@article{Vistisen2023,

title = {Empagliflozin is associated with lower cardiovascular risk compared with dipeptidyl peptidase-4 inhibitors in adults with and without cardiovascular disease: EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study results from Europe and Asia.},

author = {Dorte Vistisen and Bendix Carstensen and Patorno Elisabetta and Stefanie Lanzinger and Elise Chia-Hui Tan and Daisuke Yabe and Dae Jung Kim and Wayne H-H Sheu and Cheli Melzer-Cohen and Reinhard W Holl and Júlio Núñez and Kyoung Hwa Ha and Sigrun Halvorsen and Gisle Langslet and Avraham Karasik and Thomas Nyström and Leo Niskanen and Sonia Guleria and Riho Klement and Marc Carrasco and Johannes Foersch and Christina Shay and Lisette Koeneman and Fabian Hoti and Soulmaz Fazeli Farsani and Kamlesh Khunti and Francesco Zaccardi and Anuradhaa Subramanian and Krishnarajah Nirantharakumar},

doi = {10.1186/s12933-023-01963-9},

issn = {1475-2840 (Electronic)},

year  = {2023},

date = {2023-01-01},

journal = {Cardiovascular diabetology},

volume = {22},

issue = {1},

pages = {233},

institution = {EMPRISE EU},

abstract = {BACKGROUND: Studies that have reported lower risk for cardiovascular outcomes in users of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) are limited by residual cofounding and lack of information on prior cardiovascular disease (CVD). This study compared risk of cardiovascular events in patients within routine care settings in Europe and Asia with type 2 diabetes (T2D) initiating empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) stratified by pre-existing CVD and history of heart failure (HF). METHODS AND RESULTS: Adults initiating empagliflozin and DPP-4i in 2014-2018/19 from 11 countries in Europe and Asia were compared using propensity score matching and Cox proportional hazards regression to assess differences in rates of primary outcomes: hospitalisation for heart failure (HHF), myocardial infarction (MI), stroke; and secondary outcomes: cardiovascular mortality (CVM), coronary revascularisation procedure, composite outcome including HHF or CVM, and 3-point major adverse cardiovascular events (MACE: MI, stroke and CVM). Country-specific results were meta-analysed and pooled hazard ratios (HR) with 95% confidence intervals (CI) from random-effects models are presented. In total, 85,244 empagliflozin/DPP4i PS-matched patient pairs were included with overall mean follow-up of 0.7 years. Among those with pre-existing CVD, lower risk was observed for HHF (HR 0.74; 95% CI 0.64-0.86), CVM (HR 0.55; 95% CI 0.38-0.80), HHF or CVM (HR 0.57; 95% CI 0.48-0.67) and stroke (HR 0.79; 95% CI 0.67-0.94) in patients initiating empagliflozin vs DPP-4i. Similar patterns were observed among patients without pre-existing CVD and those with and without pre-existing HF. CONCLUSION: These results from diverse patient populations in routine care settings across Europe and Asia demonstrate that initiation of empagliflozin compared to DPP-4i results in favourable cardioprotective effects regardless of pre-existing CVD or HF status.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nash2023,

title = {Exposure to Domestic Abuse and the Subsequent Development of Atopic Disease in Women.},

author = {Katrina Nash and Sonica Minhas and Nicholas Metheny and Krishna M Gokhale and Julie Taylor and Caroline Bradbury-Jones and Siddhartha Bandyopadhyay and Krishnarajah Nirantharakumar and Nicola J Adderley and Joht Singh Chandan},

doi = {10.1016/j.jaip.2023.03.016},

issn = {2213-2201 (Electronic)},

year  = {2023},

date = {2023-01-01},

journal = {The journal of allergy and clinical immunology. In practice},

volume = {11},

issue = {6},

pages = {1752-1756.e3},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cooper2023,

title = {Prevalence and demographic variation of cardiovascular, renal, metabolic, and mental health conditions in 12 million english primary care records.},

author = {Jennifer Cooper and Krishnarajah Nirantharakumar and Francesca Crowe and Amaya Azcoaga-Lorenzo and Colin McCowan and Thomas Jackson and Aditya Acharya and Krishna Gokhale and Niluka Gunathilaka and Tom Marshall and Shamil Haroon},

doi = {10.1186/s12911-023-02296-z},

issn = {1472-6947 (Electronic)},

year  = {2023},

date = {2023-01-01},

journal = {BMC medical informatics and decision making},

volume = {23},

issue = {1},

pages = {220},

abstract = {BACKGROUND: Primary care electronic health records (EHR) are widely used to study long-term conditions in epidemiological and health services research. Therefore, it is important to understand how well the recorded prevalence of these conditions in EHRs, compares to other reliable sources overall, and varies by socio-demographic characteristics. We aimed to describe the prevalence and socio-demographic variation of cardiovascular, renal, and metabolic (CRM) and mental health (MH) conditions in a large, nationally representative, English primary care database and compare with prevalence estimates from other population-based studies. METHODS: This was a cross-sectional study using the Clinical Practice Research Datalink (CPRD) Aurum primary care database. We calculated prevalence of 18 conditions and used logistic regression to assess how this varied by age, sex, ethnicity, and socio-economic status. We searched the literature for population prevalence estimates from other sources for comparison with the prevalences in CPRD Aurum. RESULTS: Depression (16.0%, 95%CI 16.0-16.0%) and hypertension (15.3%, 95%CI 15.2-15.3%) were the most prevalent conditions among 12.4 million patients. Prevalence of most conditions increased with socio-economic deprivation and age. CRM conditions, schizophrenia and substance misuse were higher in men, whilst anxiety, depression, bipolar and eating disorders were more common in women. Cardiovascular risk factors (hypertension and diabetes) were more prevalent in black and Asian patients compared with white, but the trends in prevalence of cardiovascular diseases by ethnicity were more variable. The recorded prevalences of mental health conditions were typically twice as high in white patients compared with other ethnic groups. However, PTSD and schizophrenia were more prevalent in black patients. The prevalence of most conditions was similar or higher in the primary care database than diagnosed disease prevalence reported in national health surveys. However, screening studies typically reported higher prevalence estimates than primary care data, especially for PTSD, bipolar disorder and eating disorders. CONCLUSIONS: The prevalence of many clinically diagnosed conditions in primary care records closely matched that of other sources. However, we found important variations by sex and ethnicity, which may reflect true variation in prevalence or systematic differences in clinical presentation and practice. Primary care data may underrepresent the prevalence of undiagnosed conditions, particularly in mental health.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{AzfrAli2023,

title = {Cardiometabolic screening and monitoring in patients prescribed antipsychotic drugs in primary care: A population-based cohort study.},

author = {Ruba Azfr Ali and Zahraa Jalal and Joht Singh Chandan and Anuradhaa Subramanian and Nicola J Adderley and Krishnarajah Nirantharakumar and Krishna M Gokhale and Vibhu Paudyal},

doi = {10.1016/j.comppsych.2023.152419},

issn = {1532-8384 (Electronic)},

year  = {2023},

date = {2023-01-01},

journal = {Comprehensive psychiatry},

volume = {127},

pages = {152419},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Shah2023,

title = {Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.},

author = {Anoop D Shah and Anuradhaa Subramanian and Jadene Lewis and Samir Dhalla and Elizabeth Ford and Shamil Haroon and Valerie Kuan and Krishnarajah Nirantharakumar},

doi = {10.1371/journal.pone.0290583},

issn = {1932-6203 (Electronic)},

year  = {2023},

date = {2023-01-01},

journal = {PloS one},

volume = {18},

issue = {9},

pages = {e0290583},

abstract = {BACKGROUND: Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes. AIMS: To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis. METHODS: We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis. RESULTS: We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression. CONCLUSIONS: Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Azcoaga-Lorenzo2023,

