Epidemiology of Diabetic Foot Infection in the Metro-Detroit Area with a Focus on Independent Predictors for Pathogens Resistant to Recommended Empiric Antimicrobial Therapy

Background. The polymicrobial nature of diabetic foot infection (DFI) and the emergence of antimicrobial resistance have complicated DFI treatment. Current treatment guidelines for deep DFI recommend coverage of methicillin-resistant Staphylococcus aureus (MRSA) and susceptible Enterobacteriaceae. This study aimed to describe the epidemiology of DFI and to identify predictors for DFI associated with multidrug-resistant organisms (MDROs) and pathogens resistant to recommended treatment (PRRT). Methods. Adult patients admitted to Detroit Medical Center from January 2012 to December 2015 with DFI and positive cultures were included. Demographics, comorbidities, microbiological history, sepsis severity, and antimicrobial use within 3 months before DFI were obtained retrospectively. DFI-PRRT was defined as a DFI associated with a pathogen resistant to both vancomycin and ceftriaxone. DFI-MDRO pathogens included MRSA in addition to PRRT. Results. Six-hundred forty-eight unique patients were included, with a mean age of 58.4 ± 13.7 years. DFI-MDRO accounted for 364 (56%) of the cohort, and 194 (30%) patients had DFI-PRRT. Independent predictors for DFI-PRRT included history of PRRT in a diabetic foot ulcer, antimicrobial exposure in the prior 90 days, peripheral vascular disease, and chronic kidney disease. Long-term care facility residence was independently associated with DFI due to ceftriaxone-resistant Enterobacteriaceae, and recent hospitalization was an independent predictor of DFI due to vancomycin-resistant Enterococcus. Conclusions. An unexpectedly high prevalence of DFI-PRRT pathogens was identified. History of the same pathogen in a prior diabetic foot ulcer and recent antimicrobial exposure were independent predictors of DFI-PRRT and should be considered when selecting empiric DFI therapy

Spatial, temporal, and demographic patterns in prevalence of chewing tobacco use in 204 countries and territories, 1990-2019 : a systematic analysis from the Global Burden of Disease Study 2019

Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Findings In 2019, 273 center dot 9 million (95% uncertainty interval 258 center dot 5 to 290 center dot 9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 center dot 72% (4 center dot 46 to 5 center dot 01). 228 center dot 2 million (213 center dot 6 to 244 center dot 7; 83 center dot 29% [82 center dot 15 to 84 center dot 42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global agestandardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 center dot 21% [-1 center dot 26 to -1 center dot 16]), similar progress was not observed for chewing tobacco (0 center dot 46% [0 center dot 13 to 0 center dot 79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 center dot 94% [-1 center dot 72 to -0 center dot 14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Summary Background Chewing tobacco and other types of smokeless tobacco use have had less attention from the global health community than smoked tobacco use. However, the practice is popular in many parts of the world and has been linked to several adverse health outcomes. Understanding trends in prevalence with age, over time, and by location and sex is important for policy setting and in relation to monitoring and assessing commitment to the WHO Framework Convention on Tobacco Control. Methods We estimated prevalence of chewing tobacco use as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 using a modelling strategy that used information on multiple types of smokeless tobacco products. We generated a time series of prevalence of chewing tobacco use among individuals aged 15 years and older from 1990 to 2019 in 204 countries and territories, including age-sex specific estimates. We also compared these trends to those of smoked tobacco over the same time period. Findings In 2019, 273 & middot;9 million (95% uncertainty interval 258 & middot;5 to 290 & middot;9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 & middot;72% (4 & middot;46 to 5 & middot;01). 228 & middot;2 million (213 & middot;6 to 244 & middot;7; 83 & middot;29% [82 & middot;15 to 84 & middot;42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global age standardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 & middot;21% [-1 & middot;26 to -1 & middot;16]), similar progress was not observed for chewing tobacco (0 & middot;46% [0 & middot;13 to 0 & middot;79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 & middot;94% [-1 & middot;72 to -0 & middot;14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Copyright (c) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Cardiac Function and Diastolic Dysfunction in Behcet’s Disease: A Systematic Review and Meta-Analysis

