Pre-Pandemic Versus Early COVID-19 Perinatal Outcomes at a Military Hospital.

PURPOSE: The purpose of this study was to examine the impact of the first year of COVID-19 pandemic on maternal and neonatal outcomes at a large military treatment facility in Southern California. STUDY DESIGN AND METHODS: A retrospective review of maternal and neonatal medical records was conducted between January 1, 2019, and December 31, 2020. Outcomes measured included stillbirth rate, neonatal intensive care unit admission, neonatal death, cesarean birth, and postpartum hemorrhage. RESULTS: A total of 4,425 records were analyzed. Rates of stillbirth between the years did not vary. The neonatal death rate decreased more than 50% in 2020 (p = .149). Cesarean births rose by 2.7% in 2020 (p = .046). Rates of postpartum hemorrhage did not vary between years. CLINICAL IMPLICATIONS: The impact of COVID-19 on maternal and neonatal outcomes at a military treatment facility in the first year of the COVID-19 pandemic provides guidance for optimizing perinatal health care. Vertical transmission of COVID-19 is low and routine testing of asymptomatic neonates of positive mothers may not be necessary. COVID-19 infections should not be an indication for cesarean birth and are not associated with neonatal deaths or NICU admission.

Providing technical assistance: lessons learned from the first three years of the WHO Adolescent and Youth Sexual and Reproductive Health and Rights Technical Assistance Coordination Mechanism.

Young people's sexual and reproductive health (SRH) continues to be a major challenge in low and middle-income countries, with implications for public health now and in the future. Fortunately there is a growing array of evidence-based interventions, and commitments from governments, development partners and donors, to support programmes that aim to improve young people's SRH.However, in some situations, the technical assistance that governments feel that they need to strengthen and implement national policies and strategies, to move from words to action, is not available. The WHO Adolescent and Youth Sexual and Reproductive Health and Rights (AYSRHR) Technical Assistance (TA) Coordination Mechanism was initiated to help fill this technical assistance gap; to respond to TA requests from ministries of health in ways that are timely, efficient, effective and contribute to strengthening capacity.This paper describes the process of developing the Technical Assistance Coordination Mechanism (TA Mechanism) and the outcomes, experiences and lessons learned after three years of working. It triangulates the findings from a preliminary review of the literature and discussions with selected key informants; the outcomes from a series of structured review meetings; and the documented processes and results of the technical assistance provided to countries.The lessons learned focus on three aspects of the TA Mechanism. How it was conceptualized and designed: through listening to people who provide and receive AYSRHR TA and by reviewing and synthesizing past experiences of TA provision. What the TA Mechanism has achieved: a standardized process for TA provision, at different stages for a range of AYSRHR issues in ten countries in three geographic regions. And what worked well and what did not: which common challenges was the TA Mechanism able to address and which ones persisted despite efforts to avoid or resolve them. The paper ends with the implications of the lessons learned for future action.

Characterization of the plasma metabolome and lipidome in response to sleeve gastrectomy and gastric bypass surgeries reveals molecular patterns of surgical weight loss.

OBJECTIVES: Bariatric surgery improves metabolic health, but the underlying mechanisms are not fully understood. We analyzed the effects of two types of bariatric surgery, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), on the plasma metabolome and lipidome. METHODS: We characterized the plasma metabolome (1268 metabolites) and lipidome (953 lipids) pre-operatively and at 3 and 12 months post-operatively in 104 obese adults who were previously recruited to a prospective cohort of bariatric surgery. The metabolomic and lipidomic responses to bariatric surgery over time were analyzed using multivariable linear mixed-effects models. RESULTS: There were significant changes in multiple metabolites and lipids, including rapid early changes in amino acid and peptide metabolites, including decreases in branched-chain amino acids (BCAAs), aromatic AAs, alanine and aspartate, and increases in glycine, serine, arginine and citrulline. There were also significant decreases in many triglyceride species, with increases in phosphatidylcholines and phosphatidylethanolamines. There were significant changes in metabolites related to energy metabolism that were apparent only after 12 months. We observed differences by bariatric surgery type in the changes in a small number of primary and secondary bile acids, including glycohyocholate and glyco-beta-muricholate. CONCLUSIONS: Our findings highlight the comprehensive changes in metabolites and lipids that occur over the 12 months following bariatric surgery. While both SG and RYGB caused profound changes in the metabolome and lipidome, RYGB was characterized by greater increases in bile acids following surgery.