title = {Maternal multimorbidity and preterm birth in Scotland: an observational record-linkage study.},

author = {Amaya Azcoaga-Lorenzo and Adeniyi Francis Fagbamigbe and Utkarsh Agrawal and Mairead Black and Muhammad Usman and Siang Ing Lee and Kelly-Ann Eastwood and Ngawai Moss and Rachel Plachcinski and Catherine Nelson-Piercy and Sinead Brophy and Dermot O'Reilly and Krishnarajah Nirantharakumar and Colin McCowan},

doi = {10.1186/s12916-023-03058-4},

issn = {1741-7015 (Electronic)},

year  = {2023},

date = {2023-01-01},

journal = {BMC medicine},

volume = {21},

issue = {1},

pages = {352},

institution = {MuM-PreDiCT Group},

abstract = {BACKGROUND: Multimorbidity is common in women across the life course. Preterm birth is the single biggest cause of neonatal mortality and morbidity. We aim to estimate the prevalence of multimorbidity in pregnant women and to examine the association between maternal multimorbidity and PTB. METHODS: This is a retrospective cohort study using electronic health records from the Scottish Morbidity Records. All pregnancies among women aged 15 to 49 with a conception date between 1 January 2014 and 31 December 2018 were included. Multimorbidity was defined as the presence of two or more pre-existing long-term physical or mental health conditions, and complex multimorbidity as the presence of four or more. It was calculated at the time of conception using a predefined list of 79 conditions published by the MuM-PreDiCT consortium. PTB was defined as babies born alive between 24 and less than 37 completed weeks of gestation. We used Generalised Estimating Equations adjusted for maternal age, socioeconomic status, number of previous pregnancies, BMI, and smoking history to estimate the effect of maternal pre-existing multimorbidity. Absolut rates are reported in the results and tables, whilst Odds Ratios (ORs) are adjusted (aOR). RESULTS: Thirty thousand five hundred fifty-seven singleton births from 27,711 pregnant women were included in the analysis. The prevalence of pre-existing multimorbidity and complex multimorbidity was 16.8% (95% CI: 16.4-17.2) and 3.6% (95% CI: 3.3-3.8), respectively. The prevalence of multimorbidity in the youngest age group was 10.2%(95% CI: 8.8-11.6), while in those 40 to 44, it was 21.4% (95% CI: 18.4-24.4), and in the 45 to 49 age group, it was 20% (95% CI: 8.9-31.1). In women without multimorbidity, the prevalence of PTB was 6.7%; it was 11.6% in women with multimorbidity and 15.6% in women with complex multimorbidity. After adjusting for maternal age, socioeconomic status, number of previous pregnancies, Body Mass Index (BMI), and smoking, multimorbidity was associated with higher odds of PTB (aOR = 1.64, 95% CI: 1.48-1.82). CONCLUSIONS: Multimorbidity at the time of conception was present in one in six women and was associated with an increased risk of preterm birth. Multimorbidity presents a significant health burden to women and their offspring. Routine and comprehensive evaluation of women with multimorbidity before and during pregnancy is urgently needed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Syed2023,

title = {Incidence of immune-mediated inflammatory diseases following COVID-19: a matched cohort study in UK primary care.},

author = {Umer Syed and Anuradhaa Subramanian and David C Wraith and Janet M Lord and Kirsty McGee and Krishna Ghokale and Krishnarajah Nirantharakumar and Shamil Haroon},

doi = {10.1186/s12916-023-03049-5},

issn = {1741-7015 (Electronic)},

year  = {2023},

date = {2023-01-01},

journal = {BMC medicine},

volume = {21},

issue = {1},

pages = {363},

abstract = {BACKGROUND: Some patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) go on to experience post-COVID-19 condition or long COVID. Preliminary findings have given rise to the theory that long COVID may be due in part to a deranged immune response. In this study, we assess whether there is an association between SARS-CoV-2 infection and the incidence of immune-mediated inflammatory diseases (IMIDs). METHODS: Matched cohort study using primary care electronic health record data from the Clinical Practice Research Datalink Aurum database. The exposed cohort included 458,147 adults aged 18 years and older with a confirmed SARS-CoV-2 infection and no prior diagnosis of IMIDs. They were matched on age, sex, and general practice to 1,818,929 adults with no diagnosis of confirmed or suspected SARS-CoV-2 infection. The primary outcome was a composite of any of the following IMIDs: autoimmune thyroiditis, coeliac disease, inflammatory bowel disease (IBD), myasthenia gravis, pernicious anaemia, psoriasis, rheumatoid arthritis (RA), Sjogren's syndrome, systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1DM), and vitiligo. The secondary outcomes were each of these conditions separately. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the primary and secondary outcomes, adjusting for age, sex, ethnic group, smoking status, body mass index, relevant infections, and medications. RESULTS: Six hundred and nighty six (0.15%) and 2230 (0.12%) patients in the exposed and unexposed cohort developed an IMID during the follow-up period over 0.29 person-years, giving a crude incidence rate of 4.59 and 3.65 per 1000 person-years, respectively. Patients in the exposed cohort had a 22% increased risk of developing an IMID, compared to the unexposed cohort (aHR 1.22, 95% CI 1.12 to 1.33). The incidence of three IMIDs was significantly associated with SARS-CoV-2 infection. These were T1DM (aHR 1.56, 1.09 to 2.23), IBD (aHR 1.36, 1.18 to 1.56), and psoriasis (1.23, 1.05 to 1.42). CONCLUSIONS: SARS-CoV-2 was associated with an increased incidence of IMIDs including T1DM, IBD and psoriasis. However, these findings could be potentially due to ascertainment bias. Further research is needed to replicate these findings in other populations and to measure autoantibody profiles in cohorts of individuals with COVID-19.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Haider2023,

title = {Diabetic retinopathy progression in patients under monitoring for treatment or vision loss: external validation and update of a multivariable prediction model.},

author = {Sajjad Haider and Nicola Adderley and Mohammad O Tallouzi and Salman Naveed Sadiq and David H Steel and Randhir Chavan and Ijaz Sheikh and Krishnarajah Nirantharakumar and Kym I E Snell},

doi = {10.1136/bmjopen-2023-073015},

issn = {2044-6055 (Electronic)},

year  = {2023},

date = {2023-01-01},

journal = {BMJ open},

volume = {13},

issue = {4},

pages = {e073015},

abstract = {INTRODUCTION: The number of people with diabetes mellitus is increasing globally and consequently so too is diabetic retinopathy (DR). Most patients with diabetes are monitored through the diabetic eye screening programme (DESP) until they have signs of retinopathy and these changes progress, requiring referral into hospital eye services (HES). Here, they continue to be monitored until they require treatment. Due to current pressures on HES, delays can occur, leading to harm. There is a need to triage patients based on their individual risk. At present, patients are stratified according to retinopathy stage alone, yet other risk factors like glycated haemoglobin (HbA1c) may be useful. Therefore, a prediction model that combines multiple prognostic factors to predict progression will be useful for triage in this setting to improve care.We previously developed a Diabetic Retinopathy Progression model to Treatment or Vision Loss (DRPTVL-UK) using a large primary care database. The aim of the present study is to externally validate the DRPTVL-UK model in a secondary care setting, specifically in a population under care by HES. This study will also provide an opportunity to update the model by considering additional predictors not previously available. METHODS AND ANALYSIS: We will use a retrospective cohort of 2400 patients with diabetes aged 12 years and over, referred from DESP to the NHS hospital trusts with referable DR between 2013 and 2016, with follow-up information recorded until December 2021.We will evaluate the external validity of the DRPTVL-UK model using measures of discrimination, calibration and net benefit. In addition, consensus meetings will be held to agree on acceptable risk thresholds for triage within the HES system. ETHICS AND DISSEMINATION: This study was approved by REC (ref 22/SC/0425, 05/12/2022, Hampshire A Research Ethics Committee). The results of the study will be published in a peer-reviewed journal, presented at clinical conferences. TRIAL REGISTRATION NUMBER: ISRCTN 10956293.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Phillips2023,

