1Obesity paradox, obesity orthodox, and the metabolic syndrome: An approach to unity 1 Obesity paradox and the metabolic syndrome. Abstract: 26Obesity and the accompanying metabolic syndrome are strongly associated with heightened morbidity 27 and mortality in older adults. In our review of more than 20 epidemiologic studies of major infectious 28 diseases, including leaders such as tuberculosis, community-acquired pneumonia, and sepsis, obesity was 29 associated with better outcomes. A cause-and-effect relationship between over-nutrition and survival with 30 infection is suggested by results of two preliminary studies of infections in mice, where high fat feeding 31 for 8-10 weeks provided much better outcomes. The better outcomes of infections with obesity are 32 reminiscent of many recent studies of "sterile" non-infectious medical and surgical conditions where 33 outcomes for obese patients are better than for their thinner counterparts ---and given the tag "obesity 34 paradox". Turning to the history of medicine and biological evolution, we hypothesize that the metabolic 35 syndrome has very ancient origins and is part of a lifelong metabolic program. While part of that program 36 (the metabolic syndrome) promotes morbidity and mortality with aging, it helps infants and children as 37 well as adults in their fight against infections and recovery from injuries, key roles in the hundreds of 38 centuries before the public health advances of the 20th century. We conclude with speculation on how 39 understanding the biological elements that protect obese patients with infections or injuries might be 40 applied advantageously to thin patients with the same medical challenges. experts to predict that obesity will shortly become the leading personal health problem worldwide. 52Obesity and the accompanying metabolic syndrome are typically associated with shortened life 53 expectancy, premature disability, and heightened prevalence of cardiovascular disorders, cancer, diabetes, 54and Alzheimer disease as well as multiple other disorders linked to advancing age. 55 ( ¶2) In the jeremiads inspired by obesity, the modest but deeply rooted health advantages of 56 obesity are typically neglected (Table 1). In this paper we add further to the list of advantages of obesity; 57 we review over 20 epidemiology studies of six serious infectious diseases, including tuberculosis, 58 pneumonia, and sepsis, where outcomes are inversely related to body mass index. The consistency of the 59 obesity advantage is especially remarkable because the usual measurements to express adiposity i.e. body 60 mass index (BMI; the weight in kilograms divided by the square of the height in meters) as well as waist 61 circumference or neck circumference are such rough approximations of total body fat or of visceral fat or 62 of metabolic syndrome. The connection between body mass index and the metabolic syndrome in 63 epidemiology studies is further loosened by impressive ethnic differences (Figure 1) [1] and changes in 64 individuals with aging. ...

Background Although many randomised controlled trials (RCTs) and systematic reviews of treatment for latent tuberculosis (TB) infection (LTBI) have been conducted, previous analyses have not been able directly compare all utilised regimens. To address this we systematically searched for RCTs of LTBI treatment, then used a Bayesian network approach, which allows indirect headto-head comparisons, to determine the most efficacious regimens at preventing active TB and those that caused the fewest adverse events. Methods PubMed, EMBASE and Web of Science were systematically mined using a search strategy developed to find RCTs of LTBI treatment. Animal studies, non-RCTs, and RCTs without at least one of our two endpoints were excluded. No language restrictions were made. Extracted data were inputted into a full random effects mixed treatment compartment model, based on code by Ades, Welton and Lu, and implemented in WinBUGS. Odds ratios for all possible comparisons in the network and hierarchical rankings for the different treatments were obtained from the model with point estimates taken as the median of the posterior distribution and 95% credibility intervals (CrI) from the appropriate percentiles. Study quality was individually assessed. Results 1,344 publications were generated by our search strategy, of which 52 fitted our criteria. 31 studies contained extractable data on adverse events and 44 on the development of active TB. 14 regimens were compared; an extract of the full results is presented (Table 1). Conclusion Our Bayesian approach allows a novel, integrated, overview of the comparative efficacy and safety of different LTBI regimens, as well as a clear identification of the knowledge gaps where inference is difficult due to sparse data. The results of our study can therefore be used to inform guidelines and plan vital future LTBI treatment RCTs.