Genotype-based "virtual" metabolomics in a clinical biobank identifies novel metabolite-disease associations.

Introduction: Circulating metabolites act as biomarkers of dysregulated metabolism and may inform disease pathophysiology. A portion of the inter-individual variability in circulating metabolites is influenced by common genetic variation. We evaluated whether a genetics-based "virtual" metabolomics approach can identify novel metabolite-disease associations. Methods: We examined the association between polygenic scores for 724 metabolites with 1,247 clinical phenotypes in the BioVU DNA biobank, comprising 57,735 European ancestry and 15,754 African ancestry participants. We applied Mendelian randomization (MR) to probe significant relationships and validated significant MR associations using independent GWAS of candidate phenotypes. Results and Discussion: We found significant associations between 336 metabolites and 168 phenotypes in European ancestry and 107 metabolites and 56 phenotypes in African ancestry. Of these metabolite-disease pairs, MR analyses confirmed associations between 73 metabolites and 53 phenotypes in European ancestry. Of 22 metabolitephenotype pairs evaluated for replication in independent GWAS, 16 were significant (false discovery rate p < 0.05). These included associations between bilirubin and X-21796 with cholelithiasis, phosphatidylcholine (16:0/22:5n3,18:1/20:4) and arachidonate with inflammatory bowel disease and Crohn's disease, and campesterol with coronary artery disease and myocardial infarction. These associations may represent biomarkers or potentially targetable mediators of disease risk.

Locum doctor working and quality and safety: a qualitative study in English primary and secondary care.

BACKGROUND: The use of temporary doctors, known as locums, has been common practice for managing staffing shortages and maintaining service delivery internationally. However, there has been little empirical research on the implications of locum working for quality and safety. This study aimed to investigate the implications of locum working for quality and safety. METHODS: Qualitative semi-structured interviews and focus groups were conducted with 130 participants, including locums, patients, permanently employed doctors, nurses and other healthcare professionals with governance and recruitment responsibilities for locums across primary and secondary healthcare organisations in the English NHS. Data were collected between March 2021 and April 2022. Data were analysed using reflexive thematic analysis and abductive analysis. RESULTS: Participants described the implications of locum working for quality and safety across five themes: (1) 'familiarity' with an organisation and its patients and staff was essential to delivering safe care; (2) 'balance and stability' of services reliant on locums were seen as at risk of destabilisation and lacking leadership for quality improvement; (3) 'discrimination and exclusion' experienced by locums had negative implications for morale, retention and patient outcomes; (4) 'defensive practice' by locums as a result of perceptions of increased vulnerability and decreased support; (5) clinical governance arrangements, which often did not adequately cover locum doctors. CONCLUSION: Locum working and how locums were integrated into organisations posed some significant challenges and opportunities for patient safety and quality of care. Organisations should take stock of how they work with the locum workforce to improve not only quality and safety but also locum experience and retention.

The consumption of animal products is associated with plasma levels of alpha-aminoadipic acid (2-AAA).

