Talking in primary care (TIP): protocol for a cluster-randomised controlled trial in UK primary care to assess clinical and cost-effectiveness of communication skills e-learning for practitioners on patients' musculoskeletal pain and enablement.

INTRODUCTION: Effective communication can help optimise healthcare interactions and patient outcomes. However, few interventions have been tested clinically, subjected to cost-effectiveness analysis or are sufficiently brief and well-described for implementation in primary care. This paper presents the protocol for determining the effectiveness and cost-effectiveness of a rigorously developed brief eLearning tool, EMPathicO, among patients with and without musculoskeletal pain. METHODS AND ANALYSIS: A cluster randomised controlled trial in general practitioner (GP) surgeries in England and Wales serving patients from diverse geographic, socioeconomic and ethnic backgrounds. GP surgeries are randomised (1:1) to receive EMPathicO e-learning immediately, or at trial end. Eligible practitioners (eg, GPs, physiotherapists and nurse practitioners) are involved in managing primary care patients with musculoskeletal pain. Patient recruitment is managed by practice staff and researchers. Target recruitment is 840 adults with and 840 without musculoskeletal pain consulting face-to-face, by telephone or video. Patients complete web-based questionnaires at preconsultation baseline, 1 week and 1, 3 and 6 months later. There are two patient-reported primary outcomes: pain intensity and patient enablement. Cost-effectiveness is considered from the National Health Service and societal perspectives. Secondary and process measures include practitioner patterns of use of EMPathicO, practitioner-reported self-efficacy and intentions, patient-reported symptom severity, quality of life, satisfaction, perceptions of practitioner empathy and optimism, treatment expectancies, anxiety, depression and continuity of care. Purposive subsamples of patients, practitioners and practice staff take part in up to two qualitative, semistructured interviews. ETHICS APPROVAL AND DISSEMINATION: Approved by the South Central Hampshire B Research Ethics Committee on 1 July 2022 and the Health Research Authority and Health and Care Research Wales on 6 July 2022 (REC reference 22/SC/0145; IRAS project ID 312208). Results will be disseminated via peer-reviewed academic publications, conference presentations and patient and practitioner outlets. If successful, EMPathicO could quickly be made available at a low cost to primary care practices across the country. TRIAL REGISTRATION NUMBER: ISRCTN18010240.

Liposomal drug delivery strategies to eradicate bacterial biofilms: Challenges, recent advances, and future perspectives.

Typical antibiotic treatments are often ineffectual against biofilm-related infections since bacteria residing within biofilms have developed various mechanisms to resist antibiotics. To overcome these limitations, antimicrobial-loaded liposomal nanoparticles are a promising anti-biofilm strategy as they have demonstrated improved antibiotic delivery and eradication of bacteria residing in biofilms. Antibiotic-loaded liposomal nanoparticles revealed remarkably higher antibacterial and anti-biofilm activities than free drugs in experimental settings. Moreover, liposomal nanoparticles can be used efficaciously for the combinational delivery of antibiotics and other antimicrobial compounds/peptide which facilitate, for instance, significant breakdown of the biofilm matrix, increased bacterial elimination from biofilms and depletion of metabolic activity of various pathogens. Drug-loaded liposomes have mitigated recurrent infections and are considered a promising tool to address challenges associated to antibiotic resistance. Furthermore, it has been demonstrated that surface charge and polyethylene glycol modification of liposomes have a notable impact on their antibacterial biofilm activity. Future investigations should tackle the persistent hurdles associated with development of safe and effective liposomes for clinical application and investigate novel antibacterial treatments, including CRISPR-Cas gene editing, natural compounds, phages, and nano-mediated approaches. Herein, we emphasize the significance of liposomes in inhibition and eradication of various bacterial biofilms, their challenges, recent advances, and future perspectives.

Riemerella anatipestifer UvrC is required for iron utilization, biofilm formation and virulence.

RESEARCH HIGHLIGHTS: Deletion of uvrC in R. anatipestfer Yb2 significantly reduced its biofilm formation.uvrC deletion led to reduced tolerance to H2O2- and HOCl-induced oxidative stress.The iron utilization of uvrC deleted mutant was significantly reduced.The uvrC deletion in R. anatipestifer Yb2 attenuated its virulence.

