Antibiotic Prophylaxis for Leptospirosis

BACKGROUND: Leptospira infection is a global zoonosis with significant health impact for agricultural workers and those persons whose work or recreation takes them into endemic areas. OBJECTIVES: This systematic review assessed the current literature for evidence for or against use of antibiotic prophylaxis against Leptospira infection (leptospirosis). SEARCH STRATEGY: The authors searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and SCI-Expanded as well as relevant professional society meeting abstracts until January 2009. SELECTION CRITERIA: Prospective, randomised clinical trials studying antibiotic prophylaxis against leptospirosis were selected. DATA COLLECTION AND ANALYSIS: Data collection abstracted participant demographics and outcomes as well as features of trial design and quality. Trial results were analysed to independently determine outcomes, while multiple trial data was pooled when relevant. MAIN RESULTS: Three trials were included, all of which evaluated doxycyline use. Trial quality suffered from a lack of intention-to-treat analysis and variability across trials in methodology and targeted outcomes. One trial assessed post-exposure prophylaxis in an indigenous population after a flood without apparent efficacy in reduction of clinical or laboratory identified Leptospira infection. Two trials assessed pre-exposure prophylaxis, one among deployed soldiers and another in an indigenous population. Despite an odds ratio of 0.05 (95% CI 0.01 to 0.36) for laboratory-identified infection among deployed soldiers on doxycyline in one of these two trials, pooled data showed no statistically significant reduction in Leptospira infection among participants (Odds ratio 0.28 (95% CI 0.01 to 7.48). Minor adverse events (predominantly nausea and vomiting) were more common among those on doxycycline with an odds ratio of 11 (95% CI 2.1 to 60). AUTHORS\u27 CONCLUSIONS: Regular use of weekly oral doxycycline 200 mg increases the odds for nausea and vomiting with unclear benefit in reducing Leptospira seroconversion or clinical consequences of infection

First Things First: Effectiveness and Scalability of a Basic Prehospital Trauma Care Program for Lay First-Responders in Kampala, Uganda

BACKGROUND: We previously showed that in the absence of a formal emergency system, lay people face a heavy burden of injuries in Kampala, Uganda, and we demonstrated the feasibility of a basic prehospital trauma course for lay people. This study tests the effectiveness of this course and estimates the costs and cost-effectiveness of scaling up this training. METHODS AND FINDINGS: For six months, we prospectively followed 307 trainees (police, taxi drivers, and community leaders) who completed a one-day basic prehospital trauma care program in 2008. Cross-sectional surveys and fund of knowledge tests were used to measure their frequency of skill and supply use, reasons for not providing aid, perceived utility of the course and kit, confidence in using skills, and knowledge of first-aid. We then estimated the cost-effectiveness of scaling up the program. At six months, 188 (62%) of the trainees were followed up. Their knowledge retention remained high or increased. The mean correct score on a basic fund of knowledge test was 92%, up from 86% after initial training (n = 146 pairs, p = 0.0016). 97% of participants had used at least one skill from the course: most commonly haemorrhage control, recovery position and lifting/moving and 96% had used at least one first-aid item. Lack of knowledge was less of a barrier and trainees were significantly more confident in providing first-aid. Based on cost estimates from the World Health Organization, local injury data, and modelling from previous studies, the projected cost of scaling up this program was $0.12 per capita or$25-75 per life year saved. Key limitations of the study include small sample size, possible reporter bias, preliminary local validation of study instruments, and an indirect estimate of mortality reduction. CONCLUSIONS: Lay first-responders effectively retained knowledge on prehospital trauma care and confidently used their first-aid skills and supplies for at least six months. The costs of scaling up this intervention to cover Kampala are very modest. This may be a cost-effective first step toward developing formal emergency services in Uganda other resource-constrained settings. Further research is needed in this critical area of trauma care in low-income countries

Seasonal Influenza Vaccine and Protection against Pandemic (H1N1) 2009-Associated Illness among US Military Personnel

