Medicine residents' understanding of the biostatistics and results in the medical literature

Context  Physicians depend on the medical literature to keep current with clinical information. Little is known about residents' ability to understand statistical methods or how to appropriately interpret research outcomes. Objective  To evaluate residents' understanding of biostatistics and interpretation of research results. Design, Setting, and Participants  Multiprogram cross-sectional survey of internal medicine residents. Main Outcome Measure  Percentage of questions correct on a biostatistics/study design multiple-choice knowledge test. Results  The survey was completed by 277 of 367 residents (75.5%) in 11 residency programs. The overall mean percentage correct on statistical knowledge and interpretation of results was 41.4% (95% confidence interval [CI], 39.7%-43.3%) vs 71.5% (95% CI, 57.5%-85.5%) for fellows and general medicine faculty with research training (P < .001). Higher scores in residents were associated with additional advanced degrees (50.0% [95% CI, 44.5%-55.5%] vs 40.1% [95% CI, 38.3%-42.0%]; P < .001); prior biostatistics training (45.2% [95% CI, 42.7%-47.8%] vs 37.9% [95% CI, 35.4%-40.3%]; P = .001); enrollment in a university-based training program (43.0% [95% CI, 41.0%-45.1%] vs 36.3% [95% CI, 32.6%-40.0%]; P = .002); and male sex (44.0% [95% CI, 41.4%-46.7%] vs 38.8% [95% CI, 36.4%-41.1%]; P = .004). On individual knowledge questions, 81.6% correctly interpreted a relative risk. Residents were less likely to know how to interpret an adjusted odds ratio from a multivariate regression analysis (37.4%) or the results of a Kaplan-Meier analysis (10.5%). Seventy-five percent indicated they did not understand all of the statistics they encountered in journal articles, but 95% felt it was important to understand these concepts to be an intelligent reader of the literature. Conclusions  Most residents in this study lacked the knowledge in biostatistics needed to interpret many of the results in published clinical research. Residency programs should include more effective biostatistics training in their curricula to successfully prepare residents for this important lifelong learning skill.      

Association of workload of on-call medical interns with on-call sleep duration, shift duration, and participation in educational activities

Vineet M. Arora, MD, MA; Emily Georgitis, MD; Juned Siddique, DrPH; Ben Vekhter, PhD; James N. Woodruff, MD; Holly J. Humphrey, MD; David O. Meltzer, MD, PhD

JAMA. 2008;300(10):1146-1153.

Context  Further restrictions in resident duty hours are being considered, and it is important to understand the association between workload, sleep loss, shift duration, and the educational time of on-call medical interns.

Objective  To assess whether increased on-call intern workload, as measured by the number of new admissions on-call and the number of previously admitted patients remaining on the service, was associated with reductions in on-call sleep, increased total shift duration, and lower likelihood of participation in educational activities.

Design, Setting, and Participants  Prospective cohort study of medical interns at a single US academic medical center from July 1, 2003, through June 24, 2005. Of the 81 interns, 56 participated (69%), for a total of 165 general medicine inpatient months resulting in 1100 call nights.

Main Outcome Measures  On-call sleep duration, estimated by wrist watch actigraphy; total shift duration, measured from paging logs; and participation in educational activities (didactic lectures or bedside teaching), measured by experience sampling method via a personal digital assistant.

Results  Mean (SD) sleep duration on-call was 2.8 (1.5) hours and mean (SD) shift duration was 29.9 (1.7) hours. Interns reported spending 11% of their time in educational activities. Early in the academic year (July to October), each new on-call admission was associated with less sleep (–10.5 minutes [95% confidence interval {CI}, –16.8 to –4.2 minutes]; P < .001) and a longer shift duration (13.2 minutes [95% CI, 3.2-23.3 minutes]; P = .01). A higher number of previously admitted patients remaining on the service was associated with a lower odds of participation in educational activities (odds ratio, 0.82 [95% CI, 0.70-0.96]; P = .01]. Call nights during the week and early in the academic year were associated with the most sleep loss and longest shift durations.

Conclusion  In this study population, increased on-call workload was associated with more sleep loss, longer shift duration, and a lower likelihood of participation in educational activities.

