Influence of a Child's Sex on Medulloblastoma Outcome

Context.— Aggressive treatment of medulloblastoma, the most common pediatric brain tumor, has not improved survival. Identifying better prognostic indicators may warrant less morbid therapy. Objective.— To investigate the role of sex on outcome of medulloblastoma. Design.— Retrospective study of significant factors for survival with a median follow-up of 82 months. Setting.— University medical center. Patients.— A total of 109 consecutive, pediatric patients treated for primary medulloblastoma from 1970 to 1995 with surgery and postoperative radiotherapy and, after 1979, chemotherapy. Main Outcome Measures.— Factors independently associated with survival. Results.— The final multivariate model predicting improved survival included sex (hazard ratio, 0.52; 95% confidence interval [CI], 0.29-0.92; P=.03; favoring female), metastases at presentation (hazard ratio, 2.01; 95% CI, 1.14-3.52; P=.02), and extent of surgical resection (hazard ratio, 0.60; 95% CI, 0.34-1.04; P=.07; favoring greater resection). The overall, 5-year freedom from progression was 40% and survival was 49%. Radiotherapy dose (P=.72), and chemotherapy (P=.90) did not significantly affect a disease outcome. Conclusions.— The sex of the child was an important predictor for survival of medulloblastoma; girls had a much better outcome. The difference in survival between sexes should be evaluated in prospective, clinical trials.      

Effect of Prolonged Methylprednisolone Therapy in Unresolving Acute Respiratory Distress Syndrome: A Randomized Controlled Trial

Context.— No pharmacological therapeutic protocol has been found effective in modifying the clinical course of acute respiratory distress syndrome (ARDS) and mortality remains greater than 50%. Objective.— To determine the effects of prolonged methylprednisolone therapy on lung function and mortality in patients with unresolving ARDS. Design.— Randomized, double-blind, placebo-controlled trial. Setting.— Medical intensive care units of 4 medical centers. Participants.— Twenty-four patients with severe ARDS who had failed to improve lung injury score (LIS) by the seventh day of respiratory failure. Interventions.— Sixteen patients received methylprednisolone and 8 received placebo. Methylprednisolone dose was initially 2 mg/kg per day and the duration of treatment was 32 days. Four patients whose LIS failed to improve by at least 1 point after 10 days of treatment were blindly crossed over to the alternative treatment. Main Outcome Measures.— Primary outcome measures were improvement in lung function and mortality. Secondary outcome measures were improvement in multiple organ dysfunction syndrome (MODS) and development of nosocomial infections. Results.— Physiological characteristics at the onset of ARDS were similar in both groups. At study entry (day 9 [SD, 3] of ARDS), the 2 groups had similar LIS, ratios of PaO₂ to fraction of inspired oxygen (FIO₂), and MODS scores. Changes observed by study day 10 for methylprednisolone vs placebo were as follows: reduced LIS (mean [SEM], 1.7 [0.1] vs 3.0 [0.2]; P<.001); improved ratio of PaO₂ to FIO₂ (mean [SEM], 262 [19] vs 148 [35]; P<.001); decreased MODS score (mean [SEM], 0.7 [0.2] vs 1.8 [0.3]; P<.001); and successful extubation (7 vs 0; P=.05). For the treatment group vs the placebo group, mortality associated with the intensive care unit was 0 (0%) of 16 vs 5 (62%) of 8 (P=.002) and hospital-associated mortality was 2 (12%) of 16 vs 5 (62%) of 8 (P=.03). The rate of infections per day of treatment was similar in both groups, and pneumonia was frequently detected in the absence of fever. Conclusions.— In this study, prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement in lung injury and MODS scores and reduced mortality.      

Effect of a Garlic Oil Preparation on Serum Lipoproteins and Cholesterol Metabolism: A Randomized Controlled Trial

