Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Pathways to Severe COVID‐19 for People with Obesity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167064/1/oby23099.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167064/2/oby23099_am.pd

Current smoking and COVID-19 risk: results from a population symptom app in over 2.4 million people

Background: The association between current tobacco smoking, the risk of developing symptomatic COVID-19 and the severity of illness is an important information gap. Methods: UK users of the Zoe COVID Symptom Study App provided baseline data including demographics, anthropometrics, smoking status and medical conditions, and were asked to log their condition daily. Participants who reported that they did not feel physically normal were then asked by the app to complete a series of questions, including 14 potential COVID-19 symptoms and about hospital attendance. The main study outcome was the development of “classic” symptoms of COVID-19 during the pandemic defined as fever, new persistent cough and breathlessness and their association with current smoking. The number of concurrent COVID-19 symptoms was used as a proxy for severity and the pattern of association between symptoms was also compared between smokers and non-smokers. Results: Between 24th March 2020 to 23rd April 2020, data were available on 2,401,982 participants, mean(SD) age 43.6(15.1) years, 63.3% female, overall smoking prevalence 11.0%. 834,437 (35%) participants reported being unwell and entered one or more symptoms. Current smokers were more likely to report symptoms suggesting a diagnosis of COVID-19; classic symptoms adjusted OR[95%CI] 1.14[1.10 to 1.18]; >5 symptoms 1.29[1.26 to 1.31]; >10 symptoms 1.50[1.42 to 1.58]. The pattern of association between reported symptoms did not vary between smokers and non-smokers. Interpretation: These data are consistent with people who smoke being at an increased risk of developing symptomatic COVID-19

Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition

Individual risk of type 2 diabetes (T2D) is modified by perturbations of adipose mass, distribution and function. To investigate mechanisms responsible, we explored the molecular, cellular, and whole-body effects of T2D-associated alleles near KLF14. We show that KLF14 diabetes-risk alleles act in adipose tissue to reduce KLF14 expression, and modulate, in trans, expression of &gt;400 genes. We demonstrate that, in human cellular studies, reduced KLF14 expression increases pre-adipocyte proliferation but disrupts lipogenesis, and, in mice, adipose-specific deletion of Klf14 partially recapitulates the human phenotype of insulin resistance, dyslipidemia and T2D. We show that KLF14 T2D risk-allele carriers shift body fat from gynoid to abdominal stores, and display a marked increase in adipocyte cell size: these effects on fat distribution, and the T2D-association, are female-specific. Metabolic risk associated with variation at this imprinted locus depends on both the sex of the subject, and of the parent from whom the risk-allele derives The replicated genome-wide significant T2D association signal at chr7q32.3 maps to a 45kb recombination interval, extending from 3kb to 48kb upstream of KLF141,2 (Figure 1a-c). In previous work based on microarray-derived RNA expression data, KLF14, which encodes an imprinted transcription factor, was exposed as the likely cis-effector gene for this locus in subcutaneous adipose tissue1 and revealed to be a trans-regulator of a programme of adipose tissue expression3. The KLF family of zinc-finger binding proteins have wide-ranging regulatory roles in biological processes such as proliferation, differentiation and growth4,5. However, little is known about KLF14, a single exon gene whose transcription is limited to the maternally inherited chromosome in embryonic, extra-embryonic, and adult tissue in humans and mice6.</p

Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition

Individual risk of type 2 diabetes (T2D) is modified by perturbations of adipose mass, distribution and function. To investigate mechanisms responsible, we explored the molecular, cellular, and whole-body effects of T2D-associated alleles near KLF14. We show that KLF14 diabetes-risk alleles act in adipose tissue to reduce KLF14 expression, and modulate, in trans, expression of >400 genes. We demonstrate that, in human cellular studies, reduced KLF14 expression increases pre-adipocyte proliferation but disrupts lipogenesis, and, in mice, adipose-specific deletion of Klf14 partially recapitulates the human phenotype of insulin resistance, dyslipidemia and T2D. We show that KLF14 T2D risk-allele carriers shift body fat from gynoid to abdominal stores, and display a marked increase in adipocyte cell size: these effects on fat distribution, and the T2D-association, are female-specific. Metabolic risk associated with variation at this imprinted locus depends on both the sex of the subject, and of the parent from whom the risk-allele derives The replicated genome-wide significant T2D association signal at chr7q32.3 maps to a 45kb recombination interval, extending from 3kb to 48kb upstream of KLF141,2 (Figure 1a-c). In previous work based on microarray-derived RNA expression data, KLF14, which encodes an imprinted transcription factor, was exposed as the likely cis-effector gene for this locus in subcutaneous adipose tissue1 and revealed to be a trans-regulator of a programme of adipose tissue expression3. The KLF family of zinc-finger binding proteins have wide-ranging regulatory roles in biological processes such as proliferation, differentiation and growth4,5. However, little is known about KLF14, a single exon gene whose transcription is limited to the maternally inherited chromosome in embryonic, extra-embryonic, and adult tissue in humans and mice6.</p

Polygenic Risk Predicts Obesity in Both White and Black Young Adults

OBJECTIVE:To test transethnic replication of a genetic risk score for obesity in white and black young adults using a national sample with longitudinal data. DESIGN AND METHODS:A prospective longitudinal study using the National Longitudinal Study of Adolescent Health Sibling Pairs (n = 1,303). Obesity phenotypes were measured from anthropometric assessments when study members were aged 18-26 and again when they were 24-32. Genetic risk scores were computed based on published genome-wide association study discoveries for obesity. Analyses tested genetic associations with body-mass index (BMI), waist-height ratio, obesity, and change in BMI over time. RESULTS:White and black young adults with higher genetic risk scores had higher BMI and waist-height ratio and were more likely to be obese compared to lower genetic risk age-peers. Sibling analyses revealed that the genetic risk score was predictive of BMI net of risk factors shared by siblings. In white young adults only, higher genetic risk predicted increased risk of becoming obese during the study period. In black young adults, genetic risk scores constructed using loci identified in European and African American samples had similar predictive power. CONCLUSION:Cumulative information across the human genome can be used to characterize individual level risk for obesity. Measured genetic risk accounts for only a small amount of total variation in BMI among white and black young adults. Future research is needed to identify modifiable environmental exposures that amplify or mitigate genetic risk for elevated BMI