JAMA current issue

• Pediatric Mortality Due to Inborn Errors of Metabolism in Victoria, Australia: A Population-Based Study [Research Letters]
• AIDS Conference: Encouraging Advances Amid Funding Worries for Global Treatment [Medical News & Perspectives]
• Mechanics [Poetry and Medicine]
• This Week in JAMA [This Week in JAMA]
• Addition of Severe Combined Immunodeficiency as a Contraindication for Administration of Rotavirus Vaccine [From the Centers for Disease Control and Prevention]
• Adjuvant Chemotherapy With Fluorouracil Plus Folinic Acid vs Gemcitabine Following Pancreatic Cancer Resection: A Randomized Controlled Trial [Original Contribution]
  

  Context  Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer. Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer.

  Objective  To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer.

  Design, Setting, and Patients  The European Study Group for Pancreatic Cancer (ESPAC)-3 trial, an open-label, phase 3, randomized controlled trial conducted in 159 pancreatic cancer centers in Europe, Australasia, Japan, and Canada. Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection; patients were randomized between July 2000 and January 2007 and underwent at least 2 years of follow-up.

  Interventions  Patients received either fluorouracil plus folinic acid (folinic acid, 20 mg/m², intravenous bolus injection, followed by fluorouracil, 425 mg/m² intravenous bolus injection given 1-5 days every 28 days) (n = 551) or gemcitabine (1000 mg/m² intravenous infusion once a week for 3 of every 4 weeks) (n = 537) for 6 months.

  Main Outcome Measures  Primary outcome measure was overall survival; secondary measures were toxicity, progression-free survival, and quality of life.

  Results  Final analysis was carried out on an intention-to-treat basis after a median of 34.2 (interquartile range, 27.1-43.4) months' follow-up after 753 deaths (69%). Median survival was 23.0 (95% confidence interval [CI], 21.1-25.0) months for patients treated with fluorouracil plus folinic acid and 23.6 (95% CI, 21.4-26.4) months for those treated with gemcitabine (²₁ = 0.7; P = .39; hazard ratio, 0.94 [95% CI, 0.81-1.08]). Seventy-seven patients (14%) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events, compared with 40 patients (7.5%) receiving gemcitabine, who had 52 events (P < .001). There were no significant differences in either progression-free survival or global quality-of-life scores between the treatment groups.

  Conclusion  Compared with the use of fluorouracil plus folinic acid, gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer.

  Trial Registration  clinicaltrials.gov Identifier: NCT00058201

  
  
  
• About This Journal [About This Journal]
• Reuse of Nevirapine in Exposed HIV-Infected Children After Protease Inhibitor-Based Viral Suppression: A Randomized Controlled Trial [Original Contribution]
  

  Context  Protease inhibitor (PI)–based therapy is recommended for infants infected with human immunodeficiency virus (HIV) who were exposed to nevirapine for prevention of mother-to-child HIV transmission. However, there are limitations of continuing PI-based therapy indefinitely and reuse of nevirapine has many advantages.

  Objective  To test whether nevirapine-exposed infants who initially achieve viral suppression with PI-based therapy can maintain viral suppression when switched to nevirapine-based therapy.

  Design, Setting, and Patients  Randomized trial conducted between April 2005 and May 2009 at a hospital in Johannesburg, South Africa, among 195 children who achieved viral suppression less than 400 copies/mL for 3 or more months from a cohort of 323 nevirapine-exposed children who initiated PI-based therapy before 24 months of age.

  Interventions  Control group children continued to receive ritonavir-boosted lopinavir, stavudine, and lamivudine (n = 99). Switch group children substituted nevirapine for ritonavir-boosted lopinavir (n = 96).

  Main Outcome Measures  Children were followed up for 52 weeks after randomization. Plasma HIV-1 RNA of greater than 50 copies/mL was the primary end point. Confirmed viremia greater than 1000 copies/mL was used as a criterion to consider regimen changes for children in either group (safety end point).

  Results  Plasma viremia greater than 50 copies/mL occurred less frequently in the switch group (Kaplan-Meier probability, 0.438; 95% CI, 0.334-0.537) than in the control group (0.576; 95% CI, 0.470-0.668) (P = .02). Confirmed viremia greater than 1000 copies/mL occurred more frequently in the switch group (0.201; 95% CI, 0.125-0.289) than in the control group (0.022; 95% CI, 0.004-0.069) (P < .001). CD4 cell response was better in the switch group (median CD4 percentage at 52 weeks, 34.7) vs the control group (CD4 percentage, 31.3) (P = .004). Older age (relative hazard [RH], 1.71; 95% CI, 1.08-2.72) was associated with viremia greater than 50 copies/mL in the control group. Inadequate adherence (RH, 4.14; 95% CI, 1.18-14.57) and drug resistance (RH, 4.04; 95% CI, 1.40-11.65) before treatment were associated with confirmed viremia greater than 1000 copies/mL in the switch group.

  Conclusion  Among HIV-infected children previously exposed to nevirapine, switching to nevirapine-based therapy after achieving viral suppression with a ritonavir-boosted lopinavir regimen resulted in lower rates of viremia greater than 50 copies/mL than maintaining the primary ritonavir-boosted lopinavir regimen.