Context.— Garlic-containing drugs have been used in the treatment of hypercholesterolemia even though their efficacy is not generally established. Little is known about the mechanisms of action of the possible effects on cholesterol in humans. Objective.— To estimate the hypocholesterolemic effect of garlic oil and to investigate the possible mechanism of action. Design.— Double-blind, randomized, placebo-controlled trial. Setting.— Outpatient lipid clinic. Patients.— We investigated 25 patients (mean age, 58 years) with moderate hypercholesterolemia. Intervention.— Steam-distilled garlic oil preparation (5 mg twice a day) vs placebo each for 12 weeks with wash-out periods of 4 weeks. Main Outcome Measures.— Serum lipoprotein concentrations, cholesterol absorption, and cholesterol synthesis. Results.— Baseline lipoprotein profiles were (mean [SD]): total cholesterol, 7.53 (0.75) mmol/L (291 [29] mg/dL); low-density lipoprotein cholesterol (LDL-C), 5.35 (0.78) mmol/L (207 [30] mg/dL); high-density lipoprotein cholesterol (HDL-C), 1.50 (0.41) mmol/L (58 [16] mg/dL); and triglycerides, 1.45 (0.73) mmol/L (127 [64] mg/dL). Lipoprotein levels were virtually unchanged at the end of both treatment periods (mean difference [95% confidence interval]): total cholesterol, 0.085 (-0.201 to 0.372) mmol/L (3.3 [-7.8 to 14.4] mg/dL), P=.54; LDL-C, 0.001 (-0.242 to 0.245) mmol/L (0.04 [-9.4 to 9.5] mg/dL), P=.99; HDL-C, 0.050 (-0.028 to 0.128) mmol/L (1.9 [-1.1 to 4.9] mg/dL), P=.20; triclycerides, 0.047 (-0.229 to 0.135) mmol/L (4.2 [-20.3 to 12.0]) mg/dL, P=.60. Cholesterol absorption (37.5% [10.5%] vs 38.3% [10.7%], P=.58), cholesterol synthesis (12.7 [6.5] vs 13.4 [6.6] mg/kg of body weight per day, P=.64), mevalonic acid excretion (192 [66] vs 187 [66] µg/d, P=.78), and changes in the ratio of lathosterol to cholesterol in serum (4.4% [24.3%] vs 10.6% [21.1%], P=.62) were not different in garlic and placebo treatment. Conclusions.— The commercial garlic oil preparation investigated had no influence on serum lipoproteins, cholesterol absorption, or cholesterol synthesis. Garlic therapy for treatment of hypercholesterolemia cannot be recommended on the basis of this study.      

Zinc Gluconate Lozenges for Treating the Common Cold in Children: A Randomized Controlled Trial

Context.— The common cold is one of the most frequently occurring illnesses and is responsible for substantial morbidity and economic loss. Biochemical evidence suggests that zinc may be an effective treatment, and zinc gluconate glycine (ZGG) lozenges have been shown to reduce the duration of cold symptoms in adults. Objective.— To determine the efficacy of ZGG treatment of colds in children and adolescents. Design.— A randomized, double-masked, placebo-controlled study. Setting.— Two suburban school districts in Cleveland, Ohio. Patients.— A total of 249 students in grades 1 through 12 were enrolled within the first 24 hours of experiencing at least 2 of 9 symptoms of the common cold. Intervention.— Zinc lozenges, 10 mg, orally dissolved, 5 times a day (in grades 1-6) or 6 times a day (in grades 7-12). Main Outcome Measures.— Time to resolution of cold symptoms based on subjective daily symptom scores for cough, headache, hoarseness, muscle ache, nasal congestion, nasal drainage, scratchy throat, sore throat, and sneezing. Results.— Time to resolution of all cold symptoms did not differ significantly between students receiving zinc (n=124) and those receiving placebo (n=125) (median, 9 days; 95% confidence interval [CI], 8-9 days; median, 9 days, 95% CI, 7-10 days, respectively; P=.71). There were no significant differences in the time to resolution of any of the 9 symptoms studied. Compared with controls, more students in the zinc group reported adverse effects (88.6% vs 79.8%; P=.06); bad taste (60.2% vs 37.9%; P=.001); nausea (29.3% vs 16.1%; P=.01); mouth, tongue, or throat discomfort (36.6% vs 24.2%; P=.03); and diarrhea (10.6% vs 4.0%; P=.05). Conclusions.— In this community-based, randomized controlled trial, ZGG lozenges were not effective in treating cold symptoms in children and adolescents. Further studies with virologic testing are needed to clarify what role, if any, zinc may play in treating cold symptoms.      

Importance of Hemodynamic Factors in the Prognosis of Symptomatic Carotid Occlusion

Context.— The relative importance of hemodynamic factors in the pathogenesis and treatment of stroke in patients with carotid artery occlusion remains controversial. Objective.— To test the hypothesis that stage II cerebral hemodynamic failure (increased oxygen extraction measured by positron emission tomography [PET]) distal to symptomatic carotid artery occlusion is an independent risk factor for subsequent stroke in medically treated patients. Design and Setting.— Prospective, blinded, longitudinal cohort study of patients referred from a group of regional hospitals between 1992 and 1996. Patients.— From 419 subjects referred, 81 with previous stroke or transient ischemic attack in the territory of an occluded carotid artery were enrolled. All were followed up to completion of the study, with average follow-up of 31.5 months. Main Outcome Measures.— Telephone contact every 6 months recorded the subsequent occurrence of all stroke, ipsilateral ischemic stroke, and death. Results.— Stroke occurred in 12 of 39 patients with stage II hemodynamic failure and in 3 of 42 patients without (P=.005); stroke was ipsilateral in 11 of 39 patients with stage II hemodynamic failure and in 2 of 42 patients without (P=.004). Six deaths occurred in each group (P=.94). The age-adjusted relative risk conferred by stage II hemodynamic failure was 6.0 (95% confidence interval [CI], 1.7-21.6) for all stroke and 7.3 (95% CI, 1.6-33.4) for ipsilateral stroke. Conclusions.— Stage II hemodynamic failure defines a subgroup of patients with symptomatic carotid occlusion who are at high risk for subsequent stroke when treated medically. A randomized trial evaluating surgical revascularization in this high-risk subgroup is warranted.      

