Randomized clinical trials to identify optimal antibiotic treatment duration

Background Antibiotic resistance is a major barrier to the continued success of antibiotic treatment. Such resistance is often generated by overly long durations of antibiotic treatment. A barrier to identifying the shortest effective treatment duration is the cost of the sequence of clinical trials needed to determine shortest optimal duration. We propose a new method to identify the optimal treatment duration of an antibiotic treatment regimen. Methods Subjects are randomized to varying treatment durations and the cure proportions of these durations are linked using a logistic regression model, making effective use of information across all treatment duration groups. In this paper, Monte Carlo simulation is used to evaluate performance of such a model. Results Using a hypothetical dataset, the logistic regression model is seen to provide increased precision in defining the point estimate and confidence interval (CI) of the cure proportion at each treatment duration. When applied to the determination of non-inferiority, the regression model allows identification of the shortest duration meeting the predefined non-inferiority margin. Conclusions This analytic strategy represents a practical way to develop shortened regimens for tuberculosis and other infectious diseases. Application of this strategy to clinical trials of antibiotic therapy could facilitate decreased antibiotic usage, reduce cost, minimize toxicity, and decrease the emergence of antibiotic resistance

Strongyloidiasis in a nonagenarian who previously worked in conservancy services

published_or_final_versio

Global warming: is weight loss a solution?

The current climate change has been most likely caused by the increased greenhouse gas emissions. We have looked at the major greenhouse gas, carbon dioxide (CO2), and estimated the reduction in the CO2 emissions that would occur with the theoretical global weight loss. The calculations were based on our previous weight loss study, investigating the effects of a low-carbohydrate diet on body weight, body composition and resting metabolic rate of obese volunteers with type 2 diabetes. At 6 months we observed decreases in weight, fat mass, fat free mass and CO2 production. We estimated that a 10 kg weight loss of all obese and overweight people would result in a decrease of 49.560 Mt of CO2 per year, which would equal to 0.2 % of the CO2 emitted globally in 2007. This reduction could help meet the CO2 emission reduction targets and unquestionably would be of a great benefit to the global health

Factors influencing place of delivery for women in Kenya: an analysis of the Kenya Demographic and Health Survey, 2008/2009

Background Maternal mortality in Kenya increased from 380/100000 live births to 530/100000 live births between 1990 and 2008. Skilled assistance during childbirth is central to reducing maternal mortality yet the proportion of deliveries taking place in health facilities where such assistance can reliably be provided has remained below 50% since the early 1990s. We use the 2008/2009 Kenya Demographic and Health Survey data to describe the factors that determine where women deliver in Kenya and to explore reasons given for home delivery. Methods Data on place of delivery, reasons for home delivery, and a range of potential explanatory factors were collected by interviewer-led questionnaire on 3977 women and augmented with distance from the nearest health facility estimated using health facility Global Positioning System (GPS) co-ordinates. Predictors of whether the woman’s most recent delivery was in a health facility were explored in an exploratory risk factor analysis using multiple logistic regression. The main reasons given by the woman for home delivery were also examined. Results Living in urban areas, being wealthy, more educated, using antenatal care services optimally and lower parity strongly predicted where women delivered, and so did region, ethnicity, and type of facilities used. Wealth and rural/urban residence were independently related. The effect of distance from a health facility was not significant after controlling for other variables. Women most commonly cited distance and/or lack of transport as reasons for not delivering in a health facility but over 60% gave other reasons including 20.5% who considered health facility delivery unnecessary, 18% who cited abrupt delivery as the main reason and 11% who cited high cost. Conclusion Physical access to health facilities through distance and/or lack of transport, and economic considerations are important barriers for women to delivering in a health facility in Kenya. Some women do not perceive a need to deliver in a health facility and may value health facility delivery less with subsequent deliveries. Access to appropriate transport for mothers in labour and improving the experiences and outcomes for mothers using health facilities at childbirth augmented by health education may increase uptake of health facility delivery in Kenya

Effectiveness of early intervention programs for parents of preterm infants: a meta-review of systematic reviews

