Incident Chlamydia trachomatis Infections Among Inner-city Adolescent Females

Context.— Adolescents are at highest risk for infection with Chlamydia trachomatis, an important preventable cause of pelvic inflammatory disease and subsequent tubal factor infertility in US women. Current guidelines for delivery of adolescent primary care services recommend yearly chlamydia screening for those adolescent females considered to be at risk. Objectives.— To describe the epidemiology of prevalent and incident chlamydia infection among adolescent females to assess the appropriate interval for chlamydia screening and to define risk factors that would identify adolescent females to target for screening. Design.— Prospective longitudinal study. Patients.— A consecutive sample of 3202 sexually active females 12 through 19 years old making 5360 patient visits over a 33-month period, January 1994 through September 1996. Setting.— Baltimore, Md, family planning, sexually transmitted disease, and school-based clinics. Intervention.— Testing for C trachomatis by polymerase chain reaction. Main Outcome Measures.— Prevalence and incidence of C trachomatis infections; predictors of positive test result for C trachomatis. Results.— Chlamydia infection was found in 771 first visits (24.1%) and 299 repeat visits (13.9%); 933 adolescent females (29.1%) had at least 1 positive test result. Females who were 14 years old had the highest age-specific chlamydia prevalence rate (63 [27.5%] of 229 cases; P=.01). The chlamydia incidence rate was 28.0 cases per 1000 person-months (95% confidence interval, 24.9-31.5 cases). The median time was 7.2 months to a first positive chlamydia test result and 6.3 months to a repeat positive test result among those with repeat visits. Independent predictors of chlamydia infection—reason for clinic visit, clinic type, prior sexually transmitted diseases, multiple or new partners, or inconsistent condom use—failed to identify a subset of adolescent females with the majority of infections. Conclusions.— A high prevalence and incidence of C trachomatis infection were found among adolescent females. We, therefore, recommend screening all sexually active adolescent females for chlamydia infection every 6 months, regardless of symptoms, prior infections, condom use, or multiple partner risks.      

Role of Seroconversion in Confirming Cure of Helicobacter pylori Infection

Context.— The role of serologic testing to confirm cure of Helicobacter pylori infection after antimicrobial therapy is not completely defined. Objective.— To determine the utility of serologic testing in confirming cure of H pylori infection more than 1 year after therapy. Design.— A prospective, before-after interventional trial. Setting.— An outpatient clinical research laboratory in an academic, urban Veterans Affairs medical center. Participants.— Twenty-three otherwise healthy men and women with active H pylori infection demonstrated by gastric biopsy and with positive H pylori serologic findings. Intervention.— A 14-day course of bismuth, tetracycline, and metronidazole. Main Outcome Measures.— Determination of IgG serum antibodies to H pylori at baseline, 1 month, 3 months, and approximately 18 months after completion of therapy compared with serial gastric mucosal biopsy specimens with stains for H pylori and for histologic examination as the criterion standard. Results.— Fifteen (65%) of 23 subjects were cured of their H pylori infection as assessed by gastric biopsy, with elimination of gastritis; median antibody levels declined from 92.5 U/mL at baseline to undetectable levels at 18 months. The other 8 subjects (35%) were not cured and had persistent gastritis at 18 months; median antibody levels declined from 130.6 U/mL at baseline to 89.7 U/mL at 18 months. Sensitivity and specificity of seroconversion (from a positive to negative test result) in detecting cure of H pylori infection were 60% and 100%, respectively. Conclusion.— Undetectable antibody levels beyond the first year of therapy accurately confirm cure of H pylori infection in initially seropositive healthy subjects, with reasonable sensitivity.      

Outbreak of Salmonella Serotype Hartford Infections Associated With Unpasteurized Orange Juice