Masking Author Identity in Peer Review: What Factors Influence Masking Success?

Context.— In a previous study, we found that masking success was higher at a journal that masked reviewers to author identity. We hypothesized that masking policy or other factors could be associated with masking success. Objectives.— To evaluate differences in success of masking reviewers to author identity at 7 biomedical journals and to identify factors associated with these differences. Design.— Written questionnaire. Participants.— Reviewers at 3 journals with a long-standing policy of masking author identity (Annals of Emergency Medicine, Epidemiology, and Journal of the American Geriatrics Society) and 4 journals without a policy of masking author identity (Annals of Internal Medicine, JAMA, Obstetrics & Gynecology, and Ophthalmology). Main Outcome Measures.— Masking success (percentage of reviewers successfully masked) and reviewer characteristics associated with masking. Results.— There was no significant difference in masking success between journals with a policy of masking (60%) and those without (58%) (P=.92). We found no association between masking success and a policy of masking when adjusted for the reviewer characteristics of age, sex, years of reviewing experience, number of articles published, number of articles reviewed, percentage of time spent in research, editorial experience, or academic rank (odds ratio [OR], 1.3; 95% confidence interval [CI], 0.64-2.8; P=.43). In multivariable analysis of reviewer characteristics, reviewers spending a greater percentage of time in research, the only significant predictor of masking success, were less likely to be successfully masked (OR, 1.01; 95% CI, 1.00-1.02) (P=.04). Conclusions.— Masking success appears unrelated to a journal policy of masking, but is associated with reviewers' research experience and could be affected by other characteristics. Using reviewers with less research and reviewing experience might increase masking success, but the effect on review quality is unknown.      

Improved Survival Among HIV-Infected Individuals Following Initiation of Antiretroviral Therapy

Context.— Clinical trials have established the efficacy of antiretroviral therapy with double- and triple-drug regimens for individuals infected with the human immunodeficiency virus (HIV), but the effectiveness of these regimens in the population of patients not enrolled in clinical trials is unknown. Objective.— To characterize survival following the initiation of antiretroviral therapy among HIV-infected individuals in the province of British Columbia. Design.— Prospective, population-based cohort study of patients with antiretroviral therapy available free of charge (median follow-up, 21 months). Setting.— Province of British Columbia, Canada. Patients.— All HIV-positive men and women 18 years of age or older in the province who were first prescribed any antiretroviral therapy between October 1992 and June 1996 and whose CD4⁺ cell counts were less than 0.350x10⁹/L. Main Outcome Measures.— Rates of progression from initiation of antiretroviral therapy to death or a primary acquired immunodeficiency syndrome (AIDS) diagnosis for subjects who initially received zidovudine-, didanosine-, or zalcitabine-based therapy (ERA-I) and for those who initially received therapy regimens including lamivudine or stavudine (ERA-II). Results.— A total of 1178 patients (951 ERA-I, 227 ERA-II) were eligible. A total of 390 patients died (367 ERA-I, 23 ERA-II), yielding a crude mortality rate of 33.1%. ERA-I group subjects were almost twice as likely to die as ERA-II group subjects, with a mortality risk ratio of 1.86 (95% confidence interval [CI], 1.21-2.86; P=.005). After adjusting for Pneumocystis carinii and Mycobacterium avium prophylaxis use, AIDS diagnosis, CD4⁺ cell count, sex, and age, ERA-I participants were 1.93 times (95% CI, 1.25-2.97; P=.003) more likely to die than ERA-II participants. Among patients without AIDS when treatment was started, ERA-I participants were 2.50 times (95% CI, 1.59-3.93; P<.001) more likely to progress to AIDS or death than ERA-II participants. Conclusion.— The HIV-infected individuals who received initial therapy with regimens including stavudine or lamivudine had significantly lower mortality and longer AIDS-free survival than those who received initial therapy with regimens limited to zidovudine, didanosine, and zalcitabine.      

Improved Prognosis of Thoracic Aortic Aneurysms: A Population-Based Study

Context.— Managing thoracic aortic aneurysms identified incidentally by increased use of computed tomography, echocardiography, and magnetic resonance imaging is problematic, especially in the elderly. Objective.— To ascertain whether the previously reported poor prognosis for individuals with thoracic aortic aneurysms has changed with better medical therapies and improved surgical techniques that can now be applied to aneurysm management. Design.— Population-based cohort study. Setting and Patients.— All 133 patients with the diagnosis of degenerative thoracic aortic aneurysms among Olmsted County, Minnesota, residents between 1980 and 1994 compared with a previously reported cohort of similar patients between 1951 and 1980. Main Outcome Measures.— The primary clinical end points were incidence, cumulative rupture risk, rupture risk as a function of aneurysm size, and survival. Results.— In contrast to abdominal aortic aneurysms, for which men are affected predominately, 51% of thoracic aortic aneurysms were identified in women who were considerably older at recognition than men (mean age, 75.9 vs 62.8 years, respectively; P=.01). The overall incidence rate of 10.4 per 100,000 person-years (95% confidence interval [CI], 8.6-12.2) between 1980 and 1994 was more than 3-fold higher than the rate from 1951 to 1980. The cumulative risk of rupture was 20% after 5 years. Seventy-nine percent of ruptures occurred in women (P=.01). The 5-year risk of rupture as a function of aneurysm size at recognition was 0% for aneurysms less than 4 cm in diameter, 16% (95% CI, 4%-28%) for those 4 to 5.9 cm, and 31% (95% CI, 5%-56%) for aneurysms 6 cm or more. Overall 5-year survival improved to 56% (95% CI, 48%-66%) between 1980 and 1994 compared with only 19% between 1951 and 1980 (P<.01). Conclusions.— In this population, elderly women represent an increasing portion of all patients with clinically recognized thoracic aortic aneurysms and constitute the majority of patients whose aneurysm eventually ruptures. Overall survival for thoracic aortic aneurysms has improved significantly in the past 15 years.      