     

Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial

Context  Combination therapy is now widely advocated as first-line treatment for uncomplicated malaria in Africa. However, it is not clear which treatment regimens are optimal or how to best assess comparative efficacies in highly endemic areas. Objective  To compare the efficacy and safety of 3 leading combination therapies for the treatment of uncomplicated malaria. Design, Setting, and Participants  Single-blind randomized clinical trial, conducted between November 2004 and June 2006, of treatment for all episodes of uncomplicated malaria in children in an urban community in Kampala, Uganda. A total of 601 healthy children (aged 1-10 years) were randomly selected and were followed up for 13 to 19 months, receiving all medical care at the study clinic. Interventions  Study participants were randomized to receive 1 of 3 combination therapies (amodiaquine plus sulfadoxine-pyrimethamine, amodiaquine plus artesunate, or artemether-lumefantrine) when diagnosed with their first episode of uncomplicated malaria. The same assigned treatment was given for all subsequent episodes. Main Outcome Measure  28-Day risk of parasitological failure (unadjusted and adjusted by genotyping to distinguish recrudescence from new infection) for each episode of uncomplicated malaria treated with study drugs. Results  Of enrolled children, 329 of 601 were diagnosed with at least 1 episode of uncomplicated malaria, and 687 episodes of Plasmodium falciparum malaria were treated with study drugs. The 28-day risk of treatment failure (unadjusted by genotyping) for individual episodes of malaria were 26.1% (95% CI, 21.1%-32.1%) for amodiaquine plus sulfadoxine-pyrimethamine, 17.4% (95% CI, 13.1%-23.1%) for amodiaquine plus artesunate, and 6.7% (95% CI, 3.9%-11.2%) for artemether-lumefantrine (P<.05 for all pairwise comparisons). When only recrudescent treatment failures were considered, the risks of failure were 14.1% (95% CI, 10.3%-19.2%), 4.6% (95% CI, 2.5%-8.3%), and 1.0% (95% CI, 0.3%-4.0%) for the same order of study drugs, respectively (P.008 for all pairwise comparisons, except amodiaquine plus artesunate vs artemether-lumefantrine, P = .05). There were no deaths or cases of severe malaria. Significant reductions in anemia (9.3% [95% CI, 7.0%-12.0%] at enrollment vs 0.6% [95% CI, 0.1%-2.2%] during the last 2 months of follow-up; P<.001) and asymptomatic parasitemia (18.6% [95% CI, 15.5%-22.1%] at enrollment vs 2.3% [95% CI, 1.5%-3.5%] during the last 2 months of follow-up; P<.001) were observed according to routine testing. Conclusions  Artemether-lumefantrine was the most efficacious treatment for uncomplicated malaria in the study population. With all study regimens, the provision of prompt and reasonably effective facility-based treatment was associated with good outcomes in long-term health measures. Trial Registration  isrctn.org Identifier: ISRCTN37517549      

Use of an automated, load-distributing band chest compression device for out-of-hospital cardiac arrest resuscitation

Context  Only 1% to 8% of adults with out-of-hospital cardiac arrest survive to hospital discharge. Objective  To compare resuscitation outcomes before and after an urban emergency medical services (EMS) system switched from manual cardiopulmonary resuscitation (CPR) to load-distributing band (LDB) CPR. Design, Setting, and Patients  A phased, observational cohort evaluation with intention-to-treat analysis of 783 adults with out-of-hospital, nontraumatic cardiac arrest. A total of 499 patients were included in the manual CPR phase (January 1, 2001, to March 31, 2003) and 284 patients in the LDB-CPR phase (December 20, 2003, to March 31, 2005); of these patients, the LDB device was applied in 210 patients. Intervention  Urban EMS system change from manual CPR to LDB-CPR. Main Outcome Measures  Return of spontaneous circulation (ROSC), with secondary outcome measures of survival to hospital admission and hospital discharge, and neurological outcome at discharge. Results  Patients in the manual CPR and LDB-CPR phases were comparable except for a faster response time interval (mean difference, 26 seconds) and more EMS-witnessed arrests (18.7% vs 12.6%) with LDB. Rates for ROSC and survival were increased with LDB-CPR compared with manual CPR (for ROSC, 34.5%; 95% confidence interval [CI], 29.2%-40.3% vs 20.2%; 95% CI, 16.9%-24.0%; adjusted odds ratio [OR], 1.94; 95% CI, 1.38-2.72; for survival to hospital admission, 20.9%; 95% CI, 16.6%-26.1% vs 11.1%; 95% CI, 8.6%-14.2%; adjusted OR, 1.88; 95% CI, 1.23-2.86; and for survival to hospital discharge, 9.7%; 95% CI, 6.7%-13.8% vs 2.9%; 95% CI, 1.7%-4.8%; adjusted OR, 2.27; 95% CI, 1.11-4.77). In secondary analysis of the 210 patients in whom the LDB device was applied, 38 patients (18.1%) survived to hospital admission (95% CI, 13.4%-23.9%) and 12 patients (5.7%) survived to hospital discharge (95% CI, 3.0%-9.3%). Among patients in the manual CPR and LDB-CPR groups who survived to hospital discharge, there was no significant difference between groups in Cerebral Performance Category (P = .36) or Overall Performance Category (P = .40). The number needed to treat for the adjusted outcome survival to discharge was 15 (95% CI, 9-33). Conclusion  Compared with resuscitation using manual CPR, a resuscitation strategy using LDB-CPR on EMS ambulances is associated with improved survival to hospital discharge in adults with out-of-hospital nontraumatic cardiac arrest.      

