Venous thromboembolism in adults screened for Sickle Cell Trait: a population based cohort study with nested case-control analysis

Objective: To determine whether sickle cell carriers (‘sickle cell trait’) have an increased risk of venous thromboembolism (VTE). Design: Cohort study with nested case-control analysis. Setting: General population with data from 609 UK general practices in the Clinical Practice Research Datalink (CPRD). Participants: All individuals registered with a CPRD general practice between 1998 and 2013, with a medical record of screening for sickle cell between 18 and 75 years of age. Main outcomes measures: Incidence of VTE per 10,000 person-years among sickle cell carriers and non-carriers; and adjusted odds ratio (OR) for VTE among sickle cell carriers compared to non-carriers. Results: We included 30,424 individuals screened for sickle cell, with a follow-up time of 179,503 person-years, identifying 55 VTEs in 6,758 sickle cell carriers and 125 VTEs in 23,666 non-carriers. VTE incidence amongst sickle cell carriers (14.9/10,000 person-years; 95% CI: 11.4 to 19.4) was significantly higher than non-carriers (8.8/10,000 person-years; 95% CI: 7.4 to 10.4). Restricting analysis to confirmed non-carriers was non-significant, but performed on a small sample. In the case-control analysis (180 cases matched to 1,775 controls by age and gender), sickle cell carriers remained at increased risk of VTE after adjusting for body mass index, pregnancy, smoking status and ethnicity (OR 1.78, 95% CI: 1.18 to 2.69, p-value 0.006 ), with the greatest risk for pulmonary embolism (OR 2.27, 95% CI: 1.17 to 4.39, p-value 0.011). Conclusions: Although absolute numbers are small, in a general population screened for sickle cell, carriers have a higher incidence and risk of VTE, particularly pulmonary embolism, than non-carriers. Clinicians should be aware of this elevated risk in the clinical care of sickle cell carriers, or when discussing carrier screening, and explicitly attend to modifiable risk factors for VTE in these individuals. More complete primary care coding of carrier status could improve analysis

Healthcare Utilisation, Morbidities and Alcohol Use Monitoring Prior to Alcoholic Psychosis Diagnosis

Aims The aim of this study was to describe healthcare utilisation, morbidities and monitoring of alcohol use in patients prior to a diagnosis of alcoholic psychosis in order to inform the early identification of patients at risk. Methods Using linked general practice and hospitalisation data in England (April 1997 to June 2014), we identified 1731 individuals (≥18 years) with a clinical recorded diagnosis of alcoholic psychosis and 17,310 matched controls without the disorder, we examined all prior general practitioner (family doctor) visits, hospitalisations, medically recorded morbidities and alcohol assessment/interventions records. Poisson regression models were used to compare rates of healthcare utilisation in people with alcoholic psychosis to those without. Logistic regression models were used to evaluate the association between alcoholic psychosis and prior morbidities. Results Patients with alcoholic psychosis showed increased levels of healthcare utilisation at least 5 years prior to their diagnosis. The most common reasons for prior healthcare visits were seizures and injuries and there was >4-fold higher rate of seizures, unintentional injuries and self-harm incidents among these patients up to 10 years prior to diagnosis, compared to the control population. A high proportion (78%) of patients had their alcohol consumption recorded, 50% had a record of heavy drinking but only one in five had any evidence of receiving an alcohol-related intervention. Conclusion Patients present more often with seizures and injuries than the general population several years prior to a diagnosis of alcoholic psychosis. These visits represent opportunities for preventive action and imply that we may be missing opportunities to intervene

Sex and age differences in the early identification and treatment of alcohol use: a population-based study of patients with alcoholic cirrhosis