BACKGROUND AND AIMS: The cardiometabolic disease-associated metabolite, alpha-aminoadipic acid (2-AAA) is formed from the breakdown of the essential dietary amino acid lysine. However, it was not known whether elevated plasma levels of 2-AAA are related to dietary nutrient intake. We aimed to determine whether diet is a determinant of circulating 2-AAA in healthy individuals, and whether 2-AAA is altered in response to dietary modification. METHODS AND RESULTS: We investigated the association between 2-AAA and dietary nutrient intake in a cross-sectional study of healthy individuals (N = 254). We then performed a randomized cross-over dietary intervention trial to investigate the effect of lysine supplementation (1 week) on 2-AAA in healthy individuals (N = 40). We further assessed the effect of a vegetarian diet on 2-AAA in a short-term (4-day) dietary intervention trial in healthy omnivorous women (N = 35). We found that self-reported dietary intake of animal products, including meat, poultry, and seafood, was associated with higher plasma 2-AAA cross-sectionally (P < 0.0001). Supplementary dietary lysine (5g/day) caused no significant increase in plasma 2-AAA; however, plasma 2-AAA was altered by general dietary modification. Further, plasma 2-AAA was significantly reduced by a short-term vegetarian diet (P = 0.003). CONCLUSION: We identified associations between plasma 2-AAA and consumption of animal products, which were validated in a vegetarian dietary intervention trial, but not in a trial designed to specifically increase the 2-AAA amino acid precursor lysine. Further studies are warranted to investigate whether implementation of a vegetarian diet improves cardiometabolic risk in individuals with elevated 2-AAA.

Comparing the clinical practice and prescribing safety of locum and permanent doctors: observational study of primary care consultations in England.

BACKGROUND: Temporary doctors, known as locums, are a key component of the medical workforce in the NHS but evidence on differences in quality and safety between locum and permanent doctors is limited. We aimed to examine differences in the clinical practice, and prescribing safety for locum and permanent doctors working in primary care in England. METHODS: We accessed electronic health care records (EHRs) for 3.5 million patients from the CPRD GOLD database with linkage to Hospital Episode Statistics from 1st April 2010 to 31st March 2022. We used multi-level mixed effects logistic regression to compare consultations with locum and permanent GPs for several patient outcomes including general practice revisits; prescribing of antibiotics; strong opioids; hypnotics; A&E visits; emergency hospital admissions; admissions for ambulatory care sensitive conditions; test ordering; referrals; and prescribing safety indicators while controlling for patient and practice characteristics. RESULTS: Consultations with locum GPs were 22% more likely to involve a prescription for an antibiotic (OR = 1.22 (1.21 to 1.22)), 8% more likely to involve a prescription for a strong opioid (OR = 1.08 (1.06 to 1.09)), 4% more likely to be followed by an A&E visit on the same day (OR = 1.04 (1.01 to 1.08)) and 5% more likely to be followed by an A&E visit within 1 to 7 days (OR = 1.05 (1.02 to 1.08)). Consultations with a locum were 12% less likely to lead to a practice revisit within 7 days (OR = 0.88 (0.87 to 0.88)), 4% less likely to involve a prescription for a hypnotic (OR = 0.96 (0.94 to 0.98)), 15% less likely to involve a referral (OR = 0.85 (0.84 to 0.86)) and 19% less likely to involve a test (OR = 0.81 (0.80 to 0.82)). We found no evidence that emergency admissions, ACSC admissions and eight out of the eleven prescribing safety indicators were different if patients were seen by a locum or a permanent GP. CONCLUSIONS: Despite existing concerns, the clinical practice and performance of locum GPs did not appear to be systematically different from that of permanent GPs. The practice and performance of both locum and permanent GPs is likely shaped by the organisational setting and systems within which they work.

Branched-chain amino acids and type 2 diabetes: a bidirectional Mendelian randomization analysis.

