lower minimum (trough) concentrations and area under the concentration-time curve (AUC0–12) profiles and higher Cl/F values compared with patients with urinary protein excretion of less than 1 g/day. Patients with serum albumin levels less than 4 g/dl had higher mycophenolic acid unbound clearance and MPAG renal clearance from 0–12 hours versus those with serum albumin levels of 4 g/dl or greater. Recycling AUC (AUC6–12), as well as sex and age (both equally), predicted renal clearance of [mycophenolic acid glucuronide].î (M. S. Joy, Melanie_Joy@med.unc.edu)
Management of Heart Failure: A practice insights article analyzes high-impact articles on management of heart failure (pp. 82–120). Compiled by a panel of 10 authors and reviewers, the collection of short study summaries updates a 2004 review and serves ìas a teaching tool, reference resource, or review of the heart failure literature for pharmacy clinicians, physicians, and students.î (C. A. Jackevicius, cjackevicius@westernu.edu)
Faculty Development: An ACCP position statement (pp. 124–6) is published on clinical faculty development, along with a review of ìessential componentsî of such programs (p. 127).

>>>PNN NewsWatch
* In an update posted on the FDA website, the agency affirmed its position that elevated LDL-cholesterol levels are a risk factor for cardiovascular diseases such as heart attack, stroke and sudden death, and that lowering LDL cholesterol reduces the risk of these diseases. The comments are a follow-up to FDA’s Jan. 25, 2008, Early Communication describing the agency’s review of data from ENHANCE (Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia). Preliminary and final results from ENHANCE showed no significant differences between simvastatin alone and simvastatin–ezetimibe in terms of the thickness of the walls of the carotid arteries, despite a significantly greater lowering of LDL-cholesterol levels in patients taking simvastatin–ezetimibe. After assessing these findings, FDA concluded: ìThe results from ENHANCE do not change FDA’s position on the benefits of lowering LDL cholesterol. Based on currently available data, patients should not stop taking Vytorin or other cholesterol-lowering drugs and should talk to their doctor or other health care professional if they have any questions about Vytorin, Zetia, or the ENHANCE trial.î

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 © 2009, 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, 2009 * Vol. 16, No. 6
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Jan. 10 issue of Lancet (2009; 372).
Insulin-Induced Amyloidosis: A case of apparent insulin resistance was resolved when clinicians realized that a 62-year-old Japanese man had developed ìinsulin ballsî in the abdomen at the locations he used regularly used for injection (p. 184). When seen in Aug. 2005, the patients had been using insulin glargine and insulin lispro since Jan. 2004, and his daily requirement had increased from 66 to 94 units. Initial examination showed nothing remarkable, but after the dose had to be increased to 116 units/day, clinicians re-examined the patient and found two abdominal lumps, one of each side (see MRI image in article). The authors, showing that the lumps consisted of amyloid and monoclonal antibodies to human insulin, write: ìThe patient had noticed the lumps several months previously; he routinely injected insulin into the nodules, since they were easily grasped, and injection was less painful than elsewhere. We administered insulin via a different part of the abdomen; hypoglycaemia ensued. We rapidly decreased insulin doses. Good blood glucose concentrations were obtained with a total daily dose of 24 units.Ö When last seen, in November, 2008, the patient needed 66 units a day of insulin—injected outside the lumps, which were smaller than before.î (T. Nagase, tnagase@tokyo-med.ac.jp)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2009; 337).
Comorbidity as ADR Risk Factor: Among 28,548 older adults, comorbidities—especially those managed in the community—are a significant predictor of repeat hospital admissions for adverse drug reactions, while advancing age is not, researchers report (a2752). Using the Western Australian data linkage system to identify patients admitted for an ADR and followed for 3 years, the investigators found: ì5,056 (17.7%) patients had a repeat admission for an ADR. Repeat ADRs were associated with sex (hazard ratio 1.08, 95% confidence interval 1.02 to 1.15, for men), first admission in 1995–9 (2.34, 2.00 to 2.73), length of hospital stay (1.11, 1.05 to 1.18, for stays 14 days), and Charlson comorbidity index (1.71, 1.46 to 1.99, for score 7); 60% of comorbidities were recorded and taken into account in analysis. In contrast, advancing age had no effect on repeat ADRs. Comorbid congestive cardiac failure (1.56, 1.43 to 1.71), peripheral vascular disease (1.27, 1.09 to 1.48), chronic pulmonary disease (1.61, 1.45 to 1.79), rheumatological disease (1.65, 1.41 to 1.92), mild liver disease (1.48, 1.05 to 2.07), moderate to severe liver disease (1.85, 1.18 to 2.92), moderate diabetes (1.18, 1.07 to 1.30), diabetes with chronic complications (1.91, 1.65 to 2.22), renal disease (1.93, 1.71 to 2.17), any malignancy including lymphoma and leukaemia (1.87, 1.68 to 2.09), and metastatic solid tumours (2.25, 1.92 to 2.64) were strong predictive factors. Comorbidities requiring continuing care predicted a reduced likelihood of repeat hospital admissions for ADRs (cerebrovascular disease 0.85, 0.73 to 0.98; dementia 0.62, 0.49 to 0.78; paraplegia 0.73, 0.59 to 0.89).î (M. Zhang, min.zhang@uwa.edu.au)

>>>PNN JournalWatch
* Pregnancy and Optimal Care of HIV-Infected Patients, in Clinical Infectious Diseases, 2009; 48: early release. (B. L. Anderson, banderson@wihri.org)
* Vaccines and Autism: A Tale of Shifting Hypotheses, in
Clinical Infectious Diseases, 2009; 48: early release. (P. A. Offit, ffit@email.chop.edu">offit@email.chop.edu)
* Psychostimulant Treatment and the Developing Cortex in Attention Deficit Hyperactivity Disorder, in
American Journal of Psychiatry, 2009; 166: 58–63. (P. Shaw, shawp@mail.nih.gov)
* Recent Advances in Cardiopulmonary Resuscitation: Cardiocerebral Resuscitation, in
Journal of the American College of Cardiology, 2009; 53: 149–57. (G. A. Ewy, gaewy@aol.com)
* Impaired Endothelial Nitric Oxide Bioavailability: A Common Link Between Aging, Hypertension, and Atherogenesis?, in
Journal of the American Geriatrics Society, 2009; 57: 140–5. (T. Walsh, thomaswalsh_3@hotmail.com)
* May You Live To Be 120. . . Revised, in
Journal of the American Geriatrics Society, 2009; 57: 168. (L. G. Hodgson, lynne.hodgson@quinnipiac.edu)
* Finding the Optimal Postnatal Dexamethasone Regimen for Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Systematic Review of Placebo-Controlled Trials, in
Pediatrics, 2009; 123: 367–77. (W. Onland)

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 © 2009, 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, 2009 * Vol. 16, No. 7
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Jan. 12 issue of the Archives of Internal Medicine (2009; 169).
Vasopressin, Epinephrine, & Corticosteroids for In-Hospital Cardiac Arrest: Survival of patients with refractory in-hospital cardiac arrest was greater when vasopressin–epinephrine was combined with methylprednisolone during resuscitation and stress-dose hydrocortisone was administered for postresuscitation shock, according to a small study from one center (pp. 15–24). Compared with epinephrine alone during resuscitation and placebo during postresuscitation shock, the study intervention produced these outcomes in 100 consecutive patients: ìStudy group patients vs controls had more frequent return of spontaneous circulation (39 of 48 patients [81%] vs 27 of 52 [52%]; P = .003) and improved survival to hospital discharge (9 [19%] vs 2 [4%]; P = .02). Study group patients with postresuscitation shock vs corresponding controls had improved survival to hospital discharge (8 of 27 patients [30%] vs 0 of 15 [0%]; P = .02), improved hemodynamics and central venous oxygen saturation, and more organ failure–free days. Adverse events were similar in the 2 groups.î (S. D. Mentzelopoulos, sdmentzelopoulos@yahoo.com)
Estrogen–Testosterone & Breast Cancer: Supporting the results of an earlier study, data from the Women’s Health Initiative Observational Study link use of exogenous estrogen–testosterone to a modest, nonsignificant increase in risk of breast cancer (pp. 41–6). During a mean follow-up period of 4.6 years, these results were recorded among 31,842 postmenopausal women who used E + T or nonhormonal therapy: ìThirty five women using E + T at visit 3 developed invasive breast cancer. Use of E + T had a nonsignificant impact on invasive breast cancer risk (adjusted hazard ratio, 1.42; 95% confidence interval, 0.95–2.11). The most commonly used E + T preparation, Estratest, was associated with a significant elevation in invasive breast cancer (adjusted hazard ratio, 1.78; 95% confidence interval, 1.05–3.01). However, rates of breast cancer were lower in longer-term E + T users than in shorter-term E + T users.î (R. B. Ness, roberta.b.ness@uth.tmc.edu)
Sleep & Common Colds: Lack of sleep—and a lack of quality sleep—predisposes patients to infection with rhinovirus, researchers report (pp. 62–7). Among 153 healthy men and women aged 21 to 55 years, exposure to rhinovirus resulted in infections with these patterns observable over the next 5 days based on prior sleep patterns: ìThere was a graded association with average sleep duration: participants with less than 7 hours of sleep were 2.94 times (95% confidence interval [CI], 1.18–7.30) more likely to develop a cold than those with 8 hours or more of sleep. The association with sleep efficiency was also graded: participants with less than 92% efficiency were 5.50 times (95% CI, 2.08–14.48) more likely to develop a cold than those with 98% or more efficiency. These relationships could not be explained by differences in prechallenge virus-specific antibody titers, demographics, season of the year, body mass, socioeconomic status, psychological variables, or health practices. The percentage of days feeling rested was not associated with colds.î (S. Cohen, scohen@cmu.edu)
Continuity of Care & ICU Use at End of Life: Among 21,183 Medicare beneficiaries aged 66 years or older with terminal lung cancer, outpatient-to-inpatient continuity of care worsened during the 1990s and early 2000s, according to an analysis of the linked Surveillance, Epidemiology, and End Results–Medicare database (pp. 81–6). But those ìwho experienced outpatient-to-inpatient continuity of care were less likely to spend time in the ICU before death,î conclude the researchers, adding these details: ìOutpatient-to-inpatient continuity decreased from 60.1% in 1992 to 51.5% in 2002 (P < .001). Factors associated with decreased continuity included male sex, black race, low socioeconomic status, being unmarried, treatment by a hospitalist, and treatment in a teaching hospital. Use of the ICU increased by 5.8% per year from 1993 to 2002. After adjustment for patient characteristics, patients with outpatient-to-inpatient continuity of care had a 25.1% reduced odds of entering the ICU during their terminal hospitalization.î (G. Sharma, gulshan.sharma@utmb.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 © 2009, 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, 2009 * Vol. 16, No. 8
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 14 issue of JAMA (2009; 301).
Neurodevelopmental Outcomes with High-Dose DHA: Bayley Mental Development Index scores at 18 months’ corrected age were higher among preterm girls fed high-dose docosahexaenoic acid, compared with standard amounts of DHA, but boys did not enjoy the same benefit of the supplements (pp. 175–82). A group of infants, all born at less than 33 weeks’ gestation, received either high-dose (approximately 1% of total fatty acids) or standard DHA (approximately 0.3% total fatty acids) beginning on the second to fourth day of life and continuing to the corrected age. Results showed: ìOf the 657 infants enrolled, 93.5% completed the 18-month follow-up. Bayley MDI scores did not differ between the high- and standard-DHA groups (mean difference, 1.9; 95% confidence interval [CI], −1.0 to 4.7). The MDI among girls fed the high-DHA diet was higher than girls fed standard DHA in unadjusted and adjusted analyses (unadjusted mean difference, 4.7; 95% CI, 0.5–-8.8; adjusted mean difference, 4.5; 95% CI, 0.5–8.5). The MDI among boys did not differ between groups. For infants born weighing less than 1,250 g, the MDI in the high-DHA group was higher than with standard DHA in the unadjusted comparison (mean difference, 4.7; 95% CI, 0.2–9.2) but did not reach statistical significance following adjustment for gestational age, sex, maternal education, and birth order (mean difference, 3.8; 95% CI, −0.5 to 8.0). The MDI among infants born weighing at least 1,250 g did not differ between groups.î (M. Makrides, maria.makrides@cywhs.sa.gov.au)
Drug Addiction & the Criminal Justice System: How people in a punish-and-protect criminal justice system can get care for drug abuse and addiction is explored (pp. 183–90): ìDespite increasing evidence that addiction is a treatable disease of the brain, most individuals do not receive treatment. Involvement in the criminal justice system often results from illegal drug-seeking behavior and participation in illegal activities that reflect, in part, disrupted behavior ensuing from brain changes triggered by repeated drug use. Treating drug-involved offenders provides a unique opportunity to decrease substance abuse and reduce associated criminal behavior. Emerging neuroscience has the potential to transform traditional sanction-oriented public safety approaches by providing new therapeutic strategies against addiction that could be used in the criminal justice system. We summarize relevant neuroscientific findings and evidence-based principles of addiction treatment that, if implemented in the criminal justice system, could help improve public heath and reduce criminal behavior.î (N. D. Volkow, nvolkow@nida.nih.gov)
Treating Fibromyalgia Syndrome with Antidepressants: Pain, depression, fatigue, sleep disturbances, and health-related quality of life are significantly improved by antidepressants in patients with fibromyalgia syndrome, authors of meta-analysis report (pp. 198–209): ìEighteen randomized controlled trials (median duration, 8 weeks; range, 4–28 weeks) involving 1,427 participants were included. Overall, there was strong evidence for an association of antidepressants with reduction in pain (SMD, −0.43; 95% confidence interval [CI], −0.55 to −0.30), fatigue (SMD, −0.13; 95% CI, −0.26 to −0.01), depressed mood (SMD, −0.26; 95% CI, −0.39 to −0.12), and sleep disturbances (SMD, −0.32; 95% CI, −0.46 to −0.18). There was strong evidence for an association of antidepressants with improved health-related quality of life (SMD, −0.31; 95% CI, −0.42 to −0.20). Effect sizes for pain reduction were large for TCAs (SMD, −1.64; 95% CI, −2.57 to −0.71), medium for MAOIs (SMD, −0.54; 95% CI, −1.02 to −0.07), and small for SSRIs (SMD, −0.39; 95% CI, −0.77 to −0.01) and SNRIs (SMD, −0.36; 95% CI, −0.46 to −0.25).î (W. H‰user, whaeuser@klinikum-saarbruecken.de)
Stop Sliding-Scale Insulin: If insulin is dosed on a sliding scale, why not antibiotics and oxygen too, the author of a commentary asks (pp. 213-4): ìPerhaps next July or the following summer, when the senior resident is explaining to the intern hyperglycemia management for a newly admitted patient with pneumonia, the discussion will revolve around basal insulin, prandial insulin, and correction-dose insulin based on a protocol that all hyperglycemic patients receive throughout the entire health care system.î (I. B. Hirsch)

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 © 2009, 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, 2009 * Vol. 16, No. 9
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 15 issue of the New England Journal of Medicine (2009; 360).
Antipsychotic Agents & Sudden Cardiac Death: Risks of sudden cardiac death are similar among users of antipsychotic agents in both the first (typical) and second (atypical) generations, researchers report, adding that risks rise with drug doses (pp. 225–35). Among some 90,000 Tennessee Medicaid beneficiaries who were using one agent in these classes exclusively, these trends were noted in comparison with 186,000 matched nonusers of antipsychotic drugs: ìCurrent users of typical and of atypical antipsychotic drugs had higher rates of sudden cardiac death than did nonusers of antipsychotic drugs, with adjusted incidence-rate ratios of 1.99 (95% confidence interval [CI], 1.68 to 2.34) and 2.26 (95% CI, 1.88 to 2.72), respectively. The incidence-rate ratio for users of atypical antipsychotic drugs as compared with users of typical antipsychotic drugs was 1.14 (95% CI, 0.93 to 1.39). Former users of antipsychotic drugs had no significantly increased risk (incidence-rate ratio, 1.13; 95% CI, 0.98 to 1.30). For both classes of drugs, the risk for current users increased significantly with an increasing dose. Among users of typical antipsychotic drugs, the incidence-rate ratios increased from 1.31 (95% CI, 0.97 to 1.77) for those taking low doses to 2.42 (95% CI, 1.91 to 3.06) for those taking high doses (P < 0.001). Among users of atypical agents, the incidence-rate ratios increased from 1.59 (95% CI, 1 .03 to 2.46) for those taking low doses to 2.86 (95% CI, 2.25 to 3.65) for those taking high doses (P = 0.01). The findings were similar in the cohort that was matched for propensity score.î (W. A. Ray, cindy.naron@vanderbilt.edu)
Use of antipsychotic agents should be curtailed until the relative risks and benefits of the drugs can be better assessed, editorialists write, offering these specifics (
pp. 294–6): ìClozapine, one of the most effective antipsychotic drugs, may be underused in patients who have schizophrenia that is resistant to treatment because patients and physicians worry about the risk of agranulocytosis or the burden of monitoring the white-cell count. A formal model for decision analysis similar to that used for clozapine would bring clarity about the risks and benefits of such a therapeutic risk-management program, and make it possible to use findings such as those reported in the current study as a springboard to detailed data-driven clinical recommendations. Until then, in patient populations for whom the evidence of the efficacy of antipsychotic medications is limited and the risk of a fatal side effect is clear, prudence would suggest that the use of these drugs should be reduced sharply.î (S. Schneeweiss, Brigham and Women’s Hosp., Boston)
Effectiveness of Pneumococcal Vaccine: Cases of pneumococcal meningitis have been lower among both children and adults in the years since the pediatric heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in 2000, but recent increases in rates of meningitis caused by non-PCV7 strains are a concern, according to a population-based analysis of data from eight U.S. sites (pp. 244–56). ìWe identified 1379 cases of pneumococcal meningitis,î write the investigators. ìThe incidence declined from 1.13 cases to 0.79 case per 100,000 persons between 1998–1999 and 2004–2005 (a 30.1% decline, P < 0.001). Among persons younger than 2 years of age and those 65 years of age or older, the incidence decreased during the study period by 64.0% and 54.0%, respectively (P < 0.001 for both groups). Rates of PCV7-serotype meningitis declined from 0.66 case to 0.18 case (a 73.3% decline, P < 0.001) among patients of all ages. Although rates of PCV7-related–serotype disease decreased by 32.1% (P = 0.08), rates of non-PCV7–serotype disease increased from 0.32 to 0.51 (an increase of 60.5%, P < 0.001). The percentages of cases from non-PCV7 serotypes 19A, 22F, and 35B each increased significantly during the study period. On average, 27.8% of isolates were nonsusceptible to penicillin, but fewer isolates were nonsusceptible to chloramphenicol (5.7%), meropenem (16.6%), and cefotaxime (11.8%). The proportion of penicillin-nonsusceptible isolates decreased between 1998 and 2003 (from 32.0% to 19.4%, P = 0.01) but increased between 2003 and 2005 (from 19.4% to 30.1%, P = 0.03).î (L. H. Harrison, lharriso@edc.pitt.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 © 2009, 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. 16, 2009 * Vol. 16, No. 10
Providing news and information about medications and their proper use

>>>Cardiology Highlights
Source:
Jan. 20 issue of the Journal of the American College of Cardiology (2009; 53).
Oral Contraceptives & CVD: Risks of myocardial infarction, venous thromboembolism, and other forms of cardiovascular disease among users of hormonal contraceptives are uncertain, according to a review article (pp. 221–31): ìA variety of basic science, animal, and human data suggests that contraceptive hormones have antiatheromatous effects; however, relatively less is known regarding the impact on atherosclerosis, thrombosis, vasomotion, and arrhythmogenesis. Newer generation OC formulations in use indicate no increased myocardial infarction risk for current users, but a persistent increased risk of venous thromboembolism. There are no cardiovascular data available for the newest generation contraceptive hormone formulations, including those that contain newer progestins that lower blood pressure, as well as the nonoral routes (transdermal and vaginal). Current guidelines indicate that, as with all medication, contraceptive hormones should be selected and initiated by weighing risks and benefits for the individual patient. Women 35 years and older should be assessed for cardiovascular risk factors including hypertension, smoking, diabetes, nephropathy, and other vascular diseases, including migraines, prior to use. Existing data are mixed with regard to possible protection from OCs for atherosclerosis and cardiovascular events; longer-term cardiovascular follow-up of menopausal women with regard to prior OC use, including subgroup information regarding adequacy of ovulatory cycling, the presence of hyperandrogenic conditions, and the presence of prothrombotic genetic disorders is needed to address this important issue.î (C. N. B. Merz, merz@cshs.org)
Intensive Glycemic Control and Cardiovascular Events: Recently released studies generally support a goal A1C level below 7%, concludes an expert consensus document from the American College of Cardiology and the American Heart Association (pp. 298–304). Panelists considered evidence from the Action in Diabetes and Vascular Disease—Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, the Veterans Affairs Diabetes Trial (VADT), and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study in making the following recommendations to clinicians:
*
Microvascular disease: Lowering A1C to below or around 7% has been shown to reduce microvascular and neuropathic complications of type 1 and type 2 diabetes. Therefore, the A1C goal for nonpregnant adults in general is <7%. ADA, A-level recommendation; ACC/AHA, Class I recommendation (Level of Evidence A).
*
Macrovascular disease: In type 1 and type 2 diabetes, randomized controlled trials of intensive versus standard glycemic control have not shown a significant reduction in CVD outcomes during the randomized portion of the trials. However, long-term follow-up of the [Diabetes Control and Complications Trial (DCCT)] and [U.K. Prospective Diabetes Study (UKPDS)] cohorts suggests that treatment to A1C targets below or around 7% in the years soon after the diagnosis of diabetes is associated with long-term reduction in risk of macrovascular disease. Until more evidence becomes available, the general goal of <7% appears reasonable. ADA, B level recommendation; ACC/AHA, Class IIb recommendation (Level of Evidence: A).

>>>PNN NewsWatch
* In an update to its ongoing safety review of montelukast (see PNN, Mar. 28, 2008) and other leukotriene modifiers, FDA this week provided new information on risks of suicidal events in children aged 6 years and older and adults. While not yet reaching a definitive conclusion about this and other neuropsychiatric adverse events with these drugs, FDA said that data from 41 placebo-controlled trials of montelukast showed that only one adult patient had suicidal ideation while on active therapy, with no completed suicides. Likewise, 45 studies of zafirlukast showed no patients with suicidal ideation or completed suicides during use of this agent, and 11 similar trials showed no suicidal problems among patients taking zileuton.
*
PNN will not be published on Mon., Jan 19, M. L. 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 © 2009, 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, 2009 * Vol. 16, No. 11
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release article from and Jan. 20 issue of the Annals of Internal Medicine (2009; 150).
QTc Interval Screening Before Methadone Treatment: For patients beginning treatment with methadone, clinicians should discuss the risk of drug-associated arrhythmias and ask about any history of structural heart disease, arrhythmia, or syncope, an expert panel suggests (early release). Based on panel members’ review of available literature, these additional recommendations are offered (M. J. Krantz, Colorado Prevention Ctr., Denver):
* Obtain a pretreatment ECG for all patients to measure the QTc interval and a follow-up ECG within 30 days and annually. If the methadone dosage exceeds 100 mg/d or patients have unexplained syncope or seizures, additional ECGs should be obtained.
* In patients whose QTc interval is between 450 and 500 msec, clinicians should discuss the risks and benefits of methadone therapy and increase the frequency of monitoring. Additional actions must be considered when the QTc interval exceeds 500 msec: Consider discontinuing or reducing the methadone dose, eliminating contributing factors such as other drugs that promote hypokalemia, and using alternative therapies.
* Clinicians should be aware of drug interactions involving methadone and other medications that prolong the QT interval or decrease the elimination of methadone.
Bariatric Surgery & Type 2 Diabetes: Bariatric procedures and how they may affect the enteroinsular axis is reviewed, with authors making these points (pp. 94–103): ìBariatric surgery leads to substantial and durable weight reduction. Nearly 30% of patients who undergo bariatric surgery have type 2 diabetes, and for many of them, diabetes resolves after surgery (84% to 98% for bypass procedures and 48% to 68% for restrictive procedures). Glycemic control improves in part because of caloric restriction but also because gut peptide secretion changes. Gut peptides, which mediate the enteroinsular axis, include the incretins glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, as well as ghrelin and peptide YY. Bariatric surgery (particularly bypass procedures) alters secretion of these gut hormones, which results in enhanced insulin secretion and sensitivity.Ö Familiarity with these effects can help physicians decide among the different surgical procedures and avoid postoperative hypoglycemia.î (M. L. Vetter, marion.vetter@uphs.upenn.edu)

>>>PNN NewsWatch
* A new U.S. President takes office at noon today, and the reform of the nation’s ailing health care system could be central to recovery from the worst economic crisis since the Great Depression. In addressing health care, Barack Obama will be moving toward a universal health care plan for all Americans as he identifies ways to level the competitive playing field for American employers, In his confirmation hearing, HHS Secretary–Designate Tom Daschle—who will also serve as the health reform czar in the Obama White House—specifically mentioned pharmacists as a group that ìcan play a far more important roleî in the new health system. Two assessments of the possibilities for health care reform were in last Thursday’s New England Journal of Medicine (pp. 205–7 and 208–9), and a new BMJ podcast covers similar ground.
*
FDA is warning of potentially serious hazards of using topical anesthetics for relieving pain from mammography and other medical tests and conditions. The agency said these products can cause serious, life-threatening adverse effects, (irregular heartbeat, seizures, breathing difficulties, coma and even death) when they are applied to a large area of skin or when the area of application is covered.