Examining the relationship between psychosocial adversity and inhibitory control: an fMRI study of children growing up in extreme poverty.

Exposure to psychosocial adversity (PA) is associated with poor behavioral, physical, and mental health outcomes in adulthood. Growing evidence suggests that deficits in executive functions may in part moderate these outcomes, with inhibitory control as an example of such a putative moderator. However, much of the literature examining the development of inhibitory control has been based on children in higher resource environments, and little is known how growing up in a low resource setting might exacerbate the link between inhibitory control and health outcomes. In this context we collected fMRI data during a Go/No-Go inhibitory control task and PA variables for 68 children 5 to 7 years of age living in Dhaka, Bangladesh, an area with a high prevalence of PA. The children's mothers completed behavioral questionnaires to assess the child's PA and their own PA. Whole-brain activation underlying inhibitory control was examined using the No-Go versus Go contrast, and associations with PA variables were assessed using whole-brain regressions. Childhood neglect was associated with weaker activation in the right posterior cingulate, whereas greater family conflict, economic stress, and maternal PA factors were associated with greater activation in the left medial frontal gyrus, right superior and middle frontal gyrus, and left cingulate gyrus. These data suggest that neural networks supporting inhibitory control processes may vary as a function of exposure to different types of PA, particularly between those related to threat and deprivation. Furthermore, increased activation in children with greater PA may serve as a compensatory mechanism, allowing them to maintain similar behavioral task performance.

High Prevalence of Multidrug-Resistant Bacteria in the Trachea of Intensive Care Units Admitted Patients: Evidence from a Bangladeshi Hospital.

Recent research has shown that antibiotic-resistant microorganisms are becoming more prevalent in intensive care units (ICUs) at an exponential rate. Patients in the ICU can get infected by pathogens due to invasive operation procedures and critical health conditions. This study primarily emphasized tracheal samples from ICU patients due to their reliance on ventilators, increasing their susceptibility to Ventilator-Associated Pneumonia (VAP). Moreover, the rise of multidrug-resistant (MDR) pathogens makes treatment strategies more challenging for these patients. In this study, we tested 200 tracheal specimens to determine the prevalence of microorganisms and analyzed the antibiotic susceptibility of these isolates against regular antibiotics, including 4th generation drugs. Among the 273 isolates, 81% were gram-negative bacteria, 10% were gram-positive bacteria, and 9% were fungi. The most prevalent gram-negative bacteria were Acinetobacter spp. (34%), Klebsiella spp. (22%), Pseudomonas spp. (14%), and Escherichia coli (9.2%). The most prevalent gram-positive bacteria were Staphylococcus aureus (5.9%), and the fungi were Candida spp. (7.3%). Among the most prevalent bacteria, except Staphylococcus aureus isolates, around 90% were resistant to multiple drugs, whereas 60% of Acinetobacter spp. and Pseudomonas spp. were extensively drug resistant. Sensitivity analysis against the gram-negative and gram-positive drug panel using a one-way ANOVA test followed by Tukey's post hoc test showed that in the in vitro assay, colistin was the most effective antibiotic against all gram-negative bacteria. In contrast, linezolid, vancomycin, and fusidic acid were most effective against all gram-positive bacteria. Regular monitoring of nosocomial infections and safe management of highly resistant bacteria can help prevent future pandemics.

Defining a Childhood Type 1 Diabetes Cohort, Clinical Practice Measures, and Outcomes Within Administrative Data in British Columbia.