Publication Bias and Research on Passive Smoking: Comparison of Published and Unpublished Studies

Context.— The results of reviews may be biased by delays in publication and failure to publish nonsignificant results. Objective.— To determine the extent of unpublished results on the health effects of passive smoking and whether passive smoking studies with statistically nonsignificant results would have longer time to publication than those with statistically significant results. Design.— Semistructured telephone interviews of principal investigators of published or unpublished studies funded between 1981 and 1995, identified by information obtained from 76 (85%) of 89 organizations contacted that potentially funded research on passive smoking. Participants.— Seventy-eight investigators were eligible and could be located; 65 (83%) responded. They had conducted 61 studies of the health effects of passive smoke in humans or animals between 1981 and 1995 that met the criteria for the analysis of time to publication. Main Outcome Measure.— Time to publication for published studies and statistical significance of results of published and unpublished studies. Results.— Fourteen of the 61 studies were unpublished. Median time to publication was 5 years (95% confidence interval [CI], 4-7 years) for statistically nonsignificant studies and 3 years (95% CI, 3-5 years) for statistically significant studies (P=.004). Statistically significant results (P=.004), experimental study design (P=.01), study size less than or equal to 500 (P=.01), and animals as subjects (P=.03) were predictive of time to publication. When the studies with human participants were analyzed separately, only statistically significant data were predictive of publication (P=.007). Multivariate analysis of all studies indicated that statistical significance (P=.001) and study design (P=.01) were the only independent predictors of time to publication, while for the human studies only statistical significance was predictive of publication (P=.007). Conclusion.— There is a publication delay for passive smoking studies with nonsignificant results compared with those with significant results.      

Sodium Reduction and Weight Loss in the Treatment of Hypertension in Older Persons: A Randomized Controlled Trial of Nonpharmacologic Interventions in the Elderly (TONE)

Context.— Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly, but there is a paucity of evidence from randomized controlled trials in support of this recommendation. Objective.— To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension. Design.— Randomized controlled trial. Participants.— A total of 875 men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication. Setting.— Four academic health centers. Intervention.— The 585 obese participants were randomized to reduced sodium intake, weight loss, both, or usual care, and the 390 nonobese participants were randomized to reduced sodium intake or usual care. Withdrawal of antihypertensive medication was attempted after 3 months of intervention. Main Outcome Measure.— Diagnosis of high blood pressure at 1 or more follow-up visits, or treatment with antihypertensive medication, or a cardiovascular event during follow-up (range, 15-36 months; median, 29 months). Results.— The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake (relative hazard ratio, 0.69; 95% confidence interval [CI], 0.59-0.81; P<.001) and, in obese participants, among those assigned vs not assigned to weight loss (relative hazard ratio, 0.70; 95% CI, 0.57-0.87; P<.001). Relative to usual care, hazard ratios among the obese participants were 0.60 (95% CI, 0.45-0.80; P<.001) for reduced sodium intake alone, 0.64 (95% CI, 0.49-0.85; P=.002) for weight loss alone, and 0.47 (95% CI, 0.35-0.64; P<.001) for reduced sodium intake and weight loss combined. The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups. Conclusion.— Reduced sodium intake and weight loss constitute a feasible, effective, and safe nonpharmacologic therapy of hypertension in older persons.      