title = {Inequalities in the management of diabetic kidney disease in UK primary care: A cross-sectional analysis of a large primary care database.},

author = {Katherine Phillips and Jonathan M Hazlehurst and Christelle Sheppard and Srikanth Bellary and Wasim Hanif and Muhammad Ali Karamat and Francesca L Crowe and Anna Stone and G Neil Thomas and Javeria Peracha and Anthony Fenton and Christopher Sainsbury and Krishnarajah Nirantharakumar and Indranil Dasgupta},

doi = {10.1111/dme.15153},

issn = {1464-5491 (Electronic)},

year  = {2023},

date = {2023-01-01},

journal = {Diabetic medicine : a journal of the British Diabetic Association},

pages = {e15153},

abstract = {AIMS: To determine differences in the management of diabetic kidney disease (DKD) relevant to patient sex, ethnicity and socio-economic group in UK primary care. METHODS: A cross-sectional analysis as of January 1, 2019 was undertaken using the IQVIA Medical Research Data dataset, to determine the proportion of people with DKD managed in accordance with national guidelines, stratified by demographics. Robust Poisson regression models were used to calculate adjusted risk ratios (aRR) adjusting for age, sex, ethnicity and social deprivation. RESULTS: Of the 2.3 million participants, 161,278 had type 1 or 2 diabetes, of which 32,905 had DKD. Of people with DKD, 60% had albumin creatinine ratio (ACR) measured, 64% achieved blood pressure (BP, <140/90 mmHg) target, 58% achieved glycosylated haemoglobin (HbA1c, <58 mmol/mol) target, 68% prescribed renin-angiotensin-aldosterone system (RAAS) inhibitor in the previous year. Compared to men, women were less likely to have creatinine: aRR 0.99 (95% CI 0.98-0.99), ACR: aRR 0.94 (0.92-0.96), BP: aRR 0.98 (0.97-0.99), HbA(1c) : aRR 0.99 (0.98-0.99) and serum cholesterol: aRR 0.97 (0.96-0.98) measured; achieve BP: aRR 0.95 (0.94-0.98) or total cholesterol (<5 mmol/L) targets: aRR 0.86 (0.84-0.87); or be prescribed RAAS inhibitors: aRR 0.92 (0.90-0.94) or statins: aRR 0.94 (0.92-0.95). Compared to the least deprived areas, people from the most deprived areas were less likely to have BP measurements: aRR 0.98 (0.96-0.99); achieve BP: aRR 0.91 (0.8-0.95) or HbA(1c) : aRR 0.88 (0.85-0.92) targets, or be prescribed RAAS inhibitors: aRR 0.91 (0.87-0.95). Compared to people of white ethnicity; those of black ethnicity were less likely to be prescribed statins aRR 0.91 (0.85-0.97). CONCLUSIONS: There are unmet needs and inequalities in the management of DKD in the UK. Addressing these could reduce the increasing human and societal cost of managing DKD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Thayakaran2023,

title = {Seasonal variation of serum potassium and related prescription pattern: an ecological time series.},

author = {Rasiah Thayakaran and Richard Hotham and Krishna M Gokhale and Nicola J Adderley and Joht Singh Chandan and Krishnarajah Nirantharakumar},

doi = {10.1136/jcp-2023-208759},

issn = {1472-4146 (Electronic)},

year  = {2023},

date = {2023-01-01},

journal = {Journal of clinical pathology},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Subramanian2023,

title = {Sodium-glucose cotransporter-2 inhibitors and the risk of gout in patients with type 2 diabetes mellitus: A propensity-score-matched, new-user design study with an active comparator using the IQVIA Medical Research Data UK database},

author = {Anuradhaa Subramanian and Krishna Gokhale and Christopher Sainsbury and Krishnarajah Nirantharakumar and Konstantinos A. Toulis},

doi = {10.1111/DOM.14858},

issn = {14631326},

year  = {2023},

date = {2023-01-01},

journal = {Diabetes, Obesity and Metabolism},

volume = {25},

issue = {1},

pages = {156-165},

publisher = {John Wiley and Sons Inc},

abstract = {Aim: To conduct a pharmacoepidemiological study to explore the association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and gout in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: A retrospective open cohort study using the IQVIA Medical Research Data UK database was performed between November 1, 2012 and December 31, 2018, estimating the risk of gout in patients with T2DM who were new users of SGLT2 inhibitors, compared to propensity-score-matched new users of dipeptidyl peptidase-4 (DPP-4) inhibitors. Results: A total of 85 incident cases of gout were recorded over 30 389 person-years of observation in 13 617 new users of SGLT2 inhibitors and 29 426 new users of DPP-4 inhibitors. Crude incidence rates (IRs) per 1000 person-years were 2.90 and 2.47 for new users of SGLT2 inhibitors and DPP-4 inhibitors, respectively. The unadjusted hazard ratio (HR) was 1.18 (95% confidence interval [CI] 0.76-1.83). The adjusted HR was 1.20 (95% CI 0.77-1.86). In the at-treatment analysis, crude IRs per 1000 person-years were found to be 2.68 and 2.53 for SGLT2 inhibitor and DPP-4 inhibitor users, respectively. In the adjusted model, the adjusted HR was 1.3 (95% CI 0.90-2.29). Sensitivity analyses did not change the findings. Conclusions: In this nationwide study, no difference in the incidence of gout was documented in patients treated with SGLT2 inhibitors compared to DPP-4 inhibitor users. This neutral finding remained consistent in sensitivity analyses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gardner2023,

title = {Risk of progression from pre-diabetes to type 2 diabetes in a large UK adult cohort},

author = {Michael P. Gardner and Jingya Wang and Jonathan M. Hazlehurst and Chris Sainsbury and Jacqueline Blissett and Krishnarajah Nirantharakumar and Neil Thomas and Srikanth Bellary},

doi = {10.1111/DME.14996},

issn = {14645491},

year  = {2023},

date = {2023-01-01},

journal = {Diabetic Medicine},

volume = {40},

issue = {3},

publisher = {John Wiley and Sons Inc},

abstract = {Aims: People with pre-diabetes are at high risk of progressing to type 2 diabetes. This progression is not well characterised by ethnicity, deprivation and age, which we describe in a large cohort of individuals with pre-diabetes. Methods: A retrospective cohort study with The Health Improvement Network (THIN) database was conducted. Patients aged 18 years and over and diagnosed with pre-diabetes [HbA1c 42 mmol/mol (6.0%) to 48 mmol/mol (6.5%) were included]. Cox proportional hazards regression was used to calculate adjusted hazard rate ratios (aHR) for the risk of progression from pre-diabetes to type 2 diabetes for each of the exposure categories [ethnicity, deprivation (Townsend), age and body mass index (BMI)] separately. Results: Of the baseline population with pre-diabetes (n = 397,853), South Asian (aHR 1.31; 95% CI 1.26–1.37) or Mixed-Race individuals (aHR 1.22; 95% CI 1.11–1.33) had an increased risk of progression to type 2 diabetes compared with those of white European ethnicity. Likewise, deprivation (aHR 1.17; 95% CI 1.14–1.20; most vs. least deprived) was associated with an increased risk of progression. Both younger (aHR 0.63; 95% CI 0.58–0.69; 18 to <30 years) and older individuals (aHR 0.85; 95% CI 0.84–0.87; ≥65 years) had a slower risk of progression from pre-diabetes to type 2 diabetes, than middle-aged (40 to <65 years) individuals. Conclusions: South Asian or Mixed-Race individuals and people with social deprivation had an increased risk of progression from pre-diabetes to type 2 diabetes. Clinicians need to recognise the differing risk across their patient populations to implement appropriate prevention strategies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Keerthy2023,