Prevalence of chlamydial and gonococcal infections among young adults in the United States

Context  Chlamydial and gonococcal infections are important causes of pelvic inflammatory disease, ectopic pregnancy, and infertility. Although screening for Chlamydia trachomatis is widely recommended among young adult women, little information is available regarding the prevalence of chlamydial and gonococcal infections in the general young adult population. Objective  To determine the prevalence of chlamydial and gonoccoccal infections in a nationally representative sample of young adults living in the United States. Design, Setting, and Participants  Cross-sectional analyses of a prospective cohort study of a nationally representative sample of 14 322 young adults aged 18 to 26 years. In-home interviews were conducted across the United States for Wave III of The National Longitudinal Study of Adolescent Health (Add Health) from April 2, 2001, to May 9, 2002. This study sample represented 66.3% of the original 18 924 participants in Wave I of Add Health. First-void urine specimens using ligase chain reaction assay were available for 12 548 (87.6%) of the Wave III participants. Main Outcome Measures  Prevalences of chlamydial and gonococcal infections in the general young adult population, and by age, self-reported race/ethnicity, and geographic region of current residence. Results  Overall prevalence of chlamydial infection was 4.19% (95% confidence interval [CI], 3.48%-4.90%). Women (4.74%; 95% CI, 3.93%-5.71%) were more likely to be infected than men (3.67%; 95% CI, 2.93%-4.58%; prevalence ratio, 1.29; 95% CI, 1.03-1.63). The prevalence of chlamydial infection was highest among black women (13.95%; 95% CI, 11.25%-17.18%) and black men (11.12%; 95% CI, 8.51%-14.42%); lowest prevalences were among Asian men (1.14%; 95% CI, 0.40%-3.21%), white men (1.38%; 95% CI, 0.93%-2.03%), and white women (2.52%; 95% CI, 1.90%-3.34%). Prevalence of chlamydial infection was highest in the south (5.39%; 95% CI, 4.24%-6.83%) and lowest in the northeast (2.39%; 95% CI, 1.56%-3.65%). Overall prevalence of gonorrhea was 0.43% (95% CI, 0.29%-0.63%). Among black men and women, the prevalence was 2.13% (95% CI, 1.46%-3.10%) and among white young adults, 0.10% (95% CI, 0.03%-0.27%). Prevalence of coinfection with both chlamydial and gonococcal infections was 0.030% (95% CI, 0.18%-0.49%). Conclusions  The prevalence of chlamydial infection is high among young adults in the United States. Substantial racial/ethnic disparities are present in the prevalence of both chlamydial and gonococcal infections.      

Informing resource-poor populations and the delivery of entitled health and social services in rural India: a cluster randomized controlled trial

Context  A lack of awareness about entitled health and social services may contribute to poor delivery of such services in developing countries, especially among individuals of low socioeconomic status. Objective  To determine the impact of informing resource-poor rural populations about entitled services. Design, Setting, and Participants  Community-based, cluster randomized controlled trial conducted from May 2004 to May 2005 in 105 randomly selected village clusters in Uttar Pradesh state in India. Households (548 intervention and 497 control) were selected by a systematic sampling design, including both low-caste and mid- to high-caste households. Intervention  Four to 6 public meetings were held in each intervention village cluster to disseminate information on entitled health services, entitled education services, and village governance requirements. No intervention took place in control village clusters. Main Outcome Measures  Visits by nurse midwife; prenatal examinations, tetanus vaccinations, and prenatal supplements received by pregnant women; vaccinations received by infants; excess school fees charged; occurrence of village council meetings; and development work in villages. Results  At baseline, there were no significant differences in self-reported delivery of health and social services. After 1 year, intervention villagers reported better delivery of several services compared with control villagers: in a multivariate analysis, 30% more prenatal examinations (95% confidence interval [CI], 17%-43%; P < .001), 27% more tetanus vaccinations (95% CI, 12%-41%; P < .001), 24% more prenatal supplements (95% CI, 8%-39%; P = .003), 25% more infant vaccinations (95% CI, 8%-42%; P = .004), and decreased excess school fees of 8 rupees (95% CI, 4-13 rupees; P < .001). In a difference-in-differences analysis, 21% more village council meetings were reported (95% CI, 5%-36%; P = .01). There were no improvements in visits by a nurse midwife or in development work in the villages. Both low-caste and mid- to high-caste intervention households reported significant improvements in service delivery. Conclusions  Informing resource-poor rural populations in India about entitled services enhanced the delivery of health and social services among both low- and mid- to high-caste households. Interventions that emphasize educating resource-poor populations about entitled services may improve the delivery of such services. Trial Registration  clinicaltrials.gov Identifier: NCT00421291      