OBJECTIVE: Genetic studies have suggested that the branched-chain amino acids (BCAAs) valine, leucine, and isoleucine have a causal association with type 2 diabetes (T2D). However, inferences are based on a limited number of genetic loci associated with BCAAs. METHODS: Instrumental variables (IVs) for each BCAA were constructed and validated using large well-powered data sets and their association with T2D was tested using a two-sample inverse-variance weighted Mendelian randomization approach. Sensitivity analyses were performed to ensure the accuracy of the findings. A reverse association was assessed using instrumental variables for T2D. RESULTS: Estimated effect sizes between BCAA IVs and T2D, excluding outliers, were as follows: valine (ß = 0.14 change in log-odds per SD change in valine, 95% CI: -0.06 to 0.33, p = 0.17), leucine (ß = 0.15, 95% CI: -0.02 to 0.32, p = 0.09), and isoleucine (ß = 0.13, 95% CI: -0.08 to 0.34, p = 0.24). In contrast, T2D IVs were positively associated with each BCAA, i.e., valine (ß = 0.08 per SD change in levels per log-odds change in T2D, 95% CI: 0.05 to 0.10, p = 1.8 × 10-9 ), leucine (ß = 0.06, 95% CI: 0.04 to 0.09, p = 4.5 × 10-8 ), and isoleucine (ß = 0.06, 95% CI: 0.04 to 0.08, p = 2.8 × 10-8 ). CONCLUSIONS: These data suggest that the BCAAs are not mediators of T2D risk but are biomarkers of diabetes.

Identification of Clinical Drivers of Left Atrial Enlargement Through Genomics of Left Atrial Size.

BACKGROUND: Greater left atrial size is associated with a higher incidence of cardiovascular disease and mortality, but the full spectrum of diagnoses associated with left atrial enlargement in sex-stratified clinical populations is not well known. Our study sought to identify genetic risk mechanisms affecting left atrial diameter (LAD) in a clinical cohort. METHODS: Using Vanderbilt deidentified electronic health record, we studied 6163 females and 5993 males of European ancestry who had at least 1 LAD measure and available genotyping. A sex-stratified polygenic score was constructed for LAD variation and tested for association against 1680 International Classification of Diseases code-based phenotypes. Two-sample univariable and multivariable Mendelian randomization approaches were used to assess etiologic relationships between candidate associations and LAD. RESULTS: A phenome-wide association study identified 25 International Classification of Diseases code-based diagnoses in females and 11 in males associated with a polygenic score of LAD (false discovery rate q<0.01), 5 of which were further evaluated by Mendelian randomization (waist circumference [WC], atrial fibrillation, heart failure, systolic blood pressure, and coronary artery disease). Sex-stratified differences in the genetic associations between risk factors and a polygenic score for LAD were observed (WC for females; heart failure, systolic blood pressure, atrial fibrillation, and WC for males). By multivariable Mendelian randomization, higher WC remained significantly associated with larger LAD in females, whereas coronary artery disease, WC, and atrial fibrillation remained significantly associated with larger LAD in males. CONCLUSIONS: In a clinical population, we identified, by genomic approaches, potential etiologic risk factors for larger LAD. Further studies are needed to confirm the extent to which these risk factors may be modified to prevent or reverse adverse left atrial remodeling and the extent to which sex modifies these risk factors.

Genotype-based "virtual" metabolomics in a clinical biobank identifies novel metabolite-disease associations.

Circulating metabolites act as biomarkers of dysregulated metabolism, and may inform disease pathophysiology. A portion of the inter-individual variability in circulating metabolites is influenced by common genetic variation. We evaluated whether a genetics-based "virtual" metabolomics approach can identify novel metabolite-disease associations. We examined the association between polygenic scores for 726 metabolites (derived from OMICSPRED) with 1,247 clinical phenotypes in 57,735 European ancestry and 15,754 African ancestry participants from the BioVU DNA Biobank. We probed significant relationships through Mendelian randomization (MR) using genetic instruments constructed from the METSIM Study, and validated significant MR associations using independent GWAS of candidate phenotypes. We found significant associations between 336 metabolites and 168 phenotypes in European ancestry and 107 metabolites and 56 phenotypes among African ancestry. Of these metabolite-disease pairs, MR analyses confirmed associations between 73 metabolites and 53 phenotypes in European ancestry. Of 22 metabolite-phenotype pairs evaluated for replication in independent GWAS, 16 were significant (false discovery rate p<0.05). Validated findings included the metabolites bilirubin and X-21796 with cholelithiasis, phosphatidylcholine(16:0/22:5n3,18:1/20:4) and arachidonate(20:4n6) with inflammatory bowel disease and Crohn's disease, and campesterol with coronary artery disease and myocardial infarction. These associations may represent biomarkers or potentially targetable mediators of disease risk.