Aim: To estimate sex differences in health-care utilization among harmful/hazardous drinkers in the period before alcoholic cirrhosis diagnosis, and estimate sex differences in the extent to which alcohol use and brief alcohol interventions were documented for these individuals compared with a control cohort. Design: Retrospective study using linked general practice and hospital admissions data in England. Setting: Three hundred and fifty-seven general practitioner (GP) practices in England. Participants: A total of 2479 individuals with alcoholic cirrhosis (mean age at diagnosis = 56years), of whom 67% were men; and 24 790 controls without the disease. Measurements: Rates of primary care visits and hospital admissions prior to the diagnosis of alcoholic cirrhosis for men and women, and the proportion of men and women with alcohol consumption and/or alcohol brief intervention documented in their medical record. Findings: Compared with the general population, patients with alcoholic cirrhosis used primary and secondary health-care services more frequently in the years leading up to their diagnosis. In the years prior to diagnosis, men used primary and secondary health-care services more than did women (P for sex interaction P < 0.0001). Men were more likely than women to have their alcohol use recorded [odds ratio (OR) men = 1.96, 95% confidence interval (CI) = 1.7–2.3; women = 1.63, 95% CI = 1.4–1.8, P for sex interaction P < 0.0017]. By contrast, alcohol interventions were recorded more commonly among women (OR men = 4.3, 95% CI = 3.7–4.9; women = 5.8, 95% CI = 4.7–6.9, P for sex interaction = 0.07), although less common with increasing age (P for age interaction = 0.009). Conclusions: In the United Kingdom, prior to alcoholic cirrhosis diagnosis, excess health-care utilization is higher in men than women and men are more likely than women to have their alcohol use recorded. However, women appear to be more likely than men to receive alcohol brief interventions

Slight ligand modifications within multitopic linear hydroxamates promotes connectivity differences in Cu(II) 1-D coordination polymers

© 2021 The Authors. Published by Royal Society of Chemistry. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1039/D1CE00807BThe novel multitopic ligands N-hydroxy-4-((2-hydroxy-3-methoxybenzyl)amino)benzamide (L3H3) and N-hydroxy-4-((2- hydroxybenzyl)amino)benzamide (L4H3) have been synthesised through the Schiff base coupling and subsequent reduction of 4-aminophenylhydroxamic acid and either o-vanillin (to give L3H3) or 2-hydroxybenzaldehyde (to give L4H3). These linear multitopic ligands bind Cu(II) centres at both the hydroxamate and phenol ends to form the 1-D coordination polymers [Cu(II)(L3H2)2]n (1) and {[Cu(II)(L4H2)2].2MeOH}n (2). Slight differences in the structures of L3H3 and L4H3 lead to significant extended connectivity changes upon Cu(II) metalation that are exampled by a 27% decrease in intra-chain Cu(II)…Cu(II) distance upon moving from 1 to 2. The significant conformation and metal binding differences shown by L3H2 and L4H2 in 1 and 2 respectively have been rationalised using density functional theory (DFT) calculations. Hirschfeld surface analysis has been employed to assess and visualise the intra- and intermolecular interactions in both complexes.Published onlin

Persistence of health inequalities in childhood injury in the UK: a population-based cohort study of children under 5

BACKGROUND: Injury is a significant cause of childhood death and can result in substantial long-term disability. Injuries are more common in children from socio-economically deprived families, contributing to health inequalities between the most and least affluent. However, little is known about how the relationship between injuries and deprivation has changed over time in the UK. METHODS: We conducted a cohort study of all children under 5 registered in one of 495 UK general practices that contributed medical data to The Health Improvement Network database between 1990–2009. We estimated the incidence of fractures, burns and poisonings by age, sex, socio-economic group and calendar period and adjusted incidence rate ratios (IRR) comparing the least and most socio-economically deprived areas over time. Estimates of the UK annual burden of injuries and the excess burden attributable to deprivation were derived from incidence rates. RESULTS: The cohort of 979,383 children experienced 20,804 fractures, 15,880 burns and 10,155 poisonings, equating to an incidence of 75.8/10,000 person-years (95% confidence interval 74.8–76.9) for fractures, 57.9 (57.0–58.9) for burns and 37.3 (35.6–38.0) for poisonings. Incidence rates decreased over time for burns and poisonings and increased for fractures (p<0.001 test for trend for each injury). They were significantly higher in more deprived households (IRR test for trend p<0.001 for each injury type) and these gradients persisted over time. We estimate that 865 fractures, 3,763 burns and 3,043 poisonings could be prevented each year in the UK if incidence rates could be reduced to those of the most affluent areas. CONCLUSIONS: The incidence of burns and poisonings declined between 1990 and 2009 but increased for fractures. Despite these changes, strong socio-economic inequalities persisted resulting in an estimated 9,000 additional medically-attended injuries per year in under-5s