Changes in rates of autopsy-detected diagnostic errors over time: a systematic review

Context  Substantial discrepanies exist between clinical diagnoses and findings at autopsy. Autopsy may be used as a tool for quality management to analyze diagnostic discrepanies. Objective  To determine the rate at which autopsies detect important, clinically missed diagnoses, and the extent to which this rate has changed over time. Data Sources  A systematic literature search for English-language articles available on MEDLINE from 1966 to April 2002, using the search terms autopsy, postmortem changes, post-mortem, postmortem, necropsy, and posthumous, identified 45 studies reporting 53 distinct autopsy series meeting prospectively defined criteria. Reference lists were reviewed to identify additional studies, and the final bibliography was distributed to experts in the field to identify missing or unpublished studies. Study Selection  Included studies reported clinically missed diagnoses involving a primary cause of death (major errors), with the most serious being those likely to have affected patient outcome (class I errors). Data Extraction  Logistic regression was performed using data from 53 distinct autopsy series over a 40-year period and adjusting for the effects of changes in autopsy rates, country, case mix (general autopsies; adult medical; adult intensive care; adult or pediatric surgery; general pediatrics or pediatric inpatients; neonatal or pediatric intensive care; and other autopsy), and important methodological features of the primary studies. Data Synthesis  Of 53 autopsy series identified, 42 reported major errors and 37 reported class I errors. Twenty-six autopsy series reported both major and class I error rates. The median error rate was 23.5% (range, 4.1%-49.8%) for major errors and 9.0% (range, 0%-20.7%) for class I errors. Analyses of diagnostic error rates adjusting for the effects of case mix, country, and autopsy rate yielded relative decreases per decade of 19.4% (95% confidence interval [CI], 1.8%-33.8%) for major errors and 33.4% (95% [CI], 8.4%-51.6%) for class I errors. Despite these decreases, we estimated that a contemporary US institution (based on autopsy rates ranging from 100% [the extrapolated extreme at which clinical selection is eliminated] to 5% [roughly the national average]), could observe a major error rate from 8.4% to 24.4% and a class I error rate from 4.1% to 6.7%. Conclusion  The possibility that a given autopsy will reveal important unsuspected diagnoses has decreased over time, but remains sufficiently high that encouraging ongoing use of the autopsy appears warranted.      

Opening of specialty cardiac hospitals and use of coronary revascularization in medicare beneficiaries

Context  Although proponents argue that specialty cardiac hospitals provide high-quality cost-efficient care, strong financial incentives for physicians at these facilities could result in greater procedure utilization. Objective  To determine whether the opening of cardiac hospitals was associated with increasing population-based rates of coronary revascularization. Design, Setting, and Patients  In a study of Medicare beneficiaries from 1995 through 2003, we calculated annual population-based rates for total revascularization (coronary artery bypass graft [CABG] plus percutaneous coronary intervention [PCI]), CABG, and PCI. Hospital referral regions (HRRs) were used to categorize health care markets into those where (1) cardiac hospitals opened (n = 13), (2) new cardiac programs opened at general hospitals (n = 142), and (3) no new programs opened (n = 151). Main Outcome Measures  Rates of change in total revascularization, CABG, and PCI using multivariable linear regression models with generalized estimating equations. Results  Overall, rates of change for total revascularization were higher in HRRs after cardiac hospitals opened when compared with HRRs where new cardiac programs opened at general hospitals and HRRs with no new programs (P<.001 for both comparisons). Four years after their opening, the relative increase in adjusted rates was more than 2-fold higher in HRRs where cardiac hospitals opened (19.2% [95% confidence interval {CI}, 6.1%-32.2%], P<.001) when compared with HRRs where new cardiac programs opened at general hospitals (6.5% [95% CI, 3.2%-9.9%], P<.001) and HRRs with no new programs (7.4% [95% CI, 3.2%-11.5%], P<.001). These findings were consistent when rates for CABG and PCI were considered separately. For PCI, this growth appeared largely driven by increased utilization among patients without acute myocardial infarction (42.1% [95% CI, 21.4%-62.9%], P<.001). Conclusion  The opening of a cardiac hospital within an HRR is associated with increasing population-based rates of coronary revascularization in Medicare beneficiaries.      