title = {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},

author = {Deepiksana Keerthy and Joht Singh Chandan and Juste Abramovaite and Krishna Margadhamane Gokhale and Siddhartha Bandyopadhyay and Ed Day and Steven Marwaha and Matthew R. Broome and Krishnarajah Nirantharakumar and Clara Humpston},

doi = {10.1017/S003329172100386X},

issn = {14698978},

year  = {2023},

date = {2023-01-01},

journal = {Psychological Medicine},

volume = {53},

issue = {5},

pages = {2106-2115},

publisher = {Cambridge University Press},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gooden2023,

title = {A matched cohort study investigating premature, accentuated, and accelerated aging in people living with HIV},

author = {Tiffany E. Gooden and Jingya Wang and Dawit T. Zemedikun and Stephen Taylor and Sheila Greenfield and Semira Manaseki-Holland and Krishnarajah Nirantharakumar and G. Neil Thomas},

doi = {10.1111/HIV.13375},

issn = {14681293},

year  = {2023},

date = {2023-01-01},

journal = {HIV Medicine},

volume = {24},

issue = {5},

pages = {640-647},

publisher = {John Wiley and Sons Inc},

abstract = {Introduction: The impact of HIV infection on the aging process is disputed and largely unknown. We aimed to identify whether people living with HIV experience premature, accelerated, and/or accentuated aging by investigating the development of four age-related non-communicable diseases in people living with versus without HIV. Methods: This population-based matched cohort study design used UK-based primary care electronic health records from the IQVIA Medical Research Database. Between January 2000 and January 2020, all people living with and without HIV aged ≥18 years were eligible. Outcomes included cardiovascular disease (CVD), hypertension, type 2 diabetes mellitus (T2DM), and chronic kidney disease (CKD), which were identified by Read codes. We used age at diagnosis to investigate premature aging and age at exit date to investigate accentuation and acceleration. For each outcome, people with and without HIV were excluded if they had the outcome of interest at baseline. Participants were matched based on propensity scores (1:1 ratio). Linear regression was used to report any difference in age at diagnosis between the two groups and to report the prevalence trends for age at exit date. Results: In total, 8880 people living with HIV were matched with 8880 people without HIV and were found to have an earlier onset of CVD (54.5 vs. 56.8; p = 0.002). Similarly, people living with HIV had an earlier onset of hypertension (49.7 vs. 51.4; p = 0.002). No difference was found for T2DM or CKD (53.4 vs. 52.6; p = 0.368 and 57.6 vs. 58.1; p = 0.483, respectively). The burden of CKD increased over time, whereas no difference in the burden was found for the other conditions. Conclusion: The earlier development of CVD and hypertension in people living with HIV than in those without HIV indicates premature aging, whereas the increased burden of CKD indicates accelerated aging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Okoth2023c,

title = {The association between menstrual cycle characteristics and cardiometabolic outcomes in later life: a retrospective matched cohort study of 704,743 women from the UK},

author = {Kelvin Okoth and William Parry Smith and G. Neil Thomas and Krishnarajah Nirantharakumar and Nicola J. Adderley},

doi = {10.1186/S12916-023-02794-X},

issn = {17417015},

year  = {2023},

date = {2023-01-01},

journal = {BMC Medicine},

volume = {21},

issue = {1},

publisher = {BioMed Central Ltd},

abstract = {Background: Female reproductive factors are gaining prominence as factors that enhance cardiovascular disease (CVD) risk; nonetheless, menstrual cycle characteristics are under-recognized as a factor associated with CVD. Additionally, there is limited data from the UK pertaining to menstrual cycle characteristics and CVD risk. Methods: A UK retrospective cohort study (1995–2021) using data from a nationwide database (The Health Improvement Network). Women aged 18–40 years at index date were included. 252,325 women with history of abnormal menstruation were matched with up to two controls. Two exposures were examined: regularity and frequency of menstrual cycles; participants were assigned accordingly to one of two separate cohorts. The primary outcome was composite cardiovascular disease (CVD). Secondary outcomes were ischemic heart disease (IHD), cerebrovascular disease, heart failure (HF), hypertension, and type 2 diabetes mellitus (T2DM). Cox proportional hazards regression models were used to derive adjusted hazard ratios (aHR) of cardiometabolic outcomes in women in the exposed groups compared matched controls. Results: During 26 years of follow-up, 20,605 cardiometabolic events occurred in 704,743 patients. Compared to women with regular menstrual cycles, the aHRs (95% CI) for cardiometabolic outcomes in women with irregular menstrual cycles were as follows: composite CVD 1.08 (95% CI 1.00–1.19), IHD 1.18 (1.01–1.37), cerebrovascular disease 1.04 (0.92–1.17), HF 1.30 (1.02–1.65), hypertension 1.07 (1.03–1.11), T2DM 1.37 (1.29–1.45). The aHR comparing frequent or infrequent menstrual cycles to menstrual cycles of normal frequency were as follows: composite CVD 1.24 (1.02–1.52), IHD 1.13 (0.81–1.57), cerebrovascular disease 1.43 (1.10–1.87), HF 0.99 (0.57–1.75), hypertension 1.31 (1.21–1.43), T2DM 1.74 (1.52–1.98). Conclusions: History of either menstrual cycle irregularity or frequent or infrequent cycles were associated with an increased risk of cardiometabolic outcomes in later life. Menstrual history may be a useful tool in identifying women eligible for periodic assessment of their cardiometabolic health.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Almulhem2022,

title = {Ramadan is not associated with increased infection risk in Pakistani and Bangladeshi populations: Findings from controlled interrupted time series analysis of UK primary care data},

author = {Munerah Almulhem and Rasiah Thayakaran and Shahjehan Hanif and Tiffany Gooden and Neil Thomas and Jonathan Hazlehurst and Abd A. Tahrani and Wasim Hanif and Krishnarajah Nirantharakumar},

doi = {10.1371/JOURNAL.PONE.0262530},

issn = {19326203},

year  = {2022},

date = {2022-01-01},

journal = {PLoS ONE},

volume = {17},

issue = {1 January},

publisher = {Public Library of Science},

abstract = {Background The effect of fasting on immunity is unclear. Prolonged fasting is thought to increase the risk of infection due to dehydration. This study describes antibiotic prescribing patterns before, during, and after Ramadan in a primary care setting within the Pakistani and Bangladeshi populations in the UK, most of whom are Muslims, compared to those who do not observe Ramadan. Method Retrospective controlled interrupted time series analysis of electronic health record data from primary care practices. The study consists of two groups: Pakistanis/Bangladeshis and white populations. For each group, we constructed a series of aggregated, daily prescription data from 2007 to 2017 for the 30 days preceding, during, and after Ramadan, respectively. Findings Controlling for the rate in the white population, there was no evidence of increased antibiotic prescription in the Pakistani/Bangladeshi population during Ramadan, as compared to before Ramadan (IRR: 0.994; 95% CI: 0.988–1.001},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Okoth2022,

title = {Long term miscarriage-related hypertension and diabetes mellitus. Evidence from a United Kingdom population-based cohort study},

author = {Kelvin Okoth and Anuradhaa Subramanian and Joht Singh Chandan and Nicola J. Adderley and G. Neil Thomas and Krishnarajah Nirantharakumar and Christina Antza},

