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.      

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.      

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.      

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.      

Reviewing the Reviews: The Example of Chronic Fatigue Syndrome

Objective.— To test the hypothesis that the selection of literature in review articles is unsystematic and is influenced by the authors' discipline and country of residence. Data Sources.— Reviews in English published between 1980 and March 1996 in MEDLINE, EMBASE (BIDS), PSYCHLIT, and Current Contents were searched. Study Selection.— Reviews of chronic fatigue syndrome (CFS) were selected. Articles explicitly concerned with a specialty aspect of CFS and unattributed, unreferenced, or insufficiently referenced articles were discarded. Data Extraction.— Record of data sources in each review was noted as was the departmental specialty of the first author and his or her country of residence. The references cited in each index paper were tabulated by assigning them to 6 specialty categories, by article title, and by assigning them to 8 categories, by country of journal publication. Data Synthesis.— Of 89 reviews, 3 (3.4%) reported on literature search and described search method. Authors from laboratory-based disciplines preferentially cited laboratory references, while psychiatry-based disciplines preferentially cited psychiatric literature (P=.01). A total of 71.6% of references cited by US authors were from US journals, while 54.9% of references cited by United Kingdom authors were published in United Kingdom journals (P=.001). Conclusion.— Citation of the literature is influenced by review authors' discipline and nationality.      

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.      

Possible Effectiveness of Clarithromycin and Rifabutin for Cryptosporidiosis Chemoprophylaxis in HIV Disease

Context.— Cryptosporidium parvum infection, a common cause of diarrhea in persons infected with the human immunodeficiency virus (HIV), is difficult to treat or prevent. Objective.— To evaluate relative rates of cryptosporidiosis in HIV-infected patients who were either receiving or not receiving chemoprophylaxis or treatment for Mycobacterium avium complex. Design.— Analysis of prospectively collected data from HIV-infected patients' visits to their physicians since 1992. Setting.— Ten (8 private, 2 publicly funded) HIV clinics in 9 US cities. Patients.— A total of 1019 HIV-infected patients with CD4⁺ cell counts less than 0.075x10⁹/L. Main Outcome Measures.— Incidence of clinical cryptosporidiosis during treatment with clarithromycin, rifabutin, and azithromycin. Results.— Five of the 312 patients reportedly taking clarithromycin developed cryptosporidiosis vs 30 of the 707 patients not taking clarithromycin (relative hazard [RH], 0.25 [95% confidence interval (CI), 0.10-0.67]; P =.004).Two of the 214 patients taking rifabutin developed cryptosporidiosis vs 33 of the 805 not taking rifabutin (RH, 0.15 [95% CI, 0.04-0.62]; P=.01). Prophylactic efficacy of either drug was 75% or greater. No protective effect was seen in the 54 patients reportedly taking azithromycin (RH, 1.48 [95% CI, 0.44-5.04]; P=.46). Conclusions.— Clarithromycin and rifabutin were highly protective against development of cryptosporidiosis in immune-suppressed HIV-infected persons in this analysis; further study is warranted.      

Preemptive Epidural Analgesia and Recovery From Radical Prostatectomy: A Randomized Controlled Trial