Prevalence of HPV infection among females in the United States

Context  Human papillomavirus (HPV) infection is estimated to be the most common sexually transmitted infection. Baseline population prevalence data for HPV infection in the United States before widespread availability of a prophylactic HPV vaccine would be useful. Objective  To determine the prevalence of HPV among females in the United States. Design, Setting, and Participants  The National Health and Nutrition Examination Survey (NHANES) uses a representative sample of the US noninstitutionalized civilian population. Females aged 14 to 59 years who were interviewed at home for NHANES 2003-2004 were examined in a mobile examination center and provided a self-collected vaginal swab specimen. Swabs were analyzed for HPV DNA by L1 consensus polymerase chain reaction followed by type-specific hybridization. Demographic and sexual behavior information was obtained from all participants. Main Outcome Measures  HPV prevalence by polymerase chain reaction. Results  The overall HPV prevalence was 26.8% (95% confidence interval [CI], 23.3%-30.9%) among US females aged 14 to 59 years (n = 1921). HPV prevalence was 24.5% (95% CI, 19.6%-30.5%) among females aged 14 to 19 years, 44.8% (95% CI, 36.3%-55.3%) among women aged 20 to 24 years, 27.4% (95% CI, 21.9%-34.2%) among women aged 25 to 29 years, 27.5% (95% CI, 20.8%-36.4%) among women aged 30 to 39 years, 25.2% (95% CI, 19.7%-32.2%) among women aged 40 to 49 years, and 19.6% (95% CI, 14.3%-26.8%) among women aged 50 to 59 years. There was a statistically significant trend for increasing HPV prevalence with each year of age from 14 to 24 years (P<.001), followed by a gradual decline in prevalence through 59 years (P = .06). HPV vaccine types 6 and 11 (low-risk types) and 16 and 18 (high-risk types) were detected in 3.4% of female participants; HPV-6 was detected in 1.3% (95% CI, 0.8%-2.3%), HPV-11 in 0.1% (95% CI, 0.03%-0.3%), HPV-16 in 1.5% (95% CI, 0.9%-2.6%), and HPV-18 in 0.8% (95% CI, 0.4%-1.5%) of female participants. Independent risk factors for HPV detection were age, marital status, and increasing numbers of lifetime and recent sex partners. Conclusions  HPV is common among females in the United States. Our data indicate that the burden of prevalent HPV infection among females was greater than previous estimates and was highest among those aged 20 to 24 years. However, the prevalence of HPV vaccine types was relatively low.      

Effects of reviparin, a low-molecular-weight heparin, on mortality, reinfarction, and strokes in patients with acute myocardial infarction presenting with ST-segment elevation

Context  Although reperfusion therapy, aspirin, -blockers, and angiotensin-converting enzyme inhibitors reduce mortality when used early in patients with acute myocardial infarction (MI), mortality and morbidity remain high. No antithrombotic or newer antiplatelet drug has been shown to reduce mortality in acute MI. Objective  To evaluate the effects of reviparin, a low-molecular-weight heparin, when initiated early and given for 7 days in addition to usual therapy on the primary composite outcome of death, myocardial reinfarction, or strokes at 7 and 30 days. Design, Setting, and Patients  A randomized, double-blind, placebo-controlled trial (Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment Evaluation [CREATE]) of 15 570 patients with ST-segment elevation or new left bundle-branch block, presenting within 12 hours of symptom onset at 341 hospitals in India and China from July 2001 through July 2004. Intervention  Reviparin or placebo subcutaneously twice daily for 7 days. Main Outcome Measure  Primary composite outcome of death, myocardial reinfarction, or stroke at 7 and 30 days. Results  The primary composite outcome was significantly reduced from 854 (11.0%) of 7790 patients in the placebo group to 745 (9.6%) of 7780 in the reviparin group (hazard ratio [HR], 0.87; 95% CI, 0.79-0.96; P = .005). These benefits persisted at 30 days (1056 [13.6%] vs 921 [11.8%] patients; HR, 0.87; 95% CI, 0.79-0.95; P = .001) with significant reductions in 30-day mortality (877 [11.3%] vs 766 [9.8%]; HR, 0.87; 95% CI, 0.79-0.96; P = .005) and reinfarction (199 [2.6%] vs 154 [2.0%]; HR, 0.77; 95% CI, 0.62-0.95; P = .01), and no significant differences in strokes (64 [0.8%] vs 80 [1.0%]; P = .19). Reviparin treatment was significantly better when it was initiated very early after symptom onset at 7 days (<2 hours: HR, 0.70; 95% CI, 0.52-0.96; P = .03; 30/1000 events prevented; 2 to <4 hours: HR, 0.81; 95% CI, 0.67-0.98; P = .03; 21/1000 events prevented; 4 to <8 hours: HR, 0.85; 95% CI, 0.73-0.99; P = .05; 16/1000 events prevented; and 8 hours: HR, 1.06; 95% CI, 0.86-1.30; P = .58; P = .04 for trend). There was an increase in life-threatening bleeding at 7 days with reviparin and placebo (17 [0.2%] vs 7 [0.1%], respectively; P = .07), but the absolute excess was small (1 more per 1000) vs reductions in the primary outcome (18 fewer per 1000) or mortality (15 fewer per 1000). Conclusions  In patients with acute ST-segment elevation or new left bundle-branch block MI, reviparin reduces mortality and reinfarction, without a substantive increase in overall stroke rates. There is a small absolute excess of life-threatening bleeding but the benefits outweigh the risks.      