doi = {10.1371/JOURNAL.PONE.0261769},

issn = {19326203},

year  = {2022},

date = {2022-01-01},

journal = {PLoS ONE},

volume = {17},

issue = {1 January},

publisher = {Public Library of Science},

abstract = {Background Miscarriages affect up to a fifth of all pregnancies and are associated with substantial psychological morbidity. However, their relationship with cardiometabolic risk factors is not well known. Therefore, in this study we aimed to estimate the burden of cardiovascular risk factors including diabetes mellitus (type 1 or 2) and hypertension in women with miscarriage compared to women without a record of miscarriage. Methods A population-based retrospective cohort study was conducted using IVQIA Medical Research Data UK (IMRD-UK) between January 1995 and May 2016, an anonymised electronic health records database that is representative of the UK population. A total of 86,509, 16-50-year-old women with a record of miscarriage (exposed group) were matched by age, smoking status, and body mass index to 329,865 women without a record of miscarriage (unexposed group). Patients with pre-existing hypertension and diabetes were excluded. Adjusted incidence rate ratios (aIRR) and 95% confidence intervals (95% CI) for diabetes and hypertension were estimated using multivariable Poisson regression models offsetting for person-years follow-up. Results The mean age at cohort entry was 31 years and median follow up was 4.6 (IQR 1.7-9.4) years. During the study period, a total of 792 (IR 1.44 per 1000 years) and 2525 (IR 1.26 per 1000 years) patients developed diabetes in the exposed and unexposed groups, respectively. For hypertension, 1995 (IR 3.73 per 1000 years) and 1605 (IR 3.39 per 1000 years) new diagnoses were recorded in the exposed and unexposed groups, respectively. Compared to unexposed individuals, women with a record miscarriage were more likely to develop diabetes (aIRR = 1.25, 95% CI: 1.15-1.36; p<0.001) and hypertension (aIRR = 1.07, 95% CI: 1.02-1.12; p = 0.005). Conclusions Women diagnosed with miscarriage were at increased risk of developing diabetes mellitus and hypertension. Women with history of miscarriage may benefit from periodic monitoring of their cardiometabolic health.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lee2022,

title = {Decreased renal function is associated with incident dementia: An IMRD-THIN retrospective cohort study in the UK},

author = {Siang Ing Lee and Jennifer Cooper and Anthony Fenton and Anuradhaa Subramanian and Tom Taverner and Krishna M. Gokhale and Katherine Phillips and Mitesh Patel and Lorraine Harper and G. Neil Thomas and Krishnarajah Nirantharakumar},

doi = {10.1002/ALZ.12539},

issn = {15525279},

year  = {2022},

date = {2022-01-01},

journal = {Alzheimer's and Dementia},

volume = {18},

issue = {10},

pages = {1943-1956},

publisher = {John Wiley and Sons Inc},

abstract = {Introduction: Decreased renal function is a potential risk factor for dementia. Methods: This retrospective cohort study of 2.8 million adults aged ≥50 years used the IMRD-THIN database, representative of UK primary care, from January 1, 1995 to February 24, 2020. The associations between estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (ACR) with incident all-cause dementia were analyzed using Cox regression. Results: In the eGFR cohort (n = 2,797,384), worsening renal dysfunction was associated with increased hazard of all-cause dementia, with greatest hazard at eGFR 15–30 ml/min/1.73min2 (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.19–1.33). In the ACR cohort (n = 641,912), the hazard of dementia increased from ACR 3–30 mg/mmol (HR 1.13, 95% CI 1.10–1.15) to ACR > 30 mg/mmol (HR 1.25, 95% CI 1.18–1.33). Discussion: Worsening eGFR and albuminuria have graded associations with the risk of dementia, which may have significant implications for the care of patients with kidney disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Okoth2022b,

title = {Sex-specific temporal trends in the incidence and prevalence of cardiovascular disease in young adults: a population-based study using UK primary care data},

author = {Kelvin Okoth and Francesca Crowe and Tom Marshall and G. Neil Thomas and Krishnarajah Nirantharakumar and Nicola J. Adderley},

doi = {10.1093/EURJPC/ZWAC024},

issn = {20474881},

year  = {2022},

date = {2022-01-01},

journal = {European Journal of Preventive Cardiology},

volume = {29},

issue = {10},

pages = {1387-1395},

publisher = {Oxford University Press},

abstract = {Aims: There is concern that cardiovascular disease (CVD) in young adults is rising. However, current trends in the UK are unknown. We investigated sex-specific trends in the incidence and prevalence of CVD in young UK adults. Methods and results: A series of annual (1998-2017) cohort and cross-sectional studies were conducted to estimate incidence rates and prevalence in men and women aged 16-50. Joinpoint regression models were fitted to evaluate changes in trends. From 1998 to 2017, incidence and prevalence had an overall downward trend for ischaemic heart disease (IHD) and angina, while coronary revascularization, stroke/transient ischaemic attack (TIA), and heart failure (HF) had an upward trend in both sexes. Myocardial infarction (MI) trends were stable in men and increased in women. For incidence, the average annual percentage change (AAPC) for men vs. women, respectively, was IHD -2.6% vs. -3.4%; angina -7.0% vs. -7.3%; MI 0.01% vs. 2.3%; revascularization 1.1% vs. 3.9%; stroke/TIA 1.9% vs. 0.6%; HF 5.6% vs. 5.0% (P for trend <0.05 for all except MI and revascularization in men and stroke/TIA in women). For prevalence, AAPCs for men vs. women, respectively, were IHD -2.8% vs. -4.9%; angina -7.2% vs. -7.8%; MI -0.2% vs. 2.0; revascularization 3.2% vs. 4.1%; stroke/TIA 3.1% vs. 3.6%; HF 5.0% vs. 3.0% (P for trend <0.05 for all except MI in men). In recent years, IHD and revascularization trends levelled off, while stroke/TIA and HF trends increased in both sexes. Conclusion: Overall trends in incidence and prevalence of CVD are worsening in young adults. Factors behind unfavourable trends warrant investigation and public health intervention.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Phillips2022,

title = {Trends in the pharmacological management of atrial fibrillation in UK general practice 2008-2018},

author = {Katherine Phillips and Anuradhaa Subramanian and G. Neil Thomas and Nazish Khan and Joht Singh Chandan and Paul Brady and Tom Marshall and Krishnarajah Nirantharakumar and Larissa Fabritz and Nicola Jaime Adderley},

doi = {10.1136/HEARTJNL-2021-319338},

issn = {1468201X},

year  = {2022},

date = {2022-01-01},

journal = {Heart},

volume = {108},

issue = {7},

pages = {517-522},

publisher = {BMJ Publishing Group},

abstract = {Objective The pharmacological management of atrial fibrillation (AF) comprises anticoagulation, for stroke prophylaxis, and rate or rhythm control drugs to alleviate symptoms and prevent heart failure. The aim of this study was to investigate trends in the proportion of patients with AF prescribed pharmacological therapies in the UK between 2008 and 2018. Methods Eleven sequential cross-sectional analyses were performed yearly from 2008 to 2018. Data were derived from an anonymised UK primary care database. Outcomes were the proportion of patients with AF prescribed anticoagulants, rhythm and rate control drugs in the whole cohort, those at high risk of stroke and those with coexisting heart failure. Results Between 2008 and 2018, the proportion of patients prescribed anticoagulants increased from 45.3% (95% CI 45.0% to 45.7%) to 71.1% (95% CI 70.7% to 71.5%) driven by increased prescription of non-vitamin K antagonist anticoagulants. The proportion of patients prescribed rate control drugs remained constant between 2008 and 2018 (69.3% (95% CI 68.9% to 69.6%) to 71.6% (95% CI 71.2% to 71.9%)). The proportion of patients prescribed rhythm control therapy by general practitioners (GPs) decreased from 9.5% (95% CI 9.3% to 9.7%) to 5.4% (95% CI 5.2% to 5.6%). Conclusions There has been an increase in the proportion of patients with AF appropriately prescribed anticoagulants following National Institute for Health and Care Excellence and European Society of Cardiology guidelines, which correlates with improvements in mortality and stroke outcomes. Beta-blockers appear increasingly favoured over digoxin for rate control. There has been a steady decline in GP prescribing rates for rhythm control drugs, possibly related to concerns over efficacy and safety and increased availability of AF ablation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gooden2022,

title = {The risk of mental illness in people living with HIV in the UK: a propensity score-matched cohort study},

author = {Tiffany E. Gooden and Mike Gardner and Jingya Wang and Joht S. Chandan and Abi Beane and Rashan Haniffa and Stephen Taylor and Sheila Greenfield and Semira Manaseki-Holland and G. Neil Thomas and Krishnarajah Nirantharakumar},

doi = {10.1016/S2352-3018(21)00319-2},

issn = {23523018},

year  = {2022},

date = {2022-01-01},

journal = {The Lancet HIV},

volume = {9},

issue = {3},

pages = {e172-e181},

publisher = {Elsevier Ltd},

abstract = {Background: Prevalence of mental illness is higher in people living with HIV than in the general population, but the incidence of composite mental illness and its components is unclear. We aimed to identify the risk of incident mental illness along with individual conditions of depression, anxiety, and severe mental illness in people living with HIV in the UK. Methods: Data for this population-based cohort were extracted from the IQVIA Medical Research Database, a nationally representative UK-based database of primary care electronic health records. We included adults (aged ≥18 years) living with HIV, matched with adults without HIV using propensity score matching (1:1 ratio). The primary outcome was composite mental illness comprising a diagnosis of depression, anxiety, or severe mental illness. Secondary outcomes were individual mental health conditions. Cox proportional hazard regression models were used to compare the risk of each outcome between people with and without HIV. Each model excluded those with the outcome at baseline. Individuals were followed up prospectively. The study period was from Jan 1, 2000, to Jan 1, 2020. Findings: Of 7167 people living with HIV without mental illness at baseline, 586 developed a mental illness (incidence rate 19·6 per 1000 person-years) compared with 418 of 7167 people without HIV (incidence rate 12·1 per 1000 person-years), resulting in an adjusted hazard ratio (HR) of 1·63 (95% CI 1·44–1·85). People living with HIV had higher incidence rates for depression (15·4 per 1000 person-years), anxiety (7·2 per 1000 person-years), and severe mental illness (1·6 per 1000 person-years) compared with people without HIV (7·9, 5·0, and 0·6 per 1000 person-years, respectively), with adjusted HRs of 1·94 (95% CI 1·68–2·24) for depression, 1·38 (1·15–1·66) for anxiety, and 2·18 (1·41–3·39) for severe mental illness. Interpretation: People living with HIV have an increased risk for developing composite mental illness, depression, anxiety, and severe mental illness compared with people without HIV. People living with HIV should be regularly screened for mental illness; however, there is a strong need to improve prevention of mental illness in people living with HIV and for more outreach programmes to ensure that no groups of people living with HIV are being underdiagnosed. Funding: None.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Adderley2022,

title = {Development and external validation of prognostic models for COVID-19 to support risk stratification in secondary care},

author = {Nicola J. Adderley and Thomas Taverner and Malcolm James Price and Christopher Sainsbury and David Greenwood and Joht Singh Chandan and Yemisi Takwoingi and Rashan Haniffa and Isaac Hosier and Carly Welch and Dhruv Parekh and Suzy Gallier and Krishna Gokhale and Alastair K. Denniston and Elizabeth Sapey and Krishnarajah Nirantharakumar},

doi = {10.1136/BMJOPEN-2021-049506},

issn = {20446055},

year  = {2022},

date = {2022-01-01},

journal = {BMJ Open},

volume = {12},

issue = {1},

publisher = {BMJ Publishing Group},

abstract = {Objectives Existing UK prognostic models for patients admitted to the hospital with COVID-19 are limited by reliance on comorbidities, which are under-recorded in secondary care, and lack of imaging data among the candidate predictors. Our aims were to develop and externally validate novel prognostic models for adverse outcomes (death and intensive therapy unit (ITU) admission) in UK secondary care and externally validate the existing 4C score. Design Candidate predictors included demographic variables, symptoms, physiological measures, imaging and laboratory tests. Final models used logistic regression with stepwise selection. Setting Model development was performed in data from University Hospitals Birmingham (UHB). External validation was performed in the CovidCollab dataset. Participants Patients with COVID-19 admitted to UHB January-August 2020 were included. Main outcome measures Death and ITU admission within 28 days of admission. Results 1040 patients with COVID-19 were included in the derivation cohort; 288 (28%) died and 183 (18%) were admitted to ITU within 28 days of admission. Area under the receiver operating characteristic curve (AUROC) for mortality was 0.791 (95% CI 0.761 to 0.822) in UHB and 0.767 (95% CI 0.754 to 0.780) in CovidCollab; AUROC for ITU admission was 0.906 (95% CI 0.883 to 0.929) in UHB and 0.811 (95% CI 0.795 to 0.828) in CovidCollab. Models showed good calibration. Addition of comorbidities to candidate predictors did not improve model performance. AUROC for the International Severe Acute Respiratory and Emerging Infection Consortium 4C score in the UHB dataset was 0.753 (95% CI 0.720 to 0.785). Conclusions The novel prognostic models showed good discrimination and calibration in derivation and external validation datasets, and performed at least as well as the existing 4C score using only routinely collected patient information. The models can be integrated into electronic medical records systems to calculate each individual patient's probability of death or ITU admission at the time of hospital admission. Implementation of the models and clinical utility should be evaluated.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gokhale2022,

title = {Metformin and risk of age-related macular degeneration in individuals with type 2 diabetes: a retrospective cohort study},

author = {Krishna M. Gokhale and Nicola J. Adderley and Anuradhaa Subramanian and Wen Hwa Lee and Diana Han and Jesse Coker and Tasanee Braithwaite and Alastair K. Denniston and Pearse A. Keane and Krishnarajah Nirantharakumar},

doi = {10.1136/BJOPHTHALMOL-2021-319641},

issn = {14682079},

year  = {2022},

date = {2022-01-01},

journal = {British Journal of Ophthalmology},

publisher = {BMJ Publishing Group},

abstract = {Background: Age-related macular degeneration (AMD) in its late stages is a leading cause of sight loss in developed countries.Some previous studies have suggested that metformin may be associated with a reduced risk of developing AMD, but the evidence is inconclusive.Aims: To explore the relationship between metformin use and development of AMD among patients with type 2 diabetes in the UK.Methods: A large, population-based retrospective open cohort study with a time-dependent exposure design was carried out using IQVIA Medical Research Data, 1995-2019.Patients aged ≥40 with diagnosed type 2 diabetes were included.The exposed group was those prescribed metformin (with or without any other antidiabetic medications); the comparator (unexposed) group was those prescribed other antidiabetic medications only.The exposure status was treated as time varying, collected at 3-monthly time intervals.Extended Cox proportional hazards regression was used to calculate the adjusted HRs for development of the outcome, newly diagnosed AMD.Results: A total of 173 689 patients, 57% men, mean (SD) age 62.8 (11.6) years, with incident type 2 diabetes and a record of one or more antidiabetic medications were included in the study.Median follow-up was 4.8 (IQR 2.3-8.3, range 0.5-23.8) years.3111 (1.8%) patients developed AMD.The adjusted HR for diagnosis of AMD was 1.02 (95% CI 0.92 to 1.12) in patients prescribed metformin (with or without other antidiabetic medications) compared with those prescribed any other antidiabetic medication only.Conclusion: We found no evidence that metformin was associated with risk of AMD in primary care patients requiring treatment for type 2 diabetes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Adderley2022b,

title = {Headache, Opiate Use, and Prescribing Trends in Women with Idiopathic Intracranial Hypertension: A Population-Based Matched Cohort Study},

author = {Nicola Jaime Adderley and Anuradhaa Subramanian and Mary Perrins and Krishnarajah Nirantharakumar and Susan P. Mollan and Alexandra Jean Sinclair},