Background. Cardiovascular involvement in Behcet’s disease (BD) is reported and has variable manifestations. It is not clear if diastolic dysfunction (DD) is increased in BD. Our objective was to evaluate the existing literature to determine if cardiac dysfunction, particularly DD, was more prevalent in these patients. Methods. A systematic review and meta-analysis of the available studies analyzing the echocardiographic findings in BD was conducted using a random-effects model. Mean differences were used to calculate the effect sizes of the echocardiographic parameters of interest. Results. A total of 22 studies with 1624 subjects were included in the analysis. Patients with BD had statistically significantly larger mean left atrial dimension (0.08, p=0.0008), greater aortic diameter (0.16, p=0.02), significantly reduced ejection fraction (−1.08, p<0.0001), significantly prolonged mitral deceleration time (14.20, p<0.0001), lower E/A ratio (−0.24, p=0.05), and increased isovolumetric relaxation time (7.29, p<0.00001). Conclusion. DD is increased in patients with BD by the presence of several echocardiographic parameters favoring DD as compared to controls. The meta-analysis also identified that LA dimension is increased in BD patients. EF has also been found to be lower in BD patients. Aortic diameter was also increased in BD patients as compared to controls

Bioethanol production using vegetable peels medium and the effective role of cellulolytic bacterial (Bacillus subtilis) pre-treatment [version 2; referees: 2 approved]

Background:  The requirement of an alternative clean energy source is increasing with the elevating energy demand of modern age. Bioethanol is considered as an excellent candidate to satiate this demand. Methods: Yeast isolates were used for the production of bioethanol using cellulosic vegetable wastes as substrate. Efficient bioconversion of lignocellulosic biomass into ethanol was achieved by the action of cellulolytic bacteria (Bacillus subtilis).  After proper isolation, identification and characterization of stress tolerances (thermo-, ethanol-, pH-, osmo- & sugar tolerance), optimization of physiochemical parameters for ethanol production by the yeast isolates was assessed. Very inexpensive and easily available raw materials (vegetable peels) were used as fermentation media. Fermentation was optimized with respect to temperature, reducing sugar concentration and pH. Results: It was observed that temperatures of 30°C and pH 6.0 were optimum for fermentation with a maximum yield of ethanol. The results indicated an overall increase in yields upon the pretreatment of Bacillus subtilis; maximum ethanol percentages for isolate SC1 obtained after 48-hour incubation under pretreated substrate was 14.17% in contrast to untreated media which yielded 6.21% after the same period. Isolate with the highest ethanol production capability was identified as members of the ethanol-producing Saccharomyces species after stress tolerance studies and biochemical characterization using Analytical Profile Index (API) ® 20C AUX and nitrate broth test. Introduction of Bacillus subtilis increased the alcohol production rate from the fermentation of cellulosic materials. Conclusions: The study suggested that the kitchen waste can serve as a raw material in ethanol fermentation

Trends and Predictors of Transcatheter Aortic Valve Implantation Related In-Hospital Mortality (From the National Inpatient Sample Database)

Existing surgical aortic valve replacement risk models accurately predict the post- surgical aortic valve replacement morbidity and mortality, but factors associated with post transcatheter aortic valve Implantation (TAVI) mortality are not well known. The National Inpatient Sample was queried to identify all cases of TAVI. The association of baseline comorbidities with in-hospital mortality was determined using a binary logistic regression model to obtain adjusted odds ratios (aOR). A total of 161,049 patients underwent TAVI between 2010 and 2017. Of these, 157,151 (97.6%) survived while 3,898 (2.4%) died during hospitalization. The baseline characteristics of TAVI-survivors and non-survivors showed a significant amount of variation, including age (80 vs 82 years, p ≤ 0.0001) and female sex (46% vs 52%, p ≤ 0.0001), respectively. The non-survivors had significantly higher adjusted odds of renal failure requiring hemodialysis (aOR 2.59, 95% CI 2.24 to 2.99, p ≤ 0.0001), history of mediastinal radiation (aOR 2.71, 95% CI 1.02 to 7.20, p = 0.05), liver disease (aOR 3.04, 95% CI 2.63 to 3.51, p ≤ 0.0001), pneumonia (aOR 2.47, 95% CI 2.15 to 2.83, p ≤ 0.0001), cardiogenic shock (aOR 9.83, 95% CI 8.93 to 10.82, p ≤ 0.0001), ventricular tachycardia (aOR 2.12, 95% CI 1.88 to 2.40, p ≤ 0.0001), acute ST-elevation myocardial infarction (aOR 7.38, 95% CI 5.53 to 9.84, p ≤ 0.0001), stroke (aOR 2.25, 95% CI 1.99 to 2.54, p ≤ 0.0001), and acute infective endocarditis (aOR 5.74, 95% CI 3.65 to 9.02, p ≤ 0.0001) compared to TAVI-survivors. The yearly trend of mortality showed an increase in the absolute number of TAVI procedures and mortality but the yearly rate showed a decline in mortality after an initial peak during 2012.Patients with renal failure on dialysis, ST-elevation myocardial infarction, cardiogenic shock, infective endocarditis, liver disease and pneumonia have a higher rate of in-hospital mortality post TAVI