Association of alpha-aminoadipic acid with cardiometabolic risk factors in healthy and high-risk individuals.

Introduction: Plasma levels of the metabolite alpha-aminoadipic acid (2-AAA) have been associated with risk of type 2 diabetes (T2D) and atherosclerosis. However, little is known about the relationship of 2-AAA to other cardiometabolic risk markers in pre-disease states, or in the setting of comorbid disease. Methods: We measured circulating 2-AAA using two methods in 1) a sample of 261 healthy individuals (2-AAA Study), and 2) in a sample of 134 persons comprising 110 individuals with treated HIV, with or without T2D, a population at high risk of metabolic disease and cardiovascular events despite suppression of circulating virus, and 24 individuals with T2D without HIV (HATIM Study). We examined associations between plasma 2-AAA and markers of cardiometabolic health within each cohort. Results and discussion: We observed differences in 2-AAA by sex and race in both cohorts, with higher levels observed in men compared with women, and in Asian compared with Black or white individuals (P<0.05). There was no significant difference in 2-AAA by HIV status within individuals with T2D in the HATIM Study. We confirmed associations between 2-AAA and dyslipidemia in both cohorts, where high 2-AAA associated with low HDL cholesterol (P<0.001) and high triglycerides (P<0.05). As expected, within the cohort of people with HIV, 2-AAA was higher in the setting of T2D compared to pre-diabetes or normoglycemia (P<0.001). 2-AAA was positively associated with body mass index (BMI) in the 2-AAA Study, and with waist circumference and measures of visceral fat volume in HATIM (all P<0.05). Further, 2-AAA associated with increased liver fat in persons with HIV (P<0.001). Our study confirms 2-AAA as a marker of cardiometabolic risk in both healthy individuals and those at high cardiometabolic risk, reveals relationships with adiposity and hepatic steatosis, and highlights important differences by sex and race. Further studies are warranted to establish molecular mechanisms linking 2-AAA to disease in other high-risk populations.

The use of locum doctors in the NHS - results of a national survey of NHS Trusts in England.

BACKGROUND: Locum working in healthcare organisations has benefits for individual doctors and organisations but there are concerns about the impact of locum working on continuity of care, patient safety, team function and cost. We conducted a national survey of NHS Trusts in England to explore locum work, and better understand why and where locum doctors were needed; how locum doctors were engaged, supported, perceived and managed; and any changes being made in the way locums are used. METHODS: An online survey was sent to 191 NHS Trusts and 98 were returned (51%) including 66 (67%) acute hospitals, 26 (27%) mental health and six (6%) community health providers. Data was analysed using frequency tables, t-tests and correlations. Free-text responses were analysed using thematic analysis. RESULTS: Most NHS Trusts use locums frequently and for varying lengths of time. Trusts prefer to use locums from internal locum banks but frequently rely on locum agencies. The benefits of using locums included maintaining workforce capacity and flexibility. Importantly, care provided by locums was generally viewed as the same or somewhat worse when compared to care provided by permanent doctors. The main disadvantages of using locum agencies included cost, lack of familiarity and impact on organisational development. Some respondents felt that locums could be unreliable and less likely to be invested in quality improvement. NHS Trusts were broadly unfamiliar with the national guidance from NHS England for supporting locums and there was a focus on processes like compliance checks and induction, with less focus on providing feedback and support for appraisal. CONCLUSIONS: Locum doctors provide a necessary service within NHS Trusts to maintain workforce capacity and provide patient care. There are potential issues related to the way that locums are perceived, utilised, and supported which might impact the quality of the care that they provide. Future research should consider the arrangements for locum working and the performance of locums and permanent doctors, investigating the organisation of locums in order to achieve safe and high-quality care for patients.