doi = {10.1212/WNL.0000000000201064},

issn = {1526632X},

year  = {2022},

date = {2022-01-01},

journal = {Neurology},

volume = {99},

issue = {18},

pages = {E1968-E1978},

publisher = {Lippincott Williams and Wilkins},

abstract = {Background and ObjectivesPhysician prescribing habits for opiates and headache therapies have not been previously evaluated in a large, matched cohort study in idiopathic intracranial hypertension (IIH). Our objective was to evaluate opiate and headache medication prescribing habits in women with IIH compared with matched women with migraine and population controls. We also investigated the occurrence of new onset headache in IIH compared with population controls.MethodsWe performed a population-based matched, retrospective cohort study to explore headache outcomes. Cross-sectional analyses were used to describe medication prescribing patterns. We used data from IQVIA Medical Research Data, an anonymized, nationally representative primary care electronic medical record database in the United Kingdom, from January 1, 1995, to September 25, 2019. Women aged 16 years and older were eligible for inclusion. Women with IIH (exposure) were matched by age and body mass index with up to 10 control women without IIH but with migraine (migraine controls), and without IIH or migraine (population controls).ResultsA total of 3,411 women with IIH, 13,966 migraine controls, and 33,495 population controls were included. The adjusted hazard ratio for new onset headache in IIH compared with population controls was 3.09 (95% CI 2.78-3.43). In the first year after diagnosis, 58% of women with IIH were prescribed acetazolamide and 20% topiramate. In total, 20% of women with IIH were prescribed opiates within the first year of their diagnosis, reducing to 17% after 6 years, compared with 8% and 11% among those with migraine, respectively. Twice as many women with IIH were prescribed opiates compared with migraine controls, and 3 times as many women with IIH were prescribed opiates compared with population controls. Women with IIH were also prescribed more headache preventative medications compared with migraine controls.DiscussionWomen with IIH were more likely to be prescribed opiate and simple analgesics compared with both migraine and population controls. Women with IIH trialed more preventative medications over their disease course suggesting that headaches in IIH may be more refractory to treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gooden2022b,

title = {Incidence of Cardiometabolic Diseases in People With and Without Human Immunodeficiency Virus in the United Kingdom: A Population-Based Matched Cohort Study},

author = {Tiffany E. Gooden and Mike Gardner and Jingya Wang and Kate Jolly and Deirdre A. Lane and Laura A. Benjamin and Henry C. Mwandumba and Vanessa Kandoole and Isaac B. Lwanga and Stephen Taylor and Semira Manaseki-Holland and Gregory Y. H. Lip and Krishnarajah Nirantharakumar and G. Neil Thomas},

doi = {10.1093/INFDIS/JIAB420},

issn = {15376613},

year  = {2022},

date = {2022-01-01},

journal = {Journal of Infectious Diseases},

volume = {225},

issue = {8},

pages = {1348-1356},

publisher = {Oxford University Press},

abstract = {Background: Evidence on the risk of cardiovascular disease (CVD) and CVD risk factors in people with human immunodeficiency virus (PWH) is limited. We aimed to identify the risk of composite CVD, individual CVD events, and common risk factors. Methods: This was a nationwide, population-based, cohort study comparing adult (≥18 years old) PWH with people without human immunodeficiency virus (HIV) matched on age, sex, ethnicity, and location. The primary outcome was composite CVD comprising stroke, myocardial infarction, peripheral vascular disease, ischemic heart disease, and heart failure. The secondary outcomes were individual CVD events, hypertension, diabetes, chronic kidney disease (CKD), and all-cause mortality. Cox proportional hazard regression models were used to examine the risk of each outcome. Results: We identified 9233 PWH and matched them with 35 721 HIV-negative individuals. An increased risk was found for composite CVD (adjusted hazard ratio [aHR], 1.50; 95% confidence interval [CI], 1.28-1.77), stroke (aHR, 1.42; 95% CI, 1.08-1.86), ischemic heart disease (aHR, 1.55; 95% CI, 1.24-1.94), hypertension (aHR, 1.37; 95% CI, 1.23-1.53), type 2 diabetes (aHR, 1.28; 95% CI, 1.09-1.50), CKD (aHR, 2.42; 95% CI, 1.98-2.94), and all-cause mortality (aHR, 2.84; 95% CI, 2.48-3.25). Conclusions: PWH have a heightened risk for CVD and common CVD risk factors, reinforcing the importance for regular screening for such conditions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Subramanian2022,

title = {Symptoms and risk factors for long COVID in non-hospitalized adults},

author = {Anuradhaa Subramanian and Krishnarajah Nirantharakumar and Sarah Hughes and Puja Myles and Tim Williams and Krishna M. Gokhale and Tom Taverner and Joht Singh Chandan and Kirsty Brown and Nikita Simms-Williams and Anoop D. Shah and Megha Singh and Farah Kidy and Kelvin Okoth and Richard Hotham and Nasir Bashir and Neil Cockburn and Siang Ing Lee and Grace M. Turner and Georgios V. Gkoutos and Olalekan Lee Aiyegbusi and Christel McMullan and Alastair K. Denniston and Elizabeth Sapey and Janet M. Lord and David C. Wraith and Edward Leggett and Clare Iles and Tom Marshall and Malcolm J. Price and Steven Marwaha and Elin Haf Davies and Louise J. Jackson and Karen L. Matthews and Jenny Camaradou and Melanie Calvert and Shamil Haroon},

doi = {10.1038/S41591-022-01909-W},

issn = {1546170X},

year  = {2022},

date = {2022-01-01},

journal = {Nature Medicine},

volume = {28},

issue = {8},

pages = {1706-1714},

publisher = {Nature Research},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vitalis2022,

title = {The Impact of Atrial Fibrillation on Outcomes of Peripheral Arterial Disease: Analysis of Routinely Collected Primary Care Data},

author = {Antonios Vitalis and Krishnarajah Nirantharakumar and Rasiah Thayakaran and Rajiv K. Vohra and Mark Kay and Alena Shantsila and Gregory Y. H. Lip},

doi = {10.1016/J.AMJMED.2021.10.021},

issn = {15557162},

year  = {2022},

date = {2022-01-01},

journal = {American Journal of Medicine},

volume = {135},

issue = {4},

pages = {488-492},

publisher = {Elsevier Inc.},

abstract = {Background: The combination of peripheral arterial disease and atrial fibrillation is linked with high risk of mortality and stroke. This study aims to investigate the impact of atrial fibrillation on patients with diagnosed peripheral arterial disease. Methods: This is a retrospective study using The Health Improvement Network database, which contains prospectively collected data from participating primary care practices. Patients with a new diagnosis of peripheral arterial disease between January 8, 1995 and January 5, 2017 were identified in the database alongside relevant demographic information, clinical history, and medications. Every patient in the dataset with peripheral arterial disease and baseline atrial fibrillation (case) was matched to a patient without atrial fibrillation (control) with similar characteristics using propensity score matching. Cox-regression analysis was performed and hazard ratios (HR) calculated for the outcomes of death, stroke, ischemic heart disease, heart failure, and major amputation. Results: Prevalence of atrial fibrillation in this cohort was 10.2%. All patients with peripheral arterial disease and atrial fibrillation (n = 5685) were matched with 5685 patients without atrial fibrillation but otherwise similar characteristics. After multivariate analysis, atrial fibrillation was independently associated with mortality (HR 1.18; 95% confidence interval [CI], 1.12-1.26; P <.01), cerebrovascular events (HR 1.35; 95% CI, 1.17-1.57; P <.01), and heart failure (HR 1.87; 95% CI, 1.62-2.15; P <.01), but not with ischemic heart disease or limb loss. Conclusion: In peripheral arterial disease patients, atrial fibrillation is a risk factor for mortality, stroke, and heart failure. This emphasizes the need for proactive surveillance and holistic management of these patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wang2022,

