Utility of Nontraditional Risk Markers in Atherosclerotic Cardiovascular Disease Risk Assessment

AbstractBackgroundThe improvement in discrimination gained by adding nontraditional cardiovascular risk markers cited in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines to the atherosclerotic cardiovascular disease (ASCVD) risk estimator (pooled cohort equation [PCE]) is untested.ObjectivesThis study assessed the predictive accuracy and improvement in reclassification gained by the addition of the coronary artery calcium (CAC) score, the ankle–brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) levels, and family history (FH) of ASCVD to the PCE in participants of MESA (Multi-Ethnic Study of Atherosclerosis).MethodsThe PCE was calibrated (cPCE) and used for this analysis. The Cox proportional hazards survival model, Harrell’s C statistics, and net reclassification improvement analyses were used. ASCVD was defined as myocardial infarction, coronary heart disease–related death, or fatal or nonfatal stroke.ResultsOf 6,814 MESA participants not prescribed statins at baseline, 5,185 had complete data and were included in this analysis. Their mean age was 61 years; 53.1% were women, 9.8% had diabetes, and 13.6% were current smokers. After 10 years of follow-up, 320 (6.2%) ASCVD events occurred. CAC score, ABI, and FH were independent predictors of ASCVD events in the multivariable Cox models. CAC score modestly improved the Harrell’s C statistic (0.74 vs. 0.76; p = 0.04); ABI, hsCRP levels, and FH produced no improvement in Harrell’s C statistic when added to the cPCE.ConclusionsCAC score, ABI, and FH were independent predictors of ASCVD events. CAC score modestly improved the discriminative ability of the cPCE compared with other nontraditional risk markers

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization

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

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Electrocardiographic spatial QRS-T angle and incident cardiovascular disease in HIV-infected patients (from the Strategies for the Management of Antiretroviral Therapy [SMART] study)

Widening of the electrocardiographic (ECG) spatial QRS-T angle has been predictive of cardiovascular disease (CVD) events in the general population. However, its prognostic significance in human immunodeficiency virus (HIV)-infected patients remains unknown. The spatial QRS-T angle was derived from the baseline resting 12-lead electrocardiogram of 4,453 HIV-infected patients aged 43.5 – 9.3 years from the Strategies for Management of Antiretroviral Therapy (SMART) trial. CVD events were identified during a median followup of 28.7 months. Quartiles of the spatial QRS-T angle was calculated for men and women separately, and values in the upper quartile were considered as a widened angle (values >74 for women and >93 for men). A multivariate Cox proportional hazards analysis was used to examine the association between a widened baseline spatial QRS-T angle and incident CVD events. During 11,965 person-years of follow-up, 152 CVD events occurred at a rate of 1.27 events/100 person-years. The rate of CVD events in those with a widened spatial QRS-T angle was almost double the rate in those with a normal spatial QRS-T angle (rate ratio 1.94, 95% confidence interval 1.40 to 2.69; p 50% increased risk of CVD events compared to a normal spatial QRS-T angle (hazard ratio 1.53, 95% confidence interval 1.07 to 2.17; p [ 0.02). No interaction was seen by SMART trial arm (p value for interaction[0.37) or gender (p value for interaction[0.84). In conclusion, a widened spatial QRS-T angle was independently predictive of CVD events in HIV-infected patients receiving antiretroviral therapy. This highlights the potential role of routine electrocardiography as a simple noninvasive CVD risk-screening tool in HIV-infected patients

Prevalence of atrial fibrillation and association with clinical, sociocultural, and ancestral correlates among Hispanic/Latinos: The Hispanic Community Health Study/Study of Latinos

Hispanics/Latinos represent the largest ethnic minority group in the United States. Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States. The purpose of this study was to provide data on the prevalence of AF and its correlates in a representative Hispanic/Latino population–based sample inclusive of all background groups. Hispanic Community Health Study/Study of Latinos participants (n=16,415; 60% women; 59% age >45 years) were enrolled between March 2008 and June 2011, representing individuals of Cuban, Dominican, Mexican, Puerto Rican, Central American, and South American heritage. AF was defined by the 12-lead electrocardiogram and/or participant self-report of a physician diagnosis. Hispanic background–specific AF prevalence rates were determined. Weighted sequential logistic regression models were adjusted for demographic factors (age and sex) and clinical variables (diabetes, hypertension, body mass index, tobacco use, and estimated glomerular filtration rate). The overall weighted prevalence of AF was 1.0% (n=162), with the highest prevalence in Hispanics of Dominican and Puerto Rican backgrounds (1.9% and 2.5% respectively) and the lowest in those of Mexican background (0.3%). Diabetes, hypertension, renal disease, left ventricular hypertrophy determined by the electrocardiogram, alcohol use, and English language preference (greater acculturation) (P < .01 for all) were significantly associated with higher AF prevalence. Multivariate analysis by Hispanic/Latino background group showed that Hispanics of Dominican and Puerto Rican backgrounds were at a 3- to 6-fold higher risk of AF than their Mexican counterparts. In a diverse representative population of Hispanics/Latinos, overall AF prevalence was low and varied significantly across Hispanic/Latino background groups independent of clinical or demographic factors