COVID-19 Infection: Implications for Perioperative and Critical Care Physicians.

Healthcare systems worldwide are responding to Coronavirus Disease 2019 (COVID-19), an emerging infectious syndrome caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. Patients with COVID-19 can progress from asymptomatic or mild illness to hypoxemic respiratory failure or multisystem organ failure, necessitating intubation and intensive care management. Healthcare providers, and particularly anesthesiologists, are at the frontline of this epidemic, and they need to be aware of the best available evidence to guide therapeutic management of patients with COVID-19 and to keep themselves safe while doing so. Here, the authors review COVID-19 pathogenesis, presentation, diagnosis, and potential therapeutics, with a focus on management of COVID-19-associated respiratory failure. The authors draw on literature from other viral epidemics, treatment of acute respiratory distress syndrome, and recent publications on COVID-19, as well as guidelines from major health organizations. This review provides a comprehensive summary of the evidence currently available to guide management of critically ill patients with COVID-19

Tuning thermal properties and microphase separation in aliphatic polyester ABA copolymers

Four alkyl substituted β-lactones were investigated as monomers in ring opening polymerisation to produce a family of poly(3-hydroxyalkanoate)s. Homopolymers were synthesised using a robust aluminium salen catalyst, resulting in polymers with low dispersity (Đ < 1.1) and predictable molecular weights. ABA triblock copolymers were prepared using poly(L-lactic acid) as the A block and the afore- mentioned poly(3-hydroxyalkanoate) as the B block via a sequential addition method. Characterisation of these copolymers determined they were well controlled with low dispersities and predictable molecular weight. DSC analysis determined copolymers prepared from β-butyrolactone or β-valerolactone yielded polymers with tunable and predictable thermal properties. Copolymers prepared from β-heptanolactone yielded a microphase separated material as indicated by SAXS, with two distinct Tgs. The polymers could be readily cast into flexible films and their improved tensile properties were explored

Association of 6-Minute Walk Performance and Physical Activity With Incident Ischemic Heart Disease Events and Stroke in Peripheral Artery Disease.

BackgroundWe determined whether poorer 6-minute walk performance and lower physical activity levels are associated with higher rates of ischemic heart disease (IHD) events in people with lower extremity peripheral artery disease (PAD).Methods and resultsFive hundred ten PAD participants were identified from Chicago-area medical centers and followed prospectively for 19.0±9.5 months. At baseline, participants completed the 6-minute walk and reported number of blocks walked during the past week (physical activity). IHD events were systematically adjudicated and consisted of new myocardial infarction, unstable angina, and cardiac death. For 6-minute walk, IHD event rates were 25/170 (14.7%) for the third (poorest) tertile, 10/171 (5.8%%) for the second tertile, and 6/169 (3.5%) for the first (best) tertile (P=0.003). For physical activity, IHD event rates were 21/154 (13.6%) for the third (poorest) tertile, 15/174 (8.6%) for the second tertile, and 5/182 (2.7%) for the first (best) tertile (P=0.001). Adjusting for age, sex, race, smoking, body mass index, comorbidities, and physical activity, participants in the poorest 6-minute walk tertile had a 3.28-fold (95% CI 1.17 to 9.17, P=0.024) higher hazard for IHD events, compared with those in the best tertile. Adjusting for confounders including 6-minute walk, participants in the poorest physical activity tertile had a 3.72-fold (95% CI 1.24 to 11.19, P=0.019) higher hazard for IHD events, compared with the highest tertile.ConclusionsSix-minute walk and physical activity predict IHD event rates in PAD. Further study is needed to determine whether interventions that improve 6-minute walk, physical activity, or both can reduce IHD events in PAD

Using ordinal logistic regression to evaluate the performance of laser-Doppler predictions of burn-healing time