Meta-Analysis Comparing Culprit-Only Versus Complete Multivessel Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction

ST-segment elevation myocardial infarction (STEMI) in patients with concomitant multivessel coronary artery disease is associated with poor prognosis. We sought to determine the merits of percutaneous coronary intervention of the culprit-only revascularization (COR) compared with multivessel revascularization (MVR) approach. Multiple databases were queried to identify relevant articles. Data were analyzed using a random-effect model to calculate unadjusted odds ratio (OR) and relative risk. A total of 28 studies comprising 26,892 patients, 18,377 in the COR and 8,515 in the MVR group were included. The mean age of patients was 63 years, comprising 72% of male patients. The baseline characteristics of the 2 treatment groups were comparable. On a median follow-up of 1-year, COR was associated with a significantly higher odds of major adverse cardiovascular events (MACE; OR 1.36, 95% confidence interval [CI] 1.10 to 1.70, p = 0.005), angina (OR 2.28, 95% CI 1.83 to 2.85, p ≤ 0.00001) and revascularization (OR 1.76, 95% CI 1.22 to 2.54, p = 0.002) compared with patients undergoing MVR for STEMI. The all-cause mortality (OR 1.18, 95% CI 0.91 to 1.53, p = 0.22), cardiovascular mortality (OR 1.30, 95% CI 0.98 to 1.72, p = 0.07), rate of heart failure (OR 1.17, 95% CI 0.86 to 1.59, p = 0.31), need for coronary artery bypass graft (CABG) (OR 1.47, 95% CI 0.82 to 2.64, p = 0.19), repeat myocardial infarction (MI) events (OR 1.23, 95% CI 0.93 to 1.64, p = 0.15) and risk of stroke (OR 1.27 95% CI 0.68 to 2.34, p = 0.45%) were similar between the two groups. A subgroup analysis based on follow-up duration and study design mostly followed the results of the pooled analysis except that the risk of repeat MI events were significantly lower in the MVR group across RCTs (OR 1.46, 95% CI 1.10 to 1.94, p = 0.009). In contrast to the culprit-only approach, MVR in patients with STEMI is associated with a significant reduction in MACE, angina and need for revascularization

Percutaneous Coronary Intervention in Patients With Cardiac Allograft Vasculopathy: a Nationwide Inpatient Sample (NIS) Database Analysis

Cardiac allograft vasculopathy (CAV) is a major cause of heart transplant failure and mortality. The role of percutaneous coronary intervention (PCI) in these patients remains unknown. Methods: The National Inpatient Sample (NIS) (2015-2017) was queried to identify all cases of CAV. The merits of PCI were determined using a propensity-matched multivariate logistic regression model. Adjusted odds ratios (aOR) for in-hospital complications were calculated. Results: A total of 2,380 patients (PCI 185, no-PCI 21,95) with CAV were included in the analysis. There was no significant difference in the odds of major bleeding (OR 1.87, 95% CI 0.94-3.7, P = 0.11), post-procedure bleeding (P = 0.37), cardiogenic shock (OR 0.87, 95% CI 0.45-1.69, P = 0.80), acute kidney injury (uOR 0.92, 95% CI 0.68-1.24, P = 0.64), cardiopulmonary arrest (OR 0.84, 95% CI 0.34-2.11, P = 0.88), and in-hospital mortality (OR 1.59, 95% CI 0.91-2.79, P = 0.14) between patients undergoing PCI compared to those treated conservatively. A propensity-matched analysis closely followed the results of unadjusted crude analysis. Conclusion: PCI in CAV may be associated with increased in-hospital complications and higher resource utilization