Context.— Acidic foods such as orange juice have been thought to be unlikely vehicles of foodborne illness. Objective.— To investigate an outbreak of Salmonella enterica serotype Hartford (Salmonella Hartford) infections among persons visiting a theme park in Orlando, Fla, in 1995. Design.— Review of surveillance data, matched case-control study, laboratory investigation, and environmental studies. Setting.— General community. Participants.— The surveillance case definition was Salmonella Hartford or Salmonella serogroup C₁ infection in a resident of or a visitor to Orlando in May or June 1995. In the case-control study, case patients were limited to theme park hotel visitors and controls were matched to case patients by age group and hotel check-in date. Main Outcome Measures.— Risk factors for infection and source of implicated food. Results.— Sixty-two case patients from 21 states were identified. Both Salmonella Hartford and Salmonella enterica serotype Gaminara (Salmonella Gaminara) were isolated from stool samples of 1 ill person. Thirty-two case patients and 83 controls were enrolled in the case-control study. Ninety-seven percent of case patients had drunk orange juice in the theme park vs 54% of controls (matched odds ratio, undefined; 95% confidence interval, 5.2 to undefined). The orange juice was unpasteurized and locally produced. Salmonella Gaminara was isolated from 10 of 12 containers of orange juice produced during May and July, indicating ongoing contamination of juice probably because of inadequately sanitized processing equipment. Conclusions.— Unpasteurized orange juice caused an outbreak of salmonellosis in a large Florida theme park. All orange juice was recalled and the processing plant closed. Pasteurization or other equally effective risk-management strategies should be used in the production of all juices.      

Community-Acquired Methicillin-Resistant Staphylococcus aureus in Children With No Identified Predisposing Risk

Context.— Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections in children have occurred primarily in individuals with recognized predisposing risks. Community-acquired MRSA infections in the absence of identified risk factors have been reported infrequently. Objectives.— To determine whether community-acquired MRSA infections in children with no identified predisposing risks are increasing and to define the spectrum of disease associated with MRSA isolation. Design.— Retrospective review of medical records. Patients.— Hospitalized children with S aureus isolated between August 1988 and July 1990 (1988-1990) and between August 1993 and July 1995 (1993-1995). Setting.— The University of Chicago Children's Hospital. Main Outcome Measures.— Prevalence of community-acquired MRSA over time, infecting vs colonizing isolates, and risk factors for disease. Results.— The number of children hospitalized with community-acquired MRSA disease increased from 8 in 1988-1990 to 35 in 1993-1995. Moreover, the prevalence of community-acquired MRSA without identified risk increased from 10 per 100000 admissions in 1988-1990 to 259 per 100000 admissions in 1993-1995 (P<.001), and a greater proportion of isolates produced clinical infection. The clinical syndromes associated with MRSA in children without identified risk were similar to those associated with community-acquired methicillin-susceptible S aureus. Notably, 7 (70%) of 10 community-acquired MRSA isolates obtained from children with an identified risk were nonsusceptible to at least 2 drugs, compared with only 6 (24%) of 25 isolates obtained from children without an identified risk (P=.02). Conclusions.— These findings demonstrate that the prevalence of community-acquired MRSA among children without identified risk factors is increasing.      

Bartenders' Respiratory Health After Establishment of Smoke-Free Bars and Taverns

Context.— The association between environmental tobacco smoke (ETS) exposure and respiratory symptoms has not been well established in adults. Objective.— To study the respiratory health of bartenders before and after legislative prohibition of smoking in all bars and taverns by the state of California. Design.— Cohort of bartenders interviewed before and after smoking prohibition. Setting and Participants.— Bartenders at a random sample of bars and taverns in San Francisco. Main Outcome Measures.— Interviews assessed respiratory symptoms, sensory irritation symptoms, ETS exposure, personal smoking, and recent upper respiratory tract infections. Spirometric assessment included forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) measurements. Results.— Fifty-three of 67 eligible bartenders were interviewed. At baseline, all 53 bartenders reported workplace ETS exposure. After the smoking ban, self-reported ETS exposure at work declined from a median of 28 to 2 hours per week (P<.001). Thirty-nine bartenders (74%) initially reported respiratory symptoms. Of those symptomatic at baseline, 23 (59%) no longer had symptoms at follow-up (P<.001). Forty-one bartenders (77%) initially reported sensory irritation symptoms. At follow-up, 32 (78%) of these subjects had resolution of symptoms (P<.001). After prohibition of workplace smoking, we observed improvement in mean FVC (0.189 L; 95% confidence interval [CI], 0.082-0.296 L; 4.2% change) and, to a lesser extent, mean FEV₁ (0.039 L; 95% CI, -0.030 to 0.107 L; 1.2% change). Complete cessation of workplace ETS exposure (compared with continued exposure) was associated with improved mean FVC (0.287 L; 95% CI, 0.088-0.486; 6.8% change) and mean FEV₁ (0.142 L; 95% CI, 0.020-0.264 L; 4.5% change), after controlling for personal smoking and recent upper respiratory tract infections. Conclusion.— Establishment of smoke-free bars and taverns was associated with a rapid improvement of respiratory health.      