>>>PNN JournalWatch
* Effect and Cost-Effectiveness of Step-up Versus Step-down Treatment with Antacids, H2-Receptor Antagonists, and Proton Pump Inhibitors in Patients with New Onset Dyspepsia (DIAMOND study): A Primary-Care-Based Randomised Controlled Trial, in Lancet, 2009; 373: 215–25. (C. J. van Marrewijk, c.vanmarrewijk@antrg.umcn.nl)
* Does Single Application of Topical Chloramphenicol to High Risk Sutured Wounds Reduce Incidence of Wound Infection After Minor Surgery? Prospective Randomised Placebo Controlled Double Blind Trial, in
BMJ, 2009; 338: a2812. (C. F. Heal, clare.heal@jcu.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 © 2009, 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, 2009 * Vol. 16, No. 12
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 21 issue of JAMA (2009; 301).
Escitalopram for Older Adults with Generalized Anxiety Disorder: While cumulative response rates were higher among older adults with generalized anxiety disorder taking escitalopram than with placebo, intention-to-treat response rates were not significantly different in a 12-week, 177-participant study (pp. 295–303). Comparing drug doses of 10–20 mg with placebo, investigators found: ìIn the primary analytic strategy in which participants (n = 33) were censored at the time of dropout, mean cumulative response rate for escitalopram was 69% (95% confidence interval [CI], 58%–80%) vs 51% (95% CI, 40%–62%) for placebo (P = .03). A conservative intention-to-treat analysis showed no difference in mean cumulative response rate between escitalopram and placebo (57%; 95% CI, 46%–67%; vs 45%; 95% CI, 35%–55%; P = .11). Participants treated with escitalopram showed greater improvement than with placebo in anxiety symptoms and role functioning (Clinical Global Impressions-Improvement scale: effect size, 0.93; 95% CI, 0.50–1.36; P < .001; Penn State Worry Questionnaire: 0.30; 95% CI, 0.23–0.48; P = .01; activity limitations: 0.32; 95% CI, 0.01–0.63; P = .04; and the role-emotional impairment and social function: 0.96; 95% CI, 0.03–1.90; P = .04). Adverse effects of escitalopram (P < .05 vs placebo) were fatigue or somnolence (35 patients [41.1%]), sleep disturbance (12 [14.1%]), and urinary symptoms (8 [9.4%]).î (E. J. Lenze, lenzee@wustl.edu)
Therapeutic Foods in Severe Wasting: Among malnourished children aged 6 to 60 months in 12 villages in Niger, short-term supplementation with ready-to-use therapeutic foods reduced decline in weight-for-height scores and the incidence of wasting/severe wasting over an 8-month follow-up period (pp. 277–85). The RUTF product, manufactured by a French company, Plumpy’nut, provides 500 kcal/d and was distributed to intervention villages. Compared with children in nonintervention villages, those on the supplement had a 36% reduction in incidence of wasting and a 58% decrease in incidence of severe wasting. (S. Isanaka, sisanaka@hsph.harvard.edu)
Commenting on the study, an editorialist writes (
pp. 327–8): ìCommunity-based research on the effects of supplements on nutritional status in children should be designed in such a way to clearly guide policy and program design. This implies going beyond individual outcomes to a more integrated approach considering acceptance, use, effects, cost, and cost-effectiveness of the supplements compared with alternative approaches.î (L. M. Neufeld, neufeld@insp.mx)

>>>PNN NewsWatch
* FDA last week licensed RiaSTAP (CSL Behring, Marburg, Germany), an orphan drug for the treatment of bleeding in patients with congenital fibrinogen deficiency. RiaSTAP is an intravenous fibrinogen concentrate made from the plasma of healthy human blood donors. The product is indicated for patients with afibrinogenemia and for those patients with hypofibrinogenemia (serum fibrinogen levels below 50 mg/dL). The product is not indicated for patients with dysfibrinogenemia, who may have normal fibrinogen levels but defective fibrinogen function. Patients such as these are at risk for both bleeding and clotting complications. The licensing of RiaSTAP was supported by a study of 15 patients with afibrinogenemia who achieved the target level of fibrinogen expected to prevent bleeding after they received 70 mg/kg of the drug. In addition, plasma from 14 of the 15 patients showed increased maximum clot firmness, a surrogate marker likely to predict clinical benefit. Fever and headache were the most common adverse reactions. FDA added that clinical benefit of RiaSTAP will be further verified in a postmarketing study that will include both afibrinogenemic and hypofibrinogenemic patients.
* The White House website, updated yesterday in conjunction with Barack Obama’s inauguration, lists
lower drug costs as a major goal of the new President’s health care agenda. Strategies center around greater use of generic drugs: allowing the importation of safe medicines from other developed countries, increasing the use of generic drugs in public programs, and taking on drug companies that block cheaper generic medicines from the market.

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 © 2009, 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, 2009 * Vol. 16, No. 13
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 23 issue of the New England Journal of Medicine (2009; 360).
Steroids for Wheezing in Young Children: Two research articles and an editorial cast doubt on treatment of wheezing in young children with corticosteroids.
Oral prednisolone was not more effective than placebo among 687 preschool children presenting to three English hospitals with mild-to-moderate wheezing, researchers report (
pp. 329–38). Comparing a 5-day course of oral prednisolone 10–20 mg once daily with placebo, the investigators found these results in an intention-to-treat analysis: ìThere was no significant difference in the duration of hospitalization between the placebo group and the prednisolone group (13.9 hours vs. 11.0 hours; ratio of geometric means, 0.90; 95% confidence interval, 0.77 to 1.05) or in the interval between hospital admission and signoff for discharge by a physician. In addition, there was no significant difference between the two study groups for any of the secondary outcomes or for the number of adverse events.î (J. Grigg, j.grigg@qmul.ac.uk)
Preemptive use of high-dose fluticasone in young children with viral-induced wheezing reduced later use of rescue oral corticosteroids but was associated with significantly smaller gains in height and weight (
pp. 339–53). The authors concluded that long-term adverse effects would need to be better clarified before fluticasone propionate 750 mcg by inhalation twice daily could be recommended for routine clinical practice, adding these details concerning the 129 children included in the study: ìOver a median period of 40 weeks, 8% of upper respiratory tract infections in the fluticasone group led to treatment with rescue systemic corticosteroids, as compared with 18% in the placebo group (odds ratio, 0.49; 95% confidence interval [CI], 0.30 to 0.83). Children who were treated with fluticasone, as compared with those who were given placebo, had smaller mean (± SD) gains from baseline in height (6.23 ± 2.62 cm [unadjusted value]; z score, –0.19 ± 0.42 vs. 6.56 ± 2.90 cm [unadjusted value]; z score, 0.00 ± 0.48; difference between groups in z score from baseline to end point, –0.24 [95% CI, –0.40 to –0.08]) and in weight (1.53 ± 1.17 kg [unadjusted value]; z score, –0.15 ± 0.48 vs. 2.17 ± 1.79 kg [unadjusted value]; z score, 0.11 ± 0.43; difference between groups in z score from baseline to end point, –0.26 [95% CI, –0.41 to –0.09]). There were no significant differences between the groups in basal cortisol level, bone mineral density, or adverse events.î (F. M. Ducharme, francine.m.ducharme@umontreal.ca)
An editorialist provides this advice about treatment of acute episodic wheezing in preschool children (
pp. 409–10): ìBeta-2 agonists that are inhaled through an appropriate spacer, with a mask if age appropriate, should be given. Prophylactic or intermittent use of leukotriene receptor antagonists may be beneficial, but comparisons with intermittent inhaled corticosteroids are needed. However, a recent study that compared the use of intermittent therapy with albuterol with therapy with nebulized budesonide (arguably a mode of delivery inferior to a metered-dose inhaler and spacer), oral montelukast, or placebo in preschool children with episodic wheezing resulted in only very modest improvements in the severity of attacks. Prednisolone should be administered to preschoolers only when they are severely ill in the hospital. Intermittent, high-dose inhaled corticosteroids should not be used.î (A. Bush, Royal Brompton Hosp., London)
Clopidogrel Pharmacogenetics: Two articles, released in advance of publication (see PNN, Dec. 29) and a related editorial (pp. 411–3; J. E. Freedman, Boston U., Boston) demonstrate the importance of pharmacogenetics in the clinical use of clopidogrel. Any of several reduced-function CYP2C19 alleles, found in 30% of the study population, result in ìsignificantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of major adverse cardiovascular events, including stent thrombosis,î the first study concluded (pp. 354–62; J. L. Mega, jmega@partners.org). Similarly, the second study shows that patients with reduced-function alleles have higher rates of subsequent cardiovascular events than other patients, with especially pronounced differences among those undergoing percutaneous coronary interventions (pp. 363–75; T. Simon, tabassome.simon@sat.aphp.fr).

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 © 2009, 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. 23, 2009 * Vol. 16, No. 14
Providing news and information about medications and their proper use

>>>Allergy/Immunology Report
Source:
Jan. issue of the Journal of Allergy and Clinical Immunology (2009; 123).
Gene–Environment Interactions in Asthma: A number of genes with small effects may be at play in patients with asthma, a different situation than for less complex diseases in which one or a few genes have large effects (pp. 3–11). That assessment is provided in a review article that adds this information between the interactions among patients’ genes and environments: ìGenetic effects may in part differ with respect to a subject’s environmental exposures, although some genes may also exert their effect independently of the environment. Whereas the geneticist uses highly advanced, rapid, comprehensive technologies to assess even subtle changes in the human genome, the researcher interested in environmental exposures is often confronted with crude information obtained from questionnaires or interviews. There is thus substantial need to develop better tools for individual exposure assessment in all relevant environmental fields. Despite these limitations, a number of important gene-environment interactions have been identified. These interactions point to the biology of environmental exposures as the involved genetic variation is suggestive of certain underlying mechanisms. Furthermore, the identification of subjects who are particularly susceptible to environmental hazards through genetic analyses helps to estimate better the strength of effect of environmental exposures. Finally, the analysis of gene–environment interactions may result in a reconciliation of seemingly contradictory findings from studies not taking environmental exposures into account.î (E. von Mutius, Erika.von.Mutius@med.uni-muenchen.de)
Asthma Symptoms & Omalizumab Concentrations: Among patients with severe asthma who had responded to omalizumab, re-emergence of clinical symptoms correlated well with drug concentrations and free IgE levels when the drug doses were reduced or discontinued, INvestigation of Omalizumab in seVere Asthma TrEatment (INNOVATE) researchers report (pp. 107–13.e3). Using a pharmacokinetic–pharmacodynamic binding model to calculate free IgE, omalizumab, and total IgE concentrations during the 28-week treatment and 16-week follow-up, the investigators found: ìThe model accurately fitted omalizumab and free and total IgE, allowing reconstruction of the entire time course for each patient. Free IgE was rapidly suppressed below the 50 ng/mL (20.8 IU/mL) target, although there was a notable period before clinical measures stabilized. After treatment cessation, free IgE and omalizumab returned toward baseline and, after a delay, asthma symptoms re-emerged. Model-derived omalizumab and free IgE concentrations correlated well with changes in clinical outcomes, particularly in omalizumab-treated responders. Asthma symptoms exhibited different correlations during response onset compared with response offset (hysteresis), indicative of physiological time delays between changes in IgE levels and pulmonary function.î (P. J. Lowe, phil.lowe@novartis.com)
Cardiovascular Disease & Beta-2 Agonists in Asthma: Use of short-acting beta-2 agonists is explored as a cause of cardiovascular disease among patients with asthma and no prior CVD (pp. 124–30.e1). In the North West Adelaide Health Study, patient questionnaires that explored physician-diagnosed asthma and CVD revealed these relationships among risk factors in 6,925 patients: ìResults are expressed as odds ratios (ORs) and 95% CIs. By using multivariable logistic regression, after adjustment for risk factors, in female subjects incident CVD/stroke events were associated with asthma (OR, 3.24; 95% CI, 1.55–6.78), with no effect modification by atopy (P for interaction = .61), and with as-required short-acting beta-2-agonist use (OR, 2.66; 95% CI, 1.06–6.61). In male subjects events were associated with daily cough/sputum (OR, 1.92; 95% CI, 1.05–3.50) and FEV1 of less than 80% of predicted value but an FEV1/forced vital capacity ratio of greater than 0.70 (OR, 2.15; 95% CI, 0.91–5.09; P = .08). Although few CVD/stroke events occurred in male subjects with asthma, a significant interaction with atopic status was found (P = .05).î (S. L. Appleton, sarah.appleton@adelaide.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 © 2009, 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, 2009 * Vol. 16, No. 15
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Jan. 24 issue of Lancet (2009; 372).
Endocrine Treatment for Advanced Prostate Cancer: Addition of radiotherapy to endocrine treatment of locally advanced prostate cancer decreased the 10-year mortality by one-half and decreased the overall mortality rate with an acceptable level of adverse effects, researchers report (pp. 301–8). The study population included 875 patients in Scandinavia, and they received 3 months of total androgen blockade followed by continuous endocrine treatment using flutamide with or without radiotherapy. Results showed: ìAfter a median follow-up of 7.6 years, 79 men in the endocrine alone group and 37 men in the endocrine plus radiotherapy group had died of prostate cancer. The cumulative incidence at 10 years for prostate-cancer-specific mortality was 23.9% in the endocrine alone group and 11.9% in the endocrine plus radiotherapy group (difference 12.0%, 95% CI 4.9—19.1%), for a relative risk of 0.44 (0.30—0.66). At 10 years, the cumulative incidence for overall mortality was 39.4% in the endocrine alone group and 29.6% in the endocrine plus radiotherapy group (difference 9.8%, 0.8—18.8%), for a relative risk of 0.68 (0.52—0.89). Cumulative incidence at 10 years for PSA recurrence was substantially higher in men in the endocrine-alone group (74.7% vs 25.9%, p < 0.0001; HR 0.16; 0.12—0.20). After 5 years, urinary, rectal, and sexual problems were slightly more frequent in the endocrine plus radiotherapy group.î (A. Widmark, Anders.Widmark@onkologi.umu.se)
Clopidogrel Pharmacogenetics: Adding to the information published in last week’s New England Journal of Medicine, authors from one of those same research groups demonstrate the importance of CYP2C19 pharmacogenetics in young patients on clopidogrel (pp. 309–17). Analysis of polymorphisms in patients younger than 45 who were exposed to clopidogrel for 1 month or longer showed these patterns: ìMedian clopidogrel exposure time was 1.07 years (IQR 0.28—3.0). Baseline characteristics were balanced between carriers (heterozygous *1/*2, n = 64; homozygous *2/*2, n=9) and non-carriers (n = 186) of CYP2C19*2 variant. The primary endpoint occurred more frequently in carriers than in non-carriers (15 vs 11 events; hazard ratio [HR] 3.69 [95% CI 1.69—8.05], p = 0.0005), as did stent thrombosis (eight vs four events; HR 6.02 [1.81—20.04], p = 0.0009). The detrimental effect of the CYP2C19*2 genetic variant persisted from 6 months after clopidogrel initiation up to the end of follow-up (HR 3.00 [1.27—7.10], p = 0.009). After multivariable analysis, the CYP2C19*2 genetic variant was the only independent predictor of cardiovascular events (HR 4.04 [1.81—9.02], p = 0.0006).î (G. Montalescot, gilles.montalescot@psl.aphp.fr)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2009; 337).
Steroid Injection for Rotator Cuff Disease: Short-term outcomes are similar with systemic and local ultrasound-guided corticosteroid injections for rotator cuff disease, according to a study of 106 patients with symptoms of at least 3 months’ duration (a3112). Corticosteroid and lidocaine were injected into the subacromial bursa with ultrasound guidance in the local group, with these results noted in comparison with the systemic group that received those agents in the gluteus: ìSix weeks after the intervention, the mean difference in improvement in overall shoulder pain and disability index score between the local group and the systemic group was –5.2 (95% confidence interval –13.9 to 3.5); it was –4.1 (–12.3 to 4.1, P = 0.32) after adjustment for baseline score. A small but statistically significant difference in improvement between groups occurred in favour of the local group for two secondary outcome measures: the Western Ontario rotator cuff index (8.1, 0.7 to 15.6) and change in main complaint (2.0, 0 to 4).î (O. M. Ekeberg, .m.ekeberg@medisin.uio.no">o.m.ekeberg@medisin.uio.no)

>>>PNN JournalWatch
* Vicks VapoRub Induces Mucin Secretion, Decreases Ciliary Beat Frequency, and Increases Tracheal Mucus Transport in the Ferret Trachea, in Chest, 2009; 135: 143–8. (B. K. Rubin, brubin@wfubmc.edu)
* Partnering to Reduce Risks and Improve Cardiovascular Outcomes; American Heart Association Initiatives in Action for Consumers and Patients, in
Circulation, 2009; 119: 340–50. (D. W. Jones, djones@ovc.umsmed.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 © 2009, 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, 2009 * Vol. 16, No. 16
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Jan. 26 issue of the Archives of Internal Medicine (2009; 169).
Clinical Information Technologies & Inpatient Outcomes: Fewer inpatient complications, lower mortality rates, and lower costs were recorded at hospitals with automated notes and records, order entry, and clinical decision support, compared with facilities without such health information technologies. a study shows (pp. 108–14). Using the Clinical Information Technology Assessment Tool, researchers found these results at Texas urban hospitals: ìWe received a sufficient number of responses from 41 of 72 hospitals (58%). For all medical conditions studied, a 10-point increase in the automation of notes and records was associated with a 15% decrease in the adjusted odds of fatal hospitalizations (0.85; 95% confidence interval, 0.74–0.97). Higher scores in order entry were associated with 9% and 55% decreases in the adjusted odds of death for myocardial infarction and coronary artery bypass graft procedures, respectively. For all causes of hospitalization, higher scores in decision support were associated with a 16% decrease in the adjusted odds of complications (0.84; 95% confidence interval, 0.79–0.90). Higher scores on test results, order entry, and decision support were associated with lower costs for all hospital admissions (–$110, –$132, and –$538, respectively; P < .05).î (R. Amarasingham, ramara@parknet.pmh.org)
These results should stimulate inquiry and action at medium and large hospitals, an editorialist writes (
pp. 105–7): ìAt the end of the day, does this article mean that hospitals should now climb on the [health information technology] bandwagon? The data are too circumstantial to answer this definitively, but they provide another extremely important set of results. More of such analyses should be done, and they are likely to be helpful in convincing policy experts including skeptics like those at the [Congressional Budget Office] of the benefits when these technologies are in routine use. For large- and medium-sized hospitals, it appears that the time is now. This article by Amarasingham et al also provides some of the first evidence about the benefits of computerizing clinical documentation, which should be high on the ‘to do’ list of organizations.î (D. W. Bates, dbates@partners.org)
Analgesics & Risk of Breast Cancer: In the Nurses Health Study II, use of aspirin and other NSAIDs was not associated with a reduced risk of breast cancer among premenopausal women (pp. 115–21). Looking at analgesic use among 112,292 women, the researchers found: ìOverall, 1,345 cases of invasive premenopausal breast cancer were documented. Regular use of aspirin (2 times per week) was not significantly associated with breast cancer risk (relative risk, 1.07; 95% confidence interval, 0.89–1.29). Regular use of either nonaspirin NSAIDs or acetaminophen also was not consistently associated with breast cancer risk. Results did not vary by frequency (days per week), dose (tablets per week), or duration of use. Furthermore, associations with each drug category did not vary substantially by estrogen and progesterone receptor status of the tumor.î (A. H. Eliassen, heather.eliassen@channing.harvard.edu)
In an invited commentary, authors call for caution in applying the results of this report (
p. 121): ìThe authors’ conclusion that ‘chemopreventive use of aspirin or other NSAIDs for breast cancer among premenopausal women is not warranted’ on the basis of this single study is too broad. One might suggest that the justification to proceed with prospective clinical trials for potentially useful cancer risk–reductive interventions rests on the preponderance of preliminary data from multiple sources—mechanism, observational associations, preclinical studies in vitro, and preclinical studies in vivo.î (M. Kakarala, mkakaral@umich.edu)

>>>PNN NewsWatch
* Clinicians should re-evaluate the need for starting or continuing PPI therapy in patients taking clopidogrel in light of published information about a drug interaction involving the pair, FDA advised yesterday in an early communication. Noting that the recommendation extends to Prilosec OTC, the agency added that potential alternative agents such as histamine-2 antagonists and antacids have no known effect on the antiplatelet actions of clopidogrel. Studies are under way to better elucidate the effects of genetics and other drugs on clopidogrel, 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 © 2009, 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, 2009 * Vol. 16, No. 17
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 28 issue of JAMA (2009; 301).
BNP-Guided Treatment of Heart Failure: Compared with symptom-guided treatment, heart failure therapy guided by N-terminal BNP did not improve overall clinical outcomes or quality of life, according to data from the Trial of Intensified vs Standard Medical Therapy in Elderly Patients with Congestive Heart Failure (TIME-CHF) (pp. 383–92). Included in the analysis were 499 patients aged 60 years or older with CHF of New York Heart Association class II or greater. Treatment was guided by either symptoms or BNP levels of 2 times or less of the upper limit of normal, with these results: ìHeart failure therapy guided by N-terminal BNP and symptom-guided therapy resulted in similar rates of survival free of all-cause hospitalizations (41% vs 40%, respectively; hazard ratio [HR], 0.91 [95% CI, 0.72–1.14]; P = .39). Patients’ quality-of-life metrics improved over 18 months of follow-up but these improvements were similar in both the N-terminal BNP–guided and symptom-guided strategies. Compared with the symptom-guided group, survival free of hospitalization for heart failure, a secondary end point, was higher among those in the N-terminal BNP–guided group (72% vs 62%, respectively; HR, 0.68 [95% CI, 0.50–0.92]; P = .01). Heart failure therapy guided by N-terminal BNP improved outcomes in patients aged 60 to 75 years but not in those aged 75 years or older (P < .02 for interaction).î (M. Pfisterer, pfisterer@email.ch)
Considering results from 5 studies of BNP-guided therapy of CHF, editorialists reach this conclusion (
pp. 432–4): ìThe strategy of using N-terminal BNP–guided therapy appears safe in patients younger than 75 years (ie, no excess of hypotension, renal failure, or hyperkalemia) and some data suggest a modest reduction in mortality for some patients. Future trials need to prospectively analyze biomarker-guided therapy in a larger number of patients to ensure adequate power to definitively answer the question of whether this strategy reduces clinically important events including mortality, and should include sufficient numbers of older patients and women, as well as a detailed prespecified protocol for therapy choices and uptitration schedules. The detailed clinical plan should consider reduction of diuretics if no pulmonary or systemic congestion is present and include a flexible diuretic regimen as recommended in current practice guidelines. A detailed plan of approach to BNP levels will tend to minimize individual physician behavior as a confounder. Therefore, the TIME-CHF study places N-terminal BNP–guided therapy into perspective and introduces important caveats in the use of BNP levels in clinical practice.î (I. L. PiÒa, ilppina@aol.com)
Genome-wide Interrogation in Childhood Acute Lymphoblastic Leukemia: In children with acute lymphoblastic leukemia, a genome-wide interrogation of 476,796 germline single nucleotide polymorphisms shows a relationship between lower risk of residual disease and presence of SNPs related to leukemia cell biology and drug disposition (pp. 393–403). In an analysis of genotypes associated with risk of minimal residual disease, or MRD, investigators found these patterns among 318 patients in St. Jude Total Therapy protocols XIIIB and XV and 169 patients in Children’s Oncology Group trial P9906 (enrolled in 1994–2006; last follow-up, 2006): ìThere were 102 SNPs associated with MRD in both cohorts (median odds ratio, 2.18; P .0125), including 5 SNPs in the interleukin 15 (IL15) gene. Of these 102 SNPs, 21 were also associated with hematologic relapse (P < .05). Of 102 SNPs, 21 were also associated with antileukemic drug disposition, generally linking MRD eradication with greater drug exposure. In total, 63 of 102 SNPs were associated with early response, relapse, or drug disposition.î (M. V. Relling, mary.relling@stjude.org)

>>>PNN NewsWatch
* FDA warns consumers not to take Venom HYPERDRIVE 3.0 (Applied Lifescience Research Industries Inc.), a dietary supplement that the agency claims contains sibutramine. ALR Industries recalled all lots of Venom HYPERDRIVE 3.0 in Dec. after FDA laboratory analysis showed samples of the product contained undeclared sibutramine. The product was sold nationwide as well as in Canada, Europe, South Africa, and Australia.

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 © 2009, 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, 2009 * Vol. 16, No. 18
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 29 issue of the New England Journal of Medicine (2009; 360).
Gene Therapy for Adenosine Deaminase Deficiency: Administered following nonmyeloablative conditioning with busulfan, gene therapy proved a safe and effective treatment for severe combined immunodeficiency (SCID) caused by lack of the adenosine deaminase (ADA) enzyme, researchers report (pp. 447–58). In 10 children with this purine metabolic disorder, autologous CD34+ bone marrow cells transduced with a retroviral vector containing the ADA gene were administered, with these results: ìAll patients are alive after a median follow-up of 4.0 years (range, 1.8 to 8.0). Transduced hematopoietic stem cells have stably engrafted and differentiated into myeloid cells containing ADA (mean range at 1 year in bone marrow lineages, 3.5 to 8.9%) and lymphoid cells (mean range in peripheral blood, 52.4 to 88.0%). Eight patients do not require enzyme-replacement therapy, their blood cells continue to express ADA, and they have no signs of defective detoxification of purine metabolites. Nine patients had immune reconstitution with increases in T-cell counts (median count at 3 years, 1.07 x 109 per liter) and normalization of T-cell function. In the five patients in whom intravenous immune globulin replacement was discontinued, antigen-specific antibody responses were elicited after exposure to vaccines or viral antigens. Effective protection against infections and improvement in physical development made a normal lifestyle possible. Serious adverse events included prolonged neutropenia (in two patients), hypertension (in one), central-venous-catheter–related infections (in two), Epstein–Barr virus reactivation (in one), and autoimmune hepatitis (in one).î (M-G Roncarolo, m.roncarolo@hsr.it)
Writing that gene therapy is ìfulfilling its promise,î an editorialist provides this view on emerging applications of this technology (
pp. 518–21): ìThe prospects for continuing advancement of gene therapy to wider applications remain strong. Ongoing and upcoming clinical trials will use safer designs of retroviral vectors, newer types of vectors for viral gene delivery, and emerging methods for direct in situ gene repair. These approaches to the treatment of hemoglobinopathies, hemophilia, muscular dystrophy, congenital retinopathies, neurodegenerative disorders, and other genetic diseases may further fulfill the promise that gene therapy made two decades ago.î (D. B. Kohn, Childrens Hosp., Los Angeles)
Weight Loss for Urinary Incontinence: Improvement in stress urinary incontinence can be added to the list of benefits of weight reduction among overweight and obese women, according to a study of 338 patients with at least 10 incontinent episodes per week (pp. 481–90). An intensive 6-month program of diet, exercise, and behavior modification produced these results: ìThe mean (± SD) age of the participants was 53 ± 11 years. The body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) and the weekly number of incontinence episodes as recorded in a 7-day diary of voiding were similar in the intervention group and the control group at baseline (BMI, 36 ± 6 and 36 ± 5, respectively; incontinence episodes, 24 ± 18 and 24 ± 16, respectively). The women in the intervention group had a mean weight loss of 8.0% (7.8 kg), as compared with 1.6% (1.5 kg) in the control group (P < 0.001). After 6 months, the mean weekly number of incontinence episodes decreased by 47% in the intervention group, as compared with 28% in the control group (P = 0.01). As compared with the control group, the intervention group had a greater decrease in the frequency of stress-incontinence episodes (P = 0.02), but not of urge-incontinence episodes (P = 0.14). A higher proportion of the intervention group than of the control group had a clinically relevant reduction of 70% or more in the frequency of all incontinence episodes (P < 0.001), stress-incontinence episodes (P = 0.009), and urge-incontinence episodes (P = 0.04).î (L. L. Subak, subakl@obgyn.ucsf.edu)
Super-Challenge of Superbugs: Academic researchers and institutions, industry, and government need to address the ìdry pipelineî of agents for 21st century antibiotic-resistant ìsuperbugsî—especially gram-negative bacteria and enterococci—writes the author of a Perspective article (pp. 439–43; C. A. Arias, U. Texas, Houston)