Background: Various intervention programs exist for parents of preterm babies and some systematic reviews (SRs) have synthesised the evidence of their effectiveness. These reviews are, however, limited to specific interventions, components, or outcomes, and a comprehensive evidence base is lacking. The aim of this meta-review was to appraise and meta-synthesise the evidence from existing SRs to provide a comprehensive evidence base on the effectiveness of interventions for parents of preterm infants on parental and infant outcomes. Methods: We conducted a comprehensive search of the following databases to identify relevant SRs: Cochrane library, Web of science, EMBASE, CINAHL, British Nursing Index, PsycINFO, Medline, ScienceDirect, Scopus, IBSS, DOAJ, ERIC, EPPI-Centre, PROSPERO, WHO Library. Additional searches were conducted using authors’ institutional libraries, Google Scholar, and the reference lists of identified reviews. Identified articles were screened in two stages against an inclusion criteria with titles and abstracts screened first followed by full-text screening. Selected SRs were appraised using the AMSTAR tool. Extracted data using a predesigned tool were synthesised narratively examining the direction of impact on outcomes. Results: We found 11 SRs eligible for inclusion that synthesised a total of 343 quantitative primary studies. The average quality of the SRs was ‘medium’. Thirty four interventions were reported across the SRs with considerable heterogeneity in the structural framework and the targeted outcomes that included maternal-infant dyadic, maternal/parental, and infant outcomes. Among all interventions, Kangaroo Care (KC) showed the most frequent positive impact across outcomes (n = 19) followed by Mother Infant Transaction Program (MITP) (n = 14). Other interventions with most consistent positive impact on infant outcomes were Modified-Mother Infant Transaction Program (M-MITP) (n = 6), Infant Health and Development Program (IHDP) (n = 5) and Creating Opportunities for Parent Empowerment (COPE) (n = 5). Overall, interventions with both home and facility based components showed the most frequent positive impact across outcomes. Conclusions: Neonatal care policy and planning for preterm babies should consider the implementation of interventions with most positive impact on outcomes. The heterogeneity in interventions and outcomes calls for the development and implementation of an integrated program for parents of preterm infants with a clearly defined global set of parental and infant outcomes

Vitamin D in the general population of young adults with autism in the Faroe Islands

Vitamin D deficiency has been proposed as a possible risk factor for developing autism spectrum disorder (ASD). 25-Hydroxyvitamin D3 (25(OH)D3) levels were examined in a cross-sectional population-based study in the Faroe Islands. The case group consisting of a total population cohort of 40 individuals with ASD (aged 15–24 years) had significantly lower 25(OH)D3 than their 62 typically-developing siblings and their 77 parents, and also significantly lower than 40 healthy age and gender matched comparisons. There was a trend for males having lower 25(OH)D3 than females. Effects of age, month/season of birth, IQ, various subcategories of ASD and Autism Diagnostic Observation Schedule score were also investigated, however, no association was found. The very low 25(OH)D3 in the ASD group suggests some underlying pathogenic mechanism

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

Measuring Adiposity in Patients: The Utility of Body Mass Index (BMI), Percent Body Fat, and Leptin

Background: Obesity is a serious disease that is associated with an increased risk of diabetes, hypertension, heart disease, stroke, and cancer, among other diseases. The United States Centers for Disease Control and Prevention (CDC) estimates a 20 % obesity rate in the 50 states, with 12 states having rates of over 30%. Currently, the body mass index (BMI) is most commonly used to determine adiposity. However, BMI presents as an inaccurate obesity classification method that underestimates the epidemic and contributes to failed treatment. In this study, we examine the effectiveness of precise biomarkers and duel-energy x-ray absorptiometry (DXA) to help diagnose and treat obesity. Methodology/Principal Findings: A cross-sectional study of adults with BMI, DXA, fasting leptin and insulin results wer

Adaptive Management and the Value of Information: Learning Via Intervention in Epidemiology

Optimal intervention for disease outbreaks is often impeded by severe scientific uncertainty. Adaptive management (AM), long-used in natural resource management, is a structured decision-making approach to solving dynamic problems that accounts for the value of resolving uncertainty via real-time evaluation of alternative models. We propose an AM approach to design and evaluate intervention strategies in epidemiology, using real-time surveillance to resolve model uncertainty as management proceeds, with foot-and-mouth disease (FMD) culling and measles vaccination as case studies. We use simulations of alternative intervention strategies under competing models to quantify the effect of model uncertainty on decision making, in terms of the value of information, and quantify the benefit of adaptive versus static intervention strategies. Culling decisions during the 2001 UK FMD outbreak were contentious due to uncertainty about the spatial scale of transmission. The expected benefit of resolving this uncertainty prior to a new outbreak on a UK-like landscape would be £45–£60 million relative to the strategy that minimizes livestock losses averaged over alternate transmission models. AM during the outbreak would be expected to recover up to £20.1 million of this expected benefit. AM would also recommend a more conservative initial approach (culling of infected premises and dangerous contact farms) than would a fixed strategy (which would additionally require culling of contiguous premises). For optimal targeting of measles vaccination, based on an outbreak in Malawi in 2010, AM allows better distribution of resources across the affected region; its utility depends on uncertainty about both the at-risk population and logistical capacity. When daily vaccination rates are highly constrained, the optimal initial strategy is to conduct a small, quick campaign; a reduction in expected burden of approximately 10,000 cases could result if campaign targets can be updated on the basis of the true susceptible population. Formal incorporation of a policy to update future management actions in response to information gained in the course of an outbreak can change the optimal initial response and result in significant cost savings. AM provides a framework for using multiple models to facilitate public-health decision making and an objective basis for updating management actions in response to improved scientific understanding