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.      

Pretreatment Evaluation of Chronic Hepatitis C: Risks, Benefits, and Costs

Context.— Chronic hepatitis C (CHC) infection affects nearly 4 million people in the United States. Treatment with interferon alfa-2b has been limited by its cost and low likelihood of long-term response. Objective.— To examine the cost-effectiveness of alternative pretreatment management strategies for patients with CHC. Design.— Decision and cost-effectiveness analysis using a Markov model to examine prevalence of genotypes, viral load, and histological characteristics in relation to the sustained response rate with treatment. Data were based on a previously published decision model and a MEDLINE literature search for hepatitis C, biopsy, and liver from 1966 to 1996. Patients.— A hypothetical population of patients with CHC infection and elevated serum alanine aminotransferase level. Interventions.— Combinations of liver biopsy, genotyping, and quantitative viral load determination prior to a single 6-month course of interferon alfa-2b; empirical interferon treatment; and conservative management. Main Outcome Measures.— Proportion of sustained responders, lifetime costs, life expectancy, and quality-adjusted life expectancy. Results.— Strategies involving hepatitis C virus (HCV) RNA testing had marginal cost-effectiveness ratios up to $4400 per discounted quality-adjusted life-year gained but would miss up to 36% of sustained responders. Empirical interferon treatment had a marginal cost-effectiveness ratio of $12,400 per discounted quality-adjusted life-year gained and reached all potential sustained responders. Strategies involving liver biopsy were more expensive and would miss 6% of sustained responders and yield slightly lower life expectancies. Conclusions.— Routine liver biopsy before treatment with interferon increases the cost of managing patients with CHC without improving health outcomes. Using quantitative HCV RNA testing to guide therapy misses some potential sustained responders. Empirical interferon treatment has a marginal cost-effectiveness ratio within the bounds of other commonly accepted therapies and misses none of the sustained responders.      

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.      

Role of Rifampin for Treatment of Orthopedic Implant-Related Staphylococcal Infections: A Randomized Controlled Trial

Context.— Rifampin-containing regimens are able to cure staphylococcal implant-related infections based on in vitro and in vivo observations. However, this evidence has not been proven by a controlled clinical trial. Objective.— To evaluate the clinical efficacy of a rifampin combination in staphylococcal infections associated with stable orthopedic devices. Design.— A randomized, placebo-controlled, double-blind trial conducted from 1992 through 1997. Setting.— Two infectious disease services in tertiary care centers in collaboration with 5 orthopedic surgeons in Switzerland. Patients.— A total of 33 patients with culture-proven staphylococcal infection associated with stable orthopedic implants and with a short duration of symptoms of infection (exclusion limit <1 year; actual experience 0-21 days). Intervention.— Initial debridement and 2-week intravenous course of flucloxacillin or vancomycin with rifampin or placebo, followed by either ciprofloxacin-rifampin or ciprofloxacin-placebo long-term therapy. Main Outcome Measures.— Cure was defined as (1) lack of clinical signs and symptoms of infection, (2) C-reactive protein level less than 5 mg/L, and (3) absence of radiological signs of loosening or infection at the final follow-up visit at 24 months. Failure was defined as (1) persisting clinical and/or laboratory signs of infection or (2) persisting or new isolation of the initial microorganism. Results.— A total of 18 patients were allocated to ciprofloxacin-rifampin and 15 patients to the ciprofloxacin-placebo combination. Twenty-four patients fully completed the trial with a follow-up of 35 and 33 months. The cure rate was 12 (100%) of 12 in the ciprofloxacin-rifampin group compared with 7 (58%) of 12 in the ciprofloxacin-placebo group (P=.02). Nine of 33 patients dropped out due to adverse events (n=6), noncompliance (n=1), or protocol violation (n=2). Seven of the 9 patients who dropped out were subsequently treated with rifampin combinations, and 5 of them were cured without removal of the device. Conclusion.— Among patients with stable implants, short duration of infection, and initial debridement, patients able to tolerate long-term (3-6 months) therapy with rifampin-ciprofloxacin experienced cure of the infection without removal of the implant.      

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.      

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.      