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 © 2009, 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. 30, 2009 * Vol. 16, No. 19
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Feb. issue of Diabetes Care (2009; 32).
High-Dose Simvastatin Therapy: Among 20 nonobese patients with type 2 diabetes, high-dose simvastatin therapy had no direct effects on whole-body or tissue-specific insulin action and ectopic lipid deposition, and researchers concluded that ìreduction in plasma [free fatty acids] probably mediates alterations in insulin sensitivity in vivoî (pp. 209–14). Comparing the effects of 80-mg doses of simvastatin with those of placebo in patients with diabetes and assessing physiologic parameters in these patients against those of 10 healthy volunteers, the researchers found significantly lower total and LDL cholesterol values (33% and 48%, respectively) but no changes in insulin sensitivity, intracellular lipid deposition in soleus and tibialis anterior muscles and liver, or basal and insulin-suppressed endogenous glucose production. Changes in LDL cholesterol levels were negatively associated with insulin sensitivity, as were free fatty acid levels, while the latter were positively associated with changes in plasma retinol-binding protein-4. (M. Roden, michael.roden@ddz.uni-duesseldorf.de)
Racial/Ethnic Concerns About Medications: Quality-of-life concerns about diabetes-related medications are more common among Latinos and African Americans than Caucasians, a Chicago-based study concludes (pp. 311–6). In-person interviews conducted in 2004–06 revealed the following worries among 676 adult patients with type 2 diabetes: ìLatinos and African Americans had higher A1C levels than Caucasians (7.69 and 7.54% vs. 7.18%, respectively; P < 0.01). Latinos and African Americans were more likely than Caucasians to worry about drug side effects (66 and 49% vs. 39%, respectively) and medication dependency (65 and 52% vs. 39%, respectively; both P < 0.01). Ethnic minorities were also more likely to report reluctance to adding medications to their regimen (Latino 12%, African American 18%, and Caucasian 7%; P < 0.01). In analyses adjusted for demographics, income, education, and diabetes duration, current report of pain/discomfort with pills (odds ratio 2.43 [95% CI 1.39–4.27]), concern regarding disruption of daily routine (1.97 [1.14–3.42]), and African American ethnicity (2.48 [1.32–4.69]) emerged as major predictors of expressed reluctance to adding medications.î (E. S. Huang, ehuang@medicine.bsd.uchicago.edu)
Glycemic Control & Cognitive Function: In the Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, higher A1C levels were associated with lower cognitive function among patients with diabetes (pp. 221–6). Based on results of the Digit Symbol Substitution Test (DSST), Mini Mental Status Examination (MMSE), Rey Auditory Verbal Learning Test, and Stroop Test, the researchers found these relationships with clinical indicators: ìA statistically significant age-adjusted association was observed between the A1C level and the score on all four cognitive tests. Specifically, a 1% higher A1C value was associated with a significant 1.75-point lower DSST score (95% CI –1.22 to –2.28; P < 0.0001), a 0.20-point lower MMSE score (–0.11 to –0.28; P < 0.0001), a 0.11-point lower memory score (–0.02 to –0.19, P = 0.0142), and a worse score (i.e., 0.75 s more) on the Stroop Test (1.31–0.19, P = 0.0094). The association between the DSST score and A1C persisted in all multiple linear regression models. [Fasting plasma glucose] was not associated with test performance.î (T. Cukierman-Yaffe, cukierm@mcmaster.ca)
Web-Based Collaborative Care: Lower A1C levels occurred when a Web-based system was used to provide collaborative care to 83 patients with type 2 diabetes (pp. 234–9). Between 2002 and 2004, patients with A1C levels of 7.0% or more received usual care with or without the program, which included patient access to electronic medical records, secure e-mail with providers, feedback on blood glucose readings, an educational Web site, and an interactive online diary detailing exercise, diet, and medication. A1C levels declined by an average of 0.7 percentage points (95% CI, 0.2–1.3) among those receiving the Web-based care, compared with usual-care patients, while several other parameters were statistically similar between the two groups, including systolic and diastolic blood pressure, total cholesterol, and use of in-person health care services. (J. D. Ralston, ralston.j@ghc.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 © 2009, 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, 2009 * Vol. 16, No. 20
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Early-release articles from Lancet (2009; 372).
New-Generation Antidepressants: In a meta-analysis of 117 studies of 12 new-generation antidepressants, escitalopram and sertraline had the best overall efficacy and acceptability results, and authors concluded that ìsertraline might be the best choice when starting treatment for moderate to severe major depression in adults because it has the most favourable balance between benefits, acceptability, and acquisition costî (doi: 10.1016/S0140-6736(09)60046-5). Using intention-to-treat results for 25,928 participants in randomized controlled trials, the investigators determined: ìMirtazapine, escitalopram, venlafaxine, and sertraline were significantly more efficacious than duloxetine (odds ratios [OR] 1.39, 1.33, 1.30 and 1.27, respectively), fluoxetine (1.37, 1.32, 1.28, and 1.25, respectively), fluvoxamine (1.41, 1.35, 1.30, and 1.27, respectively), paroxetine (1.35, 1.30, 1.27, and 1.22, respectively), and reboxetine (2.03, 1.95, 1.89, and 1.85, respectively). Reboxetine was significantly less efficacious than all the other antidepressants tested. Escitalopram and sertraline showed the best profile of acceptability, leading to significantly fewer discontinuations than did duloxetine, fluvoxamine, paroxetine, reboxetine, and venlafaxine.î (A. Cipriani, andrea.cipriani@univr.it)
Writing that ìantidepressants are not all created equal,î an editorialist adds this perspective on this meta-analysis (
doi: 10.1016/S0140-6736(09)60047-7): ìFor the clinician, prudent engagement of the patient in treatment ideally involves giving the patient a choice. Now, the clinician can identify the four best treatments, identify individual side-effect profiles, explore costs and patients’ preferences, and collaborate in identifying the best treatment for that patient. Furthermore, clinicians can honestly state that this selection of drug, and the reports of the side-effect profiles, are from the combined results of many clinical trials, and have been judged to be relatively clear of potential bias from the drug industry. The size of the patients’ sample used to derive these results is more convincing than referring to what every country’s regulator approves for publication in a national standard compendium of pharmaceutical agents. A new gold standard of reliable information has been compiled for patients to review, particularly because these researchers have also made their data and analyses available on a public website.î (S. V. Parikh, sagar.parikh@uhn.on.ca)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2009; 337).
Depression Outcomes in Later Life: Among 234 patients aged 55 years or older at 32 general practices in the Netherlands, depression had a poor prognosis, especially when the index episode was severe, patients had a family history of the condition, or functional decline accompanied the disease (a3079). In a longitudinal cohort study with follow-up over 3 years, these trends were noted: ìThe median duration of a major depressive episode was 18.0 months (95% confidence interval 12.8 to 23.1). 35% of depressed patients recovered within one year, 60% within two years, and 68% within three years. A poor outcome was associated with severity of depression at baseline, a family history of depression, and poorer physical functioning. During follow-up functional status remained limited in patients with chronic depression but not in those who had recovered.î (E. Licht-Strunk, e.licht@vumc.nl)

>>>PNN NewsWatch
* Ethex Corp. has expanded two 2008 recalls to include more than 60 generic products recalled to wholesalers, and two generic products, hydromorphone hydrochloride and metoprolol succinate, recalled to retailer level, because of failure to comply with current Good Manufacturing Practices.

>>>PNN JournalWatch
* Topics in Type 2 Diabetes and Insulin Resistance, in Diabetes Care, 2009; 32: e13–9. (Z. T. Bloomgarden)
* Rivaroxaban: A Novel, Oral, Direct Factor Xa Inhibitor, in
Pharmacotherapy, 2009; 29: 167–81. (P. J. Abrams)
* Diabetic Retinopathy: Current Management and Experimental Therapeutic Targets, in
Pharmacotherapy, 2009; 29: 182–92. (A. B. El-Remessy, aelremessy@mcg.edu)
* New Opportunity to Improve Pediatric Emergency Preparedness: Pediatric Emergency Assessment, Recognition, and Stabilization Course, in
Pediatrics, 2009; 123: 578–80. (M. E. Ralston)

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 © 2009, 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, 2009 * Vol. 16, No. 21
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Feb. issue of Pharmacotherapy (2009; 29).
Vitamin D & Mortality During Hemodialysis: The largely unexplained benefits of vitamin D on mortality appear to extend to patients undergoing hemodialysis, researchers report, but more study is needed to ìshow definitively whether intravenous vitamin D can reduce all-cause and cause-specific mortality in patients undergoing dialysis compared with placeboî (pp. 154–64). Based on time-varying Cox proportional hazards models to assess the effects of monthly vitamin D dose and dosing regularity over 3-month intervals and amount of time patients had been on hemodialysis (< 1 yr, 1 to < 3 yrs, 3 to < 5 yrs, and 5 yrs from dialysis initiation), these outcomes were evident during up to 5.25 years of follow-up: ìAdjusted all-cause mortality risk was reduced 7–17% among patients receiving vitamin D each month of the 3-month interval, with the highest reduction among patients with shorter dialysis duration. However, regular vitamin D dosing did not show consistent benefit across dialysis duration groups for cardiovascular, infectious, cancer, or other (all deaths not attributable to cardiovascular disease, infection, or cancer) mortality.î (W. L. St. Peter, WStPeter@cdrg.org)
Montelukast & Suicide: Little support for increased rates of suicide among patients taking montelukast was found in an analysis of the United Kingdom General Practice Research Database (pp. 165–6). Among 23,500 patients who had at least one prescription for the drug during 1998–2007, the investigators found: ìThe 23,500 patients had received 252,593 prescriptions for montelukast, representing 21,050 person–years at risk for suicide. We then sought to identify all cases that had a computer-recorded diagnosis of suicide; however, no cases of suicide were found in patients exposed to montelukast during our time frame.î (H. Jick, hjick@bu.edu)
Research Using Secondary Data Sources: While the basic principles of research still apply, several considerations are relevant when secondary data sources are used for pharmacoepidemiology and outcomes research, an author writes (pp. 138–53): ìSpecial care must be taken to select an appropriate source to ensure that relevant information is available to answer the research question at hand. Special attention must also be paid to selecting the appropriate codes to represent the outcomes and exposures of interest; therefore, a general understanding of coding schemes is necessary. Although time may be saved by not prospectively collecting data, the process of manipulating the data for analysis in secondary databases can be complex. Analysis of data from secondary sources may require special procedures to overcome the lack of randomization. By familiarizing themselves with these special issues, practitioners can use secondary sources to conduct studies that make valuable contributions to the improvement of patient care.î (S. E. Harpe)
Education of Pharmacists as Clinical Scientists: Instead of a PharmD degree with residency and fellowship, pharmacists wishing to pursue careers as clinical scientists should have an advanced degree, preferably a PhD, with residency training or equivalent clinical experience, according to a document prepared by an ACCP committee (pp. 236–44): ìMany schools and colleges of pharmacy and medicine are well equipped to conduct clinical and translational research, with access to academic health centers and [Clinical and Translational Science Award] core resources such as Clinical Research Centers (formerly known as General Clinical Research Centers), genomics laboratories, and biostatistical support. These schools and colleges are ideally suited to develop research and graduate degree programs focusing on clinical and translational sciences. Such training programs aim to integrate science and the direct application of science to address important problems related to pharmacotherapy. This is best accomplished in a collaborative research environment, with the necessary research facilities to foster the development of highly competent, independent clinical scientists.î (American College of Clinical Pharmacy, accp@accp.com)
In two accompanying editorials, one set of authors agrees with the committee (
pp. 134–7; R. A. Blouin, bob_blouin@unc.edu), while another pair call for preservation of the fellowship route for PharmD graduates (pp. 129–33; J. L. Bauman, jbauman@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 © 2009, 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, 2009 * Vol. 16, No. 22
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Feb. 4 issue of JAMA (2009; 301).
Sedation of Critically Ill Patients: Compared with patients in intensive-care units treated with midazolam, dexmedetomidine provided equivalent sedation and less time on the ventilator, less delirium, and less tachycardia and hypertension, report investigators of a 375-patient trial (pp. 489–99). Included were medical/surgical patients expected to be intubated for more than 24 hours. They were evaluated with the Richmond Agitation–Sedation Scale (RASS) and the Confusion Assessment Method for the ICU, which showed the following: ìThere was no difference in percentage of time within the target RASS range (77.3% for dexmedetomidine group vs 75.1% for midazolam group; difference, 2.2% [95% confidence interval {CI}, –3.2% to 7.5%]; P = .18). The prevalence of delirium during treatment was 54% (n = 132/244) in dexmedetomidine-treated patients vs 76.6% (n = 93/122) in midazolam-treated patients (difference, 22.6% [95% CI, 14% to 33%]; P < .001). Median time to extubation was 1.9 days shorter in dexmedetomidine-treated patients (3.7 days [95% CI, 3.1 to 4.0] vs 5.6 days [95% CI, 4.6 to 5.9]; P = .01), and ICU length of stay was similar (5.9 days [95% CI, 5.7 to 7.0] vs 7.6 days [95% CI, 6.7 to 8.6]; P = .24). Dexmedetomidine-treated patients were more likely to develop bradycardia (42.2% [103/244] vs 18.9% [23/122]; P < .001), with a nonsignificant increase in the proportion requiring treatment (4.9% [12/244] vs 0.8% [1/122]; P = .07), but had a lower likelihood of tachycardia (25.4% [62/244] vs 44.3% [54/122]; P < .001) or hypertension requiring treatment (18.9% [46/244] vs 29.5% [36/122]; P = .02).î (R. R. Riker, rikerr@mmc.org)
Editorialists note the limitations of this alpha-2 agonist but proclaim ìa new era for sedation in ICU patientsî as dexmedetomidine comes into clinical use (
pp. 542–4): ìThe study by Riker et al failed to demonstrate that dexmedetomidine was superior to benzodiazepines for ensuring light sedation. However, the reduced prevalence of delirium is an important secondary outcome that both highlights the problems of traditional benzodiazepines and provides encouraging data regarding the potential benefits of dexmedetomidine. With the demonstration of the safety of dexmedetomidine at higher doses and for longer periods, clinicians now have a widened choice of sedatives and should always consider not only the need for sedation but also the possible clinical implications of the choice of sedative.î (J. P. Kress, jkress@medicine.bsd.uchicago.edu)
Smoking Cessation in Patients with Bipolar Disorder: Using the case of a 51-year-old woman with bipolar disorder who wants to stop smoking, the author of a Clinician’s Corner article discusses the importance of smoking cessation among patients with mental illness and discusses use of the Rx for Change program developed by UCSF pharmacy faculty (pp. 522–31): ìPersons with chronic mental illness and/or substance abuse constitute 22% of the US population yet are estimated to consume 44% of cigarettes. As many as 200,000 of the 435,000 annual deaths related to smoking in the United States are estimated to occur in this population. On average, patients with mental illness die 25 years earlier than the general population, and smoking is a major contributor to these premature deaths. In the past, mental health clinicians have tended not to address smoking cessation with their patients, but increasing evidence suggests that such reticence is unwarranted, as smoking cessation in this population is feasible. The approach to cessation should include standard interventions of counseling and pharmacotherapy, for which substantial evidence of efficacy exists in patients with and without mental illness. If patients with mental illness are to achieve wellness, smoking cessation must be an integral component of their treatment regimen.Ö
ìOur center is attempting to make mental health clinicians more knowledgeable about smoking cessation strategies by providing them with a tailored version of the cessation curriculum Rx for Change, prepared by pharmacy faculty at the University of California, San Francisco .Ö This curriculum demonstrated significant changes in practice behavior of psychiatric residents with respect to undertaking cessation efforts, validated through chart review. We will help disseminate that curriculum so counselors will feel more comfortable with cessation efforts.î (S. A. Schroeder,
schroeder@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 © 2009, 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, 2009 * Vol. 16, No. 23
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 5 issue of and early-release article from the New England Journal of Medicine (2009; 360).
Cetuximab in Metastatic Colorectal Cancer: Outcomes worsened with addition of cetuximab to standard first-line treatment of metastatic colorectal cancer, researchers report, pointing to a decrease in progression-free survival and inferior quality of life (pp. 563–72). In a 755-patient study, participants were randomized to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients), with these results: ìThe median progression-free survival was 10.7 months in the CB group and 9.4 in the CBC group (P = 0.01). Quality-of-life scores were lower in the CBC group. The overall survival and response rates did not differ significantly in the two groups. Treated patients in the CBC group had more grade 3 or 4 adverse events, which were attributed to cetuximab-related adverse cutaneous effects. Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had significantly decreased progression-free survival as compared with cetuximab-treated patients with wild-type–KRAS tumors or patients with mutated-KRAS tumors in the CB group.î (C. J. A. Punt, c.punt@onco.umcn.nl)
Emphasizing that ìmore is not always better,î an editorialist comments on this study (
pp. 623–5): ìAntitumor activity observed in preclinical and also uncontrolled clinical contexts may not be validated when examined in randomized trials. Furthermore, the data suggest that combining multiple forms of targeted therapies may not be analogous to combining different types of cytotoxic chemotherapy, presumably because of subtle interactions in intracellular signaling. Finally, these results underscore the fundamental importance of subjecting hypotheses to carefully conducted clinical trials. As was observed in this situation, more is not always better.î (R. J. Mayer)
Breast Cancer & Hormonal Therapy in Postmenopausal Women: Risks of breast cancer return to baseline quickly after discontinuation of estrogen/progestin therapy in postmenopausal women, concludes an analysis of data from the Women’s Health Initiative trial (pp. 573–87). Release of this study’s results in 2002 caused a precipitous drop in use of menopausal hormone therapy; in the trial, participants received either conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg daily or placebo. Analysis of temporal trends in breast cancer incidence showed the following: ìIn the clinical trial, there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study, but the number of diagnoses increased over the course of the 5.6-year intervention period. The elevated risk decreased rapidly after both groups stopped taking the study pills, despite a similar frequency of mammography. In the observational study, the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group, but this difference in incidence decreased rapidly in about 2 years, coinciding with year-to-year reductions in combined hormone use. During this period, differences in the frequency of mammography between the two groups were unchanged.î (R. T. Chlebowski, rchlebowski@gmail.com)
SCHIP Reauthorization: Legislation reauthorizing the State Children’s Health Insurance Program (SCHIP), signed into law yesterday by Pres. Obama, is analyzed (early release; J. K. Inglehart).

>>>PNN NewsWatch
* In an early communication, FDA announced that it is working with Lilly to further evaluate the incidence of serious bleeding events and mortality in patients receiving drotrecogin alfa (activated; Xigris). A study recently published in Critical Care Medicine details a retrospective analysis of 73 patients who had an increased risk of serious bleeding events and of death in patients with sepsis and baseline bleeding risk factors who received this product. While FDA reviews available data, the agency is urging health professionals and patients to report adverse effects from the use of Xigris to the FDA’s MedWatch Adverse Event Reporting program.
*
Ethex Corporation and Ther-Rx Corporation have expanded previous recall notices (see PNN, Feb. 2) to include prescription prenatal vitamins and iron supplements.

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 © 2009, 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. 6, 2009 * Vol. 16, No. 24
Providing news and information about medications and their proper use

>>>Pediatrics Highlights
Source:
Feb. issue of Pediatrics (2009; 123).
Minitablets for Preschool Children: In a study of 100 children aged 2–6 years, participants were able to swallow placebo minitablets, suggesting a new potential dosage form for use in this age group (e235–8). The tablets, 3 mm in diameter, were provided to parents, who were asked to administer one minitablet to the child. The importance of swallowing and not chewing the tablet was explained to the child. Results showed: ìOf the youngest children (2 years of age), almost one half (46%) swallowed the minitablet. The proportion increased to 53% for children 3 years of age. Children 4 years of age were more likely to swallow the minitablet than not to swallow the minitablet, with 85% of 5-year-old children swallowing the minitablet. The ability to swallow the minitablet was not affected by gender.î (S. A. Thomson)
Psychosis & Mania During ADHD Treatment: Psychosis or mania during treatment for attention-deficit/hyperactivity disorder may be adverse drug reactions, concludes an FDA analysis of data from 49 randomized controlled trials and case reports (pp. 611–6). ìA total of 11 psychosis/mania adverse events occurred during 743 person–years of double-blind treatment with these drugs, and no comparable adverse events occurred in a total of 420 person–years of placebo exposure in the same trials,î the authors report. ìThe rate per 100 person–years in the pooled active drug group was 1.48. The analysis of spontaneous postmarketing reports yielded >800 reports of adverse events related to psychosis or mania. In 90% of the cases, there was no reported history of a similar psychiatric condition. Hallucinations involving visual and/or tactile sensations of insects, snakes, or worms were common in cases in children.î (A. D. Mosholder)

>>>Psychiatry Highlights
Source:
Feb. issue of the American Journal of Psychiatry (2009; 166).
Antidepressants & Treatment-Emergent Mania in Bipolar Depression: Presence of motor activation, pressured speech, and racing thoughts appear to be predictors of treatment-emergent mania when antidepressants are used in patients with bipolar depression, according to a 10-week trial of 176 adult outpatients (pp. 164–72). Comparing symptoms in patients who responded to antidepressant treatment (n = 85), did not respond to antidepressant treatment (n = 45), and had treatment-emergent mania or hypomania (n = 46) using the Inventory of Depressive Symptomatology and the Young Mania Rating Scale (YMRS), the researchers found: ìBaseline YMRS scores were significantly different between groups. Otherwise, there were no significant between-group differences in demographic or clinical characteristics. Factor analysis showed that a subset of the YMRS items predicted treatment-emergent mania in this sample: increased motor activity, speech, and language-thought disorder.î (M. A. Frye)
Publication Bias & Antidepressant Efficacy: Authors of a Commentary article explore the issue of publication bias and the efficacy of antidepressants (pp. 140–5). After discussing recently published studies that ìsignificantly challenge widely accepted views regarding the efficacy of antidepressant medications for unipolar major depressive disorder,î the authors make these recommendations (S. J. Mathew, sanjay.mathew@mssm.edu):
* Industry-sponsored clinical trial protocols submitted for FDA review should include a projected timetable for manuscript(s) submission and list of contributing authors in a section detailing publication strategy.
* FDA should scrutinize the total number of trials conducted for an investigational new drug in making an initial determination of approval for new drug applications and consider annotating approval using three grades—high enthusiasm (when at least 75% of clinical trials were positive), moderate enthusiasm (50% of trials positive), and limited enthusiasm (drug met a minimal requirement of two positive studies).
* Improved approaches for studying depression are needed that will lead to development of better antidepressants, including use of neurophysiological, neuroimaging, genetic, and neuropsychological markers to guide patient selection and treatment.

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 © 2009, 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, 2009 * Vol. 16, No. 25
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Feb. 7 issue of Lancet (2009; 372).
Liraglutide for Type 2 Diabetes : In a comparison with glimepiride conducted in 746 patients with type 2 diabetes, liraglutide produced greater reductions in A1C levels, weight, hypoglycemia, and blood pressure, researchers report (pp. 473–81). The analogue of glucagon-like peptide 1 was administered in doses of 1.2 or 1.8 mg for 52 weeks, while glimepiride was dosed at 8 mg daily. Results showed: ìAt 52 weeks, [A1C] decreased by 0.51% (SD 1.20%) with glimepiride, compared with 0.84% (1.23%) with liraglutide 1.2 mg (difference −0.33%; 95% CI −0.53 to −0.13, p = 0.0014) and 1.14% (1.24%) with liraglutide 1.8 mg (−0.62; −0.83 to −0.42, p < 0.0001). Five patients in the liraglutide 1.2 mg, and one in 1.8 mg groups discontinued treatment because of vomiting, whereas none in the glimepiride group did so.î (A. Garber, agarber@bcm.tmc.edu)
In a related editorial, a writer sounds this cautionary note (
pp. 438–9): ìTwo cases of pancreatitis were reported during treatment with liraglutide, and recently more than 30 cases in patients taking exenatide were reviewed by US Food and Drug Administration. Therefore treatment with GLP-1 analogues should not be started in patients with a history of pancreatitis or risk factors for pancreatitis (eg, gall stones, alcoholism). Whether the reported cases of pancreatitis represent a truly increased risk during treatment with GLP-1 analogues needs to be established. The incretin-based therapies offer new options in the treatment of type 2 diabetes. However, their final role in the therapy of type 2 diabetes remains to be clarified, after carefully conducted long-term trials with cardiovascular endpoints and safety data.î (S. Madsbad, sten.madsbad@hvh.regionh.dk)
Tasimelteon for Sleep–Time Shift: Sleep initiation and maintenance were improved with tasimelteon, as were endogenous circadian rhythms, after a 5-hour time advance, according to comparisons with placebo and melatonin (pp. 482–91). A Phase II trial compared the melatonin-1/2 agonist with placebo in 39 patients, while a Phase III trial compared tasimelteon against melatonin in 411 individuals. Transient insomnia was produced through time shifts in sleep clinics, with these results: ìIn the phase II study, tasimelteon reduced sleep latency and increased sleep efficiency compared with placebo. The shift in plasma melatonin rhythm to an earlier hour was dose dependent. In the phase III study, tasimelteon improved sleep latency, sleep efficiency, and wake after sleep onset (ie, sleep maintenance). The frequency of adverse events was similar between tasimelteon and placebo.î (E. B. Klerman, ebklerman@hms.harvard.edu)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2009; 337).
Fertility Drugs and Ovarian Cancer: Data from Denmark show no association between use of fertility drugs and risk of ovarian cancer (b249). Among 54,362 women with infertility problems who were referred to Danish clinics between 1963 and 1998, these patterns were noted: ìAnalyses within cohort showed no overall increased risk of ovarian cancer after any use of gonadotrophins (rate ratio 0.83, 95% confidence interval 0.50 to 1.37), clomifene (1.14, 0.79 to 1.64), human chorionic gonadotrophin (0.89, 0.62 to 1.29), or gonadotrophin releasing hormone (0.80, 0.42 to 1.51). Furthermore, no associations were found between all four groups of fertility drugs and number of cycles of use, length of follow-up, or parity.î (A. Jensen, allan@cancer.dk)

>>>PNN NewsWatch
* FDA on Friday announced licensing of the first biological product from genetically engineered animals. Recombinant human antithrombin (ATryn, GTC Biotherapeutics) is an orphan drug indicated for prevention of blood clots in patients with hereditary antithrombin deficiency. It is obtained from the milk of goats whose DNA has been altered to include the human antithrombin gene.