OBJECTIVE: We used administrative data to 1) establish a cohort of individuals with childhood-onset type 1 diabetes (T1D) in British Columbia (BC), and 2) define T1D-related clinical practice measures. METHODS: We applied a validated diabetes case-finding definition and differentiating algorithm to linked administrative data (1992-1993 to 2019-2020). Cases were removed when they did not meet inclusion criteria for childhood-onset T1D. Clinical practice measures were defined based on clinical practice guidelines. RESULTS: We developed an administrative cohort that included 5,901 individuals with childhood-diagnosed T1D between April 1, 1996, and March 31, 2020. The mean age was 22.31 (standard deviation 8.21) years. Clinical practice measures derived included diabetes outpatient visits (N=4,935) and glycated hemoglobin tests (N=4,935), and screening for thyroid function (N=4,457), retinopathy (N=1,602), and nephropathy (N=2,369). CONCLUSIONS: We established an administrative cohort of ∼6,000 individuals with childhood-onset T1D with 20+ years of follow-up data that can be used to describe the association between clinical practice measures and clinical outcomes.

Chemical and toxicological studies on black crust formed over historical monuments as a probable health hazard.

Studies to date have mostly investigated environmental factors responsible for deterioration of historical monuments. Black crusts formed on historical monuments are considered as factor for deterioration of structures or as an indicator of environmental status of the surrounding area. Black crust formed on historical monuments has never been investigated as a health hazard. Herein, for the first time, we performed in vitro and in vivo toxicology studies of black crust formed on three culturally-rich historical monuments (Rang Ghar, Kareng Ghar, and Talatal Ghar) of the Indian subcontinent to test their toxicological effect. Black crust suspension in ultrapure water was found not to be considerably toxic to the cells upon direct short-term exposure. However, the sub-acute nasal exposure of the black crust suspension in Swiss albino mice produced lung-specific pathologies and mortality. Additionally, structural formation of the black crust along with the speciation of potentially hazardous elements (PHEs), polyaromatic hydrocarbon (PAHs), and other metals were investigated. Overall, these results indicate the potential of black crust deposited on historical monuments as health hazard owing to the atmospheric pollution of the surroundings. However, it may be noted that black crust and its components have very low possibility of health implication unless they are disturbed without proper care.

Reporting of Factorial Randomized Trials: Extension of the CONSORT 2010 Statement.

Importance: Transparent reporting of randomized trials is essential to facilitate critical appraisal and interpretation of results. Factorial trials, in which 2 or more interventions are assessed in the same set of participants, have unique methodological considerations. However, reporting of factorial trials is suboptimal. Objective: To develop a consensus-based extension to the Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement for factorial trials. Design: Using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework, the CONSORT extension for factorial trials was developed by (1) generating a list of reporting recommendations for factorial trials using a scoping review of methodological articles identified using a MEDLINE search (from inception to May 2019) and supplemented with relevant articles from the personal collections of the authors; (2) a 3-round Delphi survey between January and June 2022 to identify additional items and assess the importance of each item, completed by 104 panelists from 14 countries; and (3) a hybrid consensus meeting attended by 15 panelists to finalize the selection and wording of items for the checklist. Findings: This CONSORT extension for factorial trials modifies 16 of the 37 items in the CONSORT 2010 checklist and adds 1 new item. The rationale for the importance of each item is provided. Key recommendations are (1) the reason for using a factorial design should be reported, including whether an interaction is hypothesized, (2) the treatment groups that form the main comparisons should be clearly identified, and (3) for each main comparison, the estimated interaction effect and its precision should be reported. Conclusions and Relevance: This extension of the CONSORT 2010 Statement provides guidance on the reporting of factorial randomized trials and should facilitate greater understanding of and transparency in their reporting.

Consensus Statement for Protocols of Factorial Randomized Trials: Extension of the SPIRIT 2013 Statement.