Perinatal HIV-1 Transmission: Interaction Between Zidovudine Prophylaxis and Mode of Delivery in the French Perinatal Cohort

Context.— It is unclear whether elective cesarean delivery may have a protective effect against the transmission of human immunodeficiency virus 1 (HIV-1). Objective.— To investigate whether mode of delivery has an impact on perinatal HIV-1 transmission in the presence of zidovudine prophylaxis. Design.— A prospective cohort study. Setting.— The 85 perinatal centers in the French Perinatal Cohort, from 1985 to 1996. Patients.— A total of 2834 singleton children born to mothers with HIV-1 infection. Main Outcome Measure.— Human immunodeficiency virus 1 infection of the infant. Results.— No zidovudine was used in 1917 pregnancies and zidovudine prophylaxis was used in 902 pregnancies. Cesarean deliveries were performed in 10.9% on an emergent basis and in 8.3% electively, prior to labor or membrane rupture. In 1917 mothers who did not receive zidovudine, of 1877 with information on mode of delivery, 17.2% transmitted HIV-1 to their child. Risk factors statistically significantly associated with transmission were maternal p24 antigenemia, cervicovaginal infections during pregnancy, amniotic fluid color, and rupture of membranes 4 hours or more before delivery. Mode of delivery was not related to transmission. In 902 mothers receiving zidovudine, transmission was 6.4% in 872 with information on mode of delivery, and elective cesarean delivery (n=133) was associated with a lower transmission rate than emergent cesarean or vaginal delivery (0.8%, 11.4%, and 6.6%, respectively; P=.002). In a multivariate analysis of all mother-child pairs, including obstetrical risk factors, maternal p24 antigenemia, and zidovudine prophylaxis, interaction between mode of delivery and zidovudine prophylaxis was significant (P=.007). In the multivariate analysis of pregnancies with zidovudine prophylaxis, factors related to transmission rate were maternal p24 antigenemia, amniotic fluid color, and mode of delivery. Adjusted odds ratios (95% confidence intervals) were 1.6 (0.7-3.6) for emergent cesarean delivery and 0.2 (0.0-0.9) for elective cesarean delivery (P=.04) in comparison with vaginal delivery. Conclusions.— We observed an interaction between zidovudine prophylaxis and elective cesarean delivery in decreasing transmission of HIV-1 from mother to child. This observation may have clinical implications for prevention.      

What Are the Factors Determining Authorship and the Order of the Authors' Names?: A Study Among Authors of the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine)

Context.— Although criteria justifying authorship of scientific medical articles have been formulated, it is not well known how authorship is established in practice. Objectives.— To assess the criteria for authorship used by authors of original articles in Nederlands Tijdschrift voor Geneeskunde (NTVG, the Dutch Journal of Medicine), and to determine whether the criteria for authorship of the International Committee of Medical Journal Editors (ICMJE) are known and applied. Design.— Survey questionnaire. Setting.— Editorial office of the NTVG. Participants.— All 450 authors of 115 original articles published in 1995. Main Outcome Measures.— Author's contribution to study design, material, collection of data, statistics, and writing. Results.— Of 362 forms returned, 352 could be analyzed (78.2% response rate). The 5 questions most frequently answered affirmatively were ICMJE criteria: critical reading (86.1% of the authors), approval of the final version (84.7%), study design (74.7%), study conception (64.2%), and revision (63.4%). Authors rated their contribution 2 points higher than did their coauthors. Interestingly, 64% of the respondents met the ICMJE criteria, although 60% of the respondents did not know them. Conclusion.— Authorship was mostly in accordance with ICMJE criteria although many authors were not familiar with them.      

Oral Famciclovir for the Suppression of Recurrent Genital Herpes: A Randomized Controlled Trial