>>>PNN JournalWatch
* The Sudden Demise of Dual Renin-Angiotensin System Blockade or the Soft Science of the Surrogate End Point, in Journal of the American College of Cardiology, 2009; 53: 468–70. (F. H. Messerli, messerli.f@gmail.com)
* Antimotility Agents for the Treatment of
Clostridium difficile Diarrhea and Colitis, in Clinical Infectious Diseases, 2009; 48: 598–605. (H. L. Koo, koo@bcm.tmc.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 © 2009, 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, 2009 * Vol. 16, No. 26
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Feb. 9 issue of the Archives of Internal Medicine (2009; 169).
Multivitamin Use & Health Risks: In a study being criticized by the Natural Products Assoc., researchers found ìconvincing evidence that multivitamin use has little or no influence on the risk of common cancers, [cardiovascular disease], or total mortality in postmenopausal womenî (pp. 294–304). The analysis included 161,808 participants in the Women’s Health Initiative and tracked their multivitamin use over a median of 8.0 years in clinical trials and 7.9 years in a follow-up observational study. The investigators found: ìA total of 41.5% of the participants used multivitamins. After a median of 8.0 years of follow-up in the clinical trial cohort and 7.9 years in the observational study cohort, 9,619 cases of breast, colorectal, endometrial, renal, bladder, stomach, lung, or ovarian cancer; 8,751 CVD events; and 9,865 deaths were reported. Multivariate-adjusted analyses revealed no association of multivitamin use with risk of cancer (hazard ratio [HR], 0.98, and 95% confidence interval [CI], 0.91–1.05 for breast cancer; HR, 0.99, and 95% CI, 0.88–1.11 for colorectal cancer; HR, 1.05, and 95% CI, 0.90–1.21 for endometrial cancer; HR, 1.0, and 95% CI, 0.88–1.13 for lung cancer; and HR, 1.07, and 95% CI, 0.88–1.29 for ovarian cancer); CVD (HR, 0.96, and 95% CI, 0.89–1.03 for myocardial infarction; HR, 0.99, and 95% CI, 0.91–1.07 for stroke; and HR, 1.05, and 95% CI, 0.85–1.29 for venous thromboembolism); or mortality (HR, 1.02, and 95% CI, 0.97–1.07).î (M. L. Neuhouser, mneuhous@fhcrc.org)
Overrides of Medication Alerts: In ambulatory care practice, clinicians override most medication alerts presented by electronic prescribing systems, a study shows, leading investigators to conclude, ìUnless designers take steps to improve prescription alert systems, the potential benefits of electronic prescribing may not be realizedî (pp. 305–11). The study involved retrospective analysis of 233,537 medication safety alerts generated by 2,872 clinicians. Multivariate analysis showed the following: ìA total of 6.6% of electronic prescription attempts generated alerts. Clinicians accepted 9.2% of drug interaction alerts and 23.0% of allergy alerts. High-severity interactions accounted for most alerts (61.6%); clinicians accepted high-severity alerts slightly more often than moderate- or low-severity interaction alerts (10.4%, 7.3%, and 7.1%, respectively; P < .001). Clinicians accepted 2.2% to 43.1% of high-severity interaction alerts, depending on the classes of interacting medications. In multivariable analyses, we found no difference in alert acceptance among clinicians of different specialties (P = .16). Clinicians were less likely to accept a drug interaction alert if the patient had previously received the alerted medication (odds ratio, 0.03; 95% confidence interval, 0.03–0.03).î (T. Isaac, tisaac@bidmc.harvard.edu)
Statin Treatment and All-Cause Mortality: In a retrospective cohort study of 229,918 adult enrollees in an Israeli health maintenance organization, those with better continuity of statin treatment had lower mortality rates regardless of whether they had coronary heart disease (pp. 260–8). Proportion of days covered (PDC) was used to assess availability of medication to patients in the study, with these results: ìDuring a mean of 4.0 and 5.0 years of follow-up, there were 4,259 and 8,906 deaths among the primary prevention and secondary prevention cohorts, respectively. In both cohorts, continuity of treatment with statins (PDC, 90%) conferred at least a 45% reduction in risk of death compared with patients with a PDC of less than 10%. A stronger risk reduction was calculated among patients with high baseline low-density lipoprotein cholesterol level and patients initially treated with high-efficacy statins.î (G. Chodick, hodik_g@mac.org.il)
Smoking Cessation: Two research articles detail strategies for smoking cessation (pp. 230–5; H. J. Salize, hans-joachim.salize@zi-mannheim.de) and the possibility of instituting smoking-cessation and weight-loss efforts after new health diagnoses in older adults (pp. 237–42; P. S. Keenan, patricia.keenan@yale.edu), and an editorialist writes (pp. 217–8): ìThe effect of physician advice might only be as good as the availability of supportive services to which patients can be referred for specialized preventive care. Our health care system is incomplete to the extent that patients and healthy subjects do not have affordable access to evidence-based preventive services.î (S. Pagoto, sherry.pagoto@umassmed.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 © 2009, 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, 2009 * Vol. 16, No. 27
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Feb. 11 issue of JAMA (2009; 301).
Improving Care Through Coordination: Without a strong transitional care component, programs aimed at improving coordination of care are unlikely to achieve savings, concludes an analysis of Medicare claims data for 18,309 patients (pp. 603–18). Cost-neutral improvements in care resulted from programs with substantial in-person contact with patients with moderate to severe conditions, the authors add. Care coordinators in 8 of 15 programs, all of which were receiving a negotiated monthly fee per patient from the Medicare program, consulted with pharmacists about medication problems. Results showed the following: ìThirteen of the 15 programs showed no significant (P < .05) differences in hospitalizations; however, Mercy had 0.168 fewer hospitalizations per person per year (90% confidence interval [CI], –0.283 to –0.054; 17% less than the control group mean, P = .02) and Charlestown had 0.118 more hospitalizations per person per year (90% CI, 0.025–0.210; 19% more than the control group mean, P = .04). None of the 15 programs generated net savings. Treatment group members in 3 programs (Health Quality Partners [HQP], Georgetown, Mercy) had monthly Medicare expenditures less than the control group by 9% to 14% (–$84; 90% CI, –$171 to $4; P = .12; –$358; 90% CI, –$934 to $218; P = .31; and –$112; 90% CI, –$231 to $8; P = .12; respectively). Savings offset fees for HQP and Georgetown but not for Mercy; Georgetown was too small to be sustainable. These programs had favorable effects on none of the adherence measures and only a few of many quality of care indicators examined.î (R. Brown, rbrown@mathematica-mpr.com)
Such data paint a challenging picture as the nation enters a debate over the structure of its health care system, an editorialist explains (
pp. 668–70): ìThe Congressional Budget Office recently estimated that offering the new medical home model for all chronically ill Medicare beneficiaries would increase Medicare expenditures by $5.6 billion from 2010 through 2019. Such an investment would be worthwhile if it improves the quality of care and health outcomes. Balancing the Medicare budget, however, will require much more difficult political decisions among less appealing choices—raising payroll taxes to support Medicare, increasing beneficiary cost-sharing, reducing benefits, or cutting payments to physicians, hospitals, and health plans, particularly for services that are not clearly beneficial. The fiscal health of Medicare and the federal government will hinge on the new president and Congress making these difficult decisions wisely.î (J. Z. Ayanian, ayanian@hcp.med.harvard.edu)
Politicization of Professional Practice Guidelines: Use of antitrust laws to stymy development and dissemination of practice guidelines by professional associations creates the need for ìa wall of separation Ö between science, norms, and politics,î write authors of a Commentary (pp. 665–7). Citing an investigation launched by the Connecticut attorney-general following release of Lyme disease guidelines by the Infectious Diseases Society of America, the authors maintain: ìThe [chronic Lyme disease] advocacy community understandably seeks answers for the symptoms attributed to Lyme disease. But when high-quality research repeatedly was inconsistent with the group’s hypotheses, the community should have sought other answers. Instead, many advocacy organizations—and the attorney general—insisted (against the weight of evidence) on a link between the symptoms and chronic infection and continued to call for long-term antibiotic treatments. Even this was perhaps defensible—after all, medical studies cannot prove the nonexistence of a phenomenon—although physicians in the CLD community should treat their patients based on the best-available evidence. But when political leaders using the force of law sued IDSA for its appropriate scientific conclusions that differed with the results they desired, they abused the public good.î (L. O. Gostin, gostin@law.georgetown.edu)

>>>PNN NewsWatch
* Rising rates of misuse and abuse of opioids and of accidental overdose of these agents over the past decade led FDA to this week notify manufacturers of a newly required Risk Evaluation and Mitigation Strategy (REMS) to ensure that the agents’ benefits continue to outweigh their risks.

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 © 2009, 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, 2009 * Vol. 16, No. 28
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 12 issue of the New England Journal of Medicine (2009; 360).
Dronedarone for Atrial Fibrillation: In a placebo-controlled trial of 4,628 patients with atrial fibrillation, the benzofuran derivative dronedarone reduced the incidence of hospitalization due to cardiovascular events or death (pp. 668–78). ATHENA (A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg bid for the Prevention of Cardiovascular Hospitalization or Death from Any Cause in Patients with Atrial Fibrillation/Atrial Flutter) tested the new drug, which is similar to amiodarone but with a shorter half-life (about 24 hours) and with different relative effects on ion channels. Doses of 400 mg twice daily produced these effects on a primary outcome of first hospitalization due to cardiovascular events or death: ìThe mean follow-up period was 21 ± 5 months, with the study drug discontinued prematurely in 696 of the 2,301 patients (30.2%) receiving dronedarone and in 716 of the 2,327 patients (30.8%) receiving placebo, mostly because of adverse events. The primary outcome occurred in 734 patients (31.9%) in the dronedarone group and in 917 patients (39.4%) in the placebo group, with a hazard ratio for dronedarone of 0.76 (95% confidence interval [CI], 0.69 to 0.84; P < 0.001). There were 116 deaths (5.0%) in the dronedarone group and 139 (6.0%) in the placebo group (hazard ratio, 0.84; 95% CI, 0.66 to 1.08; P = 0.18). There were 63 deaths from cardiovascular causes (2.7%) in the dronedarone group and 90 (3.9%) in the placebo group (hazard ratio, 0.71; 95% CI, 0.51 to 0.98; P = 0.03), largely due to a reduction in the rate of death from arrhythmia with dronedarone. The dronedarone group had higher rates of bradycardia, QT-interval prolongation, nausea, diarrhea, rash, and an increased serum creatinine level than the placebo group. Rates of thyroid- and pulmonary-related adverse events were not significantly different between the two groups.î (S. H. Hohnloser, hohnloser@em.uni-frankfurt.de)
Zoledronic Acid in Premenopausal Breast Cancer: In premenopausal women with estrogen-responsive early breast cancer, addition of the bisphosphonate zoledronic acid to adjuvant endocrine therapy improves disease-free survival, researchers report (pp. 679–91). In the Austrian Breast and Colorectal Cancer Study Group trial 12 (ABCSG-12), 1,803 patients received goserelin 3.6 mg subcutaneously every 28 days plus tamoxifen 20 mg/day orally or anastrozole 1 mg/day orally with or without zoledronic acid 4 mg intravenously every 6 months for 3 years, with these results: ìAfter a median follow-up of 47.8 months, 137 events had occurred, with disease-free survival rates of 92.8% in the tamoxifen group, 92.0% in the anastrozole group, 90.8% in the group that received endocrine therapy alone, and 94.0% in the group that received endocrine therapy with zoledronic acid. There was no significant difference in disease-free survival between the anastrozole and tamoxifen groups (hazard ratio for disease progression in the anastrozole group, 1.10; 95% confidence interval [CI], 0.78 to 1.53; P = 0.59). The addition of zoledronic acid to endocrine therapy, as compared with endocrine therapy without zoledronic acid, resulted in an absolute reduction of 3.2 percentage points and a relative reduction of 36% in the risk of disease progression (hazard ratio, 0.64; 95% CI, 0.46 to 0.91; P = 0.01); the addition of zoledronic acid did not significantly reduce the risk of death (hazard ratio, 0.60; 95% CI, 0.32 to 1.11; P = 0.11). Adverse events were consistent with known drug-safety profiles.î (M. Gnant, michael.gnant@meduniwien.ac.at)
Payment for Smoking Cessation: Financial incentives paid to employees of a multinational company significantly increased smoking-cessation rates, compared with information only (pp. 699–709). For completing a cessation program, employees received $100; cessation of smoking within 6 months garnered $250; and for not smoking an additional 6 months past that, the company paid $400. (K. G. Volpp, volpp70@wharton.upenn.edu)

>>>PNN NewsWatch
* Yesterday’s JAMA marks the 200th anniversary of the birth of Charles Darwin with a report on his impact on medicine (pp. 663–5; J. P. Evans, jpevans@med.unc.edu). Abraham Lincoln was also born on Feb. 12, 1809, and the BBC offers an interesting quiz about the pair.

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 © 2009, 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. 13, 2009 * Vol. 16, No. 29
Providing news and information about medications and their proper use

>>>Cardiology Highlights
Source:
Feb. 17 issue of the Journal of the American College of Cardiology (2009; 53).
Drug Therapy in VFib: After testing effectiveness of antiarrhythmic drugs (AADs) in 133 patients with idiopathic ventricular fibrillation and early repolarization abnormality in the inferolateral leads, researchers recommend isoproterenol in acute cases and quinidine for chronic cases (pp. 612–9). Patients included in the analysis had more than three episodes of VF, including some with electrical storms, defined as three or more episodes within 24 hours. Individual physicians chose AADs, with these results: ìMultiple episodes of VF were observed in 33 (27%) patients. Electrical storms (34 ± 47 episodes) occurred in 16 and were unresponsive to beta-blockers (11 of 11), lidocaine/mexiletine (9 of 9), and verapamil (3 of 3), while amiodarone was partially effective (3 of 10). In contrast, isoproterenol infusion immediately suppressed electrical storms in 7 of 7 patients. Over a follow-up of 69 ± 58 months, oral AADs were poorly effective in preventing recurrent VF: beta-blockers (2 of 16), verapamil (0 of 4), mexiletine (0 of 4), amiodarone (1 of 7), and class 1C AADs (2 of 9). Quinidine was successful in 9 of 9 patients, decreasing recurrent VF from 33 ± 35 episodes to nil for 25 ± 18 months. In addition, quinidine restored a normal electrocardiogram.î (M. HaÔssaguerre, mailto:michel.haissaguerre@chu-bordeaux.fr)
Obama & Medicine: Reflecting on the election and inauguration of Barack Obama, the JACC editor implores physicians to adopt the ìselflessnessî being recommended by the new U.S. President (pp. 634–5): ìIn considering our response as physicians to the economic crisis, it seems to me that we should follow the spirit advocated by President Obama. These are hard times, and the pain is pervasive throughout society. It would be a terrific contribution if physicians were selfless and led the way by doing something to benefit others. There are certainly many ways to do this. I have thought of conducting an extra clinic just to see cardiac patients who have recently lost their jobs and health insurance at no cost. Just the act of gracefully accepting a small decrease or foregoing an increase in reimbursement for the common good, at least until the economy has recovered, would be a valuable action. At the very least, it would reflect very well on the medical profession and probably make us feel better about ourselves.î (A. N. DeMaria, ademaria@acc.org)

>>>PNN NewsWatch
* ìPharmacy Principles of Health Care Reformî were unveiled officially yesterday in a session at the National Press Club in Washington, DC. Twelve pharmacy organizations outlined three goals related to medication access and use that they maintain should be an integral part of any health reform debate: Improve quality and safety of medication use; assure patient access to needed medications and pharmacy services; and promote pharmacy and health information technology interoperability. Collaborating on the principles were the Academy of Managed Care Pharmacy, American Association of Colleges of Pharmacy, American College of Clinical Pharmacy, American Pharmacists Association, American Society of Consultant Pharmacists, American Society of Health-System Pharmacists, Food Marketing Institute, National Association of Chain Drug Stores, National Alliance of State Pharmacy Associations, National Community Pharmacists Association, Rite Aid Corporation, and Walgreen Co.
* Physicians nationwide are concerned patients are being forced to make
cutbacks on medications that could be harmful to their health, according to a survey conducted by Epocrates. Additionally, respondents reported an increase in requests for generic medications since the economy has weakened. Nearly 95% of physicians surveyed said they have some degree of concern that patients may not be complying with the prescription they wrote because of the economic climate. Physicians are primarily concerned that patients are not getting prescriptions filled or skipping doses. Respondents also fear patients are trying to extend their medication supply by splitting pills, or discontinuing treatments that help with disease prevention or maintenance without consulting their physician.
*
PNN will not be published on Mon., Feb. 16, 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 © 2009, 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, 2009 * Vol. 16, No. 30
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Feb. 14 issue of Lancet (2009; 372).
Intensive Insulin Therapy in Pediatrics: Short-term outcomes were favorable in pediatric patients who received intensive insulin therapy during stays in intensive-care units, researchers report (pp. 547–56). Among 317 infants and 383 children, intensive insulin therapy was compared with insulin infusions, with these results: ìMean blood glucose concentrations were lower in the intensive group than in the conventional group (infants: 4.8 [SD 1.2] mmol/L vs 6.4 [1.2] mmol/L, p<0.0001; children: 5.3 [1.1] mmol/L vs 8.2 [3.3] mmol/L, p < 0.0001). Hypoglycaemia (defined as blood glucose 2.2 mmol/L) occurred in 87 (25%) patients in the intensive group (p < 0.0001) versus five (1%) patients in the conventional group; hypoglycaemia defined as blood glucose less than 1.7 mmol/L arose in 17 (5%) patients versus three (1%) (p = 0.001). Duration of PICU stay was shortest in the intensively treated group (5.51 days [95% CI 4.65—6.37] vs 6.15 days [5.25—7.05], p = 0.017). The inflammatory response was attenuated at day 5, as indicated by lower C-reactive protein in the intensive group compared with baseline (−9.75 mg/L [95% CI −19.93 to 0.43] vs 8.97 mg/L [−0.9 to 18.84], p = 0.007). The number of patients with extended (>median) stay in PICU was 132 (38%) in the intensive group versus 165 (47%) in the conventional group (p = 0.013). Nine (3%) patients died in the intensively treated group versus 20 (6%) in the conventional group (p = 0.038).î (G. Van den Berghe, greet.vandenberghe@med.kuleuven.be)
Editorialists caution clinicians about the frequency of low blood glucose levels found in this study (
pp. 520–1): ìThe incidence of hypoglycaemia was high in this paediatric population (25% of the intervention group), and little is known about the long-term consequences of hypoglycaemia in children—or in adults for that matter. The authors accurately point to this paucity of evidence that the incidence of hypoglycaemia leads to adverse outcomes and, just as accurately, describe the need for long-term data to properly assess the effect of hypoglycaemia in the vulnerable paediatric population. Until these issues are resolved, we must advocate caution in extrapolation of today’s results beyond these carefully controlled clinical settings. The adult data have shown us that these protocols are not easy to disseminate and can lead to an increased incidence of adverse events.î (M. M. Levy, Mitchell_levy@brown.edu)
Prophylactic Warfarin: Compared with no warfarin in 1,590 patients with cancer and central venous catheters, warfarin thromboprophylaxis failed to reduce symptomatic catheter-related and other thromboses, leading investigators to conclude that newer treatments should be considered in this patient population (pp. 567–74). Study participants received either no warfarin, fixed warfarin doses of 1 mg/day, or dose-adjusted warfarin, with these results: ìCompared with no warfarin (n = 404), warfarin (n = 408; 324 [79%] on fixed-dose and 84 [21%] on dose-adjusted) did not reduce the rate of catheter-related thromboses (24 [6%] vs 24 [6%]; relative risk 0.99, 95% CI 0.57—1.72, p = 0.98). However, compared with fixed-dose warfarin (n = 471), dose-adjusted warfarin (n = 473) was superior in the prevention of catheter-related thromboses (13 [3%] vs 34 [7%]; 0.38, 0.20—0.71, p = 0.002). Major bleeding events were rare; an excess was noted with warfarin compared with no warfarin (7 vs 1, p = 0.07) and with dose-adjusted warfarin compared with fixed-dose warfarin (16 vs 7, p = 0.09). A combined endpoint of thromboses and major bleeding showed no difference between comparisons. We did not note a survival benefit in either comparison.î (A. M. Young, a.young@bham.ac.uk)

>>>PNN JournalWatch
* Meticillin Resistant Staphylococcus aureus in the Hospital, in BMJ, 2009; b364. (J. Kluytmans, jankluytmans@gmail.com)
* Long-term Use of Inhaled Corticosteroids and the Risk of Pneumonia in Chronic Obstructive Pulmonary Disease: A Meta-analysis, in
Archives of Internal Medicine, 2009; 169: 219–29. (S. Singh, sosingh@wfubmc.edu)
* Acute Heart Failure Syndromes, in
Journal of the American College of Cardiology, 2009; 53: 557–73. (M. Gheorghiade, m-gheorghiade@northwestern.edu)
* Mucins, Mucus, and Sputum, in
Chest, 2009; 135: 505–12. (J. A. Voynow, voyno001@mc.duke.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 © 2009, 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, 2009 * Vol. 16, No. 31
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from Annals of Internal Medicine (2009; 150).
Compendia for Off-Label Oncology Indications: A better system is needed for providing clinicians with information about off-label use of oncolytic drugs and for determining which of these uses will be covered by Medicare, according to four articles released in advance of publication. In 1993 Congress directed that unlabeled oncolytic indications be covered by Medicare if they were presented favorably in drug compendia, explains one article. The American Hospital Formulary Service Drug Information and two now out-of-print books were named as the recognized references; additional compendia were added in 2007 by the Centers for Medicare & Medicaid Services. (K. Tillman, katherine.tillman@cms.hhs.gov)
In a
second article, six approved compendia are assessed and found lacking in current information about 14 off-label uses of cancer agents. The authors write: ìThe compendia’s stated methods varied greatly from their actual practices. Compendia cited little of the available evidence, often neither the most recent nor that of highest methodological quality. Compendia differed in evidence cited, terminology, detail, presentation, and referencing. For the 14 off-label indications studied, the compendia differed in the indications included and whether and how they recommended particular agents for particular types of cancer. Update schedules varied, and documentation practices made it difficult to determine whether and when content was updated. For 1 indication, compendia citations did not increase between 2006 and 2008 despite accumulation of published evidence.î (A. P. Abernethy, amy.abernethy@duke.edu)
A
third article proposes a CMS-centered system for ìcontrolling off-label medication useî (M. R. Gillick, mgillick@partners.org), and the author of a fourth article writes: ìWe should adopt something like Gillick’s proposal to use the CMS national coverage procedures, of which the salient feature is a systematic review of the evidence by experts in doing such reviews. The CMS procedures are remarkably transparent. They include posting background material on the CMS Web site, recommendations by a panel of experts who deliberate in a public meeting, and good management of potential conflicts of interest. To implement Gillick’s proposal, CMS would probably need to add institutional expertise in oncology, as the Agency currently employs no oncologists.î (H. C. Sox, hsox@mail.acponline.org)

>>>JAMA Highlights
Source:
Feb. 18 issue of JAMA (2009; 301).
Central-Line MRSA Septicemia in ICUs: While the overall proportion of central line–associated bloodstream infections caused by methicillin-resistant Staphylococcus aureus increased by 25.8% between 1997 and 2007, the overall incidence of these infections actually decreased by 49.6% over this period, according to an analysis of data reported to the CDC by 1,684 intensive-care units (pp. 727–36). Based on 33,587 central line–associated BSIs representing 16,225,498 patient–days of surveillance, the investigators noted: ìOf evaluated ICU types, surgical, nonteaching-affiliated medical-surgical, cardiothoracic, and coronary units experienced increases in MRSA central line–associated BSI incidence in the 1997–2001 period; however, medical, teaching-affiliated medical-surgical, and pediatric units experienced no significant changes. From 2001 through 2007, MRSA central line–associated BSI incidence declined significantly in all ICU types except in pediatric units, for which incidence rates remained static.î (D. C. Burton, dburton@cdc.gov)

>>>PNN NewsWatch
* Febuxostat (Uloric, Takeda) has been approved by FDA for the chronic management of hyperuricemia in patients with gout. A once-daily oral medication available in dosages of 40 and 80 mg, febuxostat was studied in clinical trials, some lasting up to 5 years, involving more than 4,000 participants. The largest trial, CONFIRMS, demonstrated that febuxostat 80 mg was significantly superior to febuxostat 40 mg and allopurinol 300/200 mg (67%, 45%, and 42%, respectively) at achieving the primary end point of serum uric acid less than 6.0 mg/dL at the final visit. The most commonly reported adverse reactions to the new agent were liver function abnormalities, nausea, joint pain, and rash.

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 © 2009, 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, 2009 * Vol. 16, No. 32
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 19 issue of the New England Journal of Medicine (2009; 360).
Using Pharmacogenetics to Estimate Warfarin Doses: A pharmacogenetically based algorithm predicted warfarin doses that were significantly closer to required stable therapeutic doses, compared with clinical algorithm or fixed-dose methods, reports the International Warfarin Pharmacogenetics Consortium (pp. 753–64). The benefits of using pharmacogenetics were particularly greater among the nearly half of patients with relatively small or large doses, specifically those who require 21 mg/week or less or 49 mg/week or more. The investigators used clinical and genetic data from 4,043 patients to construct the two algorithms, one based on clinical variables alone and the other with genetic information factored in. A validation cohort of 1,009 participants was then used to calculate the percentage of patients with predicted doses within 20% of the actual stable therapeutic dose, with these results: ìIn the validation cohort, the pharmacogenetic algorithm accurately identified larger proportions of patients who required 21 mg of warfarin or less per week and of those who required 49 mg or more per week to achieve the target international normalized ratio than did the clinical algorithm (49.4% vs. 33.3%, P<0.001, among patients requiring 21 mg per week; and 24.8% vs. 7.2%, P<0.001, among those requiring 49 mg per week).î (International Warfarin Pharmacogenetics Consortium, iwpc@pharmgkb.org)
Editorialists call for increased incorporation of pharmacogenetics into daily practice (
pp. 811–3): ìA better understanding of individual differences in the response, either positive or negative, to medicines should be an overarching goal for pharmacotherapy over the next decade. Pharmacogenetics has the potential to increase benefit and reduce harm in people whose drug responses are not ‘average’ In some cases, randomized, controlled trials will be needed to determine whether pharmacogenetic testing is worthwhile; in others, less rigorous approaches will suffice. Given the expected volume of genetic information and the relative paucity of randomized, controlled trials involving marketed drugs, we need clear thinking about what is required for the adoption of pharmacogenetic testing.î (J. Woodcock, FDA)
Data-Mining of Prescription Records: The nuances of ìcoverageî versus ìprotectionî of the U.S. Constitution’s First Amendment are at the heart of a question about the constitutionality of a New Hampshire law that prohibits data mining of prescription records for purposes of selling information to pharmaceutical companies seeking to tailor their marketing messages to individual prescribers (pp. 745–7). ìSome degree of discretion is inevitable in First Amendment adjudication. At a minimum, however, courts should employ tests that are relevant to the constitutional values at issue in a case. The fundamental difficulty with the Central Hudson test [i.e., that the practice ‘directly’ advanced the goal of reducing medical costs without endangering patients’ health] is that it is not relevant in this way. It does not ask the right questions. The correct constitutional inquiry about statutes like New Hampshire’s is whether the regulation of a data-transmission channel is likely to impair the informed and intelligent creation of public opinion. This question may be indeterminate, but it is at least directed toward the constitutional values at stake. Because the New Hampshire statute specifically permits data miners to disclose data to the general public and to those involved in managing the health care system, and because it primarily prohibits the flow of information to pharmaceutical companies seeking to use it to persuade physicians to prescribe particular drugs, the constitutionality of the statute ought to be clear. But unfortunately, it is not.î (R. Post, Yale Law Sch., New Haven, CT)

>>>PNN NewsWatch
* A reporter needed just 2 minutes and $19 to purchase steroids at pharmacies in baseball player Alex Rodriguez’s home country, the Dominican Republic, the New York Daily News reports. ìThe pharmacist handed over one 100 mg ampule of testosterone enanthate, a 2.5 ml. syringe and a package of 10 Methandrostenolone pills, the powerful oral anabolic steroid known as Dianabol,î the reporter writes.

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 © 2009, 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. 20, 2009 * Vol. 16, No. 33
Providing news and information about medications and their proper use

>>>Rheumatology Highlights
Source:
Feb. issue of Arthritis & Rheumatism (2009; 60).
Chondroitins for Osteoarthritis: A long-term study shows that chondroitins 4 and 6 sulfate (CS) appear to be disease-modifying in patients with knee osteoarthritis (pp. 524–33). Using radiography and symptoms to assess the effects of CS 800 mg daily on joint space width (JSW) in 622 patients, the investigators found: ìThe intent-to-treat analysis demonstrated a significant reduction (P < 0.0001) in minimum JSW loss in the CS group (mean ± SEM -0.07 ± 0.03 mm) as compared with the placebo group (–0.31 ± 0.04 mm). The percentage of patients with radiographic progression 0.25 mm was significantly reduced in the CS group compared with the placebo group (28% versus 41% [P < 0.0005]; relative risk reduction 33% [95% confidence interval 16–46%]). The number of patients needed to treat was 8 (95% confidence interval 5–17). Pain improved significantly faster in the CS group than in the placebo group (P < 0.01). There were no differences in safety between groups.î (A. Kahan, andre.kahan@cch.aphp.fr)
Pamapimod for Rheumatoid Arthritis: Pamapimod, a selective inhibitor of the alpha-isoform of p38 MAP kinase, was not as effective as methotrexate in a 12-week trial of patients with rheumatoid arthritis, researchers report (pp. 335–44). American College of Rheumatology 20% improvement criteria and adverse effects (AEs) showed these trends: ìPatients assigned to receive MTX and pamapimod had similar demographics and baseline characteristics. At week 12, fewer patients taking pamapimod had an ACR20 response (23%, 18%, and 31% in the 50-, 150-, and 300-mg groups, respectively) compared with patients taking MTX (45%). Secondary efficacy end points showed a similar pattern. AEs were typically characterized as mild and included infections, skin disorders, and dizziness. Pamapimod was generally well tolerated, but the 300-mg dose appeared to be more toxic than either the 2 lower doses or MTX.î (S. B. Cohen, scohen@arthdocs.com)

>>>Allergy/Immunology Report
Source:
Feb. issue of the Journal of Allergy and Clinical Immunology (2009; 123).
Traditional Chinese Medicines in Asthma/Allergy: One of several articles on use of complementary and alternative medicine for asthma and allergies in this issue, a review article concludes that traditional Chinese medicine (TCM) herbal therapy has beneficial effects in patients with asthma (pp. 297–306). Authors reviewed 5 studies published in 2005–07, finding: ìA number of mechanisms may be responsible for efficacy of these agents. Strong preclinical study data suggest the potential efficacy of food allergy herbal formula-2 for food allergy.î (X-M Li, xiu-min.li@mssm.edu)
Probiotics for Allergies: Perinatal supplementation of probiotic bacteria to high-risk mothers and children conferred protection only to cesarean-delivered children and not the total patient population, a study of 1,223 mothers and infants shows (pp. 335–41). Mothers received the probiotic mixture (2 lactobacilli, bifidobacteria, and propionibacteria) or placebo during the last month of pregnancy, and infants received the same intervention from birth until 6 months of age. Children also received a prebiotic galacto-oligosaccharide or placebo. Cumulative incidence of allergic diseases (eczema, food allergy, allergic rhinitis, and asthma) and IgE sensitization at 5 years of age showed: ìOf the 1,018 intent-to-treat infants, 891 (88%) attended the 5-year visit. Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar: 52.6% versus 54.9% and 29.5% versus 26.6%, respectively, and 41.3% in both. No significant difference appeared in frequencies of eczema (39.3% vs 43.3%), atopic eczema (24.0% vs 25.1%), allergic rhinitis (20.7% vs 19.1%), or asthma (13.0% vs 14.1%) between groups. However, less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics (24.3% vs 40.5%; odds ratio, 0.47; 95% CI, 0.23% to 0.96%; P = .035).î (M. Kuitunen, mikael.kuitunen@hus.fi)

>>>PNN NewsWatch
* Progressive multifocal leukoencephalopathy has been reported in 4 patients, including 3 who have died, treated with efalizumab (Raptiva, Genentech) for more than 3 years, FDA is warning.