Acute renal failure in critically ill patients: a multinational, multicenter study

Context  Although acute renal failure (ARF) is believed to be common in the setting of critical illness and is associated with a high risk of death, little is known about its epidemiology and outcome or how these vary in different regions of the world. Objectives  To determine the period prevalence of ARF in intensive care unit (ICU) patients in multiple countries; to characterize differences in etiology, illness severity, and clinical practice; and to determine the impact of these differences on patient outcomes. Design, Setting, and Patients  Prospective observational study of ICU patients who either were treated with renal replacement therapy (RRT) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries. Main Outcome Measures  Occurrence of ARF, factors contributing to etiology, illness severity, treatment, need for renal support after hospital discharge, and hospital mortality. Results  Of 29 269 critically ill patients admitted during the study period, 1738 (5.7%; 95% confidence interval [CI], 5.5%-6.0%) had ARF during their ICU stay, including 1260 who were treated with RRT. The most common contributing factor to ARF was septic shock (47.5%; 95% CI, 45.2%-49.5%). Approximately 30% of patients had preadmission renal dysfunction. Overall hospital mortality was 60.3% (95% CI, 58.0%-62.6%). Dialysis dependence at hospital discharge was 13.8% (95% CI, 11.2%-16.3%) for survivors. Independent risk factors for hospital mortality included use of vasopressors (odds ratio [OR], 1.95; 95% CI, 1.50-2.55; P<.001), mechanical ventilation (OR, 2.11; 95% CI, 1.58-2.82; P<.001), septic shock (OR, 1.36; 95% CI, 1.03-1.79; P = .03), cardiogenic shock (OR, 1.41; 95% CI, 1.05-1.90; P = .02), and hepatorenal syndrome (OR, 1.87; 95% CI, 1.07-3.28; P = .03). Conclusion  In this multinational study, the period prevalence of ARF requiring RRT in the ICU was between 5% and 6% and was associated with a high hospital mortality rate.      

Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial

Context  The empirical literature on treatment of obsessive-compulsive disorder (OCD) in children and adolescents supports the efficacy of short-term OCD-specific cognitive-behavior therapy (CBT) or medical management with selective serotonin reuptake inhibitors. However, little is known about their relative and combined efficacy. Objective  To evaluate the efficacy of CBT alone and medical management with the selective serotonin reuptake inhibitor sertraline alone, or CBT and sertraline combined, as initial treatment for children and adolescents with OCD. Design, Setting, and Participants  The Pediatric OCD Treatment Study, a balanced, masked randomized controlled trial conducted in 3 academic centers in the United States and enrolling a volunteer outpatient sample of 112 patients aged 7 through 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD and a Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score of 16 or higher. Patients were recruited between September 1997 and December 2002. Interventions  Participants were randomly assigned to receive CBT alone, sertraline alone, combined CBT and sertraline, or pill placebo for 12 weeks. Main Outcome Measures  Change in CY-BOCS score over 12 weeks as rated by an independent evaluator masked to treatment status; rate of clinical remission defined as a CY-BOCS score less than or equal to 10. Results  Ninety-seven of 112 patients (87%) completed the full 12 weeks of treatment. Intent-to-treat random regression analyses indicated a statistically significant advantage for CBT alone (P = .003), sertraline alone (P = .007), and combined treatment (P = .001) compared with placebo. Combined treatment also proved superior to CBT alone (P = .008) and to sertraline alone (P = .006), which did not differ from each other. Site differences emerged for CBT and sertraline but not for combined treatment, suggesting that combined treatment is less susceptible to setting-specific variations. The rate of clinical remission for combined treatment was 53.6% (95% confidence interval [CI], 36%-70%); for CBT alone, 39.3% (95% CI, 24%-58%); for sertraline alone, 21.4% (95% CI, 10%-40%); and for placebo, 3.6% (95% CI, 0%-19%). The remission rate for combined treatment did not differ from that for CBT alone (P = .42) but did differ from sertraline alone (P = .03) and from placebo (P<.001). CBT alone did not differ from sertraline alone (P = .24) but did differ from placebo (P = .002), whereas sertraline alone did not (P = .10). The 3 active treatments proved acceptable and well tolerated, with no evidence of treatment-emergent harm to self or to others. Conclusion  Children and adolescents with OCD should begin treatment with the combination of CBT plus a selective serotonin reuptake inhibitor or CBT alone.      