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

Sticky Stories: Joe Orton, Queer History, Queer Dramaturgy

This paper investigates the resonances of Orton’s work for contemporary queer audiences. By presenting potential reasons for the rise and fall in popularity and visibility of Orton’s work for queer and gay audiences through the 1980s and 1990s, this paper looks to the queer context in which Joe Orton’s work developed in order to explore the queer social history into which it fits.  This sense of queer history is linked to contemporary notions of queer theorising about temporalities and queer dramaturgy, which offers potentially novel ways of engaging with Orton’s work queerly without twisting it to fit a ‘neat’ reading, in part because such readings tend to ‘smooth out’ the more difficult elements of the work.  In particular, the paper explores the theatrical form of farce, often articulated as conservative, in relation to queer positions, which are quite the opposite.  In so doing, the paper, by way of queer temporalities and work on queer dramaturgies, sketches out a reading strategy that does not ignore Orton’s more difficult or stickier elements, in particular his treatment of women and race

Comparing exercise interventions to increase persistence with physical exercise and sporting activity among people with hypertension or high normal blood pressure: study protocol for a randomised controlled trial

BACKGROUND: Increasing physical activity is known to have health benefits for people with hypertension and related conditions. Current general practitioner referrals for gym-based exercise increase physical activity but meta-analyses show that while these are effective the absolute health risk reduction is small due to patients failing to maintain activity levels over time. This study assesses the effectiveness of two sports-oriented interventions that are intended to bridge the intention-behaviour gap and thus increase the likelihood of sustained increases in physical activity. METHODS/DESIGN: Four-arm randomised controlled trial. The study tests two types of intervention that are intended to increase physical activity among currently inactive 18- to 74-year-old people with hypertension or high-normal blood pressure. This study will assess the effectiveness of a 12-week sports-oriented exercise programme, the efficacy of a web-delivered self-help tool to promote and support sports participation and healthy behaviour change and the effect of these interventions in combination. The control arm will be a standard care general practitioner referral for gym-based exercise. Participants will be allocated using block randomisation. The first author and primary analyst is blinded to participant allocation. The primary outcome measures will be time spent in physical activity assessed in metabolic equivalent minutes per week using the International Physical Activity Questionnaire 1 year after commencement of the intervention. Secondary outcomes include increased involvement in sporting activity and biomedical health outcomes including change in body mass index, and waist and hip measurement and reductions in blood pressure. DISCUSSION: If proven to be superior to general practitioner referrals for gym-based exercise, these sports-oriented interventions would constitute low-cost alternatives. The next stage would be a full economic evaluation of the interventions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71952900 (7 June 2013)

Independent Risk Factors for Injury in Pre-School Children: Three Population-Based Nested Case-Control Studies Using Routine Primary Care Data

Background: Injuries in childhood are largely preventable yet an estimated 2,400 children die every day because of injury and violence. Despite this, the factors that contribute to injury occurrence have not been quantified at the population scale using primary care data. We used The Health Improvement Network (THIN) database to identify risk factors for thermal injury, fractures and poisoning in pre-school children in order to inform the optimal delivery of preventative strategies. Methods: We used a matched, nested case-control study design. Cases were children under 5 with a first medically recorded injury, comprising 3,649 thermal injury cases, 4,050 fracture cases and 2,193 poisoning cases, matched on general practice to 94,620 control children. Results: Younger maternal age and higher birth order increased the odds of all injuries. Children’s age of highest injury risk varied by injury type; compared with children under 1 year, thermal injuries were highest in those age 1-2 (OR = 2.43, 95%CI 2.23–2.65), poisonings in those age 2-3 (OR = 7.32, 95%CI 6.26–8.58) and fractures in those age 3-5 (OR = 3.80, 95%CI 3.42–4.23). Increasing deprivation was an important modifiable risk factor for poisonings and thermal injuries (tests for trend p#0.001) as were hazardous/harmful alcohol consumption by a household adult (OR = 1.73, 95%CI 1.26–2.38 and OR = 1.39, 95%CI 1.07–1.81 respectively) and maternal diagnosis of depression (OR = 1.45, 95%CI 1.24–1.70 and OR = 1.16, 95%CI 1.02–1.32 respectively). Fracture was not associated with these factors, however, not living in single-adult household reduced the odds of fracture (OR = 0.88, 95%CI 0.82–0.95). Conclusions: Maternal depression, hazardous/harmful adult alcohol consumption and socioeconomic deprivation represent important modifiable risk factors for thermal injury and poisoning but not fractures in preschool children. Since these risk factors can be ascertained from routine primary care records, pre-school children’s frequent visits to primary care present an opportunity to reduce injury risk by implementing effective preventative interventions from existing national guidelines

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication