Automating incidence and prevalence analysis in open cohorts.

MOTIVATION: Data is increasingly used for improvement and research in public health, especially administrative data such as that collected in electronic health records. Patients enter and exit these typically open-cohort datasets non-uniformly; this can render simple questions about incidence and prevalence time-consuming and with unnecessary variation between analyses. We therefore developed methods to automate analysis of incidence and prevalence in open cohort datasets, to improve transparency, productivity and reproducibility of analyses. IMPLEMENTATION: We provide both a code-free set of rules for incidence and prevalence that can be applied to any open cohort, and a python Command Line Interface implementation of these rules requiring python 3.9 or later. GENERAL FEATURES: The Command Line Interface is used to calculate incidence and point prevalence time series from open cohort data. The ruleset can be used in developing other implementations or can be rearranged to form other analytical questions such as period prevalence. AVAILABILITY: The command line interface is freely available from https://github.com/THINKINGGroup/analogy_publication .

Using Repeated Measurements to Predict Cardiovascular Risk in Patients With Type 2 Diabetes Mellitus.

The QRISK cardiovascular disease (CVD) risk assessment model is not currently optimized for patients with type 2 diabetes mellitus (T2DM). We aim to identify if the abundantly available repeatedly measured data for patients with T2D improves the predictive capability of QRISK to support the decision-making process regarding CVD prevention in patients with T2DM. We identified patients with T2DM aged 25 to 85, not on statin treatment and without pre-existing CVD from the IQVIA Medical Research Data United Kingdom primary care database and then followed them up until the first diagnosis of CVD, ischemic heart disease, or stroke/transient ischemic attack. We included traditional, nontraditional risk factors and relevant treatments for our analysis. We then undertook a Cox's hazards model accounting for time-dependent covariates to estimate the hazard rates for each risk factor and calculated a 10-year risk score. Models were developed for males and females separately. We tested the performance of our models using validation data and calculated discrimination and calibration statistics. The study included 198,835 (180,143 male with 11,976 outcomes and 90,466 female with 8,258 outcomes) patients. The 10-year predicted survival probabilities for females was 0.87 (0.87 to 0.87), whereas the observed survival estimates from the Kaplan-Meier curve for all female models was 0.87 (0.86 to 0.87). The predicted and observed survival estimates for males were 0.84 (0.84 to 0.84) and 0.84 (0.83 to 0.84) respectively. The Harrell's C-index of all female models and all male models were 0.71 and 0.69 respectively. We found that including time-varying repeated measures, only mildly improved CVD risk prediction for T2DM patients in comparison to the current practice standard. We advocate for further research using time-varying data to identify if the involvement of further covariates may improve the accuracy of currently accepted prediction models.

Prodromal symptoms of rheumatoid arthritis in a primary care database: variation by ethnicity and socioeconomic status.

OBJECTIVES: To assess whether prodromal symptoms of rheumatoid arthritis (RA), as recorded in the Clinical Practice Research Datalink Aurum (CPRD) database of English primary care records, differ by ethnicity and socioeconomic status. METHODS: A cross-sectional study to determine the coding of common symptoms (≥0.1% in the sample) in the 24 months preceding RA diagnosis in CPRD Aurum, recorded between January 1st 2004 to May 1st 2022. Eligible cases were adults with a code for RA diagnosis. For each symptom, a logistic regression was performed with the symptom as dependent variable, and ethnicity and socioeconomic status as independent variables. Results were adjusted for sex, age, BMI, and smoking status. White ethnicity and the highest socioeconomic quintile were comparators. RESULTS: In total, 70115 cases were eligible for inclusion, of which 66.4% female. Twenty-one symptoms were coded in > 0.1% of cases so were included in the analysis. Patients of South Asian ethnicity had higher frequency of codes for several symptoms, with the largest difference by odds ratio being muscle cramps (OR 1.71, 1.44-2.57) and shoulder pain (1.44, 1.25-1.66). Patients of Black ethnicity had higher prevalence of several codes including unintended weight loss (2.02, 1.25-3.28) and ankle pain (1.51, 1.02-2.23). Low socioeconomic status was associated with morning stiffness (1.74, 1.08-2.80) and falls (1.37, 2.03-1.82). CONCLUSION: There are significant differences in coded symptoms between demographic groups, which must be considered in clinical practice in diverse populations and to avoid algorithmic bias in prediction tools derived from routinely collected healthcare data.

Health effects associated with exposure to intimate partner violence against women and childhood sexual abuse: a burden of proof study.

The health impacts of intimate partner violence against women and childhood sexual abuse are not fully understood. Here we conducted a systematic review by comprehensively searching seven electronic databases for literature on intimate partner violence-associated and childhood sexual abuse-associated health effects. Following the burden of proof methodology, we evaluated the evidence strength linking intimate partner violence and/or childhood sexual abuse to health outcomes supported by at least three studies. Results indicated a moderate association of intimate partner violence with major depressive disorder and with maternal abortion and miscarriage (63% and 35% increased risk, respectively). HIV/AIDS, anxiety disorders and self-harm exhibited weak associations with intimate partner violence. Fifteen outcomes were evaluated for their relationship to childhood sexual abuse, which was shown to be moderately associated with alcohol use disorders and with self-harm (45% and 35% increased risk, respectively). Associations between childhood sexual abuse and 11 additional health outcomes, such as asthma and type 2 diabetes mellitus, were found to be weak. Although our understanding remains limited by data scarcity, these health impacts are larger in magnitude and more extensive than previously reported. Renewed efforts on violence prevention and evidence-based approaches that promote healing and ensure access to care are necessary.

Health outcomes in those who have been victims of knife crime: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Knife-enabled crime is a UK public health issue leading to substantial impacts on society, victims and their families, as well as additional strain on the healthcare system. Despite the increase in knife-enabled crime and the overwhelming consequences, there is a lack of comprehensive studies exploring the long-term health outcomes of knife crime victims in the UK. The research gap hinders the development of more targeted secondary preventative interventions, resource allocation and public awareness campaigns. This systematic review aims to identify the long-term health outcomes of knife crime victims, therefore providing valuable knowledge for stakeholders, health practitioners and policymakers for a more effective public health response. METHODS AND ANALYSIS: A comprehensive search strategy was developed, focusing on four key concepts: study design, knife-related offences, outcomes and risk. Databases being searched include MEDLINE, EMBASE, PsycINFO, ProQuest Criminology Collection, Web of Science Core Collection, Google Scholar and OpenGrey. Reference lists and forward citations will be inspected for further suitable literature. The study selection will involve two independent reviewers screening the studies from the search, with disagreements resolved by a third reviewer. All UK quantitative research on long-term health outcomes of knife crime victims will be included in the review. Covidence will be used to efficiently manage data. A data extraction form has been developed which will summarise key aspects of each study that will be included in the review. Methodological Index for Non-Randomised Studies quality assessment checklist will be used to assess the studies and the Newcastle-Ottawa Scale will assess the risk of bias in each study. Findings will be narratively synthesised, and if heterogeneity is sufficient, a meta-analysis will be conducted. ETHICS AND DISSEMINATION: Ethics approval is not required for this study as no original data will be collected. The results will be disseminated through a peer-reviewed publication and conference presentation.

Cardiometabolic screening and monitoring in patients prescribed antipsychotic drugs in primary care: A population-based cohort study.

BACKGROUND: This study aimed to investigate the level of guideline adherence for cardiometabolic health monitoring for patients prescribed antipsychotic medicines in UK primary care. METHODS: In this population-based retrospective open cohort study, we used dataset of patients from the IQVIA Medical Research Data (IMRD) database between 1st January 2003 to 31st December 2018. Clinical Read codes were used to identify a cohort of adult patients with a diagnosis of Schizophrenia and at least four prescriptions of an anti-psychotic medication within 12 months of diagnosis. We then extracted data in relation to monitoring of cardiometabolic parameters (body compositions, lipids, and glucose outcomes) at baseline, then at six weeks, 12 weeks, and then 12 months. The frequency of outcome monitoring was described using descriptive statistics. FINDINGS: A total of 11,435 patients were eligible and of them (n = 9707; 84·8%) were prescribed second-generation antipsychotics (SGAs). Only a small portion of the cohort (≈2·0%) received complete monitoring (at time points) for certain outcomes. Just over half the patients (n = 6599, 52%) had evidence of any cardiometabolic baseline testing for any of the study outcomes and the high majority had at least one abnormal lab value at baseline (n = 4627, 96·7%). INTERPRETATION: In UK primary care, cardiometabolic monitoring practices among patients prescribed antipsychotics remain suboptimal. There is a need to promote guideline adherence to prevent adverse outcomes in antipsychotic users.