Background Laser-Doppler imaging (LDI) of cutaneous blood flow is beginning to be used by burn surgeons to predict the healing time of burn wounds; predicted healing time is used to determine wound treatment as either dressings or surgery. In this paper, we do a statistical analysis of the performance of the technique. Methods We used data from a study carried out by five burn centers: LDI was done once between days 2 to 5 post burn, and healing was assessed at both 14 days and 21 days post burn. Random-effects ordinal logistic regression and other models such as the continuation ratio model were used to model healing-time as a function of the LDI data, and of demographic and wound history variables. Statistical methods were also used to study the false-color palette, which enables the laser-Doppler imager to be used by clinicians as a decision-support tool. Results Overall performance is that diagnoses are over 90% correct. Related questions addressed were what was the best blood flow summary statistic and whether, given the blood flow measurements, demographic and observational variables had any additional predictive power (age, sex, race, % total body surface area burned (%TBSA), site and cause of burn, day of LDI scan, burn center). It was found that mean laser-Doppler flux over a wound area was the best statistic, and that, given the same mean flux, women recover slightly more slowly than men. Further, the likely degradation in predictive performance on moving to a patient group with larger %TBSA than those in the data sample was studied, and shown to be small. Conclusion Modeling healing time is a complex statistical problem, with random effects due to multiple burn areas per individual, and censoring caused by patients missing hospital visits and undergoing surgery. This analysis applies state-of-the art statistical methods such as the bootstrap and permutation tests to a medical problem of topical interest. New medical findings are that age and %TBSA are not important predictors of healing time when the LDI results are known, whereas gender does influence recovery time, even when blood flow is controlled for. The conclusion regarding the palette is that an optimum three-color palette can be chosen 'automatically', but the optimum choice of a 5-color palette cannot be made solely by optimizing the percentage of correct diagnoses

Looking inside the black box : a theory-based process evaluation alongside a randomised controlled trial of printed educational materials (the Ontario printed educational message, OPEM) to improve referral and prescribing practices in primary care in Ontario, Canada

Background: Randomised controlled trials of implementation strategies tell us whether (or not) an intervention results in changes in professional behaviour but little about the causal mechanisms that produce any change. Theory-based process evaluations collect data on theoretical constructs alongside randomised trials to explore possible causal mechanisms and effect modifiers. This is similar to measuring intermediate endpoints in clinical trials to further understand the biological basis of any observed effects (for example, measuring lipid profiles alongside trials of lipid lowering drugs where the primary endpoint could be reduction in vascular related deaths). This study protocol describes a theory-based process evaluation alongside the Ontario Printed Educational Message (OPEM) trial. We hypothesize that the OPEM interventions are most likely to operate through changes in physicians' behavioural intentions due to improved attitudes or subjective norms with little or no change in perceived behavioural control. We will test this hypothesis using a well-validated social cognition model, the theory of planned behaviour (TPB) that incorporates these constructs. Methods/design: We will develop theory-based surveys using standard methods based upon the TPB for the second and third replications, and survey a subsample of Ontario family physicians from each arm of the trial two months before and six months after the dissemination of the index edition of informed, the evidence based newsletter used for the interventions. In the third replication, our study will converge with the "TRY-ME" protocol (a second study conducted alongside the OPEM trial), in which the content of educational messages was constructed using both standard methods and methods informed by psychological theory. We will modify Dillman's total design method to maximise response rates. Preliminary analyses will initially assess the internal reliability of the measures and use regression to explore the relationships between predictor and dependent variable (intention to advise diabetic patients to have annual retinopathy screening and to prescribe thiazide diuretics for first line treatment of uncomplicated hypertension). We will then compare groups using methods appropriate for comparing independent samples to determine whether there have been changes in the predicted constructs (attitudes, subjective norms, or intentions) across the study groups as hypothesised, and will assess the convergence between the process evaluation results and the main trial results.The OPEM trial and OPEM process evaluation are funded by the Canadian Institute of Health Research (CIHR). The OPEM process evaluation study was developed as part of the CIHR funded interdisciplinary capacity enhancement team KT-ICEBeRG. Gaston Godin, Jeremy Grimshaw and France Légaré hold Canada Research Chairs. Louise Lemyre holds an R.S. McLaughlin Research Chair

Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis.

BACKGROUND: Many of the established risk factors for breast cancer implicate circulating hormone levels in the aetiology of the disease. Increased levels of postmenopausal endogenous oestradiol (E2) have been found to increase the risk of breast cancer, but no such association has been confirmed in premenopausal women. We carried out a meta-analysis to summarise the available evidence in women before the menopause. METHODS: We identified seven prospective studies of premenopausal endogenous E2 and breast cancer risk, including 693 breast cancer cases. From each study we extracted odds ratios of breast cancer between quantiles of endogenous E2, or for unit or s.d. increases in (log transformed) E2, or (where odds ratios were unavailable) summary statistics for the distributions of E2 in breast cancer cases and unaffected controls. Estimates for a doubling of endogenous E2 were obtained from these extracted estimates, and random-effect meta-analysis was used to obtain a pooled estimate across the studies. RESULTS: Overall, we found weak evidence of a positive association between circulating E2 levels and the risk of breast cancer, with a doubling of E2 associated with an odds ratio of 1.10 (95% CI: 0.96, 1.27). CONCLUSION: Our findings are consistent with the hypothesis of a positive association between premenopausal endogenous E2 and breast cancer risk