Context.— Preemptive analgesia can decrease the sensitization of the central nervous system that would ordinarily amplify subsequent nociceptive input, but a clear demonstration of its clinical efficacy is necessary for it to become a routine component of acute pain therapy. Objective.— To determine the impact of preemptive epidural analgesia on postoperative pain and other clinically important outcome variables after radical retropubic prostatectomy. Design and Setting.— A block randomized double-blind clinical trial lasting 20 months at a single academic medical center. Patients.— A total of 100 generally healthy and neurologically intact patients scheduled for radical retropubic prostatectomy for the treatment of prostate cancer in whom an epidural catheter for treating postoperative pain was to be placed prior to the induction of general anesthesia. Interventions.— Epidural bupivacaine, epidural fentanyl, or no epidural drug was administered prior to induction of anesthesia and throughout the entire operation, followed by aggressive postoperative epidural analgesia for all patients. Main Outcome Measures.— Daily pain scores during hospitalization and pain scores obtained 3.5, 5.5, and 9.5 weeks after hospital discharge. Results.— The patients who received epidural fentanyl or bupivacaine prior to surgical incision (preemptive analgesia) experienced 33% less pain while hospitalized (P=.007). Pain scores in those receiving preemptive analgesia were significantly lower at 9.5 weeks (P=.02), but were not significantly different at 3.5 or 5.5 weeks. At 9.5 weeks, 32 (86%) of 37 patients receiving preemptive analgesia were pain-free compared with 9 (47%) of 19 control patients (P=.004). Patients receiving preemptive analgesia were more active 3.5 weeks after surgery (P=.01), but not at 5.5 or 9.5 weeks. Conclusions.— Even in the presence of aggressive postoperative pain management, preemptive epidural analgesia significantly decreases postoperative pain during hospitalization and long after discharge, and is associated with increased activity levels after discharge.      

Effect of an Intensive Educational Program for Minority College Students and Recent Graduates on the Probability of Acceptance to Medical School

Context.— Increasing the number of minority physicians is a long-standing goal of professional associations and government. Objective.— To determine the effectiveness of an intensive summer educational program for minority college students and recent graduates on the probability of acceptance to medical school. Design.— Nonconcurrent prospective cohort study based on data from medical school applications, Medical College Admission Tests, and the Association of American Medical Colleges Student and Applicant Information Management System. Setting.— Eight US medical schools or consortia of medical schools. Participants.— Underrepresented minority (black, Mexican American, mainland Puerto Rican, and American Indian) applicants to US allopathic medical schools in 1997 (N=3830), 1996 (N=4654), and 1992 (N=3447). Intervention.— The Minority Medical Education Program (MMEP), a 6-week, residential summer educational program focused on training in the sciences and improvement of writing, verbal reasoning, studying, test taking, and presentation skills. Main Outcome Measure.— Probability of acceptance to at least 1 medical school. Results.— In the 1997 medical school application cohort, 223 (49.3%) of 452 MMEP participants were accepted compared with 1406 (41.6%) of 3378 minority nonparticipants (P=.002). Positive and significant program effects were also found in the 1996 (P=.01) and 1992 (P=.005) cohorts and in multivariate analysis after adjusting for nonprogrammatic factors likely to influence acceptance (P<.001). Program effects were also observed in students who participated in the MMEP early in college as well as those who participated later and among those with relatively high as well as low grades and test scores. Conclusions.— The MMEP enhanced the probability of medical school acceptance among its participants. Intensive summer education is a strategy that may help improve diversity in the physician workforce.      

Press Releases of Science Journal Articles and Subsequent Newspaper Stories on the Same Topic

Context.— Scientific journals issue press releases to disseminate scientific news about articles they publish. Objective.— To assess whether press releases about journal articles were associated with publication of subsequent newspaper stories. Design.— Retrospective content analysis of newspaper stories, journal press releases, and journal tables of contents. From December 1, 1996, to February 28, 1997, press releases and tables of contents were collected from BMJ, Nature, Science, and The Lancet, along with newspaper stories on scientific research published in The New York Times (United States), Le Figaro and Le Monde (France), El País and La Vanguardia (Spain), La Repubblica (Italy), and the International Herald Tribune. Main Outcome Measurements.— Number of newspaper stories that contained reference to articles appearing in the 4 scientific journals, number of newspaper stories that referred to journal articles described in press releases, and the order in which journal articles were mentioned in press releases. Results.— Of the 1060 newspaper stories analyzed, 142 referred to journal articles; of these, 119 (84%) referred to articles mentioned in press releases and 23 (16%) referred to journal articles not mentioned in press releases (comparison of proportions, P =.03). Articles described first or second were referenced in more newspapers than articles described later in the press release (P=.01 by ² analysis). Conclusions.— Journal articles described in press releases, in particular those described first or second in the press release, are associated with the subsequent publication of newspaper stories on the same topic.      

Lumbar Supports and Education for the Prevention of Low Back Pain in Industry: A Randomized Controlled Trial

Context.— Low back pain is a frequent and costly health problem. Prevention of low back pain is important both for the individual patient and from an economic perspective. Objective.— To assess the efficacy of lumbar supports and education in the prevention of low back pain in industry. Design.— A randomized controlled trial with a factorial design. Setting.— The cargo department of an airline company in the Netherlands. Participants.— A total of 312 workers were randomized, of whom 282 were available for the 6-month follow-up. Interventions.— Subjects were randomly assigned to 4 groups: (1) education (lifting instructions) and lumbar support, (2) education, (3) lumbar support, and (4) no intervention. Education consisted of 3 group sessions on lifting techniques with a total duration of 5 hours. Lumbar supports were recommended to be used during working hours for 6 months. Main Outcome Measures.— Low back pain incidence and sick leave because of back pain during the 6-month intervention period. Results.— Compliance with wearing the lumbar support at least half the time was 43%. In the 282 subjects for whom data were available, no statistically significant differences in back pain incidence (48 [36%] of 134 with lumbar support vs 51 [34%] of 148 without, P=.81) or in sick leave because of low back pain (mean, 0.4 days per month with lumbar support vs 0.4 days without, P=.52) were found among the intervention groups. In a subgroup of subjects with low back pain at baseline, lumbar supports reduced the number of days with low back pain per month (median, 1.2 vs 6.5 days per month; P=.03). Conclusions.— Overall, lumbar supports or education did not lead to a reduction in low back pain incidence or sick leave. The results of the subgroup analysis need to be confirmed by future research. Based on our results, the use of education or lumbar supports cannot be recommended in the prevention of low back pain in industry.      

Effect of Computerized Physician Order Entry and a Team Intervention on Prevention of Serious Medication Errors

Context.— Adverse drug events (ADEs) are a significant and costly cause of injury during hospitalization. Objectives.— To evaluate the efficacy of 2 interventions for preventing nonintercepted serious medication errors, defined as those that either resulted in or had potential to result in an ADE and were not intercepted before reaching the patient. Design.— Before-after comparison between phase 1 (baseline) and phase 2 (after intervention was implemented) and, within phase 2, a randomized comparison between physican computer order entry (POE) and the combination of POE plus a team intervention. Setting.— Large tertiary care hospital. Participants.— For the comparison of phase 1 and 2, all patients admitted to a stratified random sample of 6 medical and surgical units in a tertiary care hospital over a 6-month period, and for the randomized comparison during phase 2, all patients admitted to the same units and 2 randomly selected additional units over a subsequent 9-month period. Interventions.— A physician computer order entry system (POE) for all units and a team-based intervention that included changing the role of pharmacists, implemented for half the units. Main Outcome Measure.— Nonintercepted serious medication errors. Results.— Comparing identical units between phases 1 and 2, nonintercepted serious medication errors decreased 55%, from 10.7 events per 1000 patient-days to 4.86 events per 1000 (P=.01). The decline occurred for all stages of the medication-use process. Preventable ADEs declined 17% from 4.69 to 3.88 (P=.37), while nonintercepted potential ADEs declined 84% from 5.99 to 0.98 per 1000 patient-days (P=.002). When POE-only was compared with the POE plus team intervention combined, the team intervention conferred no additonal benefit over POE. Conclusions.— Physician computer order entry decreased the rate of nonintercepted serious medication errors by more than half, although this decrease was larger for potential ADEs than for errors that actually resulted in an ADE.      