  Trial Registration  clinicaltrials.gov Identifier: NCT00117728

  
  
  
• Boosting FDA's Budget [Capitol Health Call]
• Clinical Characteristics and 30-Day Outcomes for Influenza A 2009 (H1N1), 2008-2009 (H1N1), and 2007-2008 (H3N2) Infections [Original Contribution]
  

  Context  The clinical characteristics of pandemic 2009 influenza A(H1N1) infections have not been compared directly with illnesses caused by other influenza A strains.

  Objective  To compare clinical features and outcomes for 2009 H1N1, seasonal H1N1, and H3N2 influenza in a population-based cohort.

  Design, Setting, and Participants  Active surveillance with 30-day follow-up for influenza cases among children and adults living in a 14–zip code area in Wisconsin. Patients with subjective fever, chills, or cough of fewer than 8 days' duration were screened for eligibility during an outpatient or inpatient encounter. Consenting patients were interviewed and tested for influenza A during the 2007-2008 and 2008-2009 influenza seasons and from May to November 2009; 6874 patients (70%-86% of eligible patients) agreed to participate. Medical records were reviewed to assess outcomes.

  Main Outcome Measures  Hospital admission, radiographically confirmed pneumonia, and clinical characteristics of influenza A by strain.

  Results  We identified 545 2009 H1N1, 221 seasonal H1N1, and 632 H3N2 infections. The median ages of infected participants were 10, 11, and 25 years, respectively (P < .001). Hospital admission occurred within 30 days for 6 of 395 children with 2009 H1N1 (1.5%; 95% confidence interval [CI], 0.6%-3.1%), 5 of 135 with seasonal H1N1 (3.7%; 95% CI, 1.4%-8.0%), and 8 of 255 with H3N2 (3.1%; 95% CI, 1.5%-5.9%). Among adults, hospital admission occurred in 6 of 150 with 2009 H1N1 (4.0%; 95% CI, 1.6%-8.1%), 2 of 86 with seasonal H1N1 (2.3%; 95% CI, 0.3%-8.1%), and 17 of 377 with H3N2 (4.5%; 95% CI, 2.7%-7.0%). Pneumonia occurred in 10 children with 2009 H1N1 (2.5%; 95% CI, 1.3%-4.5%), 2 with seasonal H1N1 (1.5%; 95% CI, 0.2%-5.2%), and 5 with H3N2 (2.0%; 95% CI, 0.7%-4.3%). Among adults, pneumonia occurred in 6 with 2009 H1N1 (4.0%; 95% CI, 1.6%-8.1%), 2 with seasonal H1N1 (2.3%; 95% CI, 0.3%-8.1%), and 4 with H3N2 (1.1%; 95% CI, 0.3%-2.7%).

  Conclusions  In this population, individuals with 2009 H1N1 infection were younger than those with H3N2. The risk of most serious complications was not elevated in adults or children with 2009 H1N1 compared with recent seasonal strains.

  
  
  
• Sauer's Manual of Skin Diseases [Book and Media Reviews]
• Pneumococcal Conjugate Vaccination and Nasopharyngeal Acquisition of Pneumococcal Serotype 19A Strains [Original Contribution]
  

  Context  The rapid increase in multiresistant serotype 19A as a cause of invasive and respiratory pneumococcal disease has been associated in time with the widespread implementation of 7-valent pneumococcal conjugate vaccination (PCV-7) in several countries. Because spontaneous fluctuations in time and antibiotic selective pressure may have induced this serotype 19A increase, controlled studies are needed to assess the role of PCV-7.

  Objective  To examine the association of PCV-7 vaccination and nasopharyngeal acquisition of serotype 19A pneumococci, their clonal distribution, and antibiotic susceptibility.

  Design, Setting, and Patients  Post hoc per-protocol completer's analysis as part of a randomized controlled trial of nasopharyngeal Streptococcus pneumoniae carriage enrolling 1003 healthy newborns with follow-up to the age of 24 months in the Netherlands, which has low antibiotic resistance rates. The study was conducted before widespread PCV-7 implementation in infants, between July 7, 2005, and February 14, 2008. Nasopharyngeal swabs were obtained at the age of 6 weeks and at 6, 12, 18, and 24 months.

  Intervention  Infants were randomly assigned to receive 2 doses of PCV-7 at 2 and 4 months; 2 + 1 doses of PCV-7 at 2, 4, and 11 months; or no dosage (unvaccinated control group).

  Main Outcome Measure  Cumulative proportion of children with nasopharyngeal acquisition of a new serotype 19A strain from 6 through 24 months of age.