Healthcare interventions for sex workers: protocol for a scoping review.

INTRODUCTION: Sex workers, who provide sexual or erotic acts in exchange for payment, often experience multiple disadvantages, including mental ill health and substance misuse. Mainstream healthcare services are generally not configured to facilitate engagement with sex workers and therefore, services are needed that are accessible to this population. The aim of this scoping review is to understand the evidence base for approaches, services and interventions that are aimed at addressing sex workers' health needs. METHODS AND ANALYSIS: Nine databases, CINAHL, Embase, EThOS, Google Scholar, Health Management Information Consortium, MEDLINE, ProQuest Dissertations and Theses, PsycINFO and Web of Science (Core Collection), will be searched, with results limited to English language publications and those published from 2003 onwards. De-duplication, study selection and data extraction will be conducted using Covidence software. Included studies will describe or evaluate approaches, services or interventions that address the health needs of sex workers who offer services that involve physical contact with a client. ETHICS AND DISSEMINATION: No ethical review is needed. The final report will be shared with Birmingham City Council as part of ongoing work and will be disseminated by peer-reviewed publication. STUDY REGISTRATION: Open Science Framework (doi: 10.17605/OSF.IO/N7WSX).

Seasonal variation of serum potassium and related prescription pattern: an ecological time series.

Aims To assess if ambient temperature-related effects on serum potassium levels impact clinical decision-making. Methods This study is an ecological time series consisiting of 1 218 453 adult patients with at least one ACE inhibitor (ACEI) prescription who participate in a large UK primary care dataset.Descriptive statistics and a quasi-Poisson regression model using time series data at regular time intervals (monthly) were undertaken to examine the association between potassium measurements and ACEI/potassium supplement prescriptions. RESULTS: It is noted that correlating with lower ambient temperature, serum potassium values follow a seasonal pattern; peaks in winter months and troughs in summer. During summer months, there are clear annual spikes in the number of potassium prescriptions suggesting a change in prescribing practice during periods of potentially spurious hyperkalaemia. The converse pattern is seen in the ACEI prescription proportion which spikes annually during the winter period with lower average ambient temperatures. Our time series modelling demonstrated that each one unit increase in potassium is associated with a 33% increased rate of ACEI prescriptions (risk ratio, RR 1.33; 95% CI 1.12 to 1.59) and 63% decreased rate of potassium supplements (RR 0.37; 95% CI 0.32 to 0.43). CONCLUSIONS: Our findings highlight the seasonal pattern in serum potassium and we observe a corresponding alteration in prescribing practice for potassium sensitive medications. These findings demonstrate the importance of educating clinicians on the presence of seasonal potassium variability in addition to standard measurement error, and its potential impact on their prescribing activity.

The risk of all-cause mortality associated with anxiety: a retrospective cohort study using 'The Health Improvement Network' database.

BACKGROUND: Anxiety is a prevalent condition with a substantial associated burden of morbidity. Previous literature investigating effects of anxiety on mortality rates has found conflicting results. This is in part due to inadequate consideration of comorbid depression as a confounder and analysing sub-types of anxiety together. The objective of this study was to compare mortality risks in people diagnosed with anxiety. METHODS: We undertook a retrospective cohort study using the 'The Health Improvement Network' database (a UK primary care dataset) between 1st January 2005 to 1st January 2018. 345 903 patients with anxiety (exposed group) were matched to 691 449 unexposed patients. Cox regression analyses were used to adjusted hazard ratios (HRs) for mortality risk. RESULTS: During the study period 18 962 patients (5·5%) died in the exposed group compared to 32 288 (4·7%) in the unexposed group. This translated into a crude HR for all of 1·14 (95% CI 1·12 - 1·16), which remained significant after adjustment for key co-variates (including depression) giving a final HR of 1·05 (95% CI 1·03 - 1·07). When broken down by sub-type of anxiety (10·3% (35, 581) had phobias, 82·7% (385,882) has 'other' types, and 7·0% (24,262) had stress related anxiety) there were markedly different effect sizes. The adjusted model for the stress-related anxiety sub-type demonstrated a HR of 0·88 (95% CI 0·80 - 0·97). Conversely, the HR was increased in 'other' sub-types to 1·07 (95% CI 1·05 - 1·09) and non-significant in phobia types of anxiety. CONCLUSION: A complex relationship is found between anxiety and mortality. The presence of anxiety slightly increased the risk of death, but this risk varies depending on the type of anxiety diagnosed.

Exposure to Domestic Abuse and the Subsequent Development of Atopic Disease in Women.

BACKGROUND: Exposure to domestic violence and abuse (DVA) is a global public health issue associated with substantial morbidity and mortality. There are few high-quality studies that assess the impact of DVA exposure on the development of atopic disease. OBJECTIVE: To examine the association between exposure to DVA and the subsequent development of atopy. METHODS: In this population-based, retrospective, open cohort study, we identified women with no history of atopic disease between January 1, 1995 and September 30, 2019 from IQVIA Medical Research Data, an anonymized UK primary care dataset. We used clinical codes to identify exposed patients (those with a code identifying exposure to DVA; n = 13,852) and unexposed patients (n = 49,036), who were matched by age and deprivation quintile. Cox proportional hazards regression was used to calculate hazard ratios (HRs) (with 95% CIs) of developing atopic disease: asthma, atopic eczema, or allergic rhinoconjunctivitis. RESULTS: During the study period, 967 exposed women (incidence rate, 20.10/1,000 person-years) developed atopic disease, compared with 2,607 unexposed women (incidence rate, 13.24/1,000 person-years). This translated to an adjusted HR of 1.52 (95% CI, 1.41-1.64) accounting for key confounders; asthma (adjusted HR = 1.69; 95% CI, 1.44-1.99), atopic eczema (adjusted HR = 1.40; 95% CI, 1.26-1.56), and allergic rhinoconjunctivitis (adjusted HR = 1.63; 95% CI, 1.45-1.84). CONCLUSIONS: Domestic violence and abuse is a significant global public health issue. These results demonstrate a significant associated risk for developing atopic disease. Public health approaches to the prevention and detection of DVA are necessary to reduce the associated ill health burden.

Ethical reporting of research on violence against women and children: a review of current practice and recommendations for future guidelines.

Changes in research practice during the COVID-19 pandemic necessitates renewed attention to ethical protocols and reporting for data collection on sensitive topics. This review summarises the state of ethical reporting among studies collecting violence data during early stages of the pandemic. We systematically searched for journal publications from the start of the pandemic to November 2021, identifying 75 studies that collected primary data on violence against women and/or violence against children. We developed and applied a 14-item checklist of best practices to assess the transparency of ethics reporting and adherence to relevant global guidelines on violence research. Studies reported adhering to best practices on 31% of scored items. Reporting was highest for ethical clearance (87%) and informed consent/assent (84/83%) and lowest for whether measures to promote interviewer safety and support (3%), for facilitating referrals for minors and soliciting participant feedback were in place (both 0%). Violence studies employing primary data collection during COVID-19 reported on few ethical standards, obscuring stakeholder ability to enforce a 'do no harm' approach and to assess the reliability of findings. We offer recommendations and guidelines to improve future reporting and implementation of ethics within violence studies.

Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.

BACKGROUND: Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS. METHODS: We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively. FINDINGS: Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients. INTERPRETATION: In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS. REGISTRATION: The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.

Associations between primary care recorded cannabis use and mental ill health in the UK: a population-based retrospective cohort study using UK primary care data.

BACKGROUND: Cannabis use is a global public health issue associated with increased risks of developing mental health disorders, especially in young people. We aimed to investigate the relationships between cannabis exposure and risks of receiving mental illness diagnoses or treatment as outcomes. METHODS: A population based, retrospective, open cohort study using patients recorded in 'IQVIA medical research data', a UK primary care database. Read codes were used to confirm patients with recorded exposure to cannabis use who were matched up to two unexposed patients. We examined the risk of developing three categories of mental ill health: depression, anxiety or serious mental illness (SMI). RESULTS: At study entry, the exposed cohort had an increased likelihood of having experienced mental ill health [odds ratio (OR) 4.13; 95% confidence interval (CI) 3.99-4.27] and mental ill health-related prescription (OR 2.95; 95% CI 2.86-3.05) compared to the unexposed group. During the study period we found that exposure to cannabis was associated with an increased risk of developing any mental disorder [adjusted hazard ratio (aHR) 2.73; 95% CI 2.59-2.88], also noted when examining by subtype of disorder: anxiety (aHR 2.46; 95% CI 2.29-2.64), depression (aHR 2.34; 95% CI 2.20-2.49) and SMI (aHR 6.41; 95% CI 5.42-7.57). These results remained robust in sensitivity analyses. CONCLUSION: These findings point to the potential need for a public health approach to the management of people misusing cannabis. However, there is a gross under-recording of cannabis use in GP records, as seen by the prevalence of recorded cannabis exposure substantially lower than self-reported survey records.

Impact of national COVID-19 restrictions on incidence of notifiable communicable diseases in England: an interrupted time series analysis.

BACKGROUND: Non-pharmaceutical interventions (NPIs), such as travel restrictions, social distancing and isolation policies, aimed at controlling the spread of COVID-19 may have reduced transmission of other endemic communicable diseases, such as measles, mumps and meningitis in England. METHODS: An interrupted time series analysis was conducted to examine whether NPIs was associated with trends in endemic communicable diseases, using weekly reported cases of seven notifiable communicable diseases (food poisoning, measles, meningitis, mumps, scarlet fever and pertussis) between 02/01/2017 to 02/01/2021 for England. RESULTS: Following the introduction of COVID-19 restrictions, there was an 81.1% (95% CI; 77.2-84.4) adjusted percentage reduction in the total number of notifiable diseases recorded per week in England. The greatest decrease was observed for measles, with a 90.5% percentage reduction (95% CI; 86.8-93.1) from 42 to 5 cases per week. The smallest decrease was observed for food poisoning, with a 56.4% (95%CI; 42.5-54.2) decrease from 191 to 83 cases per week. CONCLUSIONS: A total reduction in the incidence of endemic notifiable diseases was observed in England following the implementation of public health measures aimed at reducing transmission of SARS-COV-2 on March 23, 2020. The greatest reductions were observed in diseases most frequently observed during childhood that are transmitted via close human-to-human contact, such as measles and pertussis. A less substantive reduction was observed in reported cases of food poisoning, likely due to dining services (i.e., home deliveries and takeaways) remaining open and providing a potential route of transmission. This study provides further evidence of the effectiveness of non-pharmaceutical public health interventions in reducing the transmission of both respiratory and food-borne communicable diseases.

Association between childhood maltreatment and atopy in the UK: A population based retrospective cohort study.

Background: Childhood maltreatment affects over one in three children worldwide and is associated with a substantial disease burden. This study explores the association between childhood maltreatment and the development of atopic disease. Methods: We did a population-based retrospective matched open cohort study using participating general practices between 1st January 1995 and 30th September 2019. Read codes were utilised to identify patients exposed to childhood maltreatment (either suspected or confirmed) who were matched to up to four unexposed patients by age, sex, general practice, and Townsend deprivation quintile. Cox regression analysis was used to calculate adjusted (age, sex, Townsend deprivation quintile) hazard ratios (aHR) for development of atopy (asthma, atopic dermatitis, or allergic rhino conjunctivitis) during follow up in those without atopy at study entry. Results: 183,897 exposed patients were matched to 621,699 unexposed patients. During the follow up period, 18,555 patients (incidence rate (IR) 28.18 per 1000 person-years) in the exposed group developed atopic disease compared to the 68,368 (IR 23.58 per 1000 person-years) in the unexposed group, translating to an adjusted HR of 1.14 (95% CI 1.12-1.15). Notably, the risk of developing asthma was aHR 1.42 (95% CI 1.37-1.46). Associations were more pronounced in analyses restricted to females and confirmed cases of childhood maltreatment only. Interpretation: Considering the substantial health burden associated with childhood maltreatment, it is important to implement public health policies aimed at enhancing: 1) detection and primary prevention of childhood maltreatment, 2) secondary and tertiary prevention interventions to reduce the burden of ill health associated with exposure to maltreatment and 3) clinical awareness of such associations and subsequent knowledge of management. Funding: None.

Comorbidity phenotypes and risk of mortality in patients with osteoarthritis in the UK: a latent class analysis.