Locum doctors in English general practices: evidence from a national survey.

BACKGROUND: Locum doctors give practices flexibility to deliver patient services but there are concerns about the impact of locum working on continuity of care, patient safety, team function, and cost. AIM: To explore locum working in English general practices, and understand why and where locum doctors were needed and how they were engaged, supported, perceived, and managed. DESIGN AND SETTING: An online survey was sent to 3745 practices. METHOD: Quantitative responses were analysed using frequency tables, t-tests, and correlations. Free-text responses were analysed using thematic analysis. RESULTS: In total, 605 (16.2%) responses were returned between June and December 2021. Practices made frequent use of locums, preferring regular locums familiar with processes and patients. Disadvantages of agency locums included cost, lack of patient familiarity, and impact on continuity of care. Care provided by locums was generally viewed as the same but sometimes worse compared with permanent GPs. Some practices reported that locums did not always perform the full range of duties, resulting in increased workload for other staff. Practices were largely unfamiliar with national guidance for organisations engaging locums, and, although processes such as verifying documentation were conducted, far fewer responders reported providing feedback, support for revalidation, or professional development. CONCLUSION: Locum working is an essential part of English general practice, but this research raises some concerns about the robustness of arrangements for locum working and the impact on quality and safety of care. Further research is needed about the clinical practice and performance of locums, and to explore how locum working can be organised in ways that assure safe and high-quality care.

Genetics of Pulmonary Pressure and Right Ventricle Stress Identify Diabetes as a Causal Risk Factor.

Background Epidemiologic studies have identified risk factors associated with pulmonary hypertension and right heart failure, but causative drivers of pulmonary hypertension and right heart adaptation are not well known. We sought to leverage unbiased genetic approaches to determine clinical conditions that share genetic architecture with pulmonary pressure and right ventricular dysfunction. Methods and Results We leveraged Vanderbilt University's deidentified electronic health records and DNA biobank to identify 14 861 subjects of European ancestry who underwent at least 1 echocardiogram with available estimates of pulmonary pressure and right ventricular function. Analyses of the study were performed between 2020 and 2022. The final analytical sample included 14 861 participants (mean [SD] age, 63 [15] years and mean [SD] body mass index, 29 [7] kg/m2). An unbiased phenome-wide association study identified diabetes as the most statistically significant clinical International Classifications of Diseases, Ninth Revision (ICD-9) code associated with polygenic risk for increased pulmonary pressure. We validated this finding further by finding significant associations between genetic risk for diabetes and a related condition, obesity, with pulmonary pressure estimate. We then used 2-sample univariable Mendelian randomization and multivariable Mendelian randomization to show that diabetes, but not obesity, was independently associated with genetic risk for increased pulmonary pressure and decreased right ventricle load stress. Conclusions Our findings show that genetic risk for diabetes is the only significant independent causative driver of genetic risk for increased pulmonary pressure and decreased right ventricle load stress. These findings suggest that therapies targeting genetic risk for diabetes may also potentially be beneficial in treating pulmonary hypertension and right heart dysfunction.

Association of alpha-aminoadipic acid (2-AAA) with cardiometabolic risk factors in healthy and high-risk individuals.