Prevalence and characteristics of chronic pain among chemically dependent patients in methadone maintenance and residential treatment facilities

Context  Little is known about the prevalence and characteristics of chronic pain among patients with different types of chemical dependency. Objectives  To estimate the prevalence and to examine the characteristics of chronic severe pain in chemically dependent populations receiving methadone maintenance or inpatient residential treatment. Design, Setting, and Participants  Representative samples of 390 patients from 2 methadone maintenance treatment programs (MMTPs) and 531 patients from 13 short-term residential substance abuse treatment (inpatient) programs, all in New York State, were surveyed in late 2000 and early 2001. Main Outcome Measure  Prevalence of chronic severe pain, defined as pain that persisted for more than 6 months and was of moderate to severe intensity or that significantly interfered with daily activities. Results  Chronic severe pain was experienced by 37% of MMTP patients (95% confidence interval [CI], 32%-41%) and 24% of inpatients (95% CI, 20%-28%; P = .03). Pain of any type or duration during the past week was reported by 80% of MMTP patients and 78% of inpatients. Among those with chronic severe pain, 65% of MMTP patients and 48% of inpatients reported high levels of pain-related interference in physical and psychosocial functioning. Among MMTP patients, correlates of chronic pain in a multivariate model were age (odds ratio [OR], 2.08; 95% CI, 1.17-3.70), chronic illness (OR, 1.88; 95% CI, 1.07-3.29), lifetime psychiatric illness (OR, 1.77; 95% CI, 1.06-2.97), psychiatric distress (OR, 1.63; 95% CI, 1.22-2.18), and time in treatment (OR, 2.23; 95% CI, 1.06-4.68). Among inpatients, the correlates of chronic pain were race (blacks vs whites: OR, 0.52; 95% CI, 0.31-0.90; Hispanics vs whites: OR, 0.48; 95% CI, 0.24-0.95), drug craving (OR, 2.78; 95% CI, 1.54-5.02), chronic illness (OR, 2.17; 95% CI, 1.37-3.43), and psychiatric distress (OR, 1.36; 95% CI, 1.03-1.81). Among those with chronic severe pain, inpatients were significantly more likely than MMTP patients to have used illicit drugs, as well as alcohol, to treat their pain complaint (51% vs 34%, P = .005) but were less likely to have been prescribed pain medications (52% vs 67%, P = .01). Conclusions  Chronic severe pain is prevalent among patients in substance abuse treatment, especially MMTP patients. Pain is associated with functional impairment and correlates of pain vary with the population. Self-medication for pain with psychoactive drugs appears especially problematic among substance users who enroll in drug-free treatment programs. Substance abuse treatment programs need to develop comprehensive and structured pain management programs.      

Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States

Context  Herpes simplex virus type 1 (HSV-1) and type 2 are common infections worldwide. Herpes simplex virus type 2 (HSV-2) is the cause of most genital herpes and is almost always sexually transmitted. In contrast, HSV-1 is usually transmitted during childhood via nonsexual contacts. Preexisting HSV-1 antibodies can alleviate clinical manifestations of subsequently acquired HSV-2. Furthermore, HSV-1 has become an important cause of genital herpes in some developed countries. Objective  To examine trends in HSV-1 and HSV-2 seroprevalence in the United States in 1999-2004 compared with 1988-1994. Design, Settings, and Participants  Cross-sectional, nationally representative surveys (US National Health and Nutrition Examination Surveys [NHANES]), were used to compare national seroprevalence estimates from 1999-2004 with those from 1988-1994, and changes in HSV-1 and HSV-2 seroprevalence since 1976-1980 were reviewed. Persons aged 14 to 49 years were included in these analyses. Main Outcome Measures  Seroprevalence of HSV-1 and HSV-2 antibodies based on results from type-specific immunodot assays; diagnosis of genital herpes. Results  The overall age-adjusted HSV-2 seroprevalence was 17.0% (95% confidence interval [CI], 15.8%-18.3%) in 1999-2004 and 21.0% (95% CI, 19.1%-23.1%) in 1988-1994, a relative decrease of 19.0% between the 2 surveys (95% CI, –28.6% to –9.5%; P<.001). Decreases in HSV-2 seroprevalence were especially concentrated in persons aged 14 to 19 years between 1988 and 2004. In adolescents aged 17 to 19 years and young adults, the decreases in HSV-2 seroprevalence were significant even after adjusting for changes in sexual behaviors. Among those infected with HSV-2, the percentage who reported having been diagnosed with genital herpes was statistically different (14.3% in 1999-2004 and 9.9% in 1988-1994; P = .02). Seroprevalence of HSV-1 decreased from 62.0% (95% CI, 59.6%-64.6%) in 1988-1994 to 57.7% (95% CI, 55.9%-59.5%) in 1999-2004, a relative decrease of 6.9% between the 2 surveys (95% CI, –11.6% to –2.3%; P = .006). Among persons infected with HSV-1 but not with HSV-2, a higher percentage reported having been diagnosed with genital herpes in 1999-2004 compared with 1988-1994 (1.8% vs 0.4%, respectively; P<.001). Conclusions  These data show declines in HSV-2 seroprevalence, suggesting that the trajectory of increasing HSV-2 seroprevalence in the United States has been reversed. Seroprevalence of HSV-1 decreased but the incidence of genital herpes caused by HSV-1 may be increasing.      

High-risk patients with acute coronary syndromes treated with low-molecular-weight or unfractionated heparin: outcomes at 6 months and 1 year in the SYNERGY trial

Context  The SYNERGY trial comparing enoxaparin and unfractionated heparin in high-risk patients with acute coronary syndromes (ACS) showed that enoxaparin was not inferior to unfractionated heparin in reducing death or nonfatal myocardial infarction (MI) at 30 days. Objective  To evaluate continued risk in this patient cohort through 6-month and 1-year follow-up. Design, Setting, and Patients  Overall, 9978 patients were randomized from August 2001 through December 2003 in 487 hospitals in 12 countries. Patients were followed up for 6 months and for 1 year. Main Outcome Measures  Six-month outcomes were death, nonfatal MI, revascularization procedures, stroke, and site-investigator–reported need for rehospitalization; 1-year outcome was all-cause death. Results  Six-month and 1-year follow-up data were available for 9957 (99.8%) and 9608 (96.3%) of 9978 patients, respectively; 541 patients (5.4%) had died at 6 months and 739 (7.4%) at 1 year. Death or nonfatal MI at 6 months occurred in 872 patients receiving enoxaparin (17.6%) vs 884 receiving unfractionated heparin (17.8%) (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.89-1.07; P = .65). In the subgroup of patients receiving consistent therapy, ie, only enoxaparin or unfractionated heparin during the index hospitalization (n = 6138), a reduction in death or nonfatal MI with enoxaparin was maintained at 180 days (HR, 0.85; 95% CI, 0.75-0.95; P = .006). Rehospitalization within 180 days occurred in 858 patients receiving enoxaparin (17.9%) and 911 receiving unfractionated heparin (19.0%) (HR, 0.94; 95% CI, 0.85-1.03; P = .17). One-year all-cause death rates were similar in the 2 treatment groups (380/4974 [7.6%] for enoxaparin vs 359/4948 [7.3%] for unfractionated heparin; HR, 1.06; 95% CI, 0.92-1.22; P = .44). One-year death rates in patients receiving consistent therapy were also similar (251/3386 [7.4%] for enoxaparin vs 213/2720 [7.8%] for unfractionated heparin; HR, 0.95; 95% CI, 0.79-1.14; P = .55). Conclusions  In the SYNERGY trial, patients continued to experience adverse cardiac events through long-term follow-up. The effect of enoxaparin on death or MI compared with that of unfractionated heparin at 6 months was similar to that observed at 30 days in the overall trial and in the consistent-therapy group. One-year death rates were also similar in both groups. High-risk patients with ACS remain susceptible to continued cardiac events despite aggressive therapies. ClinicalTrials.gov Identifier:  NCT00043784.