Impact of Hospital Volume on Operative Mortality for Major Cancer Surgery

Context.— Hospitals that treat a relatively high volume of patients for selected surgical oncology procedures report lower surgical in-hospital mortality rates than hospitals with a low volume of the procedures, but the reports do not take into account length of stay or adjust for case mix. Objective.— To determine whether hospital volume was inversely associated with 30-day operative mortality, after adjusting for case mix. Design and Setting.— Retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database in which the hypothesis was prospectively specified. Surgeons determined in advance the surgical oncology procedures for which the experience of treating a larger volume of patients was most likely to lead to the knowledge or technical expertise that might offset surgical fatalities. Patients.— All 5013 patients in the SEER registry aged 65 years or older at cancer diagnosis who underwent pancreatectomy, esophagectomy, pneumonectomy, liver resection, or pelvic exenteration, using incident cancers of the pancreas, esophagus, lung, colon, and rectum, and various genitourinary cancers diagnosed between 1984 and 1993. Main Outcome Measure.— Thirty-day mortality in relation to procedure volume, adjusted for comorbidity, patient age, and cancer stage. Results.— Higher volume was linked with lower mortality for pancreatectomy (P=.004), esophagectomy (P<.001), liver resection (P=.04), and pelvic exenteration (P=.04), but not for pneumonectomy (P=.32). The most striking results were for esophagectomy, for which the operative mortality rose to 17.3% in low-volume hospitals, compared with 3.4% in high-volume hospitals, and for pancreatectomy, for which the corresponding rates were 12.9% vs 5.8%. Adjustments for case mix and other patient factors did not change the finding that low volume was strongly associated with excess mortality. Conclusions.— These data support the hypothesis that when complex surgical oncologic procedures are provided by surgical teams in hospitals with specialty expertise, mortality rates are lower.      

Cigarette Smoking and Progression of Atherosclerosis: The Atherosclerosis Risk in Communities (ARIC) Study

Context.— Cigarette smoking is a powerful risk factor for incident heart disease and stroke, but the relationship of active and passive smoking with the progression of atherosclerosis has not been described. Objective.— To examine the impact of active smoking and exposure to environmental tobacco smoke (ETS) on the progression of atherosclerosis. Design.— A longitudinal assessment of the relationship between smoking exposure evaluated at the initial visit and the 3-year change in atherosclerosis. Setting.— A population-based cohort of middle-aged adults from 4 communities in the United States. Participants.— A total of 10914 participants from the Atherosclerosis Risk in Communities (ARIC) study enrolled between 1987 and 1989. Main Outcome Measure.— Change in atherosclerosis from baseline to the 3-year follow-up as indexed by intimal-medial thickness of the carotid artery assessed by ultrasound and adjusted for demographic characteristics, cardiovascular risk factors, and lifestyle variables. Results.— Exposure to cigarette smoke was associated with progression of atherosclerosis. Relative to never smokers and after adjustment for demographic characteristics, cardiovascular risk factors, and lifestyle variables, current cigarette smoking was associated with a 50% increase in the progression of atherosclerosis (mean progression rate over 3 years, 43.0 µm for current and 28.7 µm for never smokers, regardless of ETS exposure), and past smoking was associated with a 25% increase (mean progression rate over 3 years, 35.8 µm for past smokers and 28.7 µm for never smokers). Relative to those not exposed to ETS, exposure to ETS was associated with a 20% increase (35.2 µm for those exposed to ETS vs 29.3 µm for those not exposed). The impact of smoking on atherosclerosis progression was greater for subjects with diabetes and hypertension. Although more pack-years of exposure was independently associated with faster progression (P<.001), after controlling for the number of pack-years, the progression rates of current and past smokers did not differ (P=.11). Conclusions.— Both active smoking and ETS exposure are associated with the progression of an index of atherosclerosis. Smoking is of particular concern for patients with diabetes and hypertension. The fact that pack-years of smoking but not current vs past smoking was associated with progression of atherosclerosis suggests that some adverse effects of smoking may be cumulative and irreversible.      