Context.— Recurrent genital herpes simplex virus (HSV) may be treated episodically, but this may not be sufficient for patients with frequent recurrences. Objective.— To determine the efficacy and safety of famciclovir in the suppression of recurrent genital HSV infection. Design.— A randomized, double-blind, placebo-controlled, parallel-group study. Setting.— Thirty university, hospital, or private outpatient referral centers in Canada and Europe. Patients.— A total of 455 patients (223 men, 232 women) aged 18 years or older with a history of 6 or more episodes of genital herpes during 12 of the most recent 24 months, in the absence of suppressive therapy, received study medication. Intervention.— Oral famciclovir, 125 mg or 250 mg 3 times daily or 250 mg twice daily, or placebo for 52 weeks. Main Outcome Measures.— Time to the first recurrence of genital HSV infection; the proportion of patients remaining free of HSV recurrence at 6 months; frequency of adverse events. Results.— In an intent-to-treat analysis, famciclovir significantly delayed the time to the first recurrence of genital herpes at all dose regimens (hazard ratios, 2.9-3.3;P< .001); median time to recurrence for famciclovir recipients was 222 to 336 days compared with 47 days for placebo recipients. The proportion of patients remaining free of HSV recurrence was approximately 3 times higher in famciclovir recipients (79%-86%) than in placebo recipients (27%) at 6 months (relative risks, 2.9-3.1;P <.001); efficacy was maintained at 12 months. Famciclovir was well tolerated with an adverse experience profile comparable to placebo. Conclusions.— Oral famciclovir (125 mg or 250 mg 3 times daily or 250 mg twice daily) is an effective, well-tolerated treatment for the suppression of genital HSV infection in patients with frequent recurrences.      

Effects of Raloxifene on Serum Lipids and Coagulation Factors in Healthy Postmenopausal Women

Context.— Raloxifene is a selective estrogen receptor modulator that has estrogen-agonistic effects on bone and estrogen-antagonistic effects on breast and uterus. Objective.— To identify the effects of raloxifene on markers of cardiovascular risk in postmenopausal women, and to compare them with those induced by hormone replacement therapy (HRT). Design.— Double-blind, randomized, parallel trial. Setting.— Eight sites in the United States. Participants.— 390 healthy postmenopausal women recruited by advertisement. Intervention.— Participants were randomized to receive 1 of 4 treatments: raloxifene, 60 mg/d; raloxifene, 120 mg/d; HRT (conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone acetate, 2.5 mg/d); or placebo. Main Outcome Measures.— Change and percent change from baseline of lipid levels and coagulation parameters after 3 months and 6 months of treatment. Results.— At the last visit completed, compared with placebo, both dosages of raloxifene significantly lowered low-density lipoprotein cholesterol (LDL-C) by 12% (P<.001), similar to the 14% reduction with HRT (P<.001). Both dosages of raloxifene significantly lowered lipoprotein(a) by 7% to 8% (P<.001), less than the 19% decrease with HRT (P<.001). Raloxifene increased high-density lipoprotein-2 cholesterol (HDL₂-C) by 15% to 17% (P<.05), less than the 33% increase with HRT (P<.001). Raloxifene did not significantly change high-density lipoprotein cholesterol (HDL-C), triglycerides, or plasminogen activator inhibitor-1 (PAI-1); whereas HRT increased HDL-C by 11% and triglycerides by 20%, and decreased PAI-1 by 29% (for all, P< .001). Raloxifene significantly lowered fibrinogen by 12% to 14% (P<.001), unlike HRT, which had no effect. Neither treatment changed fibrinopeptide A or prothrombin fragment 1 and 2. Conclusions.— Raloxifene favorably alters biochemical markers of cardiovascular risk by decreasing LDL-C, fibrinogen, and lipoprotein(a), and by increasing HDL₂-C without raising triglycerides. In contrast to HRT, raloxifene had no effect on HDL-C and PAI-1, and a lesser effect on HDL₂-C and lipoprotein(a). Further clinical trials are necessary to determine whether these favorable biochemical effects are associated with protection against cardiovascular disease.      

Effect of Treatment of Isolated Systolic Hypertension on Left Ventricular Mass

Context.— Left ventricular (LV) hypertrophy is a common problem among elderly patients with isolated systolic hypertension (ISH), but the effect of treatment of ISH on LV mass is not known. Objective.— To assess the ability of antihypertensive drug treatment to reduce LV mass in ISH. Design.— Echocardiographic Substudy of the Systolic Hypertension in the Elderly Program (SHEP). Patients.— A total of 104 participants at the St Louis SHEP site who had interpretable baseline echocardiograms, 94 of whom had 3-year follow-up echocardiograms. Intervention.— The SHEP participants were randomized to placebo or active treatment with chlorthalidone (12.5-25 mg/d), with atenolol (25-50 mg/d) added if necessary to maintain goal blood pressure. Main Outcome Measure.— Change in LV mass assessed by echocardiography. Results.— Minimum follow-up was 3 years. In the active treatment group, 91% and 80% of subjects were receiving treatment with chlorthalidone alone by the end of years 1 and 3, respectively. The LV mass index was 93 g/m² in the active treatment group and 100 g/m² in the placebo group (P<.001). The LV mass index declined by 13% (95% confidence interval, - 3% to - 23%) in the active treatment group compared with a 6% increase (95% confidence interval, - 3% to + 16%) in the placebo group over 3 years (P=.01). Conclusion.— Treatment of ISH with a diuretic-based regimen reduces LV mass.      