Contemporary clinical profile and outcome of prosthetic valve endocarditis

Context  Prosthetic valve endocarditis (PVE) is associated with significant mortality and morbidity. The contemporary clinical profile and outcome of PVE are not well defined. Objectives  To describe the prevalence, clinical characteristics, and outcome of PVE, with attention to health care–associated infection, and to determine prognostic factors associated with in-hospital mortality. Design, Setting, and Participants  Prospective, observational cohort study conducted at 61 medical centers in 28 countries, including 556 patients with definite PVE as defined by Duke University diagnostic criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to August 2005. Main Outcome Measure  In-hospital mortality. Results  Definite PVE was present in 556 (20.1%) of 2670 patients with infective endocarditis. Staphylococcus aureus was the most common causative organism (128 patients [23.0%]), followed by coagulase-negative staphylococci (94 patients [16.9%]). Health care–associated PVE was present in 203 (36.5%) of the overall cohort. Seventy-one percent of health care–associated PVE occurred within the first year of valve implantation, and the majority of cases were diagnosed after the early (60-day) period. Surgery was performed in 272 (48.9%) patients during the index hospitalization. In-hospital death occurred in 127 (22.8%) patients and was predicted by older age, health care–associated infection (62/203 [30.5%]; adjusted odds ratio [OR], 1.62; 95% confidence interval [CI], 1.08-2.44; P = .02), S aureus infection (44/128 [34.4%]; adjusted OR, 1.73; 95% CI, 1.01-2.95; P = .05), and complications of PVE, including heart failure (60/183 [32.8%]; adjusted OR, 2.33; 95% CI, 1.62-3.34; P<.001), stroke (34/101 [33.7%]; adjusted OR, 2.25; 95% CI, 1.25-4.03; P = .007), intracardiac abscess (47/144 [32.6%]; adjusted OR, 1.86; 95% CI, 1.10-3.15; P = .02), and persistent bacteremia (27/49 [55.1%]; adjusted OR, 4.29; 95% CI, 1.99-9.22; P<.001). Conclusions  Prosthetic valve endocarditis accounts for a high percentage of all cases of infective endocarditis in many regions of the world. Staphylococcus aureus is now the leading cause of PVE. Health care–associated infection significantly influences the clinical characteristics and outcome of PVE. Complications of PVE strongly predict in-hospital mortality, which remains high despite prompt diagnosis and the frequent use of surgical intervention.      

Primary Prevention of Acute Coronary Events With Lovastatin in Men and Women With Average Cholesterol Levels: Results of AFCAPS/TexCAPS

Context.— Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. Objective.— To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. Design.— A randomized, double-blind, placebo-controlled trial. Setting.— Outpatient clinics in Texas. Participants.— A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). Intervention.— Lovastatin (20-40 mg daily) or placebo in addition to a low–saturated fat, low-cholesterol diet. Main Outcome Measures.— First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. Results.— After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (183 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P=.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P=.003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. Conclusions.— Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.      

Acupuncture and Amitriptyline for Pain Due to HIV-Related Peripheral Neuropathy: A Randomized Controlled Trial

Context.— Peripheral neuropathy is common in persons infected with the human immunodeficiency virus (HIV) but few data on symptomatic treatment are available. Objective.— To evaluate the efficacy of a standardized acupuncture regimen (SAR) and amitriptyline hydrochloride for the relief of pain due to HIV-related peripheral neuropathy in HIV-infected patients. Design.— Randomized, placebo-controlled, multicenter clinical trial. Each site enrolled patients into 1 of the following 3 options: (1) a modified double-blind 2 x 2 factorial design of SAR, amitriptyline, or the combination compared with placebo, (2) a modified double-blind design of an SAR vs control points, or (3) a double-blind design of amitriptyline vs placebo. Setting.— Terry Beirn Community Programs for Clinical Research on AIDS (HIV primary care providers) in 10 US cities. Patients.— Patients with HIV-associated, symptomatic, lower-extremity peripheral neuropathy. Of 250 patients enrolled, 239 were in the acupuncture comparison (125 in the factorial option and 114 in the SAR option vs control points option), and 136 patients were in the amitriptyline comparison (125 in the factorial option and 11 in amitriptyline option vs placebo option). Interventions.— Standarized acupuncture regimen vs control points, amitriptyline (75 mg/d) vs placebo, or both for 14 weeks. Main Outcome Measure.— Changes in mean pain scores at 6 and 14 weeks, using a pain scale ranging from 0.0 (no pain) to 1.75 (extremely intense), recorded daily. Results.— Patients in all 4 groups showed reduction in mean pain scores at 6 and 14 weeks compared with baseline values. For both the acupuncture and amitriptyline comparisons, changes in pain score were not significantly different between the 2 groups. At 6 weeks, the estimated difference in pain reduction for patients in the SAR group compared with those in the control points group (a negative value indicates a greater reduction for the "active" treatment) was 0.01 (95% confidence interval [CI], -0.11 to 0.12; P =.88) and for patients in the amitriptyline group vs those in the placebo group was -0.07 (95% CI, -0.22 to 0.08; P=.38). At 14 weeks, the difference for those in the SAR group compared with those in the control points group was -0.08 (95% CI, -0.21 to 0.06; P=.26) and for amitriptyline compared with placebo was 0.00 (95% CI, -0.18 to 0.19; P=.99). Conclusions.— In this study, neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy.      