Long-term Effects of Nurse Home Visitation on Children's Criminal and Antisocial Behavior: 15-Year Follow-up of a Randomized Controlled Trial

Context.— A program of home visitation by nurses has been shown to affect the rates of maternal welfare dependence, criminality, problems due to use of substances, and child abuse and neglect. However, the long-term effects of this program on children's antisocial behavior have not been examined. Objective.— To examine the long-term effects of a program of prenatal and early childhood home visitation by nurses on children's antisocial behavior. Design.— Fifteen-year follow-up of a randomized trial. Interviews were conducted with the adolescents and their biological mothers or custodial parents. Setting.— Semirural community in New York. Participants.— Between April 1978 and September 1980, 500 consecutive pregnant women with no previous live births were recruited, and 400 were enrolled. A total of 315 adolescent offspring participated in a follow-up study when they were 15 years old; 280 (89%) were born to white mothers, 195 (62%) to unmarried mothers, 151 (48%) to mothers younger than 19 years, and 186 (59%) to mothers from households of low socioeconomic status at the time of registration during pregnancy. Intervention.— Families in the groups that received home visits had an average of 9 (range, 0-16) home visits during pregnancy and 23 (range, 0-59) home visits from birth through the child's second birthday. The control groups received standard prenatal and well-child care in a clinic. Main Outcome Measures.— Children's self-reports of running away, arrests, convictions, being sentenced to youth corrections, initiation of sexual intercourse, number of sex partners, and use of illegal substances; school records of suspensions; teachers' reports of children's disruptive behavior in school; and parents' reports of the children's arrests and behavioral problems related to the children's use of alcohol and other drugs. Results.— Adolescents born to women who received nurse visits during pregnancy and postnatally and who were unmarried and from households of low socioeconomic status (risk factors for antisocial behavior), in contrast with those in the comparison groups, reported fewer instances (incidence) of running away (0.24 vs 0.60; P=.003), fewer arrests (0.20 vs 0.45; P=.03), fewer convictions and violations of probation (0.09 vs 0.47; P<.001), fewer lifetime sex partners (0.92 vs 2.48; P=.003), fewer cigarettes smoked per day (1.50 vs 2.50; P=.10), and fewer days having consumed alcohol in the last 6 months (1.09 vs 2.49; P=.03). Parents of nurse-visited children reported that their children had fewer behavioral problems related to use of alcohol and other drugs (0.15 vs 0.34; P=.08). There were no program effects on other behavioral problems. Conclusions.— This program of prenatal and early childhood home visitation by nurses can reduce reported serious antisocial behavior and emergent use of substances on the part of adolescents born into high-risk families.      

Research Design and Statistical Methods in Chinese Medical Journals

Context.— Study design and statistical analyses have improved in journals published in Western countries, but the type of research designs and statistical methods used in medical journals outside Western countries has not been assessed. Objectives.— To determine the frequency of research designs and statistical techniques used in Chinese medical journals, types of statistical errors present, and trends over a 10-year period. Design .— Evaluation of all original articles published in 5 leading journals in 1985 (N=640) and in 1995 (N=954). Main Outcome Measures.— Research designs and statistical methods. Results.— Compared with 1985, significant improvement was seen in 1995; the percentages of original articles reporting clinical trials, prospective studies, or basic science research increased from 18% to 31% (P<.001), the proportion of papers using statistical tests increased from 40% to 60% (P<.001), more sophisticated statistical methods were used, and of those articles using statistics, the proportion using appropriate methods increased from 22% to 46% (P<.001). In both years, the most commonly used statistical methods were t tests and contingency tables. The most common errors were presentation of P values without specifying the test used, use of multiple t tests instead of analysis of variance, and use of unpaired t tests when paired tests were required. Conclusions.— The use of statistical methods in Chinese medical journals research is improving, and by 1995, the frequency of using statistical methods in published articles was similar to the results determined in previous studies of journals. However, the lack of or inappropriate use of statistics remains a serious problem.      