Importance: Trial protocols outline a trial's objectives as well as the methods (design, conduct, and analysis) that will be used to meet those objectives, and transparent reporting of trial protocols ensures objectives are clear and facilitates appraisal regarding the suitability of study methods. Factorial trials, in which 2 or more interventions are assessed in the same set of participants, have unique methodological considerations. However, no extension of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement, which provides guidance on reporting of trial protocols, for factorial trials is available. Objective: To develop a consensus-based extension to the SPIRIT 2013 Statement for factorial trials. Evidence Review: The SPIRIT extension for factorial trials was developed using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework. First, a list of reporting recommendations was generated using a scoping review of methodological articles identified using a MEDLINE search (inception to May 2019), which was supplemented with relevant articles from the personal collections of the authors. Second, a 3-round Delphi survey (January to June 2022, completed by 104 panelists from 14 countries) was conducted to assess the importance of items and identify additional recommendations. Third, a hybrid consensus meeting was held, attended by 15 panelists to finalize selection and wording of the checklist. Findings: This SPIRIT extension for factorial trials modified 9 of the 33 items in the SPIRIT 2013 checklist. Key reporting recommendations were that the rationale for using a factorial design should be provided, including whether an interaction is hypothesized; the treatment groups that will form the main comparisons should be identified; and statistical methods for each main comparison should be provided, including how interactions will be assessed. Conclusions and Relevance: In this consensus statement, 9 factorial-specific items were provided that should be addressed in all protocols of factorial trials to increase the trial's utility and transparency.

Associations of diabetes, hypertension and obesity with COVID-19 mortality: a systematic review and meta-analysis.

INTRODUCTION: Despite a growing body of scholarly research on the risks of severe COVID-19 associated with diabetes, hypertension and obesity, there is a need for estimating pooled risk estimates with adjustment for confounding effects. We conducted a systematic review and meta-analysis to estimate the pooled adjusted risk ratios of diabetes, hypertension and obesity on COVID-19 mortality. METHODS: We searched 16 literature databases for original studies published between 1 December 2019 and 31 December 2020. We used the adapted Newcastle-Ottawa Scale to assess the risk of bias. Pooled risk ratios were estimated based on the adjusted effect sizes. We applied random-effects meta-analysis to account for the uncertainty in residual heterogeneity. We used contour-funnel plots and Egger's test to assess possible publication bias. RESULTS: We reviewed 34 830 records identified in literature search, of which 145 original studies were included in the meta-analysis. Pooled adjusted risk ratios were 1.43 (95% CI 1.32 to 1.54), 1.19 (95% CI 1.09 to 1.30) and 1.39 (95% CI 1.27 to 1.52) for diabetes, hypertension and obesity (body mass index ≥30 kg/m2) on COVID-19 mortality, respectively. The pooled adjusted risk ratios appeared to be stronger in studies conducted before April 2020, Western Pacific Region, low- and middle-income countries, and countries with low Global Health Security Index scores, when compared with their counterparts. CONCLUSIONS: Diabetes, hypertension and obesity were associated with an increased risk of COVID-19 mortality independent of other known risk factors, particularly in low-resource settings. Addressing these chronic diseases could be important for global pandemic preparedness and mortality prevention. PROSPERO REGISTRATION NUMBER: CRD42021204371.

Trends in antimicrobial resistance amongst Salmonella Paratyphi A isolates in Bangladesh: 1999-2021.

BACKGROUND: Typhoid and paratyphoid remain common bloodstream infections in areas with suboptimal water and sanitation infrastructure. Paratyphoid, caused by Salmonella Paratyphi A, is less prevalent than typhoid and its antimicrobial resistance (AMR) trends are less documented. Empirical treatment for paratyphoid is commonly based on the knowledge of susceptibility of Salmonella Typhi, which causes typhoid. Hence, with rising drug resistance in Salmonella Typhi, last-line antibiotics like ceftriaxone and azithromycin are prescribed for both typhoid and paratyphoid. However, unlike for typhoid, there is no vaccine to prevent paratyphoid. Here, we report 23-year AMR trends of Salmonella Paratyphi A in Bangladesh. METHODS: From 1999 to 2021, we conducted enteric fever surveillance in two major pediatric hospitals and three clinics in Dhaka, Bangladesh. Blood cultures were performed at the discretion of the treating physicians; cases were confirmed by culture, serological and biochemical tests. Antimicrobial susceptibility was determined following CLSI guidelines. RESULTS: Over 23 years, we identified 2,725 blood culture-confirmed paratyphoid cases. Over 97% of the isolates were susceptible to ampicillin, chloramphenicol, and cotrimoxazole, and no isolate was resistant to all three. No resistance to ceftriaxone was recorded, and >99% of the isolates were sensitive to azithromycin. A slight increase in minimum inhibitory concentration (MIC) is noticed for ceftriaxone but the current average MIC is 32-fold lower than the resistance cut-off. Over 99% of the isolates exhibited decreased susceptibility to ciprofloxacin. CONCLUSIONS: Salmonella Paratyphi A has remained susceptible to most antibiotics, unlike Salmonella Typhi, despite widespread usage of many antibiotics in Bangladesh. The data can guide evidence-based policy decisions for empirical treatment of paratyphoid fever, especially in the post typhoid vaccine era, and with the availability of new paratyphoid diagnostics.