  Results  Nine hundred forty-eight children completed the study. Fifty-four nasopharyngeal serotype 19A carriage isolates from 318 in the 2-dose group, 66 isolates from 327 in the 2 + 1-dose group, and 33 isolates from 303 in the unvaccinated were collected from 6 weeks through 24 months. The cumulative proportion who tested positive for new nasopharyngeal serotype 19A acquisition from 6 through 24 months of age was significantly higher in those having received the 2 + 1-dose PCV-7 schedule (16.2%; 95% confidence interval [CI], 12.6%-20.6%) vs those who were unvaccinated (9.2%; 95% CI, 6.5%-13.0%; relative risk [RR], 1.75; 95% CI, 1.14-2.70) but not after a 2-dose schedule (13.2%; 95% CI, 9.9%-17.4%; RR, 1.43; 95% CI, 0.91-2.25). There were 28 different sequence types identified, including 6 new types. The proportion of children with new 19A acquisition who had used antibiotics in the last 6 months (18.7%) did not differ among groups. Five isolates were penicillin-intermediate susceptible and another 3 were nonsusceptible to erythromycin and azithromycin, all in the vaccine groups.

  Conclusion  A 2 + 1-dose PCV-7 schedule was associated with an increase in serotype 19A nasopharyngeal acquisition compared with unvaccinated controls.

  Trial Registration  clinicaltrials.gov Identifier: NCT00189020

  
  
  
• From Research to Health Care Practice: How the UK Uses Data on Comparative Effectiveness [Medical News & Perspectives]
• Relationship Between Patient Panel Characteristics and Primary Care Physician Clinical Performance Rankings [Original Contribution]
  

  Context  Physicians have increasingly become the focus of clinical performance measurement.

  Objective  To investigate the relationship between patient panel characteristics and relative physician clinical performance rankings within a large academic primary care network.

  Design, Setting, and Participants  Cohort study using data from 125 303 adult patients who had visited any of the 9 hospital-affiliated practices or 4 community health centers between January 1, 2003, and December 31, 2005, (162 primary care physicians in 1 physician organization linked by a common electronic medical record system in Eastern Massachusetts) to determine changes in physician quality ranking based on an aggregate of Health Plan Employer and Data Information Set (HEDIS) measures after adjusting for practice site, visit frequency, and patient panel characteristics.

  Main Outcome Measures  Composite physician clinical performance score based on 9 HEDIS quality measures (reported by percentile, with lower scores indicating higher quality).

  Results  Patients of primary care physicians in the top quality performance tertile compared with patients of primary care physicians in the bottom quality tertile were older (51.1 years [95% confidence interval {CI}, 49.6-52.6 years] vs 46.6 years [95% CI, 43.8-49.5 years], respectively; P < .001), had a higher number of comorbidities (0.91 [95% CI, 0.83-0.98] vs 0.80 [95% CI, 0.66-0.95]; P = .008), and made more frequent primary care practice visits (71.0% [95% CI, 68.5%-73.5%] vs 61.8% [95% CI, 57.3%-66.3%] with >3 visits/year; P = .003). Top tertile primary care physicians compared with the bottom tertile physicians had fewer minority patients (13.7% [95% CI, 10.6%-16.7%] vs 25.6% [95% CI, 20.2%-31.1%], respectively; P < .001), non–English-speaking patients (3.2% [95% CI, 0.7%-5.6%] vs 10.2% [95% CI, 5.5%-14.9%]; P <.001), and patients with Medicaid coverage or without insurance (9.6% [95% CI, 7.5%-11.7%] vs 17.2% [95% CI, 13.5%-21.0%]; P <.001). After accounting for practice site and visit frequency differences, adjusting for patient panel factors resulted in a relative mean change in physician rankings of 7.6 percentiles (95% CI, 6.6-8.7 percentiles) per primary care physician, with more than one-third (36%) of primary care physicians (59/162) reclassified into different quality tertiles.

  Conclusion  Among primary care physicians practicing within the same large academic primary care system, patient panels with greater proportions of underinsured, minority, and non–English-speaking patients were associated with lower quality rankings for primary care physicians.

  
  
  
• Improving Drug Safety [Capitol Health Call]
• Public Reporting of Hospital Hand Hygiene Compliance--Helpful or Harmful? [Commentary]
• Hester Street [The Cover]
• Health Effects of the Gulf Oil Spill [Commentary]
• FISH AS FOOD [JAMA 100 Years Ago]
• Exclusion of Genetic Information From the Medical Record: Ethical and Medical Dilemmas [Commentary]
• Basic Biostatistics for Geneticists and Epidemiologists: A Practical Approach [Book and Media Reviews]
• Do IRBs Protect Human Research Participants? [Commentary]
• Have Polio-Free Countries Lost Sight of Need to Keep Vaccination Rates High? [Medical News & Perspectives]
• Refinement of Adjuvant Therapy for Pancreatic Cancer [Editorial]
• Gastrointestinal Anthrax After an Animal-Hide Drumming Event--New Hampshire and Massachusetts, 2009 [From the Centers for Disease Control and Prevention]
• A Theme Issue on Infectious Disease and Immunology--Call for Papers [Editorial]
• Notes From the Field: Pertussis--California, January-June 2010 [From the Centers for Disease Control and Prevention]
• Vision Screening to Detect Refractive Error [From the Archives Journals]
• Rare Pediatric Diseases [Capitol Health Call]
• Bleeding Avoidance Strategies and Percutaneous Coronary Intervention [Letters]