The Relationship Between Method of Physician Payment and Patient Trust

Context.— Trust is the cornerstone of the patient-physician relationship. Payment methods that place physicians at financial risk have raised concerns about patients' trust in physicians to act in patients' best interests. Objective.— To evaluate the extent to which methods of physician payment are related to patient trust. Design.— Cross-sectional telephone interview survey done between January and June 1997. Setting.— Health plans of a large national insurer in Atlanta, Ga, the Baltimore, Md–Washington, DC, area, and Orlando, Fla. Participants.— A total of 2086 adult managed care and indemnity patients. Main Outcome Measure.— A 10-item scale (=.94) assessing patients' trust in physicians. Results.— More fee-for-service (FFS) indemnity patients (94%) completely or mostly trust their physicians to "put their health and well-being above keeping down the health plan's costs" than salary (77%), capitated (83%), or FFS managed care patients (85%) (P<.001 for pairwise comparisons). In multivariate analyses that adjusted for potentially confounding factors, FFS indemnity patients also had higher scores on the 10-item trust scale than salary (P<.001), capitated (P<.001), or FFS managed care patients (P<.01). The effects of payment method on patient trust were reduced when a measure based on patients' reports about physician behavior (eg, Does your physician take enough time to answer your questions?) was included in the regression analyses, but the differences remained statistically significant, except for the comparison between FFS managed care and FFS indemnity patients (P=.08). Patients' perceptions of how their physicians were paid were not independently associated with trust, but the 37.7% who said they did not know how their physicians were paid had higher levels of trust than other patients (P<.01). A total of 30.2% of patients were incorrect about their physicians' method of payment. Conclusions.— Most patients trusted their physicians, but FFS indemnity patients have higher levels of trust than salary, capitated, or FFS managed care patients. Patients' reports of physician behavior accounted for part of the variation in patients' trust in physicians who are paid differently. The impact of payment methods on patient trust may be mediated partly by physician behavior.      

Abstinence and Safer Sex HIV Risk-Reduction Interventions for African American Adolescents: A Randomized Controlled Trial

Context.— African American adolescents are at high risk of contracting sexually transmitted infection with human immunodeficiency virus (HIV), but which behavioral interventions to reduce risk are most effective and who should conduct them is not known. Objective.— To evaluate the effects of abstinence and safer-sex HIV risk-reduction interventions on young inner-city African American adolescents' HIV sexual risk behaviors when implemented by adult facilitators as compared with peer cofacilitators. Design.— Randomized controlled trial with 3-, 6-, and 12-month follow-up. Setting.— Three middle schools serving low-income African American communities in Philadelphia, Pa. Participants.— A total of 659 African American adolescents recruited for a Saturday program. Interventions.— Based on cognitive-behavioral theories and elicitation research, interventions involved 8 1-hour modules implemented by adult facilitators or peer cofacilitators. Abstinence intervention stressed delaying sexual intercourse or reducing its frequency; safer-sex intervention stressed condom use; control intervention concerned health issues unrelated to sexual behavior. Main Outcome Measures.— Self-reported sexual intercourse, condom use, and unprotected sexual intercourse. Results.— Mean age of the enrollees was 11.8 years; 53% were female and 92.6% were still enrolled at 12 months. Abstinence intervention participants were less likely to report having sexual intercourse in the 3 months after intervention than were control group participants (12.5% vs 21.5%, P=.02), but not at 6- or 12-month follow-up (17.2% vs 22.7%, P=.14; 20.0% vs 23.1%, P=.42, respectively). Safer-sex intervention participants reported significantly more consistent condom use than did control group participants at 3 months (odds ratio [OR]=3.38; 95% confidence interval [CI], 1.25-9.16) and higher frequency of condom use at all follow-ups. Among adolescents who reported sexual experience at baseline, the safer-sex intervention group reported less sexual intercourse in the previous 3 months at 6- and 12-month follow-up than did control and abstinence intervention (adjusted mean days over prior 3 months, 1.34 vs 3.77 and 3.03, respectively; P.01 at 12-month follow-up) and less unprotected intercourse at all follow-ups than did control group (adjusted mean days, 0.04 vs 1.85, respectively, P<.001, at 12-month follow-up). There were no differences in intervention effects with adult facilitators as compared with peer cofacilitators. Conclusion.— Both abstinence and safer-sex interventions can reduce HIV sexual risk behaviors, but safer-sex interventions may be especially effective with sexually experienced adolescents and may have longer-lasting effects.      