Alcohol consumption, physical activity, and chronic disease risk factors: a population-based cross-sectional survey

BACKGROUND: Whether the association of alcohol consumption and cardiovascular disease is the product of confounding and the degree to which this concern applies to other behaviors are unclear. METHODS: Using the 2003 Behavioral Risk Factor Surveillance System, a population-based telephone survey of adults in the US, we compared chronic disease risk factors between 123,359 abstainers and 126,674 moderate drinkers, defined as intake of ≤ 2 drinks per day among men and ≤ 1 drink per day among women, using age- and sex- and multivariable-adjusted models. We also compared sedentary and active individuals, defined as moderate physical activity ≥ 30 minutes per day for ≥ 5 days per week, or vigorous activity for ≥ 20 minutes per day on ≥ 3 days. RESULTS: Chronic disease risk factors and features of unhealthy lifestyle were generally more prevalent among abstainers than drinkers in age- and sex-adjusted analyses, but these differences were generally attenuated or eliminated by additional adjustment for race and education. For low fruit and vegetable intake, divorced marital status, and absence of a personal physician, adjustment for race and education reversed initially positive age- and sex-adjusted associations with abstention. Comparison of sedentary and active individuals produced similar findings, with generally lower levels of risk factors among more physical active individuals. CONCLUSION: The differences between abstainers and drinkers are attenuated after adjustment for limited sociodemographic features, and sedentary and active individuals share a similar pattern. Although observational studies of both factors may be susceptible to uncontrolled confounding, our results provide no evidence that moderate drinking is unique in this regard. Ultimately, randomized trials of all such lifestyle factors will be needed to answer these questions definitively

The grinch who stole wisdom

Dr. Seuss is wise. How the Grinch Stole Christmas (Seuss, 1957) could serve as a parable for our time. It can also be seen as a roadmap for the development of contemplative wisdom. The abiding popularity of How the Grinch Stole Christmas additionally suggests that contemplative wisdom is more readily available to ordinary people, even children, than is normally thought. This matters because from the point of view of contemplatives in any of the world's philosophies or religions, people are confused about wisdom. The content of the nascent field of wisdom studies, they might say, is largely not wisdom at all but rather what it's like to live in a particular kind of prison cell, a well appointed cell perhaps, but not a place that makes possible either personal satisfaction or deep problem solving. I believe that what the contemplative traditions have to say is important; they offer a different orientation to what personal wisdom is, how to develop it, and how to use it in the world than is presently contained in either our popular culture or our sciences. In order to illustrate this I will examine, in some detail, one contemplative path within Buddhism. Buddhism is particularly useful in this respect because its practices are nontheistic and thus avoid many of the cultural landmines associated with the contemplative aspects of Western religions

Occupational cancer in Britain: Statistical methodology

An approach using the attributable fraction (AF) has been developed to estimate the current burden of occupational cancer in Britain. The AF combines the relative risk (RR) associated with exposure with the proportion exposed. For each cancer–exposure pairing, the RR is selected from key epidemiological literature such as an industry, or population-based study, meta-analysis or review. The CARcinogen EXposure (CAREX) database provides point estimates for the number of workers exposed to a range of carcinogens; alternative sources are national surveys such as the Labour Force Survey and Census of Employment. The number of workers exposed are split between high and low exposure levels matched to appropriate RRs from the literature. The relevant period for cancer development during which exposure occurred is defined as the risk exposure period (REP). Estimation of the numbers ever exposed over the REP takes into account the changes in the number of people employed in primary and manufacturing industry and service sectors in Britain where appropriate, and adjustment is made for staff turnover over the period and for life expectancy. National estimates of the population ever of working age during the REP are used for the proportion denominator. Strategies have been developed to combine exposure AFs correctly while avoiding double counting and minimising bias. The AFs are applied to national cancer deaths and registrations to obtain occupation-attributable cancer numbers. The methods are adaptable for other diseases and other geographies, and are also adaptable to more sophisticated modelling if better exposure and dose–response data are available