A comparison of excess deaths by UK country and region during the first year of the COVID-19 pandemic.

We compare the impact of the first two waves of the COVID-19 pandemic on risk of age-standardized mortality by sex, UK country, and English region. Each wave is defined as lasting 26 weeks and are consecutive beginning in 2020 week 11. The expected rate is estimated from 2015 to 2019 mean and the projected mortality trend from the same period are used to estimate excess mortality. By both measures, excess mortality was highest and lowest in regions of England, London and the South-West, respectively. Excess mortality was consistently higher for males than females.

Lipoprotein Characteristics and Incident Coronary Heart Disease: Prospective Cohort of Nearly 90 000 Individuals in UK Biobank.

Background Associations of coronary heart disease (CHD) with plasma lipids are well described, but the associations with characteristics of lipoproteins (which transport lipids) remain unclear. Methods and Results UK Biobank is a prospective study of 0.5 million adults. Analyses were restricted to 89 422 participants with plasma lipoprotein and apolipoprotein measures from Nightingale nuclear magnetic resonance spectroscopy and without CHD at baseline. CHD risk was positively associated with concentrations of very-low-density lipoproteins, intermediate-density lipoproteins, and low-density lipoproteins (LDL), and inversely associated with high-density lipoproteins. Hazard ratios (99% CIs) per SD were 1.22 (1.17-1.28), 1.16 (1.11-1.21), 1.20 (1.15-1.25), and 0.90 (0.86-0.95), respectively. Larger subclasses of very-low-density lipoproteins were less strongly associated with CHD risk, but associations did not materially vary by size of LDL or high-density lipoprotein. Given lipoprotein particle concentrations, lipid composition (including cholesterol) was not strongly related to CHD risk, except for triglyceride in LDL particles. Apolipoprotein B was highly correlated with LDL concentration (r=0.99), but after adjustment for apolipoprotein B, concentrations of very-low-density lipoprotein and high-density lipoprotein particles remained strongly related to CHD risk. Conclusions This large-scale study reliably quantifies the associations of nuclear magnetic resonance-defined lipoprotein characteristics with CHD risk. CHD risk was most strongly related to particle concentrations, and separate measurements of lipoprotein concentrations may be of greater value than the measurement by apolipoprotein B, which was largely determined by LDL concentration alone. Furthermore, there was strong evidence of positive association with mean triglyceride molecules per LDL particle but little evidence of associations with total triglycerides or other lipid and lipoprotein fractions after accounting for lipoprotein concentrations.

Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials: A Systematic Review.

Importance: Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice. Objective: To assess the reporting of observational studies that explicitly aimed to emulate a target trial. Evidence Review: We searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation. Findings: A total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation. Conclusion and Relevance: In this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.

A comprehensive analysis of all-cause and cause-specific excess deaths in 30 countries during 2020.