Plasma levels of the metabolite alpha-aminoadipic acid (2-AAA) have been associated with risk of type 2 diabetes (T2D) and atherosclerosis. However, little is known about the relationship of 2-AAA to other cardiometabolic risk markers in pre-disease states, or in the setting of comorbid disease. We measured circulating 2-AAA using two methods in 1) a sample of 261 healthy individuals (2-AAA Study), and 2) in a sample of 134 persons comprising 110 individuals with treated HIV, with or without T2D, a population at high risk of metabolic disease and cardiovascular events despite suppression of circulating virus, and 24 individuals with T2D without HIV (HATIM Study). We examined associations between plasma 2-AAA and markers of cardiometabolic health within each cohort. We observed differences in 2-AAA by sex and race in both cohorts, with higher levels observed in men compared with women, and in Asian compared with Black or white individuals (P<0.05). There was no significant difference in 2-AAA by HIV status within individuals with T2D in the HATIM Study. We confirmed associations between 2-AAA and dyslipidemia in both cohorts where high 2-AAA associated with low HDL cholesterol (P<0.001) and high triglycerides (P<0.05). As expected, within the cohort of people with HIV, 2-AAA was higher in the setting of T2D compared to pre-diabetes or normoglycemia (P<0.001). 2-AAA was positively associated with body mass index (BMI) in the 2-AAA Study, and with waist circumference and measures of visceral fat volume in HATIM (all P<0.05). Further, 2-AAA associated with increased liver fat in persons with HIV (P<0.001). Our study confirms 2-AAA as a marker of cardiometabolic risk in both healthy individuals and those at high cardiometabolic risk, reveals relationships with adiposity and hepatic steatosis, and highlights important differences by sex and race. Further studies are warranted to establish molecular mechanisms linking 2-AAA to disease in other high-risk populations.

Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease.

Cardiometabolic disease comprises cardiovascular and metabolic dysfunction and underlies the leading causes of morbidity and mortality, both within the United States and worldwide. Commensal microbiota are implicated in the development of cardiometabolic disease. Evidence suggests that the microbiome is relatively variable during infancy and early childhood, becoming more fixed in later childhood and adulthood. Effects of microbiota, both during early development, and in later life, may induce changes in host metabolism that modulate risk mechanisms and predispose toward the development of cardiometabolic disease. In this review, we summarize the factors that influence gut microbiome composition and function during early life and explore how changes in microbiota and microbial metabolism influence host metabolism and cardiometabolic risk throughout life. We highlight limitations in current methodology and approaches and outline state-of-the-art advances, which are improving research and building toward refined diagnosis and treatment options in microbiome-targeted therapies.

Use of locum doctors in NHS trusts in England: analysis of routinely collected workforce data 2019-2021.

OBJECTIVES: Temporary doctors, known as locum doctors, play an important role in the delivery of care in the National Health Service (NHS); however, little is known about the extent of locum use in NHS trusts. This study aimed to quantify and describe locum use for all NHS trusts in England in 2019-2021. SETTING: Descriptive analyses of data on locum shifts from all NHS trusts in England in 2019-2021. Weekly data were available for the number of shifts filled by agency and bank staff and the number of shifts requested by each trust. Negative binomial models were used to investigate the association between the proportion of medical staffing provided by locums and NHS trust characteristics. RESULTS: In 2019, on average 4.4% of total medical staffing was provided by locums, but this varied substantially across trusts (25th-75th centile=2.2%-6.2%). Over time, on average two-thirds of locum shifts were filled by locum agencies and a third by trusts' staff banks. On average, 11.3% of shifts requested were left unfilled. In 2019-2021, the mean number of weekly shifts per trust increased by 19% (175.2-208.6) and the mean number of weekly unfilled shifts per trust increased by 54% (32.7 to 50.4). Trusts rated by the Care Quality Commission (CQC) as inadequate or requiring improvement (incidence rate ratio=1.495; 95% CI 1.191 to 1.877), and smaller trusts had a higher use of locums. Large variability was observed across regions for use of locums, proportion of shifts filled by locum agencies and unfilled shifts. CONCLUSIONS: There were large variations in the demand for and use of locum doctors in NHS trusts. Trusts with poor CQC ratings and smaller trusts appear to use locum doctors more intensively compared with other trust types. Unfilled shifts were at a 3-year high at the end of 2021 suggesting increased demand which may result from growing workforce shortages in NHS trusts.