Effect of the Statistical Significance of Results on the Time to Completion and Publication of Randomized Efficacy Trials

Context.— Medical evidence may be biased over time if completion and publication of randomized efficacy trials are delayed when results are not statistically significant. Objective.— To evaluate whether the time to completion and the time to publication of randomized phase 2 and phase 3 trials are affected by the statistical significance of results and to describe the natural history of such trials. Design.— Prospective cohort of randomized efficacy trials conducted by 2 trialist groups from 1986 to 1996. Setting.— Multicenter trial groups in human immunodeficiency virus infection sponsored by the National Institutes of Health. Patients.— A total of 109 efficacy trials (total enrollment, 43708 patients). Main Outcome Measures.— Time from start of enrollment to completion of follow-up and time from completion of follow-up to peer-reviewed publication assessed with survival analysis. Results.— The median time from start of enrollment to publication was 5.5 years and was substantially longer for negative trials than for results favoring an experimental arm (6.5 vs 4.3 years, respectively; P<.001; hazard ratio for time to publication for positive vs negative trials, 3.7; 95% confidence interval [CI], 1.8-7.7). This difference was mostly attributable to differences in the time from completion to publication (median, 3.0 vs 1.7 years for negative vs positive trials; P<.001). On average, trials with significant results favoring any arm completed follow-up slightly earlier than trials with nonsignificant results (median, 2.3 vs 2.5 years; P=.045), but long-protracted trials often had low event rates and failed to reach statistical significance, while trials that were terminated early had significant results. Positive trials were submitted for publication significantly more rapidly after completion than were negative trials (median, 1.0 vs 1.6 years; P=.001) and were published more rapidly after submission (median, 0.8 vs 1.1 years; P=.04). Conclusion.— Among randomized efficacy trials, there is a time lag in the publication of negative findings that occurs mostly after the completion of the trial follow-up.      

Hunger in an Adult Patient Population

Context.— Although clinical observations suggest that some patients experience hunger and food insecurity, there are limited data on the prevalence of hunger in adult patients. Objective.— To determine the prevalence of hunger and food insecurity in adult patients at an urban county hospital. Design.— Cross-sectional survey conducted in 1997. Patients.— The primary survey included all patients aged 18 years or older who were admitted to the medicine, surgery, and neurology services during a 2-week period, and all patients who attended the hospital's general medicine clinic during 1 week. A second survey included primary care patients who received insulin from the hospital pharmacy during a 1-month period. Main Outcome Measures.— Rates of hunger and food insecurity. Results.— Of 709 eligible patients, 567 (participation rate, 80%) were interviewed in either the clinic (n=281) or hospital (n=286). An additional 170 patients who received insulin were interviewed by telephone (response rate, 75%). Of the primary sample, 68 (12%) respondents reported not having enough food, 75 (13%) reported not eating for an entire day, and 77 (14%) reported going hungry but not eating because they could not afford food. A total of 222 (40%) had received food stamps in the previous year and of those, 113 (50%) had their food stamps reduced or eliminated. Recipients whose food stamps had been eliminated or reduced were more likely to report not having enough food (18% vs 13%,P=.006), not eating for a whole day (20% vs 16%, P=.01), going hungry but not eating (20% vs 16%, P=.08), and cutting down on the size of meals or skipping meals (33% vs 27%,P=.01). In multivariate analysis, independent predictors of hunger included an annual income of less than $10000 (odds ratio [OR], 7.55; 95% CI, 3.01-18.92), drug use (OR, 3.56; 95% CI, 1.46-8.66), and a reduction in food stamp benefits (OR, 1.73; 95% CI, 1.01-2.96). Predictors of food insecurity included an annual income of less than $10000 (OR, 4.12; 95% confidence interval [CI], 1.98-8.58), drug use (OR, 2.11; 95% CI, 1.66-5.08), and a reduction in food stamps (OR, 2.02; 95% CI, 1.23-3.32). In addition, 103 (61%) patients in the sample of diabetics reported hypoglycemic reactions; 32 (31%) of these were attributed to inability to afford food. Conclusion.— Hunger and food insecurity are common among patients seeking care at an urban county hospital.      

Maintenance Phase Efficacy of Sertraline for Chronic Depression: A Randomized Controlled Trial

Context.— The chronic form of major depression is associated with a high rate of prevalence and disability, but no controlled research has examined the impact of long-term treatment on the course and burden of illness. Objective.— To determine if maintenance therapy with sertraline hydrochloride can effectively prevent recurrence of depression in the high-risk group of patients experiencing chronic major depression or major depression with antecedent dysthymic disorder ("double depression"). Design.— A 76-week randomized, double-blind, parallel-group study, conducted from September 1993 to November 1996. Setting.— Outpatient psychiatric clinics at 10 academic medical centers and 2 clinical research centers. Intervention.— Maintenance treatment with either sertraline hydrochloride (n=77) in flexible doses up to 200 mg or placebo (n=84). Patients.— A total of 161 outpatients with chronic major or double depression who responded to sertraline in a 12-week, double-blind, acute-phase treatment trial and continued to have a satisfactory therapeutic response during a subsequent 4-month continuation phase. Main Outcome Measure.— Time to recurrence of major depression. Results.— Sertraline afforded significantly greater prophylaxis against recurrence than did placebo (5 [6%] of 77 in the sertraline group vs 19 [23%] of 84 in the placebo group; P=.002 for the log-rank test of time-to-recurrence distributions). Clinically significant depressive symptoms reemerged in 20 (26%) of 77 patients treated with sertraline vs 42 (50%) of 84 patients who received placebo (P=.001). With use of a Cox proportional hazards model, patients receiving placebo were 4.07 times more likely (95% CI, 1.51-10.95; P=.005) to experience a depression recurrence, after adjustment for study site, type of depression, and randomization strata. Conclusions.— Maintenance therapy with sertraline is well tolerated and has significant efficacy in preventing recurrence or reemergence of depression in chronically depressed patients.      