The impact of COVID-19 on mortality from specific causes of death remains poorly understood. This study analysed cause-of-death data provided by the World Health Organization from 2011 to 2019 to estimate excess deaths in 2020 in 30 countries. Over-dispersed Poisson regression models were used to estimate the number of deaths that would have been expected if the pandemic had not occurred, separately for men and women. The models included year and age categories to account for temporal trends and changes in size and age structure of the populations. Excess deaths were calculated by subtracting observed deaths from expected ones. Our analysis revealed significant excess deaths from ischemic heart diseases (IHD) (in 10 countries), cerebrovascular diseases (CVD) (in 10 countries), and diabetes (in 19 countries). The majority of countries experienced excess mortality greater than 10%, including Mexico (+ 38·8% for IHD, + 34·9% for diabetes), Guatemala (+ 30·0% for IHD, + 10·2% for CVD, + 39·7% for diabetes), Cuba (+ 18·8% for diabetes), Brazil (+ 12·9% for diabetes), the USA (+ 15·1% for diabetes), Slovenia (+ 33·8% for diabetes), Poland (+ 30·2% for IHD, + 19·5% for CVD, + 26 1% for diabetes), Estonia (+ 26·9% for CVD, + 34·7% for diabetes), Bulgaria (+ 22·8% for IHD, + 11·4% for diabetes), Spain (+ 19·7% for diabetes), Italy (+ 18·0% for diabetes), Lithuania (+ 17·6% for diabetes), Finland (+ 13·2% for diabetes) and Georgia (+ 10·7% for IHD, + 19·0% for diabetes). In 2020, 22 out of 30 countries had a significant increase in total mortality. Some of this excess was attributed to COVID-19, but a substantial increase was also observed in deaths attributed to cardiovascular diseases and diabetes.

Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline.

BACKGROUND: Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline. METHODS/DESIGN: The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses. ETHICS AND DISSEMINATION: Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.

Predictive value of metabolic profiling in cardiovascular risk scores: analysis of 75 000 adults in UK Biobank.

BACKGROUND: Metabolic profiling (the extensive measurement of circulating metabolites across multiple biological pathways) is increasingly employed in clinical care. However, there is little evidence on the benefit of metabolic profiling as compared with established atherosclerotic cardiovascular disease (CVD) risk scores. METHODS: UK Biobank is a prospective study of 0.5 million participants, aged 40-69 at recruitment. Analyses were restricted to 74 780 participants with metabolic profiling (measured using nuclear magnetic resonance) and without CVD at baseline. Cox regression was used to compare model performance before and after addition of metabolites to QRISK3 (an established CVD risk score used in primary care in England); analyses derived three models, with metabolites selected by association significance or by employing two different machine learning approaches. RESULTS: We identified 5097 incident CVD events within the 10-year follow-up. Harrell's C-index of QRISK3 was 0.750 (95% CI 0.739 to 0.763) for women and 0.706 (95% CI 0.696 to 0.716) for men. Adding selected metabolites did not significantly improve measures of discrimination in women (Harrell's C-index of three models are 0.759 (0.747 to 0.772), 0.759 (0.746 to 0.770) and 0.759 (0.748 to 0.771), respectively) or men (0.710 (0.701 to 0.720), 0.710 (0.700 to 0.719) and 0.710 (0.701 to 0.719), respectively), and neither did it improve reclassification or calibration. CONCLUSION: This large-scale study applied both conventional and machine learning approaches to assess the potential benefit of metabolic profiling to well-established CVD risk scores. However, there was no evidence that metabolic profiling improved CVD risk prediction in this population.

Socioeconomic inequities of COVID-19 mortality in vulnerable Comunas of the City of Buenos Aires.

During the COVID-19 pandemic, the gap in health inequities was exposed and increased, showing how different vulnerable groups were affected. Our aim was to examine the correlation between an area-based health inequity index and mortality due to COVID-19 in people 60 years old or above in the City of Buenos Aires in 2020. We developed a Health Inequity Composite Index (HICI), including six core indicators. Each indicator value per Comuna was first standardized to a Z-score. All six Z-scores were summed into a final composite Z-score to rank the Comunas from lowest to highest social inequities. Comunas from the northern part of the city had lower inequities whereas those in the south had higher levels of inequities. COVID-19 age-standardized mortality rate in people 60 years or above was higher in the Comunas from the south and lower in those from the north. Finally, we found a strong positive correlation (Rho = 0.83, p < 0.0001 CI95% = 0.65-0.99) between HICI and age-standardized mortality rates from COVID-19 in people 60 years or above. Our finding of a strong correlation between the levels of health inequity and mortality calls for a concerted effort in narrowing or eliminating existing inequities.