National Patterns in the Treatment of Smokers by Physicians

Context.— Routine treatment of smokers by physicians is a national health objective for the year 2000, a quality measure for health care plans, and the subject of evidence-based clinical guidelines. There are few national data on how physicians' practices compare with these standards. Objective.— To assess recent trends in the treatment of smokers by US physicians in ambulatory care and to determine whether physicians' practices meet current standards. Design.— Analysis of 1991-1995 data from the National Ambulatory Medical Care Survey, an annual survey of a random sample of US office-based physicians. Setting.— Physicians' offices. Patients.— A total of 3254 physicians recorded data on 145716 adult patient visits. Main Outcome Measures.— The proportion of visits at which physicians (1) identified a patient's smoking status, (2) counseled a smoker to quit, and (3) used nicotine replacement therapy. Results.— Smoking counseling by physicians increased from 16% of smokers' visits in 1991 to 29% in 1993 (P<.001) and then decreased to 21% of smokers' visits in 1995 (P<.001). Nicotine replacement therapy use followed a similar pattern, increasing from 0.4% of smokers' visits in 1991 to 2.2% in 1993 (P<.001) and decreasing to 1.3% of smokers' visits in 1995 (P=.007). Physicians identified patients' smoking status at 67% of all visits in 1991; this proportion did not increase over time. Primary care physicians were more likely to provide treatment to smokers than were specialists. All physicians were more likely to treat patients with smoking-related diagnoses. Conclusions.— US physicians' treatment of smokers improved little in the first half of the 1990s, although a transient peak in counseling and nicotine replacement use occurred in 1993 after the introduction of the nicotine patch. Physicians' practices fell far short of national health objectives and practice guidelines. In particular, patient visits for diagnoses not related to smoking represent important missed opportunities for intervention.      

Low-Dose Hydrocortisone for Treatment of Chronic Fatigue Syndrome: A Randomized Controlled Trial

Context.— Chronic fatigue syndrome (CFS) is associated with a dysregulated hypothalamic–pituitary adrenal axis and hypocortisolemia. Objective.— To evaluate the efficacy and safety of low-dose oral hydrocortisone as a treatment for CFS. Design.— A randomized, placebo-controlled, double-blind therapeutic trial, conducted between 1992 and 1996. Setting.— A single-center study in a tertiary care research institution. Patients.— A total of 56 women and 14 men aged 18 to 55 years who met the 1988 Centers for Disease Control and Prevention case criteria for CFS and who withheld concomitant treatment with other medications. Intervention.— Oral hydrocortisone, 13 mg/m² of body surface area every morning and 3 mg/m² every afternoon, or placebo, for approximately 12 weeks. Main Outcome Measures.— A global Wellness scale and other self-rating instruments were completed repeatedly before and during treatment. Resting and cosyntropin-stimulated cortisol levels were obtained before and at the end of treatment. Patients recorded adverse effects on a checklist. Results.— The number of patients showing improvement on the Wellness scale was 19 (54.3%) of 35 placebo recipients vs 20 (66.7%) of 30 hydrocortisone recipients (P=.31). Hydrocortisone recipients had a greater improvement in mean Wellness score (6.3 vs 1.7 points; P=.06), a greater percentage (53% vs 29%; P=.04) recording an improvement of 5 or more points in Wellness score, and a higher average improvement in Wellness score on more days than did placebo recipients (P<.001). Statistical evidence of improvement was not seen with other self-rating scales. Although adverse symptoms reported by patients taking hydrocortisone were mild, suppression of adrenal glucocorticoid responsiveness was documented in 12 patients who received it vs none in the placebo group (P<.001). Conclusions.— Although hydrocortisone treatment was associated with some improvement in symptoms of CFS, the degree of adrenal suppression precludes its practical use for CFS.