BACKGROUND: Osteoarthritis (OA) is a common chronic condition but its association with other chronic conditions and mortality is largely unknown. This study aimed to use latent class analysis (LCA) of 30 comorbidities in patients with OA and matched controls without OA to identify clusters of comorbidities and examine the associations between the clusters, opioid use, and mortality. METHODS: A matched cohort analysis of patients derived from the IQVIA Medical Research Data (IMRD-UK) database between 2000 and 2019. 418,329 patients with newly diagnosed OA were matched to 243,170 patients without OA to identify comorbidity phenotypes. Further analysis investigated the effect of opioid use on mortality in individuals with OA and their matched controls. RESULTS: The median (interquartile range (IQR)) number of comorbidities was 2 (1-4) and 1 (0-3) in the OA and control groups respectively. LCA identified six comorbidity phenotypes in individuals with and without OA. Clusters with a high prevalence of comorbidities were characterised by hypertension, circulatory, and metabolic diseases. We identified a comorbidity cluster with the aforementioned comorbidities plus a high prevalence of chronic kidney disease, which was associated with twice the hazard of mortality in hand OA with a hazard ratio (HR) (95% CI) of 2.53 (2.05-3.13) compared to the hazard observed in hip/knee OA subtype 1.33 (1.24-1.42). The impact of opioid use in the first 12 months on hazards of mortality was significantly greater for weak opioids and strong opioids across all groups HR (95% CI) ranging from 1.11 (1.07-11.6) to 1.80 (1.69-1.92)). There was however no evidence of association between NSAID use and altered risk of mortality. CONCLUSION: This study identified six comorbidity clusters in individuals with OA and matched controls within this cohort. Opioid use and comorbidity clusters were differentially associated with the risk of mortality. The analyses may help shape the development of future interventions or health services that take into account the impact of these comorbidity clusters.

Cluster analysis of patients with granulomatosis with polyangiitis (GPA) based on clinical presentation symptoms: a UK population-based cohort study.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is small vessel vasculitis with heterogeneous clinical presentation. In the present population-based cohort study, we classified patients with GPA based on clinical features at presentation using an unsupervised clustering approach and compared their mortality, infections and frequency of comorbidities. METHODS: In this open cohort study, de-identified primary care data of patients with GPA included in the IQVIA Medical Research Data database between 1 January 1995 and 25 September 2019 was analysed retrospectively. Latent class analysis was performed to create symptom clusters of patients based on 16 categories of symptoms representing various organ involvement. All-cause mortality of resultant clusters was compared after adjusting for age, sex, Townsend deprivation quintile and smoking status at index date using extended Cox proportional hazards models. Prescription of antibiotics, considered as an indirect indicator of recurrent bacterial infection, was compared using a recurrent event model, after adjusting for quarterly use of steroid as a time-dependent covariate. Cumulative frequencies of common comorbidities were compared among the clusters at index visit, 1-year and 3-year follow-up. RESULTS: Altogether, 649 patients with GPA [median age 60.0 (IQR: 49.6-70.1)] were included. Three clusters were identified: patients with limited disease mainly with involvement of ENT and cough were classified into cluster 1 (n = 426); cluster 2 had generalised non-renal disease (n = 176); while patients in cluster 3 had renal-predominant disease (n = 47). Many patients in cluster 1 developed generalised disease at the end of 1 year. Mortality in clusters 2 and 3 was higher compared with cluster 1. Mortality in cluster 1 itself was 68% higher than the general population without GPA. The duration of antibiotics prescription and frequency of coexisting medical illnesses was also higher in clusters 2 and 3. CONCLUSIONS: In a primary care setting, patients with GPA can be classified into three distinct clusters with different prognosis, susceptibility to recurrent infections and presence of comorbidities. The tendency of cluster 1 to evolve into a more generalised disease raises questions about current immunosuppressive treatment approaches in these patients.

Long-term impact of pre-incision antibiotics on children born by caesarean section: a longitudinal study based on UK electronic health records.

