This textbook introduces a science philosophy called "information theoretic" based on Kullback-Leibler information theory. It focuses on a science philosophy based on "multiple working hypotheses" ...and statistical models to represent them.
Current challenges exist to widespread clinical implementation of genomic medicine and pharmacogenetics. The University of Florida (UF) Health Personalized Medicine Program (PMP) is a pharmacist-led, ...multidisciplinary initiative created in 2011 within the UF Clinical Translational Science Institute. Initial efforts focused on pharmacogenetics, with long-term goals to include expansion to disease-risk prediction and disease stratification. Herein we describe the processes for development of the program, the challenges that were encountered and the clinical acceptance by clinicians of the genomic medicine implementation. The initial clinical implementation of the UF PMP began in June 2012 and targeted clopidogrel use and the CYP2C19 genotype in patients undergoing left heart catheterization and percutaneous-coronary intervention (PCI). After 1 year, 1,097 patients undergoing left heart catheterization were genotyped preemptively, and 291 of those underwent subsequent PCI. Genotype results were reported to the medical record for 100% of genotyped patients. Eighty patients who underwent PCI had an actionable genotype, with drug therapy changes implemented in 56 individuals. Average turnaround time from blood draw to genotype result entry in the medical record was 3.5 business days. Seven different third party payors, including Medicare, reimbursed for the test during the first month of billing, with an 85% reimbursement rate for outpatient claims that were submitted in the first month. These data highlight multiple levels of success in clinical implementation of genomic medicine.
Race/ethnicity and socioeconomic status (SES) are social categories that capture differential exposure to conditions of life that have health consequences. Race/ethnicity and SES are linked to each ...other, but race matters for health even after SES is considered. This commentary considers the complex ways in which race combines with SES to affect health. There is a need for greater attention to understanding how risks and resources in the social environment are systematically patterned by race, ethnicity and SES, and how they combine to influence cardiovascular disease and other health outcomes. Future research needs to examine how the levels, timing and accumulation of institutional and interpersonal racism combine with other toxic exposures, over the life-course, to influence the onset and course of illness. There is also an urgent need for research that seeks to build the science base that will identify the multilevel interventions that are likely to enhance the health of all, even while they improve the health of disadvantaged groups more rapidly than the rest of the population so that inequities in health can be reduced and ultimately eliminated. We also need sustained research attention to identifying how to build the political support to reduce the large shortfalls in health.
Obesity is a risk factor for pneumonia and acute respiratory distress syndrome.
To determine whether obesity is associated with intubation or death, inflammation, cardiac injury, or fibrinolysis in ...coronavirus disease 2019 (COVID-19).
Retrospective cohort study.
A quaternary academic medical center and community hospital in New York City.
2466 adults hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection over a 45-day period with at least 47 days of in-hospital observation.
Body mass index (BMI), admission biomarkers of inflammation (C-reactive protein CRP level and erythrocyte sedimentation rate ESR), cardiac injury (troponin level), and fibrinolysis (D-dimer level). The primary end point was a composite of intubation or death in time-to-event analysis.
Over a median hospital length of stay of 7 days (interquartile range, 3 to 14 days), 533 patients (22%) were intubated, 627 (25%) died, and 59 (2%) remained hospitalized. Compared with overweight patients, patients with obesity had higher risk for intubation or death, with the highest risk among those with class 3 obesity (hazard ratio, 1.6 95% CI, 1.1 to 2.1). This association was primarily observed among patients younger than 65 years and not in older patients (
for interaction by age = 0.042). Body mass index was not associated with admission levels of biomarkers of inflammation, cardiac injury, or fibrinolysis.
Body mass index was missing for 28% of patients. The primary analyses were conducted with multiple imputation for missing BMI. Upper bounding factor analysis suggested that the results are robust to possible selection bias.
Obesity is associated with increased risk for intubation or death from COVID-19 in adults younger than 65 years, but not in adults aged 65 years or older.
National Institutes of Health.
Background
Coronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people live with CHD and may need support ...to manage their symptoms and prognosis. Exercise‐based cardiac rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane systematic review previously published in 2011.