Low Dosage and Long Treatment Duration of {beta}-Lactam: Risk Factors for Carriage of Penicillin-Resistant Streptococcus pneumoniae

Context.— The spread of drug-resistant Streptococcus pneumoniae in the community is a public health problem in developed and developing nations, but whether antibiotic use is responsible for the increase in drug resistance is not known. Objective.— To analyze the relationship between penicillin-resistant S pneumoniae (PR Sp) pharyngeal carriage and characteristics of -lactam use. Design.— Observational study of children attending 20 randomly sampled schools. Setting.— The Loiret, in the center of France. Participants.— A total of 941 children, 3 to 6 years old. Main Outcome Measure(s).— Pharyngeal carriage of S pneumoniae, antibiotic use, and medical events during the preceding 30 days. Pneumococcal penicillin G sodium minimal inhibitory concentrations and serotyping were performed. Results.— Medical illnesses and the use of antibiotics were not associated with PR Sp carriage. However, oral -lactam use was associated with an increased risk of PR Sp carriage (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.1-8.3; P=.03). Children treated by low daily doses of an oral -lactam (defined as lower than clinical recommendations) had an increased risk of PR Sp carriage, as compared with children who did not (OR, 5.9; 95% CI, 2.1-16.7; P =.002). A treatment of long duration (>5 days) with a -lactam was associated with an increased risk of PR Sp carriage (OR, 3.5; 95% CI, 1.3-9.8; P=.02). Conclusions.— Our results suggest that a low daily dose and a long duration of treatment with an oral -lactam contribute to the selective pressure in promoting pharyngeal carriage of PR Sp.      

Prophylactic Oral Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valve Replacement, or Repair: PAPABEAR: a randomized controlled trial

Context  Atrial tachyarrhythmias after cardiac surgery are associated with adverse outcomes and increased costs. Previous trials of amiodarone prophylaxis, while promising, were relatively small and yielded conflicting results. Objective  To determine whether a brief perioperative course of oral amiodarone is an effective and safe prophylaxis for atrial tachyarrhythmias after cardiac surgery overall and in important subgroups. Design, Setting, and Patients  Double-blind randomized controlled trial of 601 patients listed for nonemergent coronary artery bypass graft (CABG) surgery and/or valve replacement/repair surgery between February 1, 1999, and September 26, 2003, at a tertiary care hospital. The patients were followed up for 1 year. Intervention  Oral amiodarone (10 mg/kg daily) or placebo administered 6 days prior to surgery through 6 days after surgery (13 days). Randomization was stratified for subgroups defined by age, type of surgery, and use of preoperative -blockers. Main Outcome Measure  Incidence of atrial tachyarrhythmias lasting 5 minutes or longer that prompted therapy by the sixth postoperative day. Results  Atrial tachyarrhythmias occurred in fewer amiodarone patients (48/299; 16.1%) than in placebo patients (89/302; 29.5%) overall (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.69; P<.001); in patients younger than 65 years (19 [11.2%] vs 36 [21.1%]; HR, 0.51 [95% CI, 0.28-0.94]; P = .02); in patients aged 65 years or older (28 [21.7%] vs 54 [41.2%]; HR, 0.45 [95% CI, 0.27-0.75]; P<.001); in patients who had CABG surgery only (22 [11.3%] vs 46 [23.6%]; HR, 0.45 [95% CI, 0.26-0.79]; P = .002); in patients who had valve replacement/repair surgery with or without CABG surgery (25 [23.8%] vs 44 [44.1%]; HR, 0.51 [95% CI, 0.31-0.84; P = .008); in patients who received preoperative -blocker therapy (27 [15.3%] vs 42 [25.0%]; HR, 0.58 [95% CI, 0.34-0.99]; P = .03); and in patients who did not receive preoperative -blocker therapy (20 [16.3%] vs 48 [35.8%]; HR, 0.40 [95% CI, 0.22-0.71]; P<.001), respectively. Postoperative sustained ventricular tachyarrhythmias occurred less frequently in amiodarone patients (1/299; 0.3%) than in placebo patients (8/302; 2.6%) (P = .04). Dosage reductions of blinded therapy were more common in amiodarone patients (34/299; 11.4%) than in placebo patients (16/302; 5.3%) (P = .008). There were no differences in serious postoperative complications, in-hospital mortality, or readmission to the hospital within 6 months of discharge or in 1-year mortality. Conclusion  Oral amiodarone prophylaxis of atrial tachyarrhythmias after cardiac surgery is effective and may be safe overall and in important patient subgroups. Clinical Trials Registration  ClinicalTrials.gov Identifier: NCT00251706      

Duration of anticoagulation following venous thromboembolism: a meta-analysis

David Ost, MD; Josh Tepper, MD; Hanako Mihara, MD, MPH; Owen Lander, MD; Raphael Heinzer, MD; Alan Fein, MD

JAMA. 2005;294:706-715.