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 © 2009, 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, 2009 * Vol. 16, No. 34
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Feb. 21 issue of Lancet (2009; 372).
Ustekinumab for Psoriatic Arthritis: An investigational monoclonal antibody significantly reduced signs and symptoms of psoriatic arthritis and diminished skin lesions in a 24-center study conducted in North America and Europe (pp. 633–40). The crossover study tested ustekinumab 90 or 63 mg every week for 4 weeks (weeks 0—3) followed by placebo at weeks 12 and 16 in Group 1, or placebo for weeks 0–3 and ustekinumab 63 mg at weeks 12 and 16 in Group 2. Among the 146 study participants, the primary end point of ACR20 response at week 12 showed: ìAt week 12, 32 (42%) patients in Group 1 and ten (14%) in Group 2 achieved the primary endpoint (difference 28% [95% CI 14.0—41.6]; p = 0.0002). Of 124 (85%) participants with psoriasis affecting 3% or more body surface area, 33 of 63 (52%) in Group 1 and three of 55 (5%) in Group 2 had a 75% or greater improvement in psoriasis area and severity index score at week 12 (47% [33.2—60.6]; p < 0.0001). During the placebo-controlled period (weeks 0—12), adverse events arose in 46 (61%) patients in Group 1 and 44 (63%) in Group 2; serious adverse events were recorded in three (4%) Group 2 patients (none in Group 1).î (A. Gottlieb, agottlieb@tuftsmedicalcenter.org)
Eltrombopag for Chronic Idiopathic Thrombocytopenic Purpura: Eltrombopag, a thrombopoietin-receptor agonist approved by FDA in Nov. 2008, is ìan effective treatment for management of thrombocytopenia in chronic [idiopathic thrombocytopenic purpura],î a Phase III study shows (pp. 641–8). Comparing the drug with placebo, the investigators found: ì73 patients in the eltrombopag group and 37 in the placebo group were included in the efficacy population and were evaluable for day-43 analyses. 43 (59%) eltrombopag patients and six (16%) placebo patients responded (ie, achieved platelet counts 50 000 per µL; odds ratio [OR] 9.61 [95% CI 3.31—27.86]; p < 0.0001). Response to eltrombopag compared with placebo was not affected by predefined study stratification variables (baseline platelet counts, concomitant ITP drugs, and splenectomy status) or by the number of previous ITP treatments. Of the 34 patients in the efficacy analysis who increased their dose of eltrombopag, ten (29%) responded. Platelet counts generally returned to baseline values within 2 weeks after the end of treatment. Patients receiving eltrombopag had less bleeding at any time during the study than did those receiving placebo (OR 0.49 [95% CI 0.26—0.89]; p = 0.021). The frequency of grade 3—4 adverse events during treatment (eltrombopag, two [3%]; placebo, one [3%]) and adverse events leading to study discontinuation (eltrombopag, three [4%]; placebo, two [5%]), were similar in both groups.î (J. B. Bussel, jbussel@med.cornell.edu)
A-002 for Atherosclerosis: 1-H-indole-3-glyoxamide (A-002) reduced concentrations of a key marker of inflammation in coronary heart disease, a study shows, indicating that the agent might be useful as an antiatherosclerotic agent (pp. 649–58). In a Phase II trial, 393 adult patients with stable CHD received one of four doses of A-002, an inhibitor of secretory phospholipase A2 (sPLA2) enzymes, with these results: ìMean sPLA2-IIA concentration fell by 86.7%, from 15.7 pmol/L to 2.1 pmol/L, in the overall active treatment group, and by 4.8%, from 15.7 pmol/L to 14.3 pmol/L, in the placebo group (p < 0.0001 treatment vs placebo). The reductions in sPLA2-IIA concentration in the A-002 groups were dose dependent (ranging from 69.2% in the 50 mg group to 95.8% in the 500 mg group) and differed significantly from placebo (p < 0.0001 for all doses).î (R. S. Rosenson, rrosenso@umich.edu)

>>>PNN JournalWatch
* Is Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Combination Therapy Better than Monotherapy and Safe in Patients with CKD?, in American Journal of Kidney Diseases, 2009; 53: 192–6. (J. S. Berns, bernsj@uphs.upenn.edu)
* Dual Blockade of the Renin-Angiotensin System for Cardiorenal Protection: An Update, in
American Journal of Kidney Diseases, 2009; 53: 332–45. (M. Arici, marici@hacettepe.edu.tr)
* Pharmacological Management of Osteoporosis in Nursing Home Populations, in
Journal of the American Geriatrics Society, 2009; 57: 327–34. (S. Parikh, Sparikh3@partners.org)
* Continuous Subcutaneous Insulin Infusion Therapy: A Primer on Insulin Pumps, in
Journal of the American Pharmacists Assoc., 2009; 49: e1–e17. (S. T. Haines, shaines@umaryland.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 © 2009, 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, 2009 * Vol. 16, 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 (2009; 169).
Prevention of Macular Degeneration with Vitamin Therapy: Among 5,205 women at high risk of cardiovascular disease, daily supplementation with folic acid, pyridoxine, and cyanocobalamin reduced the risk of age-related macular degeneration, researchers report (pp. 335–41). In the Women’s Antioxidant and Folic Acid Cardiovascular Study (WAFACS), folic acid 2.5 mg/d, pyridoxine hydrochloride 50 mg/d, and cyanocobalamin 1 mg/d produced these results in comparison with placebo: ìAfter an average of 7.3 years of treatment and follow-up, there were 55 cases of AMD in the combination treatment group and 82 in the placebo group (relative risk, 0.66; 95% confidence interval, 0.47–0.93 [P = .02]). For visually significant AMD, there were 26 cases in the combination treatment group and 44 in the placebo group (relative risk, 0.59; 95% confidence interval, 0.36–0.95 [P = .03]).î (W. G. Christen, wchristen@rics.bwh.harvard.edu)
Vitamin D & Upper Respiratory Tract Infection: Mining data from the Third National Health and Nutrition Examination Survey, investigators found an inverse relationship between serum 25-hydroxyvitamin D concentrations and occurrence of recent upper respiratory tract infections (pp. 384–90). Several trends were noted among 18,883 study participants aged 12 years and older: ìThe median serum 25(OH)D level was 29 ng/mL (to convert to nanomoles per liter, multiply by 2.496) (interquartile range, 21–37 ng/mL), and 19% (95% confidence interval [CI], 18%–20%) of participants reported a recent URTI. Recent URTI was reported by 24% of participants with 25(OH)D levels less than 10 ng/mL, by 20% with levels of 10 to less than 30 ng/mL, and by 17% with levels of 30 ng/mL or more (P < .001). Even after adjusting for demographic and clinical characteristics, lower 25(OH)D levels were independently associated with recent URTI (compared with 25[OH]D levels of 30 ng/mL: odds ratio [OR], 1.36; 95% CI, 1.01–1.84 for <10 ng/mL and 1.24; 1.07–1.43 for 10 to <30 ng/mL). The association between 25(OH)D level and URTI seemed to be stronger in individuals with asthma and chronic obstructive pulmonary disease (OR, 5.67 and 2.26, respectively).î (C. A. Camargo, Jr., ccamargo@partners.org)
Difficult Encounters in Primary Care: Physician survey data from the Minimizing Error, Maximizing Outcome (MEMO) study show that patients’ requests for unnecessary medications is the single most frequently cited challenge during difficult primary care visits (pp. 410–4). The mail survey of 449 physicians in Chicago, New York, and urban and rural areas of Wisconsin shows that 36.7% of respondents cited unnecessary drugs as a frequent frustration, followed by 16.1% who often encountered patients who were frustrated with their care and 13.7% of physicians who frequently saw patients with unrealistic expectations. The authors reported these characteristics of doctors showing signs of burnout: ìPhysicians who perceived a higher volume of difficult encounters were significantly more burned out and dissatisfied with their jobs than those reporting fewer difficult encounters.Ö Most salient of our findings was that high difficulty cluster physicians were 12 times more likely than low difficulty cluster physicians to report burnout. This has critical implications for the future of primary care because fewer trainees are choosing careers in primary care, perhaps in part owing to burned-out role models.î (P. G. An, perryan@post.harvard.edu)

>>>PNN NewsWatch
* Citing cases of metabolic acidosis with the antiepileptic medication zonisamide (Zonegran, Eisai), FDA is recommending that health care professionals measure serum bicarbonate before starting treatment and periodically during treatment with the agent, even in the absence of symptoms. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing zonisamide (using dose tapering), and modifying the patient’s antiepileptic treatment as appropriate. If the decision is made to continue patients with metabolic acidosis on zonisamide, then alkali treatment should be considered.

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 © 2009, 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, 2009 * Vol. 16, No. 36
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Feb. 25 issue of JAMA (2009; 301).
Evidence Supporting Cardiovascular Guidelines: Clinical practice guidelines for cardiovascular diseases are largely based on relatively low levels of evidence or expert opinion, concludes an assessment of current guidelines that offer 1,973 recommendations (pp. 831–41). Categorizing three classes of recommendations (I: evidence that a treatment or procedure is effective, II, IIa, IIb, and III: evidence that a treatment or procedure is not effective) based on the evidence supporting them (A: higher level of evidence, B, or C: lower level of evidence), the investigators evaluated guidelines from one revision to the next. The guidelines shifted to more class II recommendations and fewer class III recommendations, while the use of class I recommendations remained fairly constant. The 16 current guidelines reporting levels of evidence, comprising a total of 2,711 recommendations, classify 314 recommendations as level of evidence A (median, 11%), and 1,246 with level of evidence C (median, 48%). The authors concluded: ìOur finding that a large proportion of recommendations in ACC/AHA guidelines are based on lower levels of evidence or expert opinion highlights deficiencies in the sources of definitive data available for the generation of cardiovascular guidelines. To remedy this problem, the medical research community needs to streamline clinical trials, focus on areas of deficient evidence, and expand funding for clinical research. In addition, the process of developing guidelines needs to be improved with information about the impact that recommendations based on lower levels of evidence has on clinical practice. Finally, clinicians need to exercise caution when considering recommendations not supported by solid evidence.î (P. Tricoci, trico001@dcri.duke.edu)
Conservative Prescribing: Physicians should use more caution and skepticism in prescribing medications, write authors of a commentary article (pp. 865–7). Among the strategies recommended are using nondrug alternatives first, being cautious about new drugs, and maintaining heightened vigilance about potential adverse drug effects. (G. D. Schiff, gschiff@partners.org)

>>>Oncology Highlights
Source:
Early-release article from the Journal of Clinical Oncology (2009; 27).
Chemoprevention of Prostate Cancer: Men being screened annually for prostate cancer should consider chemoprevention using regular doses of 5-alpha-reductase inhibitors (5-ARIs), advises a jointly issued clinical practice guideline from the American Society of Clinical Oncology and the American Urological Association (doi: 10.1200/JCO.2008.16.9599): ìAsymptomatic men with a prostate-specific antigen (PSA) 3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI.î (B. S. Kramer)

>>>PNN NewsWatch
* At its annual meeting in Naples, FL, this week, the Generic Pharmaceutical Association kicked off a 25th anniversary celebration of the 1984 signing of the Hatch–Waxman Act. Addressing the current controversy concerning equivalents of biologic drugs, House Energy and Commerce Committee Chairman Henry Waxman supported use of this model for achieving ìa workable scientific regulatory and legal pathway for biogenerics and biosimilar pharmaceuticals [that] will ensure more affordable medications for Americans and Ö spur innovation in the biotech markets.î

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 © 2009, 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, 2009 * Vol. 16, No. 37
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 26 issue of the New England Journal of Medicine (2009; 360).
Macronutrients in Weight-Loss Diets: A comparison of diets with varying percentages of fat, protein, and carbohydrate calories shows that people lose weight regardless of the types of macronutrients included in daily diets (pp. 859–73). Over a 2-year period, 811 overweight adults were assigned to one of four diets with these targeted percentages of energy derived from fat, protein, and carbohydrates: 20%, 15%, and 65%; 20%, 25%, and 55%; 40%, 15%, and 45%; and 40%, 25%, and 35%. Results showed: ìAt 6 months, participants assigned to each diet had lost an average of 6 kg, which represented 7% of their initial weight; they began to regain weight after 12 months. By 2 years, weight loss remained similar in those who were assigned to a diet with 15% protein and those assigned to a diet with 25% protein (3.0 and 3.6 kg, respectively); in those assigned to a diet with 20% fat and those assigned to a diet with 40% fat (3.3 kg for both groups); and in those assigned to a diet with 65% carbohydrates and those assigned to a diet with 35% carbohydrates (2.9 and 3.4 kg, respectively) (P > 0.20 for all comparisons). Among the 80% of participants who completed the trial, the average weight loss was 4 kg; 14 to 15% of the participants had a reduction of at least 10% of their initial body weight. Satiety, hunger, satisfaction with the diet, and attendance at group sessions were similar for all diets; attendance was strongly associated with weight loss (0.2 kg per session attended). The diets improved lipid-related risk factors and fasting insulin levels.î (F. M. Sacks)
Community rather than individual efforts may be needed when it comes to weight loss, writes an editorialist, citing experiences from the EPODE (Ensemble, prÈvenons l’obÈsitÈ des enfants [Together, let’s prevent obesity in children]) trial, which is ongoing in 200 European towns (
pp. 923–5): ìLike cholera, obesity may be a problem that cannot be solved by individual persons but that requires community action. Evidence for the efficacy of the EPODE approach is only tentative, and what works for small towns in France may not work for Mexico City or rural Louisiana. However, the apparent success of such community interventions suggests that we may need a new approach to preventing and to treating obesity and that it must be a total-environment approach that involves and activates entire neighborhoods and communities. It is an approach that deserves serious investigation, because the only effective alternative that we have at present for halting the obesity epidemic is large-scale gastric surgery.î (M. B. Katan, VU University, Amsterdam)
Ciprofloxacin-Resistant Neisseria meningitidis: Three cases of meningococcal disease caused by ciprofloxacin-resistant Neisseria meningitidis are reported and emergence of the pathogen analyzed in a brief report (pp. 886–92). Cases from North Dakota and Minnesota showed the following: ìWe conducted a pharyngeal-carriage survey and isolated the resistant strain from one asymptomatic carrier. Sequencing of the gene encoding subunit A of DNA gyrase (gyrA) revealed a mutation associated with fluoroquinolone resistance and suggests that the resistance was acquired by means of horizontal gene transfer with the commensal N. lactamica. In susceptibility testing of invasive N. meningitidis isolates from the Active Bacterial Core surveillance system between January 2007 and January 2008, an additional ciprofloxacin-resistant isolate was found, in this case from California. Ciprofloxacin-resistant N. meningitidis has emerged in North America.î (H. M. Wu, hwu@cdc.gov)

>>>PNN NewsWatch
* Drug prices are expected to increase by a weighted average of 5% in the fiscal year beginning July 1, 2009, Novation estimates. Releasing its drug price forecast reports to the entire profession for the first time, the Texas-based health care contracting services company noted that the product mix used in the forecast is based on aggregated purchases made by Novation members. Drug price changes for products under contract are expected to climb by 4.3%, while noncontracted products will increase in price by 5.9%, Novation predicted. Drug price change projections differ from total drug budget adjustments presented in the Feb. 1 American Journal of Health-System Pharmacy because of changes in volume and mix (0.5–1%) and new drugs (0.5–1%).

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 © 2009, 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. 27, 2009 * Vol. 16, No. 38
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Mar. issue of Diabetes Care (2009; 32).
Basal Insulins in Adolescent Type 1 Diabetes: In 90 adolescents with type 1 diabetes who were using a continuous glucose monitoring system during an active-controlled, randomized, open-label study, insulin glargine produced significantly greater reductions in glucose variability than did NPH/Lente insulin (pp. 387–93). The basal insulins, given as part of a multiple daily dose insulin regimen, produced these results: ìTreatment with insulin glargine resulted in significant reductions in glucose variability as measured by the SD of glucose values (adjusted mean change from baseline to week 24: –13.4 mg/dl [–0.74 mmol/l]; P 0.05), mean amplitude of glycemic excursion (–34.4 mg/dl [–1.91 mmol/l]; P 0.0001), and M value (–9.6 mg/dl [–0.53 mmol/l]; P 0.03). The corresponding reductions in glucose variability for NPH/Lente were not significant.î (N. H. White, white_n@kids.wustl.edu)
Continuous Glucose-Monitoring System: Use of a transcutaneous, real-time, continuous glucose-monitoring (CGM) system for 10 days is documented in an uncontrolled trial of adults with type 1 diabetes (pp. 436–8). The SEVEN System had been previously tested for 3, 5, and 7 days of use. Comparing fingersticks with Yellow Springs Instruments (YSI) samples drawn every 15 minutes on days 2 and 7 and in-clinic samples drawn on day 10, the researchers determined: ìThe median absolute relative difference for CGM versus YSI was 12.6, 11.3, and 14.5% on days 2, 7, and 10, respectively (P = 0.63). CGM performed better on day 10 when compared with self-monitoring of blood glucose as compared with YSI.î (S. K. Garg, satish.garg@uchsc.edu)
Fenofibrate in Patients with Diabetes: In patients with type 2 diabetes, the cardiovascular benefits of fenofibrate therapy are likely to be greater among those with components of metabolic syndrome and/or marked hypertriglyceridemia, researchers report (pp. 493–8). Analyzing data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study using Cox proportional models, the investigators found: ìMore than 80% of FIELD participants met the ATP III criteria for metabolic syndrome. Each ATP III feature of metabolic syndrome, apart from increased waist circumference, increased the absolute risk of [cardiovascular disease (CVD)] events over 5 years by at least 3%. Those with marked dyslipidemia (elevated triglycerides 2.3 mmol/l and low HDL cholesterol) were at the highest risk of CVD (17.8% over 5 years). Fenofibrate significantly reduced CVD events in those with low HDL cholesterol or hypertension. The largest effect of fenofibrate to reduce CVD risk was observed in subjects with marked dyslipidemia in whom a 27% relative risk reduction (95% CI 9–42, P = 0.005; number needed to treat = 23) was observed. Subjects with no prior CVD had greater risk reductions than the entire group.î (R. Scott, fieldtrial@ctc.usyd.edu.au)
Pay for Performance: Paying primary care providers for performance led to improvements of intermediate outcomes in patients with diabetes, a study shows, but with greater A1C reductions among whites (–0.5%) than blacks (–0.3%) or South Asians (–0.4%) (pp. 404–9; C. Millett, c.millett@imperial.ac.uk).

>>>PNN NewsWatch
* FDA ruled yesterday that manufacturers of metoclopramide must add a boxed warning to their drug labels about the risk of its long-term or high-dose use and implement a risk evaluation and mitigation strategy, or REMS, to ensure patients are provided with a medication guide that discusses this risk. Long-term use of metoclopramide has been linked to tardive dyskinesia , which is currently listed among the drug’s adverse effects. FDA explained that the development of this condition is directly related to the length of time a patient is taking metoclopramide and the number of doses taken. Those at greatest risk include the elderly, especially older women, and people who have been on the drug for a long time. According to recently published articles and FDA analyses, metoclopramide is the most common cause of drug-induced movement disorders, and about 20% of patients using metoclopramide took it for longer than 3 months. FDA also said that it is aware of continued spontaneous reports of tardive dyskinesia in patients who used metoclopramide, most of whom had taken the drug for more than 3 months.

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 © 2009, 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, 2009 * Vol. 16, No. 39
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Feb. 28 issue of Lancet (2009; 372).
Prasugrel for PCI/STEMI: Prasugrel is more effective than clopidogrel for prevention of ischemic events in patients undergoing percutaneous coronary interventions for ST-elevation myocardial infarction, according to a 3,534-patient study, which also reported that the two agents are equally safe in terms of bleeding episodes (pp. 723–31). Using a primary endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with follow-up to 15 months and secondary analyses at 30 days, the researchers report: ìAt 30 days, 115 (6.5%) individuals assigned prasugrel had met the primary endpoint compared with 166 (9.5%) allocated clopidogrel (hazard ratio 0.68 [95% CI 0.54—0.87]; p = 0.0017). This effect continued to 15 months (174 [10.0%] vs 216 [12.4%]; 0.79 [0.65—0.97]; p = 0.0221). The key secondary endpoint of cardiovascular death, myocardial infarction, or urgent target vessel revascularisation was also significantly reduced with prasugrel at 30 days (0.75 [0.59—0.96]; p = 0.0205) and 15 months (0.79 [0.65—0.97]; p = 0.0250), as was stent thrombosis. Treatments did not differ with respect to thrombolysis in myocardial infarction (TIMI) major bleeding unrelated to coronary-artery bypass graft (CABG) surgery at 30 days (p = 0.3359) and 15 months (p = 0.6451). TIMI life-threatening bleeding and TIMI major or minor bleeding were also similar with the two treatments, and only TIMI major bleeding after CABG surgery was significantly increased with prasugrel (p = 0.0033).î (G. Montalescot, gilles.montalescot@psl.aphp.fr)
Fampridine for Multiple Sclerosis: The potassium-channel blocker fampridine improved walking ability in some of 301 patients with multiple sclerosis, reducing their reports of ambulatory disability (pp. 732–8). For 14 weeks, patients received either oral fampridine 10 mg twice daily or placebo and were tested for improvements using timed 25-foot walks: ìThe proportion of timed walk responders was higher in the fampridine group (78/224 or 35%) than in the placebo group (6/72 or 8%; p < 0.0001). Improvement in walking speed in fampridine-treated timed walk responders, which was maintained throughout the treatment period, was 25.2% (95% CI 21.5% to 28.8%) and 4.7% (1.0% to 8.4%) in the placebo group. Timed walk responders showed greater improvement in 12-item multiple sclerosis walking scale scores (−6.84, 95% CI −9.65 to −4.02) than timed walk non-responders (0.05, −1.48 to 1.57; p = 0.0002). Safety data were consistent with previous studies.î (A. D. Goodman, andrew_goodman@urmc.rochester.edu)

>>>PNN NewsWatch
* Axona, an FDA-approved medical food for treatment of mild-to-moderate Alzheimer’s disease is being launched today by the biotechnology company Accera, Inc. The first-in-class medical food, dispensed by prescription, targets the metabolic deficiencies and imbalances associated with AD by providing an alternative energy source for brain cells. In a double-blind, randomized, placebo-controlled study of 152 patients with probable mild-to-moderate Alzheimer’s disease, those taking Axona demonstrated significant improvements in cognitive function by day 45. These patients also maintained a slight improvement from baseline after 90 days of daily Axona administration, whereas the placebo group demonstrated a decline. Axona’s powder formulation is mixed with water and consumed at breakfast. The product is complementary to other AD therapies.

>>>PNN JournalWatch
* Difficult to Treat Asthma in Adults, in BMJ, 2009; b494. (G. P. Currie, Graeme.currie@nhs.net)
* Agents for the Decolonization of Methicillin-Resistant
Staphylococcus aureus, in Pharmacotherapy, 2009; 29: 263–80. (K. L. LaPlante, KerryTedesco@uri.edu)
* Etravirine and Rilpivirine: Nonnucleoside Reverse Transcriptase Inhibitors with Activity Against Human Immunodeficiency Virus Type 1 Strains Resistant to Previous Nonnucleoside Agents, in
Pharmacotherapy, 2009; 29: 281–94. (I. R. McNicholl, imcnicholl@php.ucsf.edu)
* Kathleen Sebelius: One Colleague’s Take, in
Health Affairs, 2009. (C. Fleming)
* Is There a Relationship Between Patient Beliefs or Communication About Generic Drugs and Medication Utilization?, in
Medical Care, 2009; 47: 319–25. (W. H. Shrank, wshrank@partners.org)
* Improving the Prediction of Medication Compliance: The Example of Bisphosphonates for Osteoporosis, in
Medical Care, 2009; 47: 334–41. (J. R. Curtis, jcurtis@uab.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 © 2009, 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, 2009 * Vol. 16, No. 40
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from and Mar. 3 issue of the Annals of Internal Medicine (2009; 150).
Oral Vitamin K for Excessive Warfarin Anticoagulation: Among patients taking warfarin and with INRs of 4.5 to 10.0, oral vitamin K reversed overanticoagulation but did not significantly reduce bleeding more than did placebo, leading researchers to conclude that temporarily stopping warfarin may be all that is needed in this situation (pp. 293–300). At 14 clinics, oral vitamin K 1.25 mg produced these results in comparison with placebo in 724 patients: ì56 patients (15.8%) in the vitamin K group and 60 patients (16.3%) in the placebo group had at least 1 bleeding complication (absolute difference, –0.5 percentage point [95% CI, –6.1 to 5.1 percentage points]); major bleeding events occurred in 9 patients (2.5%) in the vitamin K group and 4 patients (1.1%) in the placebo group (absolute difference, 1.5 percentage points [CI, –0.8 to 3.7 percentage points]). Thromboembolism occurred in 4 patients (1.1%) in the vitamin K group and 3 patients (0.8%) in the placebo group (absolute difference, 0.3 percentage point [CI, –1.4 to 2.0 percentage points]). Other adverse effects were not assessed. The day after treatment, the INR had decreased by a mean of 1.4 in the placebo group and 2.8 in the vitamin K group (P < 0.001).î (M. A. Crowther, crowthrm@mcmaster.ca)
Lipid-Lowering Therapy in HIV Infection: Patients with HIV infection respond poorly to lipid-lowering therapy, especially when they have hypertriglyceridemia, according to a study of 829 patients with and 6,941 patients without HIV (pp. 301–13). Gemfibrozil plus nonnucleoside reverse transcriptase inhibitors–based HIV treatments had better triglyceride responses, as detailed in these results of this retrospective cohort study from 1996 to 2005: ìCompared with patients without HIV infection, patients with HIV infection beginning statin therapy had smaller reductions in low-density lipoprotein cholesterol levels (25.6% vs. 28.3%; P = 0.001), which did not vary by antiretroviral therapy class. Patients with HIV infection beginning gemfibrozil therapy had substantially smaller reductions in triglyceride levels than patients without HIV infection (44.2% vs. 59.3%; P < 0.001), and reductions with gemfibrozil varied by antiretroviral therapy class (44.0% [P = 0.001] in patients receiving PIs only, 26.4% [P < 0.001] in patients receiving PIs and nonnucleoside reverse transcriptase inhibitors [NNRTIs], and 60.3% [P = 0.94] in patients receiving NNRTIs only). Rhabdomyolysis was diagnosed in 3 patients with HIV infection and 1 patient without HIV infection. No clinically recognized cases of myositis or myopathy were observed. The risk for laboratory adverse events was low (<5%), although it was increased in patients with HIV infection.î (M. J. Silverberg, Michael.J.Silverberg@kp.org)
Health Care Reform, Compendial Controversy: The ìabundance of ideasî about how to reform the U.S. health care system ìcan be dizzying,î Annals editors write in introducing early-release articles on this subject. The articles, slated for publication in the Apr. 7 issue, review the Obama administration’s options for health care cost control, how to expand medical and behavioral resources to provide access to all, and recommendations for a 21st century health care system.
In
rapid responses to the published version of an article on the reliability of compendia for off-label oncology indications (see PNN, Feb. 18), the editor of the American Hospital Formulary Service Drug Information resource requests corrections to a table and takes exception to ìthe authors’ discussion regarding the usefulness of this study as a benchmark for future evaluation of compendiaî (G. McEvoy, gmcevoy@ashp.org).