Mortality Differences Between Men and Women Following First Myocardial Infarction

Context.— Mortality after acute myocardial infarction is worse in women than in men, even after adjustment for comorbidity and age dissimilarities between sexes. Objective.— To assess the influence of sex on survival after acute myocardial infarction. Design.— Inception cohort obtained in a prospective registry of patients with acute myocardial infarction from 1992 through 1994. Setting.— Four teaching hospitals in northeastern Spain. Patients.— All consecutive patients aged 80 years or younger with first acute myocardial infarction. A total of 331 women and 1129 men were included. Main Outcome Measure.— Survival at 28 days and mortality or readmission at 6 months. Results.— Women were older (mean, 68.6 vs 60.1 years), presented more often with diabetes (52.9% vs 23.3%), hypertension (63.9% vs 42.3%), or previous angina (44.6% vs 37.4%), and developed more severe myocardial infarctions than men (acute pulmonary edema or cardiogenic shock occurred in 24.8% of women and 10.5% of men) (all P<.02). Men were more likely than women to receive thrombolytic therapy (41.3% vs 23.9%; P<.001), but rates of percutaneous transluminal angioplasty and coronary artery bypass graft surgery at 28 days were similar among men and women. The 28-day mortality rate was significantly higher among women (18.5% for women, 8.3% for men; P<.001). Revascularization procedures at 6 months were performed in a similar proportion of women and men. However, women had higher 6-month mortality rates (25.8% in women, 10.8% in men; P<.001) and readmission rates (23.3% for women, 12.2% for men; P<.001). After adjustment, women had greater risk of death than men at 28 days (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.12-2.65) and at 6 months (OR, 1.73; 95% CI, 1.18-2.52). Conclusions.— In this study population, women experienced more lethal and severe first acute myocardial infarction than men, regardless of comorbidity, age, or previous angina.      

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.      

Tuberculin Skin Test Screening Practices Among US Colleges and Universities

Context.— Concern about transmission of Mycobacterium tuberculosis on college campuses has prompted some schools to institute tuberculin skin test screening of students, but this screening has never been evaluated. Objective.— To describe tuberculin skin test screening practices and results of screening in colleges and universities in the United States. Design and Setting.— Self-administered mail and telephone questionnaire in November and December 1995 to a stratified random sample of US 2-year and 4-year colleges and universities. Main Outcome Measures.— Type of tuberculin screening required; types of schools requiring screening; number and rate of students with positive skin test results and/or diagnosed as having tuberculosis. Results.— Of the 3148 US colleges and universities, 624 (78%) of 796 schools surveyed responded. Overall, 378 schools (61%) required tuberculin screening; it was required for all new students (US residents and international students) in 161 (26%) of 624 schools, all new international students but not new US residents in 53 (8%), and students in specific academic programs in 294 (47%). Required screening was more likely in 4-year vs 2-year schools, schools that belonged to the American College Health Association vs nonmember schools, schools with immunization requirements vs schools without, and schools with a student health clinic vs those without (P<.001 for all). Public and private schools were equally likely to require screening (64% vs 62%; P=.21). In the 378 schools with screening requirements, tine or multiple puncture tests were accepted in 95 (25%); test results were recorded in millimeters of induration in 95 (25%); and 100 (27%) reported collecting results in a centralized registry or database. Of the 168 (27%) of 624 schools accepting only Mantoux skin tests and reporting results for school years 1992-1993 through 1995-1996, 3.1% of the 348,368 students screened had positive skin test results (median percentage positive, 0.8%). International students had a significantly higher case rate for active tuberculosis than US residents (35.2 vs 1.1 per 100,000 students screened). Conclusions.— Widespread tuberculin screening of students yielded a low prevalence of skin test reactors and few tuberculosis cases. To optimize the use of limited public health resources, tuberculin screening should target students at high risk for infection.      

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.