BACKGROUND: Since changes in the national guidance in 2011, prophylactic antibiotics for women undergoing caesarean section are recommended prior to skin incision, rather than after the baby's umbilical cord has been clamped. Evidence from randomised controlled trials conducted outside the UK has shown that this reduces maternal infectious morbidity; however, the prophylactic antibiotics also cross the placenta, meaning that babies are exposed to them around the time of birth. Antibiotics are known to affect the gut microbiota of the babies, but the long-term effects of exposure to high-dose broad-spectrum antibiotics around the time of birth on allergy and immune-related diseases are unknown. OBJECTIVES: We aimed to examine whether or not in-utero exposure to antibiotics immediately prior to birth compared with no pre-incisional antibiotic exposure increases the risk of (1) asthma and (2) eczema in children born by caesarean section. DESIGN: This was a controlled interrupted time series study. SETTING: The study took place in primary and secondary care. PARTICIPANTS: Children born in the UK during 2006-18 delivered by caesarean section were compared with a control cohort delivered vaginally. INTERVENTIONS: In-utero exposure to antibiotics immediately prior to birth. MAIN OUTCOME MEASURES: Asthma and eczema in children in the first 5 years of life. Additional secondary outcomes, including other allergy-related conditions, autoimmune diseases, infections, other immune system-related diseases and neurodevelopmental conditions, were also assessed. DATA SOURCES: The Health Improvement Network (THIN) and the Clinical Practice Research Datalink (CPRD) primary care databases and the Hospital Episode Statistics (HES) database. Previously published linkage strategies were adapted to link anonymised data on mothers and babies in these databases. Duplicate practices contributing to both THIN and the CPRD databases were removed to create a THIN-CPRD data set. RESULTS: In the THIN-CPRD and HES data sets, records of 515,945 and 3,945,351 mother-baby pairs were analysed, respectively. The risk of asthma was not significantly higher in children born by caesarean section exposed to pre-incision antibiotics than in children whose mothers received post-cord clamping antibiotics, with an incidence rate ratio of 0.91 (95% confidence interval 0.78 to 1.05) for diagnosis of asthma in primary care and an incidence rate ratio of 1.05 (95% confidence interval 0.99 to 1.11) for asthma resulting in a hospital admission. We also did not find an increased risk of eczema, with an incidence rate ratio of 0.98 (95% confidence interval 0.94 to1.03) and an incidence rate ratio of 0.96 (95% confidence interval 0.71 to 1.29) for diagnosis in primary care and hospital admissions, respectively. LIMITATIONS: It was not possible to ascertain the exposure to pre-incision antibiotics at an individual level. The maximum follow-up of children was 5 years. CONCLUSIONS: There was no evidence that the policy change from post-cord clamping to pre-incision prophylactic antibiotics for caesarean sections during 2006-18 had an impact on the incidence of asthma and eczema in early childhood in the UK. FUTURE WORK: There is a need for further research to investigate if pre-incision antibiotics have any impact on developing asthma and other allergy and immune-related conditions in older children. STUDY REGISTRATION: This study is registered as researchregistry3736. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 30. See the NIHR Journals Library website for further project information.

WHAT WAS THE QUESTION?: Women giving birth by caesarean section are at risk of developing infections (such as wound infections) and are offered antibiotics at the time of their operation to reduce this risk. In 2011, the national guidelines changed from recommending antibiotics after cord clamping to giving them before the operation to further reduce the risk of maternal infection. During birth, the newborn gut is colonised by microbes. Antibiotics given to the mother before caesarean section can reach the baby through the placenta and disrupt the normal microbes that colonise the gut. These microbes are believed to play a role in the development of the immune system and altering the normal development of these microbes has been linked to children developing allergic conditions, such as asthma and eczema. This study investigated whether or not giving antibiotics before the caesarean section had a longer-term impact on children's health. WHAT DID WE DO?: We used routine NHS information already collected by hospitals and general practitioners about women who gave birth in the UK between 2006 and 2018, and their children. We compared the risk of asthma, eczema and other health conditions in the first 5 years after birth in children born by caesarean section before and after the change in hospital policies. We also compared their health with children born vaginally. WHAT DID WE FIND?: We found that there was no increased risk of asthma or eczema for children born by caesarean section after the policy decision in 2011 to give the mother antibiotics before the operation. WHAT DOES THIS MEAN?: The study findings provide further evidence for the current recommendation to give preventative antibiotics to women shortly before the caesarean section to reduce the overall risk of infections after birth.

Symptoms and risk factors for long COVID in non-hospitalized adults.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.