>>>PNN NewsWatch
* FDA announces a Consent Decree of permanent injunction that, once entered by a court, will enjoin KV Pharmaceutical Company, its ETHEX and Ther-Rx subsidiaries, and its principal officers from making and distributing adulterated and unapproved drugs. The order remains in place until the defendants sustain continuous compliance with FDA’s current Good Manufacturing Practice and new drug approval requirements for 5 years.
* CSL Biotherapies and
Good Neighbor Pharmacy have teamed up to provide community pharmacists with a promotional immunization kit to help increase the awareness of the importance of immunizations and vaccines.

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 © 2009, 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, 2009 * Vol. 16, No. 41
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Early-release articles from and Mar. 4 issue of JAMA (2009; 301).
Resistance with Oseltamivir: Oseltamivir-resistant influenza A(H1N1) viruses, emerging during the 2007–08 season without any apparent relationship to use of the medication, now represent virtually all cases of infection with this viral strain, researchers report (doi:10.1001/jama.2009.294). One of three early-release papers on oseltamivir-resistant influenza A (morbidity and mortality with the new strain, doi: 10.1001/jama.2009.297, J. Gooskens, j.gooskens@lumc.nl; editorial, doi: 10.1001/jama.2009.324, D. M. Weinstock, davidm_weinstock@dfci.harvard.edu), this article details results of ongoing CDC surveillance of samples submitted by U.S. public health laboratories during the past 1.5 years: ìDuring the 2007–2008 season, influenza A(H1N1) accounted for an estimated 19% of circulating influenza viruses in the United States. Among 1,155 influenza A(H1N1) viruses tested from 45 states, 142 (12.3%) from 24 states were resistant to oseltamivir. Data were available for 99 oseltamivir-resistant cases and 182 oseltamivir-susceptible cases from this period. Among resistant cases, median age was 19 years (range, 1 month to 62 years), 5 patients (5%) were hospitalized, and 4 patients (4%) died. None reported oseltamivir exposure before influenza diagnostic sample collection. No significant differences were found between cases of oseltamivir-resistant and oseltamivir-susceptible influenza in demographic characteristics, underlying medical illness, or clinical symptoms. Preliminary data from the 2008–2009 influenza season identified resistance to oseltamivir among 264 of 268 influenza A(H1N1) viruses (98.5%) tested.î (N. J. Dharan, nfd6@cdc.gov)
Influenza Vaccine Effectiveness: In an annually vaccinated population of military personnel, trivalent inactivated vaccine (TIV) proved more effective than intranasally administered live attenuated influenza vaccine (LAIV) (pp. 945–53). The difference was less apparent among military recruits, leading the investigators to conclude that use of LAIV may be more appropriate in vaccine-naive patients. The study was based on surveillance data from the influenza seasons beginning in 2004, 2005, and 2006, as follows: ìIn all 3 seasons, immunization with TIV was associated with lower incidence rates of health care encounters for pneumonia and influenza when compared with no immunization: 8.6 vs 19.4 for 2004–2005, 7.8 vs 10.9 for 2005–2006, and 8.0 vs. 11.7 per 1000 person-years for 2006–2007 (all P < .001). Similar estimates were obtained from propensity-matched and/or vaccine-naive cohorts. Consistently lower vaccine effect following LAIV immunization was only seen during the 2006–2007 influenza season in the total (10.7; 95% confidence interval [CI], 2.72 to 18.1; P = .03) and propensity-matched cohorts (11.8; 95% CI, 0.85 to 21.5; P = .04), and was less than effect from TIV (TIV vs LAIV, 19.8; 95% CI, 13.6 to 25.5; P < .001). Among vaccine-naive service members, however, estimates for LAIV effect were more robust for both the 2005–2006 and 2006–2007 seasons (P = .01) and were comparable with TIV (eg, LAIV, 30.2; 95% CI, 11.2 to 45.2; vs TIV, 35.3; 95% CI, 25.9 to 43.6; in 2005–2006).î (Z. Wang, zhong.wang@us.army.mil)
Clopidogrel–PPI Interaction in ACS: Following hospitalization for acute coronary syndrome, patients discharged on clopidogrel and proton-pump inhibitors have higher mortality rates and other adverse events, according to a retrospective cohort study (pp. 937–44): ìOf 8,205 patients taking clopidogrel after discharge, 63.9% (n = 5,244) were prescribed PPI at discharge, during follow-up, or both and 36.1% (n = 2,961) were not prescribed PPI. Death or rehospitalization for ACS occurred in 20.8% (n = 615) of patients taking clopidogrel without PPI and 29.8% (n = 1561) of patients taking clopidogrel plus PPI. In multivariable analyses, use of clopidogrel plus PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without PPI (adjusted odds ratio [AOR], 1.25; 95% confidence interval [CI], 1.11–1.41). Among patients taking clopidogrel after hospital discharge and prescribed PPI at any point during follow-up (n = 5,244), periods of use of clopidogrel plus PPI (compared with periods of use of clopidogrel without PPI) were associated with a higher risk of death or rehospitalization for ACS (adjusted hazard ratio, 1.27; 95% CI, 1.10–1.46).î (P. M. Ho, michael.ho@va.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 © 2009, 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, 2009 * Vol. 16, No. 42
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 5 issue of and early-release article from the New England Journal of Medicine (2009; 360).
Mepolizumab for Asthma: Use in asthma of a humanized monoclonal antibody against interleukin-5, mepolizumab, is explored in two research studies and an editorial.
In 61 patients with refractory eosinophilic asthma and a history of recurrent severe exacerbations, mepolizumab reduced the frequency of exacerbations and improved Asthma Quality of Life Questionnaire (AQLQ) scores (
pp. 973–84). Participants received monthly infusions of mepolizumab 750 mg or placebo for 1 year, and these results were noted: ìMepolizumab was associated with significantly fewer severe exacerbations than placebo over the course of 50 weeks (2.0 vs. 3.4 mean exacerbations per subject; relative risk, 0.57; 95% confidence interval [CI], 0.32 to 0.92; P = 0.02) and with a significant improvement in the score on the AQLQ (mean increase from baseline, 0.55 vs. 0.19; mean difference between groups, 0.35; 95% CI, 0.08 to 0.62; P = 0.02). Mepolizumab significantly lowered eosinophil counts in the blood (P < 0.001) and sputum (P = 0.002). There were no significant differences between the groups with respect to symptoms, FEV1 after bronchodilator use, or airway hyperresponsiveness. The only serious adverse events reported were hospitalizations for acute severe asthma.î (I. D. Pavord, ian.pavord@uhl-tr.nhs.uk)
Similarly, among 20 patients, mepolizumab reduced the number of blood and sputum eosinophils and allowed prednisone sparing in patients who had asthma with sputum eosinophilia despite prednisone treatment, compared with placebo (
pp. 985–93). Using five monthly infusions of mepolizumab 750 mg, the investigators found: ìThere were 12 asthma exacerbations in 10 patients who received placebo, 9 of whom had sputum eosinophilia at the time of exacerbation. In comparison, only one patient who received mepolizumab had an asthma exacerbation, and this episode was not associated with sputum eosinophilia (P = 0.002). Patients who received mepolizumab were able to reduce their prednisone dose by a mean (± SD) of 83.8±33.4% of their maximum possible dose, as compared with 47.7 ± 40.5% in the placebo group (P = 0.04). The use of mepolizumab was associated with a significant decrease in the number of sputum and blood eosinophils. Improvements in eosinophil numbers, asthma control, and forced expiratory volume in 1 second were maintained for 8 weeks after the last infusion. There were no serious adverse events.î (P. Nair, parames@mcmaster.ca)
Wondering whether these findings about the role of eosinophils in asthma are ìclosing the loop or opening the door,î a editorialist concludes the latter is the case (
pp. 1026–8): ìThese studies clearly confirm that in a subgroup of patients with eosinophilic asthma, eosinophils play a role in exacerbations. These particular eosinophils contribute to the pathobiology of asthma, and in this small subgroup, mepolizumab therapy had some clinical benefit. However, many patients with asthma do not have eosinophilia, and even in patients with eosinophilic asthma, mepolizumab had no effect on other physiological and clinical factors. These findings open the door, perhaps even further, to investigations of alternative cells and mediators in the broader world of asthma.î (S. E. Wenzel)
Review of Asthma: In a review article, an author describes the stepped-care approach to treatment of asthma (pp. 1002–14; C. H. Fanta, cfanta@partners.org)
Health Care Reform & the Obama Budget: Reviewing the ìbreathtakingî 2010 budget unveiled last week by the Obama administration, a writer assesses the President’s ìdown payment on health care reformî and the prospects for real change in the current Congress (doi: 10.1056/NEJMp0901927; J. K. Inglehart)

>>>PNN NewsWatch
* In Wyeth v. Levine, the U.S. Supreme Court yesterday ruled that FDA approval of drug labeling does not provide a preemptive shield against product liability suits. The New York Times reports that ìdrug companies and other businesses, supported by the Bush administration, had hoped the Vermont case would establish broader protections.î The litigation involved a musician’s loss of her arm following an intra-arterial infusion of promethazine.

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 © 2009, 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. 6, 2009 * Vol. 16, No. 43
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Mar. issue of Pharmacotherapy (2009; 29).
Pantoprazole for Variceal Bleeding: Addition of pantoprazole to octreotide treatment of variceal hemorrhage provided no identifiable added benefits, researchers report, leading them to conclude that continuously infused proton pump inhibitors require prospective study before their general use can be recommended (pp. 248–54). Retrospective chart review identified 130 adult patients who were treated for documented variceal hemorrhage, including 53 receiving standard octreotide therapy plus a prolonged continuous infusion of pantoprazole (continuous-infusion group) and 77 receiving either octreotide alone, octreotide with a short-term (< 24 h) infusion of pantoprazole, or octreotide with intermittent acid suppression (control group). Results showed: ìThe duration of therapy for variceal hemorrhage was significantly longer in the continuous-infusion group than in the control group. Transfusion requirements for packed red blood cells (mean ± SD 6.4 ± 6.5 vs 5.8 ± 6.6 units, p = 0.66) and platelets (8.8 ± 15.1 vs 5.1 ± 11.9 units, p = 0.13) were similar for the continuous-infusion group versus the control group. The continuous-infusion group, however, received significantly more units of fresh-frozen plasma than the control group (6.1 ± 10.6 vs 2.9 ± 6.2 units, p = 0.05). There was no significant difference in mortality rate between groups.î (Cesar Alaniz)
Sleep Outcomes with Ropinirole in Restless Legs Syndrome: Ropinirole improves sleep quantity and adequacy as well as decreases sleep disturbance and daytime somnolence in patients with primary restless legs syndrome, according to a meta-analysis of 6 trials of 1,679 patients (pp. 255–62). ìOur meta-analysis found that at baseline study patients slept an average of 5.8 hours/night,î the authors write. ìAt the end of 12 weeks, ropinirole-treated patients slept a mean of 2.5 hours/week more and had a 21% greater improvement from baseline in sleep adequacy scores compared with patients receiving placebo. Ropinirole-treated patients also had 14% less sleep disturbance and 8% less daytime somnolence than patients receiving placebo. Clinicians rated 63% of ropinirole-treated patients and 47% of patients receiving placebo as responders based on the [Clinical Global Impression–Improvement] scale. Mixed effects analysis of covariance was used to estimate treatment effect adjusting for study center as a random effect, as well as the following fixed effects known to affect sleep: baseline sleep characteristics, age, sex, and chronic medical conditions. All differences were statistically significant (p<0.05), even after adjusting for multiple comparisons.î (R. A. Hansen)
Warfarin and Pharmacogenomic Testing: Responding to two previous editorials that concluded that pharmacogenomic approaches to warfarin dosing are not ready for general use, an editorialist provides a different perspective by asking ìwhat would Pascal doî (pp. 245–7). His conclusion is that prudence dictates that such testing be incorporated into care now. (J. R. Teagarden, russell_teagarden@medco.com)

>>>PNN NewsWatch
* Transdermal patches that contain aluminum or other metals in their backings, including those used in nicotine-replacement therapy, can overheat during MRI scans and cause skin burns in the immediate area of the patch, FDA cautioned yesterday. The agency is reviewing the labeling and composition of patches, and until more guidance is available, recommends that patients using patches tell the referring physician about their patch use, request advice on removal and disposal before the scan and replacement afterwards, and tell the MRI facility about patch use. In addition, MRI facilities should follow published safe practice recommendations.
* President Obama kicked off his efforts to
reform the nation’s health care system with a retreat-style forum yesterday at the White House. Attendees—including the presidents of Pfizer and PhRMA but no pharmacist representatives—convened at 1 pm for a presidential address, broke into five smaller groups to address problems and potential solutions, and then reconvened at 4 pm for remarks by President Obama and surprise guest Sen. Ted Kennedy. A website, HealthReform.gov, provides a forum for information and idea exchange as the national debate on health care proceeds with a goal of Congressional action during this year.

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 © 2009, 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, 2009 * Vol. 16, No. 44
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 7 issue of Lancet (2009; 372).
Treatment of Rectal Cancer: Short-course preoperative radiotherapy proved to be an effective treatment for patients with operable rectal cancer in a comparison with selective postoperative chemoradiotherapy using 5-fluorouracil (pp. 811–20). Among 1,350 patients, these trends were noted in an intent-to-treat analysis using local recurrence as a primary outcome measure: ìAt the time of analysis, which included all participants, 330 patients had died (157 preoperative radiotherapy group vs 173 selective postoperative chemoradiotherapy), and median follow-up of surviving patients was 4 years. 99 patients had developed local recurrence (27 preoperative radiotherapy vs 72 selective postoperative chemoradiotherapy). We noted a reduction of 61% in the relative risk of local recurrence for patients receiving preoperative radiotherapy (hazard ratio [HR] 0.39, 95% CI 0.27—0.58, p < 0.0001), and an absolute difference at 3 years of 6.2% (95% CI 5.3—7.1) (4.4% preoperative radiotherapy vs 10.6% selective postoperative chemoradiotherapy). We recorded a relative improvement in disease-free survival of 24% for patients receiving preoperative radiotherapy (HR 0.76, 95% CI 0.62—0.94, p = 0.013), and an absolute difference at 3 years of 6.0% (95% CI 5.3—6.8) (77.5% vs 71.5%). Overall survival did not differ between the groups (HR 0.91, 95% CI 0.73—1.13, p = 0.40).î (D. Sebag-Montefiore, david.sebag-montefiore@leedsth.nhs.uk)
Salt Reduction in Metabolic Syndrome: Blood pressure in patients with metabolic syndrome is especially sensitive to sodium intake, report investigators who studied 1,906 Chinese participants without diabetes aged 16 years or older (pp. 829–35). During of 7 days of low-sodium diet followed by 7 days of high-sodium intake, these results were observed: ìOf the 1,881 participants with information regarding metabolic syndrome, 283 had metabolic syndrome. 1,853 participants completed the low-sodium diet and 1,845 completed the high-sodium diet. Multivariable-adjusted mean changes in blood pressure were significantly greater in participants with metabolic syndrome than in those without on both low-sodium and high-sodium diets (p < 0.0001 for all comparisons). Additionally, risk of salt sensitivity rose with increasing numbers of risk factors for metabolic syndrome. Compared with those with no risk factors, participants with four or five had a 3.54-fold increased odds (95% CI 2.05—6.11) of high salt-sensitivity during the low-sodium and a 3.13-fold increased odds (1.80—5.43) of high salt-sensitivity during the high-sodium intervention.î (J. Chen, jchen@tulane.edu)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2009; 337).
Adverse Reactions to Tocolysis During Preterm Labor: At 28 hospitals in the Netherlands and Belgium, tocolytics during preterm labor produced a high incidence of adverse reactions, researchers report (b744). Indomethacin and the Swedish agent atosiban were not linked to reactions: ìOf the 1,920 women treated with tocolytics, 1327 received a single course of treatment (69.1%), 282 sequential courses (14.7%), and 311 combined courses (16.2%). Adverse drug reactions were categorised as serious or mild in 14 cases each. The overall incidence of serious adverse drug reaction was 0.7%. Compared with atosiban, the relative risk of an adverse drug reaction for single treatment with a beta-adrenoceptor agonist was 22.0 (95% confidence interval 3.6 to 138.0) and for single treatment with a calcium antagonist was 12 (1.9 to 69). Multiple drug tocolysis led to five serious adverse drug reactions (1.6%). Multiple gestation, preterm rupture of membranes, and comorbidity were not independent risk factors for adverse drug reactions.î (R. de Heus, R.deHeus-2@umcutrecht.nl)

>>>PNN JournalWatch
* A Patient’s Guide to Taking Coumadin/Warfarin, in Circulation, 2009; 119: e220–2. (S. Z. Goldhaber, sgoldhaber@partners.org)
* Implementing American Heart Association Pediatric and Adult Nutrition Guidelines, in
Circulation, 2009; 119: 1161–75. (S. S. Gidding)
* Unfractionated Heparin Therapy in Infants and Children, in
Pediatrics, 2009; 123: e510–8. (F. Newall, fiona.newall@rch.org.au)
* Efficacy of Inhaled Corticosteroids in Infants and Preschoolers with Recurrent Wheezing and Asthma: A Systematic Review with Meta-analysis, in
Pediatrics, 2009; 123: e519–25. (J. A. Castro-Rodriguez, jacastro17@hotmail.com)

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 © 2009, 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, 2009 * Vol. 16, No. 45
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Mar. 9 issue of the Archives of Internal Medicine (2009; 169).
Palliative Sedation in the Netherlands: Dutch physicians changed prescribing patterns to comply with a national guideline for palliative sedation, or continuous deep sedation, administered with or without artificial hydration (pp. 430–7). Baseline data were gathered in 2003–05, the guideline was introduced in Dec. 2005, and follow-up patterns were surveyed in 2007, as follows: ìThe response rate [in the follow-up period] was 69.3% (n = 341). Of these physicians, 160 reported a last case of continuous sedation in both the baseline and the follow-up studies. Physicians reported a significant increase in patient involvement in decision making, from 72.3% to 82.2%. Pain remained the most often reported reason to start sedation, whereas exhaustion as a reason for sedation increased. The use of benzodiazepines increased from 69.9% to 90.4%. In the first and second measurements, symptom-directed treatment during sedation was applied in 56% to 58% of the cases. In the second period, there was more often an explicit decision to not give artificial hydration during sedation (78.8% vs 56.3%). Of the physicians, 34.2% were convinced that sedation shortened the life of the patient because of dehydration.î (J. G. J. Hasselaar, j.hasselaar@anes.umcn.nl)
Editorialists question whether this study puts the ìcart before the horseî (
p. 429): ìThe authors write, ‘The advantage of palliative sedation is that it provides an easy resolution of severe discomfort and refractory symptoms’ Easy for whom? The advantage in this case is likely the physicians’—not the patients’. It is far easier to increase the dose of midazolam than it is to wrestle with the underlying issues of a patient’s care. The option of palliative sedation, appropriately, raises issues that are difficult but essential to discuss. What communication between physician and the patient–family unit took place? How well-served are the patient and family if the issue of artificial hydration was not explicitly discussed in approximately two-thirds of the cases?î (J. H. von Gunten, cvongunten@SDHospice.org)
Vitamin C & Gout: Supplemental intake of vitamin C may be beneficial for preventing gout in men, a study concludes (pp. 502–7). Between 1986 and 2006, these vitamin C/gout patterns were recorded among 46,994 men: ìWe documented 1,317 confirmed incident cases of gout. Compared with men with vitamin C intake less than 250 mg/d, the multivariate relative risk (RR) of gout was 0.83 (95% confidence interval [CI], 0.71–0.97) for total vitamin C intake of 500 to 999 mg/d, 0.66 (0.52–0.86) for 1,000 to 1,499 mg/d, and 0.55 (0.38–0.80) for 1,500 mg/d or greater (P < .001 for trend). The multivariate RR per 500-mg increase in total daily vitamin C intake was 0.83 (95% CI, 0.77–0.90). Compared with men who did not use supplemental vitamin C, the multivariate RR of gout was 0.66 (95% CI, 0.49–0.88) for supplemental vitamin C intake of 1,000 to 1,499 mg/d and 0.55 (0.36–0.86) for 1,500 mg/d or greater (P < .001 for trend).î (H. K. Choi, hchoius@bu.edu)
Mortality Effects of Bezafibrate: The HDL cholesterol–raising agent bezafibrate lowers long-term mortality among patients in proportion to lipid responses to the drug, researchers report (pp. 508–14). In the Bezafibrate Infarction Prevention (BIP) trial, 3,026 patients with coronary heart disease had these outcomes over 16 years of follow-up after the original allocation to bezafibrate or placebo: ìMultivariate analysis demonstrated that patients allocated to bezafibrate therapy experienced a significant 11% reduction (P = .06) in the risk of long-term mortality compared with placebo-allocated patients. Mortality reduction among bezafibrate-allocated patients was related to a significant 22% (P = .008) reduction in the risk of death in patients with an upper-tertile HDL-C response to therapy, whereas among patients with a lower HDL-C response, the risk of death was similar to that of the placebo group (hazard ratio, 0.95; P = .43). Accordingly, the cumulative probability of death at 16 years was significantly lower among bezafibrate-allocated patients with an upper-tertile HDL-C response (32.1%) compared with the placebo group (37.9%; P = .02), whereas patients with a lower HDL-C response to treatment displayed a mortality rate (36.8%) similar to the placebo group (P = .57).î (S. Behar, behar@sheba.health.gov.il)

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 © 2009, 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, 2009 * Vol. 16, No. 46
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 11 issue of JAMA (2009; 301).
Tissue-Cultured Smallpox Vaccine: Attenuated tissue-cultured smallpox vaccine LC16m8 is a good candidate for use during biological attacks, as it provides major skin reactions (ìtakeîWinking and seroconversion among healthy adults and a booster effect in previously vaccinated people, according to a study conducted in Japan (pp. 1025–33). Researchers vaccinated and revaccinated 1,529 and 1,692 adults, respectively, with LC16m8 vaccine given intraepidermally using a bifurcated needle, with these results: ìThe proportions of take in vaccinia-naive and previously vaccinated individuals were 1,443 of 1,529 (94.4% [95% confidence interval {CI}, 93.2%–95.9%] and 1,465 of 1,692 (86.6% [95% CI, 85.0%–88.2%]), respectively. Seroconversion or an effective booster response among the individuals with take was elicited in 37 of 41 (90.2% [95% CI, 81.2%–99.3%]) vaccinia-naive participants and in 93 of 155 (60.0% [95% CI, 52.3%–67.7%]) previously vaccinated participants. One case of allergic dermatitis and another of erythema multiforme, both of which were mild and self-limited, were suspected to be caused by vaccination. No severe adverse events were observed.î (Y. Kanatani, ykanatan@ndmc.ac.jp)
National Tobacco Control Agenda: While the prevalence of tobacco use is now below 20% of the U.S. population, that still translates into 400,000 premature deaths annually, notes the author of a commentary discussing the need to set a national tobacco control agenda (pp. 1058–60). He writes: ìGiven that an estimated 50% of smokers will die of tobacco-caused diseases, it is essential that a coherent funding and implementation plan be developed across [the U.S. Department of Health and Human Services] to ensure that the requisite research is supported and that policies and practices that evidence shows have a high likelihood of reducing tobacco use are promoted. For example, current medications and behavioral programs are only modestly effective and typically help fewer than 30% of smokers quit over the long term. Thus, it is essential to increase the National Institutes of Health budget for cessation research, with the goal of ensuring that treatments exist so that every tobacco user, even the most highly addicted, who wishes to stop can do so. Just as efforts to reduce the morbidity and mortality associated with HIV/AIDS has resulted in 30 antiretroviral drugs that have dramatically decreased AIDS-related mortality, rapid expansion of medication development for smoking cessation is needed. Currently, only 7 medications are approved by the FDA for smoking cessation, and 5 of them are the same medication delivered in different ways.î (S. J. Leischow, sleischow@azcc.arizona.edu)

>>>Health Affairs Report
Source:
Mar/Apr issue of Health Affairs, a theme issue on health information technology (2009; 28).
E-prescribing: E-prescribing continues to be the ìlow hanging fruitî when it comes to expanding use of health information technology, according to authors of a progress report (pp. 393–403): ìAlthough the vast majority of U.S. physicians still handwrite prescriptions, adoption of electronic prescribing is slowly growing. Major barriers to adoption remain, including the inability to electronically submit prescriptions for controlled substances and confusion about standards for data exchange. Federal and state governments and private insurers are using payment and policy incentives to boost e-prescribing because they still believe in its promise for improving the quality and efficiency of health care. However, additional efforts and further investments are needed to reap the benefits of e-prescribing on a national scale.î (M. A. Friedman, Maria.Friedman1@verizon.net)
Kaiser Electronic Health Record: Implementation of an electronic health record and increased use of secure e-mail and other nontraditional, patient-centered care reduced the adjusted number of total office visits at Kaiser Permanente Hawaii by 26.2%, an analysis shows (pp. 323–33). The system was implemented in the second and third quarters of 2005, and primary care office visits dropped by 25.3% between 2004 and 2007. Specialty care office visits fell by 21.5% during this time, while scheduled telephone visits increased more than 8-fold, and secure e-mail messaging increased nearly 6-fold by 2007. (C. Chen, catherine.chen@kp.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 © 2009, 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, 2009 * Vol. 16, 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 (2009; 360).
Hospitalists & Elder Care: As the number of hospitalists has increased in the U.S., the proportion of Medicare patients being cared for in the hospital has risen similarly, according to an analysis of 5% of beneficiaries in 1995, 1997, 1999, and 2001–06 (pp. 1102–12). Hospitalists are now a stable element in acute-care facilities of all types and in all regions of the U.S., the researchers point out, noting these results: ìThe percentage of physicians in general internal medicine who were identified as hospitalists increased from 5.9% in 1995 to 19.0% in 2006, and the percentage of all claims for inpatient evaluation-and-management services by general internists that were attributed to hospitalists increased from 9.1% to 37.1% during this same period. Accompanying the increase in care by hospitalists was an increase in the percentage of all hospitalized Medicare patients who were treated by general internists (both hospitalists and traditional, non–hospital-based general internists), from 46.4% in 1995 to 61.0% in 2006. In a multilevel, multivariable analysis controlling for patient and hospital characteristics, the odds of receiving care from a hospitalist increased by 29.2% per year from 1997 through 2006. In 2006, there was marked geographic variation in the rates of care provided by hospitalists, with rates of more than 70% in some hospital-referral regions.î (Y-F Kuo, yokuo@utmb.edu)
ARRA & Health Care: Signed into law 4 weeks after President Obama’s inauguration, the $787 billion American Recovery and Reinvestment Act of 2009 contains a number of provisions that will have a direct impact on health care, the author of a perspective article explains, including ìbroad federal initiatives for biomedical and comparative effectiveness research, the adoption of health information technology, and the protection of the privacy and security of medical recordsî (pp. 1057–60). ìIn 2004, the Bush administration, by executive order, created the Office of the National Coordinator for Health Information Technology as part of the [Department of Health and Human Services],î writes the author. ìBut Congress had never established the office in law, and its funding has been only about $60 million a year. The stimulus legislation codifies the national coordinator position and office, provides $2 billion for discretionary spending, primarily for grants and loans, and sets a goal of ‘utilization of a certified electronic health record for each person in the United States by 2014.’ It establishes two federal advisory committees on health information technology—one on policy and one on standards—through which the government will work with the private sector and consumer groups to develop the specifics of a nationwide health information network. These include the design of ‘interoperable’ electronic health records that permit the seamless exchange of data among physicians, hospitals, laboratories, pharmacies, and other health care organizations, as well as methods for ensuring the privacy and security of patient data. Standards are to be developed in 2009 and tested and certified in 2010; the DHHS will certify specific products.î (R. Steinbrook, rsteinbrook@attglobal.net)

>>>PNN NewsWatch
* Margaret A. Hamburg, MD, will be appointed FDA Commissioner later this week, the media are reporting. Articles in the New York Times and Washington Post add that Joshua Sharfstein, currently health commissioner in Baltimore, will be named as Hamburg’s chief deputy. Hamburg, former commissioner of health in New York City, is the daughter of two physicians and currently serves on the board of directors of Henry Schein, a marketer of medical, dental, and veterinary products. According to the Schein website, Hamburg currently serves as senior scientist for the Nuclear Threat Initiative/Global Health and Security Initiative, and she served as principal policy advisor to HHS Secretary Donna Shalala in the second term of the Clinton administration.
* Patients with amyotrophic lateral sclerosis now have access to the investigational drug
mecasermin rinfabate (rDNA origin) injection (Iplex, Insmed), FDA announced earlier this week. The agent combines human insulin-like growth factor 1 and human insulin-like growth factor-binding protein-3.

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 © 2009, 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. 13, 2009 * Vol. 16, No. 48
Providing news and information about medications and their proper use

>>>Psychiatry Highlights
Source:
Mar. issue of the American Journal of Psychiatry (2009; 166).
SSRIs & Blood Pressure During Pregnancy: Use of SSRIs during late pregnancy is associated with increased risk of gestational hypertension and preeclampsia, according to authors who analyzed data from 5,731 women in the Slone Epidemiology Center Birth Defects Study from 1998 to 2007 (pp. 320–8). All participants delivered nonmalformed infants and had no underlying hypertension. While concluding that the relationship does not necessarily mean that SSRIs cause increased blood pressure, the investigators report these trends: ìGestational hypertension was present in 9.0% of the 5,532 women who were not treated with SSRIs and 19.1% of the 199 women who were treated with SSRIs. Among women who received treatment, gestational hypertension was present in 13.1% of the 107 women who received treatment only during the first trimester and in 26.1% of the 92 women who continued treatment beyond the first trimester. The occurrence of preeclampsia was 2.4% among women who were not treated with SSRIs, 3.7% among women who were exposed to SSRIs only during the first trimester, and 15.2% among women who continued SSRI treatment beyond the first trimester. Relative to women who did not receive treatment, the adjusted relative risk of preeclampsia was 1.4 for women who discontinued treatment and 4.9 for women who continued treatment.î (S. Toh, swtoh@hsph.harvard.edu)
An editorialist provides clinicians with these recommendations about use of SSRIs during pregnancy (
pp. 268–70): ìClinicians should consider the data in this study as preliminary. If a woman is planning pregnancy, clinicians should not discontinue SSRI medication unless it is the patient’s preference and she and her physician agree that her risk of clinical deterioration is minimal. If a pregnant woman who is receiving treatment with a SSRI develops hypertension or preeclampsia in pregnancy, it is not likely that discontinuation of her SSRI will reverse her hypertension. An underlying propensity for hypertension has probably been unmasked, and it will require antihypertensive treatment. If the condition is preeclampsia, the pathological insult occurred much earlier in pregnancy and cessation of the SSRI will not reverse it. As studies about the treatment of pregnant women with psychiatric illness accumulate, we look forward to additional data that will clarify optimal management strategies.î (K. A. Yonkers, kimberly.yonkers@yale.edu)
Glucose, Lipid Monitoring of Second-Generation Anti-psychotic Agents: Monitoring of plasma lipid and glucose levels in patients taking second-generation antipsychotic agents improved significantly after the American Diabetes Association issued guidelines in 2004 but remains dismally low, researchers report (pp. 345–53). A retrospective cohort analysis of the PharMetrics managed care database for 2000–06 shows these patterns among patients with commercial insurance: ìA total of 5,787 preguideline patients and 17,832 postguideline patients were identified. Baseline lipid testing rates were 8.4% for the preguideline cohort and 10.5% for the postguideline cohort, and the 12-week testing rates were 6.8% and 9.0%, respectively. Baseline glucose testing rates were 17.3% for the preguideline cohort and 21.8% for the postguideline cohort, and the 12-week testing rates were 14.1% and 17.9%, respectively. All four comparisons were statistically significant. Baseline and 12-week testing rates for lipids and glucose in children were the lowest of all age groups.î (D. W. Haupt, hauptd@wustl.edu)

>>>Cardiology Highlights
Source:
Mar. 17 issue of the Journal of the American College of Cardiology (2009; 53).
ìComparative Effectiveness Researchî: The JACC editor wonders just what is meant by the phrase ìcomparative effectiveness research,î to which $1.1 billion was allocated in the American Recovery and Reinvestment Act (pp. 973–5): ìMy first reaction upon learning of the CER program was to think, ‘What’s new?’ Every day we grapple with choosing the diagnostic and therapeutic modalities that will be most effective for our patients. We pride ourselves on practicing evidence-based medicine. The importance of having data upon which to guide these management decisions has long been well recognized. It seemed like the wheel was being reinvented.î (A. N. DeMaria, ademaria@acc.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 © 2009, 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, 2009 * Vol. 16, No. 49
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 14 issue of Lancet (2009; 372).
Need for Prevention in Cardiology: Patients with coronary heart disease must invest in prevention of further decline in myocardial function, conclude investigators from the EUROASPIRE (European Action on Secondary and Primary Prevention by Intervention to Reduce Events) surveys (pp. 929–40). Based on surveys of 3,180, 2,975, and 2,392 patients in EUROASPIRE I, II, and III, the investigators found: ìOverall, the proportion of patients who smoke has remained nearly the same (20.3% in EUROASPIRE I, 21.2% in II, and 18.2% in III; comparison of all surveys p = 0.64), but the proportion of women smokers aged less than 50 years has increased. The frequency of obesity (body-mass index 30 kg/m2) increased from 25.0% in EUROASPIRE I, to 32.6% in II, and 38.0% in III (p = 0.0006). The proportion of patients with raised blood pressure (140/90 mm Hg in patients without diabetes or 130/80 mm Hg in patients with diabetes) was similar (58.1% in EUROASPIRE I, 58.3% in II, and 60.9% in III; p = 0.49), whereas the proportion with raised total cholesterol (4.5 mmol/L) decreased, from 94.5% in EUROASPIRE I to 76.7% in II, and 46.2% in III (p < 0.0001). The frequency of self-reported diabetes mellitus increased, from 17.4%, to 20.1%, and 28.0% (p = 0.004).î
The group concludes, ìThese time trends show a compelling need for more effective lifestyle management of patients with coronary heart disease. Despite a substantial increase in antihypertensive and lipid-lowering drugs, blood pressure management remained unchanged, and almost half of all patients remain above the recommended lipid targets. To salvage the acutely ischaemic myocardium without addressing the underlying causes of the disease is futile; we need to invest in prevention.î (D. Wood,
d.wood@ic.ac.uk)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2009; 337).
Errors in Parenteral Med Administration: In 113 intensive-care units in 27 countries, parenteral medication errors occurred commonly during the administration stage of the drug-use process, report authors of an observational cross-sectional study (b814). These trends were compiled based on self-reports filed by ICU staff: ì861 errors affecting 441 patients were reported: 74.5 (95% confidence interval 69.5 to 79.4) events per 100 patient days. Three quarters of the errors were classified as errors of omission. Twelve patients (0.9% of the study population) experienced permanent harm or died because of medication errors at the administration stage. In a multiple logistic regression with patients as the unit of analysis, odds ratios for the occurrence of at least one parenteral medication error were raised for number of organ failures (odds ratio per increase of one organ failure: 1.19, 95% confidence interval 1.05 to 1.34); use of any intravenous medication (yes v no: 2.73, 1.39 to 5.36); number of parenteral administrations (per increase of one parenteral administration: 1.06, 1.04 to 1.08); typical interventions in patients in intensive care (yes v no: 1.50, 1.14 to 1.96); larger intensive care unit (per increase of one bed: 1.01, 1.00 to 1.02); number of patients per nurse (per increase of one patient: 1.30, 1.03 to 1.64); and occupancy rate (per 10% increase: 1.03, 1.00 to 1.05). Odds ratios for the occurrence of parenteral medication errors were decreased for presence of basic monitoring (yes v no: 0.19, 0.07 to 0.49); an existing critical incident reporting system (yes v no: 0.69, 0.53 to 0.90); an established routine of checks at nurses’ shift change (yes v no: 0.68, 0.52 to 0.90); and an increased ratio of patient turnover to the size of the unit (per increase of one patient: 0.73, 0.57 to 0.93).î (A. Valentin, andreas.valentin@meduniwien.ac.at)

>>>PNN JournalWatch
* Management of Rheumatoid Arthritis: Summary of NICE Guidance, in BMJ, 2009; b702. (C. Deighton, chris.deighton@derbyhospitals.nhs.uk)
* Docetaxel with Cyclophosphamide Is Associated with an Overall Survival Benefit Compared with Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735, in
Journal of Clinical Oncology, 2009; 27: 1177–83. (S. Jones, Steve.Jones@USOncology.com)
* Eradication of Methicillin-Resistant
Staphylococcus aureus Carriage: A Systematic Review, in Clinical Infectious Diseases, 2009; 48: 922–30. (H. S. M. Ammerlaan, H.Ammerlaan@umcutrecht.nl)
* Raltegravir: The First HIV Type 1 Integrase Inhibitor, in
Clinical Infectious Diseases, 2009; 48: 931–9. (C. Hicks, charles.hicks@duke.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 © 2009, 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, 2009 * Vol. 16, No. 50
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Mar. 17 issue of the Annals of Internal Medicine (2009; 150).
B-Type Natriuretic Peptide Testing: In a study conducted in two Australian emergency departments, researchers found no clinical benefit or improved outcomes from B-type natriuretic peptide (BNP) testing of all severely dyspneic patients (pp. 365–71). For 612 consecutive patients who presented with such symptoms in 2005–07, these results were recorded for those who did or did not receive BNP testing: ìThere were no between-group differences in hospital admission rates (85.6% [BNP group] vs. 86.6% [control group]; difference, –1.0 percentage point [95% CI, –6.5 to 4.5 percentage points]; P = 0.73), length of admission (median, 4.4 days [interquartile range, 2 to 9 days] vs. 5.0 days [interquartile range, 2 to 9 days]; P = 0.94), or management of patients in the emergency department. Test discrimination was good (area under the receiver-operating characteristic curve, 0.87 [CI, 0.83 to 0.91]). Adverse events were not measured.î (H-G Schneider, schneiderh@alfred.org.au)
ASA for Cardiovascular Disease Prevention: Use of aspirin for prevention of cardiovascular disease is studied in a research article, and recommendations are made in newly issued clinical guidelines that were developed based on a literature review that is also published in this issue.
In a post-hoc analysis of data from a randomized controlled trial, daily aspirin doses of 75–81 mg provided the best balance of efficacy and safety among 15,595 patients with cardiovascular disease or multiple risk factors (pp. 379–86). Particularly in those on dual platelet therapy, the lower aspirin doses were better, as noted in these findings about a composite outcome of myocardial infarction, stroke, or cardiovascular death (efficacy end point) or incidence of severe or life-threatening bleeding (safety end point): ìDaily aspirin doses were categorized as less than 100 mg (75 or 81 mg) (n = 7,180), 100 mg (n = 4,961), and greater than 100 mg (150 or 162 mg) (n = 3,454). The hazard of the primary efficacy end point was the same regardless of dose (adjusted hazard ratio, 0.95 [95% CI, 0.80 to 1.13] for 100 mg vs. less than 100 mg, and 1.0 [CI, 0.85 to 1.18] for greater than 100 mg vs. less than 100 mg). The hazard of the primary safety end point also did not depend on dose (adjusted hazard ratio, 0.85 [CI, 0.57 to 1.26] for 100 mg vs. less than 100 mg and 1.05 [CI, 0.74 to 1.48] for greater than 100 mg vs. less than 100 mg). In patients also receiving clopidogrel, daily aspirin doses greater than 100 mg seemed to be non–statistically significantly associated with reduced efficacy (adjusted hazard ratio, 1.16 [CI, 0.93 to 1.44]) and increased harm (adjusted hazard ratio, 1.30 [CI, 0.83 to 2.04]).î (S. R. Steinhubl,
steven.steinhubl@themedco.com)
Evidence provided by a literature review (
pp. 405–10; Agency for Healthcare Research and Quality) produced these recommendations of a U.S. Preventive Services Task Force (pp. 396–404; USPSTF):
* Encourage men age 45 to 79 years to use aspirin when the potential benefit of a reduction in myocardial infarctions outweighs the potential harm of an increase in gastrointestinal hemorrhage. (A recommendation)
* Encourage women age 55 to 79 years to use aspirin when the potential benefit of a reduction in ischemic strokes outweighs the potential harm of an increase in gastrointestinal hemorrhage. (A recommendation)
* Evidence is insufficient to assess the balance of benefits and harms of aspirin for cardiovascular disease prevention in men and women 80 years or older. (I statement)
* Do not encourage aspirin use for cardiovascular disease prevention in women younger than 55 years and in men younger than 45 years. (D recommendation)

>>>PNN NewsWatch
* With the 25th anniversary of the discovery of HIV as the causative factor in AIDS coming up on May 4 of this year, Robert C. Gallo, MD, who codiscovered the virus (with Luc Montagnier of the Pasteur Inst.) and developed a blood test for HIV infection, reflects on his achievements during the past 25 years and prospects for a vaccine in a YouTube video.

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 © 2009, 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, 2009 * Vol. 16, No. 51
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 18 issue of JAMA (2009; 301).
Modafinil & Dopamine: In 10 healthy men, modafinil blocked central dopamine transporters and increased dopamine in the brain, indicating that it has abuse potential, researchers report (pp. 1148–54). Using positron emission tomography with [11C]raclopride (D2/D3 radioligand sensitive to changes in endogenous dopamine) and [11C]cocaine (dopamine transporter radioligand), the investigators found these acute changes over an 8-month period when the volunteers took 200 or 400 mg doses of modafinil in a laboratory: ìModafinil decreased mean (SD) [11C]raclopride binding potential in caudate (6.1% [6.5%]; 95% confidence interval [CI], 1.5% to 10.8%; P = .02), putamen (6.7% [4.9%]; 95% CI, 3.2% to 10.3%; P = .002), and nucleus accumbens (19.4% [20%]; 95% CI, 5% to 35%; P = .02), reflecting increases in extracellular dopamine. Modafinil also decreased [11C]cocaine binding potential in caudate (53.8% [13.8%]; 95% CI, 43.9% to 63.6%; P < .001), putamen (47.2% [11.4%]; 95% CI, 39.1% to 55.4%; P < .001), and nucleus accumbens (39.3% [10%]; 95% CI, 30% to 49%; P = .001), reflecting occupancy of dopamine transporters.î
The authors reached this conclusion: ìIn this pilot study, modafinil acutely increased dopamine levels and blocked dopamine transporters in the human brain. Because drugs that increase dopamine have the potential for abuse, and considering the increasing use of modafinil for multiple purposes, these results suggest that risk for addiction in vulnerable persons merits heightened awareness.î (N. D. Volkow,
nvolkow@nida.nih.gov)
Pactimibe Inhibition of ACAT & Carotid Atherosclerosis: In the Carotid Atherosclerosis Progression Trial Investigating Vascular ACAT Inhibition Treatment Effects (CAPTIVATE) study, use of pactimibe to inhibit acyl coenzyme A:cholesterol acyltransferase (ACAT) yielded no effects on atherosclerosis as measured by changes in carotid intima-media thickness (CIMT) (pp. 1131–9). Ultrasound studies conducted over the 24-month trial showed these results with pactimibe 100 mg/d in comparison with placebo: ìBecause pactimibe failed to show efficacy in the intravascular coronary ultrasound ACTIVATE study, the CAPTIVATE study was terminated prematurely after a follow-up of 15 months. After 6 months of treatment with pactimibe, low-density lipoprotein cholesterol increased by 7.3% (SD, 23%) compared with 1.4% (SD, 28%) in the placebo group (P = .001). The carotid ultrasonographic scans of the 716 patients with at least 2 scans and obtained at least 40 weeks apart were analyzed. Maximum CIMT measurements did not show a pactimibe treatment effect (difference, 0.004 mm; 95% confidence interval [CI], –0.023 to 0.015 mm; P = .64); however, the less variable mean CIMT measurement revealed an increase of 0.014 mm (95% CI, –0.027 to 0.000 mm; P = .04) in patients administered pactimibe vs placebo. Major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) occurred more often in patients administered pactimibe vs placebo (10/443 [2.3%] vs 1/438 [0.2%]; P = .01).î (E. de Groot, ericdegroot@amc.uva.nl)
Endocannabinoid Signaling & Depressive Illness: Discussing recent recommendations of the European Medicines Agency to suspend rimonabant and last year’s FDA rejection of the weight-loss drug’s new drug application, authors of a commentary make these observations about endocannabinoid signaling and clinical depression (pp. 1165–6): ìPharmacologically, rimonabant and [the related drug] otenabant act through antagonism of the cannabinoid CB1 receptor; thus, these clinical developments suggest that blockade of the CB1 receptor exerts adverse effects on emotional behavior and mood regulation. Given the therapeutic potential of these drugs for the treatment of obesity and nicotine dependence, the emerging psychiatric consequences of CB1 receptor blockers are quite unfortunate; however, the termination of these compounds should not hamper future research examining alternative targets for the treatment of these disorders. Regardless, this serendipitous clinical finding may further the medical community’s understanding of the role of CB1 receptor signaling in the etiology of depressive illness and the potential of this receptor system in the development of a new class of pharmaceutical treatment for depression.î (M. N. Hill, mhill@rockefeller.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 © 2009, 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, 2009 * Vol. 16, No. 52
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 19 issue of and early-release articles from the New England Journal of Medicine (2009; 360).
Vaccine Prevention of Maternal CMV Infection: Administration of cytomegalovirus to mothers within 1 year after they have given birth reduces incident cases of maternal and congenital CMV infections, researchers report (pp. 1191–9). Administering CMV glycoprotein B vaccine or placebo at 0, 1, and 6 months to seronegative women, the investigator determined: ìWe randomly assigned 234 subjects to receive the CMV vaccine and 230 subjects to receive placebo. A scheduled interim analysis led to a stopping recommendation because of vaccine efficacy. After a minimum of 1 year of follow-up, there were 49 confirmed infections, 18 in the vaccine group and 31 in the placebo group. Kaplan–Meier analysis showed that the vaccine group was more likely to remain uninfected during a 42-month period than the placebo group (P = 0.02). Vaccine efficacy was 50% (95% confidence interval, 7 to 73) on the basis of infection rates per 100 person-years. One congenital infection among infants of the subjects occurred in the vaccine group, and three infections occurred in the placebo group. There were more local reactions (pain, erythema, induration, and warmth) and systemic reactions (chills, arthralgias, and myalgias) in the vaccine group than in the placebo group.î (R.F. Pass, rpass@peds.uab.edu)
Editorialists laud this development (
pp. 1250–2): ìIn the study by Pass et al., more adverse events occurred in vaccine recipients than in those receiving placebo, but these events were generally mild, suggesting that the vaccine’s safety is acceptable for further studies. Given the experience with rubella, vaccination to prevent congenital CMV infection is likely to require universal infant immunization, which sets a high bar for vaccine safety, particularly for a vaccine containing a new adjuvant. The development of an effective CMV vaccine remains a daunting task that will benefit from creative development and trial-design strategies. Even so, the prevention of the burden of congenital CMV infection—despite all the challenges—must remain a high priority.î (C. L. Dekker)
Genetic Compensation: French investigators, including several holding PharmD/PhD degrees, identify a case of genetic compensation in a man with a genomic disorder (pp. 1211–6): ìCytogenetic studies of the parents of a girl with the DiGeorge (or velocardiofacial) syndrome, who carried a deletion at 22q11.2, revealed an unexpected rearrangement of both 22q11.2 regions in the unaffected father. He carried a 22q11.2 deletion on one copy of chromosome 22 and a reciprocal 22q11.2 duplication on the other copy of chromosome 22. Genetic compensation, which is consistent with the normal phenotype of the father, was shown through quantitative-expression analyses of genes located within the genetic region associated with the DiGeorge syndrome. This finding has implications for genetic counseling and represents a case of genetic compensation in a human genomic disorder.î (E. Flori, elisabeth.flori@chru-strasbourg.fr)
Screening & Prostate Cancer Mortality: Two early-release articles present conflicting evidence about prostate cancer outcomes in men screened annually using prostate-specific–antigen testing and/or digital rectal examinations. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial reports no significant difference in rates of death from prostate cancer during 7–10 years of monitoring in men offered annual PSA testing for 6 years and DRE for 4 years, compared with those receiving usual care (10.1056/NEJMoa0810696; C. D. Berg, bergc@mail.nih.gov). In a second report, PSA-based screening resulted in 20% fewer deaths from prostate cancer but with a substantial risk of overdiagnosis. The European Randomized Study of Screening for Prostate Cancer offered PSA screening to men once every 4 years beginning in the early 1990s. Cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in a control group, and the risk of death from prostate cancer was 0.8 among screened men. Investigators note, ìThis means that 1,410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer.î (10.1056/NEJMoa0810084; F. H. Schrˆder, secr.schroder@erasmusmc.nl)

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 © 2009, 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. 20, 2009 * Vol. 16, No. 53
Providing news and information about medications and their proper use

>>>Allergy/Immunology Report
Source:
Mar. issue of the Journal of Allergy and Clinical Immunology (2009; 123).
High-Dose Desloratadine for Urticaria: In 30 patients with acquired cold urticaria (ACU), increased doses of desloratadine significantly reduced lesion severity (pp. 672–9). Investigators concluded that the study supports guidelines recommending high-dose desloratadine in patients nonresponsive to standard doses, citing these effects of 5 versus 20 mg doses of the drug on critical temperature threshold (CTT) and critical stimulation time threshold (CSTT) during cold provocation tests: ìCompared with placebo, 7 days of desloratadine at 5 and 20 mg/d significantly reduced the volume of cold-induced wheals and areas of hyperthermic skin and improved CTT and CSTT results. Desloratadine at 20 mg/d significantly reduced cold-induced wheal volume and CTT and CSTT values versus desloratadine at 5 mg/d. Desloratadine was well tolerated, with no increased rate of somnolence or other [adverse effects] with 20 mg of desloratadine.î (M. Maurer, marcus.maurer@charite.de)

>>>Chest Highlights
Source:
Mar. issue of Chest (2009; 135).
Asthma Management in EDs: Objective assessment of airflow rates, use of systemic steroids, and referrals are areas requiring education of physicians in emergency departments, according to a study of asthma management in 16 Ontario hospitals (pp. 724–36). Care of patients younger than 20 years and older individuals with asthma showed these trends in surveys and chart reviews of nearly 5,000 patients: ìAsthma severity, comorbidities, access to care, and prehospital management varied significantly among sites (all p < 0.001). Documentation of peak expiratory flow (27.2% of pediatric [age 7] and 44.3% of adult charts), use of systemic steroids in ED (35.2% pediatric and 33.0% adult charts) and on discharge (31.7% pediatric and 33.2% adult charts), and referrals to asthma services (2.8% pediatric and 2.7% adult charts) varied among sites (all p < 0.001). Admission (%) was directly related to time to receive systemic steroids in ED in adults (r = 0.76; p = 0.004). Repeat ED visits (%) were inversely related to new inhaled steroid prescription on discharge in adults (r = −0.64; p = 0.02).î (M. D. Lougheed, mdl@queensu.ca)
PE in COPD: Pulmonary emboli are common among patients with chronic obstructive pulmonary disorder who require hospitalization, according to a systematic review and meta-analysis (pp. 786–93). Concluding that ìa diagnosis of PE should be considered in patients with exacerbation severe enough to warrant hospitalization,î the authors write: ìOf the 2,407 articles identified, 5 met the inclusion criteria (sample size, 550 patients). Overall, the prevalence of PE was 19.9% (95% confidence interval [CI], 6.7 to 33.0%; p = 0.014). In hospitalized patients, the prevalence was higher at 24.7% (95% CI, 17.9 to 31.4%; p = 0.001) than those who were evaluated in the emergency department (3.3%). Presenting symptoms and signs were similar between patients who did and did not have PE.î (D. D. Sin, dsin@mrl.ubc.ca)

>>>PNN NewsWatch
* FDA cautioned yesterday that insulin pens and cartridges are never to be shared among patients. Sharing of insulin pens may result in transmission of hepatitis viruses, HIV, or other blood-borne pathogens, the agency warned. Insulin pens are not designed, and are not safe, for one pen to be used for more than one patient, even if needles are changed between patients, FDA continued, because any blood contamination of the pen reservoir could result in transmission of already existing blood-borne pathogens from the previous user. The FDA is working with CDC, professional societies, and health care organizations to reinforce patient and health care provider education about proper and safe use of insulin pens.
*
Cost of prescription medication continues to present ìsticker shockî to Americans, according to a Consumer Reports poll. Among 2004 interviewees, 66% learned the prescription cost at the pharmacy counter, 4% had conversations with prescribers about Rx costs, and 28% had taken ìpotentially dangerous actions to save money, such as not filling prescriptions, skipping dosages, and cutting pills in half without the approval of their doctor.î

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 © 2009, 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, 2009 * Vol. 16, No. 54
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 21 issue of Lancet (2009; 372).
Blood Pressure & Cardiovascular Events in Dialysis: Patients undergoing dialysis should routinely be treated with hypotensive agents, concludes a systematic review and meta-analysis showing that lowering of blood pressures reduces the ìvery high cardiovascular morbidity and mortality rate in this populationî (pp. 1009–15). ìWe identified eight relevant trials, which provided data for 1,679 patients and 495 cardiovascular events,î the authors write. ìWeighted mean systolic blood pressure was 4.5 mm Hg lower and diastolic blood pressure 2.3 mm Hg lower in actively treated patients than in controls. Blood pressure lowering treatment was associated with lower risks of cardiovascular events (RR 0.71, 95% CI 0.55—0.92; p = 0.009), all-cause mortality (RR 0.80, 0.66—0.96; p = 0.014), and cardiovascular mortality (RR 0.71, 0.50—0.99; p = 0.044) than control regimens. The effects seem to be consistent across a range of patient groups included in the studies.î (V. Perkovic, vperkovic@george.org.au)
Measles Immunity & HIV Infection: Measles virus transmission was not interrupted by a supplemental immunization activity (SIA) in a population with high percentages of children with HIV-1 antibodies (pp. 1025–32). Testing oral fluid samples for measles and HIV antibodies, the researchers found these patterns 3 years after an SIA in Zambia: ì1,015 children from 668 residences provided adequate specimens. 853 (84%) children had a history of measles vaccination according to either caregiver report or immunisation card. 679 children (67%) had antibodies to measles virus, and 64 (6%) children had antibodies to HIV-1. Children with antibodies to HIV-1 were as likely to have no history of measles vaccination as those without antibodies to HIV-1 (odds ratio [OR] 1.17, 95% CI 0.57—2.41). Children without measles antibodies were more likely to have never received measles vaccine than those with antibodies (adjusted OR 2.50, 1.69—3.71). In vaccinated children, 33 (61%) of 54 children with antibodies to HIV-1 also had antibodies to measles virus, compared with 568 (71%) of 796 children without antibodies to HIV-1 (p = 0.1).î (W. J. Moss, wmoss@jhsph.edu)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2009; 337).
Larval Therapy for Leg Ulcers: A cost-effectiveness analysis shows that larval therapy is equivalent to hydrogel when used for debridement of necrotic leg ulcers (doi: 10.1136/bmj.b825). Based on costs and outcomes in 267 patients with venous or mixed venous and arterial ulcers with at least 25% coverage of slough or necrotic tissue, the investigators found: ìTreatment with larval therapy cost, on average, £96.70 (109.61 euros; $140.57) more per participant per year (95% confidence interval –£491.9 to £685.8) than treatment with hydrogel. Participants treated with larval therapy healed, on average, 2.42 days before those in the hydrogel arm (95% confidence interval –0.95 to 31.91 days) and had a slightly better health related quality of life, as the annual difference in [quality-adjusted life–years] was 0.011 (95% confidence interval –0.067 to 0.071). However, none of these differences was statistically significant. The incremental cost effectiveness ratio for the base case analysis was estimated at £8826 per QALY gained and £40 per ulcer-free day. Considerable uncertainty surrounds the outcome estimates.î (M. O. Soares, ms602@york.ac.uk)

>>>PNN NewsWatch
* The dietary supplement product Zencore Plus is being recalled nationwide, FDA and Bodee LLC announced. According to an FDA lab analysis of samples, the product contains the phosphodiesterase-5 inhibitor benzamidenafil. Zencore Plus is sold in health food stores and by mail order on the Internet. Consumers who have this product in their possession should stop using it immediately, FDA advised.

>>>PNN JournalWatch
* Burden of Digestive Diseases in the United States Part II: Lower Gastrointestinal Diseases, in Gastroenterology, 2009; 136: 741–54. (J. E. Everhart)
* Clinical Practice Guideline for the Evaluation of Fever and Infection in Older Adult Residents of Long-Term Care Facilities: 2008 Update by the Infectious Diseases Society of America, in
Journal of the American Geriatrics Society, 2009; 57: 375–94. (K. P. High, khigh@wfubmc.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 © 2009, 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, 2009 * Vol. 16, No. 55
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Mar. 23 issue of the Archives of Internal Medicine (2009; 169).
Vitamin D Doses & Fracture Prevention: A meta-analysis, conducted with data from 20 randomized controlled trials of 83,000 patients, shows that vitamin D prevention of nonvertebral fractures is dependent its dose and that doses higher than 400 IU/d should reduce fractures by at least 20% in older individuals (pp. 551–61). Studies compared effects of placebo and oral vitamin D with or without calcium, with these results: ìThe pooled relative risk (RR) was 0.86 (95% confidence interval [CI], 0.77–0.96) for prevention of nonvertebral fractures and 0.91 (95% CI, 0.78–1.05) for the prevention of hip fractures, but with significant heterogeneity for both end points. Including all trials, antifracture efficacy increased significantly with a higher dose and higher achieved blood 25-hydroxyvitamin D levels for both end points. Consistently, pooling trials with a higher received dose of more than 400 IU/d resolved heterogeneity. For the higher dose, the pooled RR was 0.80 (95% CI, 0.72–0.89; n = 33 265 subjects from 9 trials) for nonvertebral fractures and 0.82 (95% CI, 0.69–0.97; n = 31 872 subjects from 5 trials) for hip fractures. The higher dose reduced nonvertebral fractures in community-dwelling individuals (–29%) and institutionalized older individuals (–15%), and its effect was independent of additional calcium supplementation.î (H. A. Bischoff-Ferrari, heike.bischoff@usz.ch)
Treatment of Hypertriglyceridemia: Therapeutic lifestyle change remains the preferred treatment for hypertriglyceridemia, a common condition among Americans, researchers report (pp. 572–8). Examining data for 5,610 participants aged 20 years or older from the National Health and Nutrition Examination Surveys from 1999 to 2004, the investigators found: ìThe unadjusted prevalence (percentage [SE]) of a TG concentration of 150 mg/dL or higher (to convert triglycerides to millimoles per liter, multiply by 0.0113) was 33.1% (0.8%); a TG concentration of 200 mg/dL or higher, 17.9% (0.7%), a TG concentration of 500 mg/dL or higher, 1.7% (0.2%), and a TG concentration of 1000 mg/dL or higher, 0.4% (0.1%). Overall, 1.3% (0.2%) of participants used 1 of 3 prescription medications indicated to treat hypertriglyceridemia (ie, fenofibrate, gemfibrozil, or niacin); this percentage was 2.6% (0.4%) among participants with a TG concentration of 150 mg/dL or higher and 3.6% (0.7%) among participants with a TG concentration of 200 mg/dL or higher.î (E. S. Ford, eford@cdc.gov)
In an invited commentary on this topic, authors write (
pp. 578–9): ìPhysicians should certainly recommend intensive lifestyle changes to their patients. If pharmacologic therapy is deemed necessary, statins have proven effects on mortality and should be tried first. Some have argued that statins reduce mortality by only 30% and that additional pharmacologic therapy to treat elevated TG concentration is warranted. However, there are no data proving that additional drug treatment will reduce mortality. If statins and lifestyle change are insufficient, then fish oil or niacin should be considered. Fibrates should be reserved for TG concentrations higher than 1,000 mg/dL that do not respond to other treatments.î (W. G. Thompson, thompson.warren@mayo.edu)
Long-term Metformin Effects: Based on improved glycemic parameters and reduced long-term risk of macrovascular disease, metformin should be continued after patients with type 2 diabetes require addition of insulin, a study of 390 patients shows (pp. 616–25). Over a follow-up period of 4.3 years, metformin failed to significantly affect a primary end point of microvascular and macrovascular morbidity and mortality, but the drug did prevent weight gain (mean weight gain, –3.07 kg [range, –3.85 to –2.28 kg]; P < .001), improve glycemic control (mean reduction in A1c level, 0.4% percentage point [95% CI, 0.55-0.25]; P < .001), and reduce insulin requirements (mean reduction, 19.63 IU/d [95% CI, 24.91-14.36 IU/d]; P < .001), and, based partly on the decreased weight, improve the macrovascular end point (hazard ratio, 0.61 (95% CI, 0.40–0.94; P = .02). (A. Kooy, kooy.a@bethesda.nl)

>>>PNN NewsWatch
* FDA has expanded its recall of tainted weight-loss products, originally announced on Dec. 22 and Jan. 8, to include 72 products.

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 © 2009, 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, 2009 * Vol. 16, No. 56
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 25 issue of JAMA (2009; 301).
Collaborative Care for Chronic Pain: Care was improved modestly but significantly through a collaborative primary care approach to management of chronic pain, report researchers from SEACAP, the Study of the Effectiveness of a Collaborative Approach to Pain (pp. 1242–52). In this cluster randomized controlled trial, 401 patients at 5 primary care clinics of a VA medical center received either usual or collaborative care, with the latter including two sessions of clinician education program, patient assessment, education and activation, symptom monitoring, feedback and recommendations to clinicians, and facilitation of specialty care. Results showed: ìIntervention patients had a mean (SD) of 10.6 (4.5) contacts with the assistance with pain treatment team. Compared with the patients receiving treatment as usual, intervention patients showed greater improvements in pain-related disability (Roland–Morris Disability Questionnaire beta, –0.101 [95% confidence interval {CI}, –0.163 to –0.040]; P = .004 and [Chronic Pain Grade (CPG)] Pain Intensity subscale beta, –0.270 [95% CI, –0.480 to –0.061]; P = .01). Among patients with baseline depression (Patient Health Questionnaire 9 [PHQ-9] score 10), there was greater improvement in depression severity in patients receiving the intervention compared with patients receiving treatment as usual (PHQ-9 beta, –0.177 [95% CI, –0.295 to –0.060]; P = .003). The differences in scores between baseline and 12 months for the assistance with pain treatment intervention group and the treatment as usual group, respectively, were –1.4 vs –0.2 for the Roland–Morris Disability Questionnaire, –4.7 vs –0.6 for the CPG Pain Intensity subscale, and –3.7 vs –1.2 for PHQ-9.î (S. K. Dobscha, steven.dobscha@va.gov)
Chlorhexidine Sponge Changes & Catheter-Related Infections: Use of chlorhexidine gluconate–impregnated sponges (CHGISs) in intravascular catheter dressings can reduce infection risk even when background infection rates are low, researchers report, adding that unsoiled dressings can be changed every 7 days rather than every 3 days (pp. 1231–41). In patients in intensive-care units, major catheter-related infections (CRIs) and colonization rates showed these patterns when dressings were changed every 3 versus every 7 days: ìOf 2,095 eligible patients, 1,636 (3,778 catheters, 28,931 catheter–days) could be evaluated. The median duration of catheter insertion was 6 (interquartile range [IQR], 4–10) days. There was no interaction between the interventions. Use of CHGIS dressings decreased the rates of major CRIs (10/1953 [0.5%], 0.6 per 1000 catheter–days vs 19/1,825 [1.1%], 1.4 per 1,000 catheter-days; hazard ratio [HR], 0.39 [95% confidence interval {CI}, 0.17–0.93]; P = .03) and catheter-related bloodstream infections (6/1,953 catheters, 0.40 per 1,000 catheter-days vs 17/1,825 catheters, 1.3 per 1,000 catheter–days; HR, 0.24 [95% CI, 0.09–0.65]). Use of CHGIS dressings was not associated with greater resistance of bacteria in skin samples at catheter removal. Severe CHGIS-associated contact dermatitis occurred in 8 patients (5.3 per 1,000 catheters). Use of CHGIS dressings prevented 1 major CRI per 117 catheters. Catheter colonization rates were 142 of 1,657 catheters (7.8%) in the 3-day group (10.4 per 1,000 catheter–days) and 168 of 1,828 catheters (8.6%) in the 7-day group (11.0 per 1,000 catheter–days), a mean absolute difference of 0.8% (95% CI, –1.78% to 2.15%) (HR, 0.99; 95% CI, 0.77–1.28), indicating noninferiority of 7-day changes. The median number of dressing changes per catheter was 4 (IQR, 3–6) in the 3-day group and 3 (IQR, 2–5) in the 7-day group (P < .001).î (J-F Timsit, jftimsit@chu-grenoble.fr)
Liability with HIT: Health information technology vendors typically insist on legal protection from flaws in software and systems, authors write, concluding with this opinion (pp. 1276–8): ìVendors shifted liability to users and inserted other contractual language that effectively concealed from users the fuller knowledge of serious faults in their HIT systems. Those steps are both counterproductive and unethical. Reducing incentives for getting software right is neither a prescription for HIT health nor for lessened patient harm. Whether the industry is obliged to accept traditional liability, regulatory oversight, or both, restricting the hold harmless/learned intermediary clauses should help to speed the repair of faulty HIT.î (R. Koppel, rkoppel@sas.upenn.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 © 2009, 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, 2009 * Vol. 16, No. 57
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release articles from and the Mar. 26 issue of the New England Journal of Medicine (2009; 360).
Use of HIT in U.S. Hospitals: Very few hospitals in the U.S. are using comprehensive electronic-records systems, researchers report, adding that ìa policy strategy focused on financial support, interoperability, and training of technical support staff may be necessary to spur adoption of electronic-records systems in U.S. hospitalsî (10.1056/NEJMsa0900592). The 2008 survey of all acute-care hospitals in this country shows: ìOn the basis of responses from 63.1% of hospitals surveyed, only 1.5% of U.S. hospitals have a comprehensive electronic-records system (i.e., present in all clinical units), and an additional 7.6% have a basic system (i.e., present in at least one clinical unit). Computerized provider-order entry for medications has been implemented in only 17% of hospitals. Larger hospitals, those located in urban areas, and teaching hospitals were more likely to have electronic-records systems. Respondents cited capital requirements and high maintenance costs as the primary barriers to implementation, although hospitals with electronic-records systems were less likely to cite these barriers than hospitals without such systems.î (A. K. Jha, ajha@hsph.harvard.edu)
Calling the American Recovery and Reinvestment Act of 2009 (ARRA) ìhistoric health care legislation of the type rarely produced by our famously incremental federal government,î the author of a commentary writes about the effects of the law on adoption of health information technology (HIT) (
10.1056/NEJMp0901592): ìFrom the standpoint of physicians, the legislation’s most important provision may be $17 billion in financial incentives intended to get doctors and hospitals to adopt and use [electronic health records (EHRs)]. Starting in 2011, physicians can receive extra Medicare payments for the ‘meaningful use’ of a ‘certified’ EHR that can exchange data with other parts of the health care system. These payments can total as much as $18,000 in the first year in the case of physicians who adopt in 2011 or 2012, with at least $15,000 for physicians who adopt in 2013 and a slightly lower amount for those who do so in 2014; incentives are gradually reduced and then ended in 2016. Thus, physicians demonstrating meaningful use starting in 2011 could collect $44,000 over 5 years. Waiting until 2013 would result in a maximum bonus of $27,000 over 3 years. Experts estimate the cost of purchasing, installing, and implementing an electronic-records system in a medical office at about $40,000.î (D. Blumenthal)
Glucose Control in Critically Ill Patients: Intensive glucose control increased mortality among adults in intensive-care units, report investigators from the NICE-SUGAR (Normoglycemia in Intensive Care Evaluation–Survival Using Glucose Algorithm Regulation) study (pp. 1283–97). Comparing intensive control, with a blood glucose goal of 81–108 mg/dL, against standard care targeted at keeping levels below 180 mg/dL, the investigators found: ìOf the 6,104 patients who underwent randomization, 3,054 were assigned to undergo intensive control and 3,050 to undergo conventional control; data with regard to the primary outcome [death from any cause within 90 days after randomization] at day 90 were available for 3,010 and 3,012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P = 0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P = 0.10). Severe hypoglycemia (blood glucose level, 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3,016 patients (6.8%) in the intensive-control group and 15 of 3,014 (0.5%) in the conventional-control group (P < 0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P = 0.84) or hospital (P = 0.86) or the median number of days of mechanical ventilation (P = 0.56) or renal-replacement therapy (P = 0.39).î (S. Finfer, sfinfer@george.org.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 © 2009, 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. 27, 2009 * Vol. 16, No. 58
Providing news and information about medications and their proper use

>>>Nephrology Highlights
Source:
Mar. and Apr. issues of the American Journal of Kidney Diseases (2009; 53).
Pentoxifylline & GFR in CKD: Use of pentoxifylline in patients with chronic kidney disease may slow the decline in glomerular filtration rates, according to a study of 40 ambulatory patients who also had hypertension and proteinuria of more than 1 g/24 h (pp. 606–16). Concluding that the observed effects may be independent of pentoxifylline’s antiproteinuric effects, the researchers note these results with 400-mg doses of the drug for up to 12 months: ìAt 1 year, the mean estimated GFR decrease was significantly less in the pentoxifylline group than the placebo group (−1.2 ± 7.0 versus −7.2 ± 8.2 mL/min/1.73 m2/y; mean difference, −6.0 mL/min/1.73 m2/y; 95% confidence interval, −11.4 to −0.6; P = 0.03). For pentoxifylline-treated participants, the mean estimated GFR decrease during treatment was slower compared with the year before study enrollment (−9.6 ± 11.9 mL/min/1.73 m2/y; mean difference, −8.4 mL/min/1.73 m2/y; 95% confidence interval, −14.8 to −2.1; P = 0.01). Proteinuria was not different between the pentoxifylline and placebo groups at baseline, 6 months, or 1 year.î (R. M. Perkins, rmperk1@yahoo.com)
Sodium Bicarbonate for Contrast-Induced Nephropathy: For hydration with the goal of preventing contrast-induced nephropathy, sodium bicarbonate is significantly more effective than normal saline, authors of a systematic review and meta-analysis report (pp. 617–27): ìTwelve trials (1,854 participants) were included. Sodium bicarbonate significantly decreased the risk of contrast-induced nephropathy (12 trials, 1,652 patients; odds ratio [OR], 0.46; 95% confidence interval [CI], 0.26 to 0.82; I2 = 55.9%) without a significant difference in need for renal replacement therapy (9 trials, 1,215 patients; OR, 0.50; 95% CI, 0.16 to 1.53; I2 = 0%), in-hospital mortality (11 trials, 1,640 patients; OR, 0.51; 95% CI, 0.15 to 1.69), or congestive heart failure compared with controls. Similar results were seen for the risk of contrast-induced nephropathy when sodium bicarbonate was compared with normal saline alone (OR, 0.39; 95% CI, 0.20 to 0.77), but not when sodium bicarbonate/N-acetylcysteine combination was compared with N-acetylcysteine/normal saline combination (OR, 0.68; 95% CI, 0.34 to 1.37). A subgroup analysis limited to published trials showed similar results (OR, 0.26; 95% CI, 0.10 to 0.64; I2 = 63.3%), whereas unpublished studies showed a nonsignificant decrease (OR, 0.85; 95% CI, 0.46 to 1.57; I2 = 25.9%) in risk of contrast-induced nephropathy.î (S. D. Navaneethan, navanes@ccf.org)
Idiopathic Retroperitoneal Fibrosis, Colchicine, & Steroids: Colchicine may enable reduction in steroid doses as well as prevent recurrence in patients with idiopathic retroperitoneal fibrosis, researchers report (pp. 628–37). In a study of 7 consecutive patients with IRPF diagnosed since 1993 at a navy hospital, colchicine with low induction doses of steroids (less than 0.5 mg/kg/d) produced these results in comparison with regimens with higher steroid doses and/or immunosuppressive drugs: ìAt month 3 of treatment, all patients had symptomatic improvement and 67% had clinical improvement. Between 8 and 12 months, 67% of patients had a decrease in retroperitoneal mass greater than 50%. No recurrence or treatment failure was observed during follow-up (mean, 72.5 months). At the last visit, all patients had a significant decrease in retroperitoneal mass (mean, 79.8% ± 19.7%). One patient died of septic shock on day 21 of treatment.î (J. Vega, jvegastieb@gmail.com)
Vitamin D in CKD: In a study of 610 elderly women with moderate chronic kidney disease, vitamin D3 800 IU daily, with or without calcium supplements, raised 25(OH)D and intact parathyroid hormone levels (pp. 408–16). ìSimilar improvements in the proportion of participants achieving 25(OH)D levels greater than 30 ng/mL at 6 months were seen in all kidney function groups,î the investigators report. (M. Chonchol, michel.chonchol@uchsc.edu)

>>>PNN NewsWatch
* Watson Pharmaceuticals has recalled lot 112680A of Propafenone HCl 225 mg tablets (expiration, 7/31/10), FDA announced this week. The drug is being recalled because some tablets may contain slightly higher levels of the active ingredient than specified.

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 © 2009, 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, 2009 * Vol. 16, No. 59
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 28 issue of Lancet (2009; 372).
Imatinib for GIST: After resection of primary gastrointestinal stromal tumor, adjuvant imatinib was safe and improved recurrence-free survival, compared with placebo, researchers report (pp. 1097–104). In this Phase III trial, patients were randomized to imatinib 400 mg or placebo daily for 1 year after resection, with these intent-to-treat results: ìAt median follow-up of 19.7 months (minimum—maximum 0—56.4), 30 (8%) patients in the imatinib group and 70 (20%) in the placebo group had had tumour recurrence or had died. Imatinib significantly improved recurrence-free survival compared with placebo (98% [95% CI 96—100] vs 83% [78—88] at 1 year; hazard ratio [HR] 0.35 [0.22—0.53]; one-sided p < 0.0001). Adjuvant imatinib was well tolerated, with the most common serious events being dermatitis (11 [3%] vs 0), abdominal pain (12 [3%] vs six [1%]), and diarrhoea (ten [2%] vs five [1%]) in the imatinib group and hyperglycaemia (two [<1%] vs seven [2%]) in the placebo group.î (R. P. DeMatteo, dematter@mskcc.org)
Herd Protection from Mass Antibiotic Distributions: Repeated mass distributions of azithromycin to children could eventually eliminate trachoma in endemic areas, even in untreated individuals, a study shows (pp. 1111–8). Four times per year, the antibiotic was distributed to 4,764 children in 24 political subunits of Amhara, Ethiopia, while treatment was delayed for 6,014 children in 12 other subunits. Looking at prevalence of ocular chlamydial infections, the researchers determined: ìAt 12 months, 637 children aged 1—10 years and 561 adults and children aged 11 years and older were analysed in the children-treated group, and 618 and 550, respectively, in the control group. The mean prevalence of infection in children decreased from 48.4% (95% CI 42.9—53.9) to 3.6% (0.8—6.4) after four mass treatments. At 12 months, the mean prevalence of infection in the untreated age group (11 years) was 47% (95% CI 33—57) less than baseline (p = 0.002), and 35% (95% CI 1—57) less than that in untreated communities (p = 0.04).î (T. M. Lietman, tom.lietman@ucsf.edu)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2009; 337).
Neonatal Vitamin A & Mortality: As a public health intervention in developing countries, administration of vitamin A supplements to neonates cannot be recommended, according to a systematic review of six randomized controlled trials (b919). Results for the first year of infancy and adverse effects during the first 7 days of vitamin A administration showed these patterns: ìThere was no convincing evidence of a reduced risk of mortality during infancy (relative risk 0.92, 95% confidence interval 0.75 to 1.12, P = 0.393 random effect; I2 = 54.1%) or of an increase in early adverse effects including bulging fontanelle (1.16, 0.81 to 1.65, P = 0.418; I2 = 65.3%). No variable emerged as a significant predictor of mortality, but data for important risk groups (high maternal night blindness prevalence and low birth weights) were restricted. Limited data (from one to four trials) did not indicate a reduced risk of mortality during the neonatal period (0.90, 0.75 to 1.08, P = 0.270; I2 = 0%), cause specific mortality, common morbidities (diarrhoea and others), and admission to hospital. There was, however, evidence of an increased risk of acute respiratory infection and a reduced risk of clinic visits.î (H. S. Sachdev, hpssachdev@gmail.com)

>>>PNN NewsWatch
* Correction: Friday’s PNN incorrectly reported that parathyroid hormone levels were raised by vitamin D3 supplementation in a study of patients with moderate chronic kidney disease. In fact, intact PTH levels were decreased by the intervention.

>>>PNN JournalWatch
* Management of Hirsutism, in BMJ, 2009; 338: b847. (G. S. Conway, g.conway@ucl.ac.uk)
* Do the Unintended Actions of Botulinum Toxin at Distant Sites Have Clinical Implications?, in
Neurology, 2009; 72: 1095–9. (A. Berardelli, alfredo.berardelli@uniroma1.it)
* Development of a Medication Therapy Management Superbill for Ambulatory Care/Community Pharmacy Practice, in
Journal of the American Pharmacists Assoc., 2009; 49: 232–6. (M. D. Hogue, mdhogue@samford.edu)
* Dextromethorphan Abuse: Clinical Effects and Management, in
Journal of the American Pharmacists Assoc., 2009; 49: e20–7. (F. Romanelli, froma2@uky.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 © 2009, 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, 2009 * Vol. 16, No. 60
Providing news and information about medications and their proper use

>>>JAPhA Highlights
Source:
Mar/Apr issue of the Journal of the American Pharmacists Assoc., a theme issue on quality in pharmacy practice (2009; 49).
Pharmacist Care of Hypertension: Compared with usual care, medication therapy management services provided by community pharmacists to patients with hypertension an diabetes significantly improved blood pressure control (pp. 164–70). In a 52-patient trial, MTM services were provided monthly to the intervention group, with these intent-to-treat results: ìThe mean intervention group [systolic blood pressure] decreased 17.32 mm Hg, whereas the mean control group SBP level increased 2.73 mm Hg (P = 0.003). The percentage of patients at goal blood pressure increased from 16.0% to 48.0% in the intervention group and decreased from 20.0% to 6.67% in the control group. Intervention group participants were 12.92 times more likely than control group participants to achieve goal blood pressure (P = 0.021). Although the mean adherence rate in the intervention group increased 7.0% while remaining fairly constant in the control group (–0.7%), this group difference was not statistically significant. (L. G. Planas, lourdes-planas@ouhsc.edu)
Dispensing Errors & Counseling: Compared with a similar study conducted 14 years previously, a 2007 assessment in 100 community pharmacies shows a similar dispensing error rate but a significantly decreased frequency of patient counseling (pp. 171–80). The study, which provided the basis of an ABC News 20/20 segment on pharmacy dispensing errors, involved presentation of prescriptions by trained shoppers and recording of pharmacy interactions on hidden video cameras. Results showed: ìOf 100 prescriptions dispensed, 22 had one or more deviation from the physician’s written order, for a 22% dispensing error rate. Three of the errors were judged to be potentially harmful when dispensed to a typical patient requiring these therapies. A total of 43 shoppers (43%) received verbal counseling, including 16 cases in which the shopper prompted counseling. All shoppers received written information with their prescription, covering an average of 90% of the required topics. Some 68% of the warfarin shoppers purchased aspirin without the pharmacist verbally warning about taking the drugs simultaneously.î (E. Flynn, flynnel@auburn.edu)
Pharmacists in Physician Group Practices: As employees of a physician group practice, pharmacists used evidence-based medicine, therapeutic interchange, academic detailing, and a local pharmacy and therapeutics committee to achieve these outcomes (pp. 181–91): ìIn 2006-2007, 71% of our hypertensive patients received generic agents compared with a network average for receiving generic agents of 43%, while the proportion of patients with controlled blood pressure increased from 45% to 60%. We saved $450,000 in inpatient costs for deep venous thrombosis.î (E. B. Devine, bdevine@u.washington.edu)

>>>PNN NewsWatch
* Everolimus (Afinitor, Novartis) oral tablets have been approved for treatment of patients with advanced renal cell carcinoma whose disease has progressed after treatment with other therapies, FDA announced yesterday. A kinase inhibitor, everolimus blocks a specific protein, mammalian target of rapamycin or mTOR, disrupting cancer cell growth, division, and metabolism. Other agents in this class, sunitinib and sorafenib, are multiple kinase inhibitors and should be used before everolimus. In clinical trials, disease progression was delayed by 5 months in patients receiving everolimus, compared with those not on the agent. Adverse reactions occurring in at least 20% of patients included inflammation in the mouth, loss of strength, diarrhea, poor appetite, edema in the extremities, shortness of breath, coughing, nausea, vomiting, rash, and fever. At least one-half of patients experienced anemia, low white blood counts, and elevations in cholesterol, triglycerides, and glucose.
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FDA yesterday licensed Ixiaro (Intercell Biomedical), a vaccine for prevention of the mosquito-borne disease Japanese encephalitis (JE). Ixiaro, a second-generation JE vaccine manufactured using cell culture technology, produced sufficient levels of antibodies in the blood to protect against JE in 800 clinical trial participants. The most commonly reported adverse events with the vaccine were headache, muscle pain and pain, swelling, and tenderness at the injection site.

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