INTRODUCTION: A novel A/H1N1 virus is the cause of the present influenza pandemic; vaccination is a key countermeasure, however, few data assessing prior seasonal vaccine effectiveness (VE) against the pandemic strain of H1N1 (pH1N1) virus are available. MATERIALS AND METHODS: Surveillance of influenza-related medical encounter data of active duty military service members stationed in the United States during the period of April-October 2009 with comparison of pH1N1-confirmed cases and location and date-matched controls. Crude odds ratios (OR) and VE estimates for immunized versus non-immunized were calculated as well as adjusted OR (AOR) controlling for sex, age group, and history of prior influenza vaccination. Separate stratified VE analyses by vaccine type (trivalent inactivated [TIV] or live attenuated [LAIV]), age groups and hospitalization status were also performed. For the period of April 20 to October 15, 2009, a total of 1,205 cases of pH1N1-confirmed cases were reported, 966 (80%) among males and over one-half (58%) under 25 years of age. Overall VE for service members was found to be 45% (95% CI, 33 to 55%). Immunization with prior season's TIV (VE = 44%, 95% CI, 32 to 54%) as well as LAIV (VE = 24%, 95% CI, 6 to 38%) were both found to be associated with protection. Of significance, VE against a severe disease outcome was higher (VE = 62%, 95% CI, 14 to 84%) than against milder outcomes (VE = 42%, 95% CI, 29 to 53%). CONCLUSION: A moderate association with protection against clinically apparent, laboratory-confirmed Pandemic (H1N1) 2009-associated illness was found for immunization with either TIV or LAIV 2008-09 seasonal influenza vaccines. This association with protection was found to be especially apparent for severe disease as compared to milder outcome, as well as in the youngest and older populations. Prior vaccination with seasonal influenza vaccines in 2004-08 was also independently associated with protection

De novoCIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): A new member of the expanding family of pyrin-associated autoinflammatory diseases

Neonatal-onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome) is characterized by fever, chronic meningitis, uveitis, sensorineural hearing loss, urticarial skin rash, and a characteristic deforming arthropathy. We investigated whether patients with this disorder have mutations in CIAS1, the gene which causes Muckle-Wells syndrome and familial cold autoinflammatory syndrome, two dominantly inherited disorders with some similarities to NOMID/CINCA syndrome

Cigarette smoking, relative weight, and menopause

To examine the interrelationships of cigarette smoking, relative weight, and the occurrence of natural menopause, the authors prospectively evaluated the experience of 66, 663 female US registered nurses who were premenopausal in 1976. Over a two-year period, 5004 women became post-menopausal. Current smokers were more likely than past or never smokers to develop menopause, although the effects of smoking diminished with age. The rate ratios of menopause for current smokers vs. never smokers (with 95% confidence limits) for women aged 30-39, 40-44, 45-49, and 50-55 years were 1.90 (1.10-3.28), 2.16 (1.73-2.69), 1.53 (1.41-1.67), and 1.20 (1.12-1.28). These rate ratios were not appreciably affected by adjustment for relative weight. Median ages at menopause were 52.4 for never smokers and 51.9, 51.0, 50.7, and 50.4 years for women who currently smoked 1-14, 15-24, 25-34, and 35 or more cigarettes per day. A crude linear relationship between relative weight and occurrence of menopause was observed. Comparing the leanest and heaviest quintiles, rate ratios for menopause among women aged 30-39, 40-44, 45-49, and 50-55 years were 1.42 (0.74-2.75), 1.26 (0.95-1.69), 1.25 (1.13-1.41) and 1.08 (0.99-1.19). The effect of relative weight was in part explained by the tendency of current smokers to weigh less than nonsmokers. After adjustment for current cigarette consumption a weak linear relationship between relative weight and menopause remained among women who smoked, although no such association was seen among nonsmokers

Relative weight and risk of breast cancer among premenopausal women

Although higher relative weight is generally considered to increase the risk of breast cancer, several case-control studies have suggested that the reverse may be true among premenopausal women. The association between Quetelot's index (a measure of relative weight calculated as weight/height) and the subsequent incidence of breast cancer was therefore examined during four years of follow-up among a cohort of 121,964 US women who were 30-55 years of age in 1976. In contrast to women who had experienced natural menopause or bilateral oophorectomy, the incidence of breast cancer among premenopausal women decreased with higher levels of relative weight Age-adjusted relative risks for increasing quintiles of Quetelef s index were 1.00, 0.90, 0.90, 0.73, and 0.66 (Mantel extension test for trend =-2.82, p = 0.005). This inverse association was not explained by known risk factors for breast cancer and was somewhat stronger when Quetelef s index was computed using reported weight at age 18 years. The excess incidence of breast cancer among lean premenopausal women, however, was limited to tumors that were less than 2.0 cm in diameter, were not associated with metastases to lymph nodes, and were well-differentiated. These findings suggest that the apparent excess risk of breast cancer among lean premenopausal women may result at least in part from easier, and thus earlier, diagnosis of less aggressive tumors

Crude and Adjusted OR for Hospitalized and Non-hospitalized Cases and Controls.

<p>Note: OR = Odds Ratio.</p><p>*Adjusted for sex, age group, and number of prior vaccinations.</p

Univariate Analysis and Characteristics of pH1N1 Cases and Controls.

<p>Note: OR = Odds Ratio.</p