Objectives
To assess the effectiveness and cost‐effectiveness of exercise‐based CR (exercise training alone or in combination with psychosocial or educational interventions) compared with usual care on mortality, morbidity and HRQL in patients with CHD.
To explore the potential study level predictors of the effectiveness of exercise‐based CR in patients with CHD.
Search methods
We updated searches from the previous Cochrane review, by searching Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 6, 2014) from December 2009 to July 2014. We also searched MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and Science Citation Index Expanded (December 2009 to July 2014).
Selection criteria
We included randomised controlled trials (RCTs) of exercise‐based interventions with at least six months’ follow‐up, compared with a no exercise control. The study population comprised men and women of all ages who have had a myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or who have angina pectoris, or coronary artery disease. We included RCTs that reported at least one of the following outcomes: mortality, MI, revascularisations, hospitalisations, health‐related quality of life (HRQL), or costs.
Data collection and analysis
Two review authors independently screened all identified references for inclusion based on the above inclusion and exclusion criteria. One author extracted data from the included trials and assessed their risk of bias; a second review author checked data. We stratified meta‐analysis by the duration of follow up of trials, i.e. short‐term: 6 to 12 months, medium‐term: 13 to 36 months, and long‐term: > 3 years.
Main results
This review included 63 trials which randomised 14,486 people with CHD. This latest update identified 16 new trials (3872 participants). The population included predominantly post‐MI and post‐revascularisation patients and the mean age of patients within the trials ranged from 47.5 to 71.0 years. Women accounted for fewer than 15% of the patients recruited. Overall trial reporting was poor, although there was evidence of an improvement in quality of reporting in more recent trials.
As we found no significant difference in the impact of exercise‐based CR on clinical outcomes across follow‐up, we focused on reporting findings pooled across all trials at their longest follow‐up (median 12 months). Exercise‐based CR reduced cardiovascular mortality compared with no exercise control (27 trials; risk ratio (RR) 0.74, 95% CI 0.64 to 0.86). There was no reduction in total mortality with CR (47 trials, RR 0.96, 95% CI 0.88 to 1.04). The overall risk of hospital admissions was reduced with CR (15 trials; RR 0.82, 95% CI 0.70 to 0.96) but there was no significant impact on the risk of MI (36 trials; RR 0.90, 95% CI 0.79 to 1.04), CABG (29 trials; RR 0.96, 95% CI 0.80 to 1.16) or PCI (18 trials; RR 0.85, 95% CI 0.70 to 1.04).
There was little evidence of statistical heterogeneity across trials for all event outcomes, and there was evidence of small study bias for MI and hospitalisation, but no other outcome. Predictors of clinical outcomes were examined across the longest follow‐up of studies using univariate meta‐regression. Results show that benefits in outcomes were independent of participants' CHD case mix (proportion of patients with MI), type of CR (exercise only vs comprehensive rehabilitation) dose of exercise, length of follow‐up, trial publication date, setting (centre vs home‐based), study location (continent), sample size or risk of bias.
Given the heterogeneity in outcome measures and reporting methods, meta‐analysis was not undertaken for HRQL. In five out of 20 trials reporting HRQL using validated measures, there was evidence of significant improvement in most or all of the sub‐scales with exercise‐based CR compared to control at follow‐up. Four trial‐based economic evaluation studies indicated exercise‐based CR to be a potentially cost‐effective use of resources in terms of gain in quality‐adjusted life years.
The quality of the evidence for outcomes reported in the review was rated using the GRADE method. The quality of the evidence varied widely by outcome and ranged from low to moderate.
Authors' conclusions
This updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control, exercise‐based CR reduces the risk of cardiovascular mortality but not total mortality. We saw a significant reduction in the risk of hospitalisation with CR but not in the risk of MI or revascularisation. We identified further evidence supporting improved HRQL with exercise‐based CR. More recent trials were more likely to be well reported and include older and female patients. However, the population studied in this review still consists predominantly of lower risk individuals following MI or revascularisation. Further well conducted RCTs are needed to assess the impact of exercise‐based CR in higher risk CHD groups and also those presenting with stable angina. These trials should include validated HRQL outcome measures, explicitly report clinical event outcomes including mortality and hospital admissions, and assess costs and cost‐effectiveness.