Second ionization constant of sulfuric acid in H2O and D2O from 150 to 300 °C at p = 11.5 MPa using flow AC conductivity.

A custom-built flow-through AC conductivity instrument was used to measure the deuterium isotope effect on the ionization quotient of bisulfate from 150 to 300 °C, at p = 11.5 MPa. Standardized solutions of KCl, HCl, KOH, KHSO4, K2SO4, and H2SO4 were prepared in light and heavy waters and their conductivities were measured and fitted with the Quint-Viallard conductivity model to obtain single ion conductivities at infinite dilution for K+, Cl-, H+, OH-, HSO4-, and SO42-. These are the first conductivities of DSO4- and SO42- measured in heavy water at any temperature, and the first ionization constants for bisulfate reported in heavy water above 225 °C. The deuterium isotope effect on the chemical equilibrium constant, ΔpK2a = pK2a,D - pK2a,H, was found to increase with temperature, in contrast to the behaviour seen for other simple oxyacids.

Sex Differences in Fatty Acid Metabolism and Blood Pressure Response to Dietary Salt in Humans.

Salt sensitivity is a trait in which high dietary sodium (Na+) intake causes an increase in blood pressure (BP). We previously demonstrated that in the gut, elevated dietary Na+ causes dysbiosis. The mechanistic interplay between excess dietary Na+-induced alteration in the gut microbiome and sex differences is less understood. The goal of this study was to identify novel metabolites in sex differences and blood pressure in response to a high dietary Na+ intake. We performed stool and plasma metabolomics analysis and measured the BP of human volunteers with salt intake above or below the American Heart Association recommendations. We also performed RNA sequencing on human monocytes treated with high salt in vitro. The relationship between BP and dietary Na+ intake was different in women and men. Network analysis revealed that fatty acids as top subnetworks differentially changed with salt intake. We found that women with high dietary Na+ intake have high levels of arachidonic acid related metabolism, suggesting a role in sex differences of the blood pressure response to Na+. The exposure of monocytes to high salt in vitro upregulates the transcription of fatty acid receptors and arachidonic acid-related genes. These findings provide potentially novel insights into metabolic changes underlying gut dysbiosis and inflammation in salt sensitivity of BP.

Individuality and ethnicity eclipse a short-term dietary intervention in shaping microbiomes and viromes.

Many diseases linked with ethnic health disparities associate with changes in microbial communities in the United States, but the causes and persistence of ethnicity-associated microbiome variation are not understood. For instance, microbiome studies that strictly control for diet across ethnically diverse populations are lacking. Here, we performed multiomic profiling over a 9-day period that included a 4-day controlled vegetarian diet intervention in a defined geographic location across 36 healthy Black and White females of similar age, weight, habitual diets, and health status. We demonstrate that individuality and ethnicity account for roughly 70% to 88% and 2% to 10% of taxonomic variation, respectively, eclipsing the effects a short-term diet intervention in shaping gut and oral microbiomes and gut viromes. Persistent variation between ethnicities occurs for microbial and viral taxa and various metagenomic functions, including several gut KEGG orthologs, oral carbohydrate active enzyme categories, cluster of orthologous groups of proteins, and antibiotic-resistant gene categories. In contrast to the gut and oral microbiome data, the urine and plasma metabolites tend to decouple from ethnicity and more strongly associate with diet. These longitudinal, multiomic profiles paired with a dietary intervention illuminate previously unrecognized associations of ethnicity with metagenomic and viromic features across body sites and cohorts within a single geographic location, highlighting the importance of accounting for human microbiome variation in research, health determinants, and eventual therapies. Trial Registration: ClinicalTrials.gov ClinicalTrials.gov Identifier: NCT03314194.