Context  Patients with venous thromboembolism (VTE) are susceptible to recurrent events, but whether prolonging anticoagulation is warranted in patients with VTE remains controversial.

Objective  To review the available evidence and quantify the risks and benefits of extending the duration of anticoagulation in patients with VTE.

Data Sources  PubMed, EMBase Pharmacology, the Cochrane database, clinical trial Web sites, and a hand search of reference lists.

Study Selection  Included studies were randomized controlled trials with results published from 1969 through 2004 and evaluating the duration of anticoagulation in patients with VTE that measured recurrent VTE. Excluded studies were those enrolling only pure populations of high-risk patients. Two independent reviewers assessed each article for inclusion and exclusion criteria, with adjudication by a third reviewer in cases of disagreement. Fifteen of 67 studies were included in the analysis.

Data Extraction  Two independent reviewers performed data extraction using a standardized form, with adjudication by the remainder of the investigators in cases of disagreement. Data regarding recurrent VTE, major bleeding, person-time at risk, and study quality were extracted.

Data Synthesis  If patients in the long-term therapy group remained receiving anticoagulation, the risk of recurrent VTE with long- vs short-term therapy was reduced (weighted incidence rate, 0.020 vs 0.126 events/person-year; rate difference, –0.106 [95% confidence interval {CI}, –0.145 to –0.067]; P<.001; pooled incidence rate ratio [IRR], 0.21 [95% CI, 0.14 to 0.31]; P<.001). If anticoagulation in the long-term therapy group was discontinued, the risk reduction was less pronounced (weighted incidence rate, 0.052 vs 0.072 events/person-year; rate difference, –0.020 [95% CI, –0.039 to –0.001]; P = .04; pooled IRR, 0.69 [95% CI, 0.53 to 0.91]; P = .009). The risk of major bleeding with long- vs short-term therapy was similar (weighted incidence rate, 0.011 vs 0.006 events/person-year; rate difference, 0.005 [95% CI, –0.002 to 0.011]; P = .14; pooled IRR, 1.80 [95% CI, 0.72 to 4.51]; P = .21).

Conclusions  Patients who receive extended anticoagulation are protected from recurrent VTE while receiving long-term therapy. The clinical benefit is maintained after anticoagulation is discontinued, but the magnitude of the benefit is less pronounced.

     

Health Economic Benefits and Quality of Life During Improved Glycemic Control in Patients With Type 2 Diabetes Mellitus: A Randomized, Controlled, Double-Blind Trial

Context.— Although the long-term health benefits of good glycemic control in patients with diabetes are well documented, shorter-term quality of life (QOL) and economic savings generally have been reported to be minimal or absent. Objective.— To examine short-term outcomes of glycemic control in type 2 diabetes mellitus (DM). Design.— Double-blind, randomized, placebo-controlled, parallel trial. Setting.— Sixty-two sites in the United States. Participants.— A total of 569 male and female volunteers with type 2 DM. Intervention.— After a 3-week, single-blind placebo-washout period, participants were randomized to diet and titration with either 5 to 20 mg of glipizide gastrointestinal therapeutic system (GITS) (n=377) or placebo (n=192) for 12 weeks. Main Outcome Measures.— Change from baseline in glucose and hemoglobin A_1c (HbA_1c) levels and symptom distress, QOL, and health economic indicators by questionnaires and diaries. Results.— After 12 weeks, mean (±SE) HbA_1c and fasting blood glucose levels decreased with active therapy (glipizide GITS) vs placebo (7.5%±0.1% vs 9.3%±0.1% and 7.0±0.1 mmol/L [126±2 mg/dL] vs 9.3±0.2 mmol/L [168±4 mg/dL], respectively; P<.001). Quality-of-life treatment differences (SD units) for symptom distress (+0.59; P<.001), general perceived health (+0.36; P=.004), cognitive functioning (+0.34; P=.005), and the overall visual analog scale (VAS) (+0.24; P=.04) were significantly more favorable for active therapy. Subscales of acuity (+0.38; P=.002), VAS emotional health (+0.35; P =.003), general health (+0.27; P =.01), sleep (+0.26; P =.04), depression (+0.25; P =.05), disorientation and detachment (+0.23; P =.05), and vitality (+0.22; P =.04) were most affected. Favorable health economic outcomes for glipizide GITS included higher retained employment (97% vs 85%; P<.001), greater productive capacity (99% vs 87%; P<.001), less absenteeism (losses=$24 vs $115 per worker per month; P <.001), fewer bed-days (losses=$1539 vs $1843 per 1000 person-days; P=.05), and fewer restricted-activity days (losses=$2660 vs $4275 per 1000 person-days; P=.01). Conclusions.— Improved glycemic control of type 2 DM is associated with substantial short-term symptomatic, QOL, and health economic benefits.