The actin cytoskeleton assembles into diverse load-bearing networks, including stress fibers (SFs), muscle sarcomeres, and the cytokinetic ring to both generate and sense mechanical forces. The LIM ...(Lin11, Isl- 1, and Mec-3) domain family is functionally diverse, but most members can associate with the actin cytoskeleton with apparent force sensitivity. Zyxin rapidly localizes via its LIM domains to failing SFs in cells, known as strain sites, to initiate SF repair and maintain mechanical homeostasis. The mechanism by which these LIM domains associate with stress fiber strain sites (SFSS) is not known. Additionally, it is unknown how widespread strain sensing is within the LIM protein family. We identify that the LIM domain-containing region of 18 proteins from the Zyxin, Paxillin, Tes, and Enigma proteins accumulate to SFSS. Moreover, the LIM domain region from the fission yeast protein paxillin like 1 (Pxl1) also localizes to SFSS in mammalian cells, suggesting that the strain sensing mechanism is ancient and highly conserved. We then used sequence and domain analysis to demonstrate that tandem LIM domains contribute additively, for SFSS localization. Employing in vitro reconstitution, we show that the LIM domain-containing region from mammalian zyxin and fission yeast Pxl1 binds to mechanically stressed F-actin networks but does not associate with relaxed actin filaments. We propose that tandem LIM domains recognize an F-actin conformation that is rare in the relaxed state but is enriched in the presence of mechanical stress.
Agromining: Farming for Metals in the Future? van der Ent, Antony; Baker, Alan J. M; Reeves, Roger D ...
Environmental science & technology,
04/2015, Letnik:
49, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Phytomining technology employs hyperaccumulator plants to take up metal in harvestable plant biomass. Harvesting, drying and incineration of the biomass generates a high-grade bio-ore. We propose ...that “agromining” (a variant of phytomining) could provide local communities with an alternative type of agriculture on degraded lands; farming not for food crops, but for metals such as nickel (Ni). However, two decades after its inception and numerous successful experiments, commercial phytomining has not yet become a reality. To build the case for the minerals industry, a large-scale demonstration is needed to identify operational risks and provide “real-life” evidence for profitability.
We briefly outline the information-theoretic (I-T) approaches to valid inference including a review of some simple methods for making formal inference from all the hypotheses in the model set ...(multimodel inference). The I-T approaches can replace the usual t tests and ANOVA tables that are so inferentially limited, but still commonly used. The I-T methods are easy to compute and understand and provide formal measures of the strength of evidence for both the null and alternative hypotheses, given the data. We give an example to highlight the importance of deriving alternative hypotheses and representing these as probability models. Fifteen technical issues are addressed to clarify various points that have appeared incorrectly in the recent literature. We offer several remarks regarding the future of empirical science and data analysis under an I-T framework.
Background: Venous thromboembolism (VTE) is a common source of perioperative morbidity and mortality.
Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend ...to support decision making about preventing VTE in patients undergoing surgery.
Methods: ASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.
Results: The panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2).
Conclusions: For patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.
Do Workplace Health Promotion (Wellness) Programs Work? Goetzel, Ron Z.; Henke, Rachel Mosher; Tabrizi, Maryam ...
Journal of occupational and environmental medicine,
2014-September, Letnik:
56, Številka:
9
Journal Article
Recenzirano
OBJECTIVE:To respond to the question, “Do workplace health promotion programs work?”
METHODS:A compilation of the evidence on workplace programsʼ effectiveness coupled with recommendations for ...critical review of outcome studies. Also, reviewed are recent studies questioning the value of workplace programs.
RESULTS:Evidence accumulated over the past three decades shows that well-designed and well-executed programs that are founded on evidence-based principles can achieve positive health and financial outcomes.
CONCLUSIONS:Employers seeking a program that “works” are urged to consider their goals and whether they have an organizational culture that can facilitate success. Employers who choose to adopt a health promotion program should use best and promising practices to maximize the likelihood of achieving positive results.
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