title = {Diabetic Foot Risk Classification at the Time of Type 2 Diabetes Diagnosis and Subsequent Risk of Mortality: A Population-Based Cohort Study},

author = {Zhaonan Wang and Jonathan Hazlehurst and Anuradhaa Subramanian and Abd A. Tahrani and Wasim Hanif and Neil Thomas and Pushpa Singh and Jingya Wang and Christopher Sainsbury and Krishnarajah Nirantharakumar and Francesca L. Crowe},

doi = {10.3389/FENDO.2022.888924},

issn = {16642392},

year  = {2022},

date = {2022-01-01},

journal = {Frontiers in Endocrinology},

volume = {13},

publisher = {Frontiers Media S.A.},

abstract = {Aim: We aimed to compare the mortality of individuals at low, moderate, and high risk of diabetic foot disease (DFD) in the context of newly diagnosed type 2 diabetes, before developing active diabetic foot problem. Methods: This was a population-based cohort study of adults with newly diagnosed type 2 diabetes utilizing IQVIA Medical Research Data. The outcome was all-cause mortality among individuals with low, moderate, and high risk of DFD, and also in those with no record of foot assessment and those who declined foot examination. Results: Of 225,787 individuals with newly diagnosed type 2 diabetes, 34,061 (15.1%) died during the study period from January 1, 2000 to December 31, 2019. Moderate risk and high risk of DFD were associated with increased mortality risk compared to low risk of DFD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.42, 1.58; aHR 2.01, 95% CI 1.84, 2.20, respectively). Individuals who declined foot examination or who had no record also had increased mortality risk of 75% and 25% vs. those at low risk of DFD, respectively (aHR 1.75, 95% CI 1.51, 2.04; aHR 1.25, 95% CI 1.20, 1.30). Conclusion: Individuals with new-onset type 2 diabetes who had moderate to high risk of DFD were more likely to die compared to those at low risk of DFD. The associations between declined foot examination and absence of foot examinations, and increased risk of mortality further highlight the importance of assessing foot risk as it identifies not only patients at risk of diabetic foot ulceration but also mortality.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gokhale2022b,

title = {The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services},

author = {Krishna Gokhale and Samiul A. Mostafa and Jingya Wang and Abd A. Tahrani and Christopher Andrew Sainsbury and Konstantinos A. Toulis and G. Neil Thomas and Zaki Hassan-Smith and Elizabeth Sapey and Suzy Gallier and Nicola Jaime Adderley and Parth Narendran and Srikanth Bellary and Tom Taverner and Sandip Ghosh and Krishnarajah Nirantharakumar and Wasim Hanif},

doi = {10.1002/EDM2.309},

issn = {23989238},

year  = {2022},

date = {2022-01-01},

journal = {Endocrinology, Diabetes and Metabolism},

volume = {5},

issue = {1},

publisher = {John Wiley and Sons Inc},

abstract = {Introduction: To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes. Methods: Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality. Results: Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95–2.03},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nichols2022,

title = {In simulated data and health records, latent class analysis was the optimum multimorbidity clustering algorithm},

author = {Linda Nichols and Tom Taverner and Francesca Crowe and Sylvia Richardson and Christopher Yau and Steven Kiddle and Paul Kirk and Jessica Barrett and Krishnarajah Nirantharakumar and Simon Griffin and Duncan Edwards and Tom Marshall},

doi = {10.1016/J.JCLINEPI.2022.10.011},

issn = {18785921},

year  = {2022},

date = {2022-01-01},

journal = {Journal of Clinical Epidemiology},

volume = {152},

pages = {164-175},

publisher = {Elsevier Inc.},

abstract = {Background and Objectives: To investigate the reproducibility and validity of latent class analysis (LCA) and hierarchical cluster analysis (HCA), multiple correspondence analysis followed by k-means (MCA-kmeans) and k-means (kmeans) for multimorbidity clustering. Methods: We first investigated clustering algorithms in simulated datasets with 26 diseases of varying prevalence in predetermined clusters, comparing the derived clusters to known clusters using the adjusted Rand Index (aRI). We then them investigated in the medical records of male patients, aged 65 to 84 years from 50 UK general practices, with 49 long-term health conditions. We compared within cluster morbidity profiles using the Pearson correlation coefficient and assessed cluster stability was in 400 bootstrap samples. Results: In the simulated datasets, the closest agreement (largest aRI) to known clusters was with LCA and then MCA-kmeans algorithms. In the medical records dataset, all four algorithms identified one cluster of 20–25% of the dataset with about 82% of the same patients across all four algorithms. LCA and MCA-kmeans both found a second cluster of 7% of the dataset. Other clusters were found by only one algorithm. LCA and MCA-kmeans clustering gave the most similar partitioning (aRI 0.54). Conclusion: LCA achieved higher aRI than other clustering algorithms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Haroon2022,

title = {Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study)},

author = {Shamil Haroon and Krishnarajah Nirantharakumar and Sarah E. Hughes and Anuradhaa Subramanian and Olalekan Lee Aiyegbusi and Elin Haf Davies and Puja Myles and Tim Williams and Grace Turner and Joht Singh Chandan and Christel McMullan and Janet Lord and David C. Wraith and Kirsty McGee and Alastair K. Denniston and Thomas Taverner and Louise J. Jackson and Elizabeth Sapey and George Gkoutos and Krishna Gokhale and Edward Leggett and Clare Iles and Christopher Frost and Gary McNamara and Amy Bamford and Tom Marshall and Dawit T. Zemedikun and Gary Price and Steven Marwaha and Nikita Simms-Williams and Kirsty Brown and Anita Walker and Karen Jones and Karen Matthews and Jennifer Camaradou and Michael Saint-Cricq and Sumita Kumar and Yvonne Alder and David E. Stanton and Lisa Agyen and Megan Baber and Hannah Blaize and Melanie Calvert},

doi = {10.1136/BMJOPEN-2021-060413},

issn = {20446055},

year  = {2022},

date = {2022-01-01},

journal = {BMJ Open},

volume = {12},

issue = {4},

publisher = {BMJ Publishing Group},

abstract = {Introduction Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies. Methods and analysis A cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year. Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy. We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation. Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group. Ethics and dissemination Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers. Trial registration number 1567490.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zemedikun2022,

title = {Comorbidity phenotypes and risk of mortality in patients with osteoarthritis in the UK: a latent class analysis},

author = {Dawit T. Zemedikun and Helena Lee and Krishnarajah Nirantharakumar and Karim Raza and Joht Singh Chandan and Janet M. Lord and Thomas A. Jackson},

doi = {10.1186/S13075-022-02909-4},

issn = {14786362},

year  = {2022},

date = {2022-01-01},

journal = {Arthritis Research and Therapy},

volume = {24},

issue = {1},

publisher = {BioMed Central Ltd},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Singh2022,

title = {Glycemic outcomes in patients with type 2 diabetes after bariatric surgery compared with routine care: a population-based, real-world cohort study in the United Kingdom},

author = {Pushpa Singh and Nicola J. Adderley and Anuradhaa Subramanian and Krishna Gokhale and Jonathan Hazlehurst and Rishi Singhal and Srikanth Bellary and Abd A. Tahrani and Krishnarajah Nirantharakumar},

doi = {10.1016/J.SOARD.2022.08.001},

issn = {18787533},

year  = {2022},

date = {2022-01-01},

journal = {Surgery for Obesity and Related Diseases},

volume = {18},

issue = {12},

pages = {1366-1376},

publisher = {Elsevier Inc.},

abstract = {Background: Clinical trials have shown that bariatric surgery (BS) is associated with better glycemic control and diabetes remission in patients with type 2 diabetes (T2D) compared with routine care. Objective: We conducted a real-world population-based study examining the impact of BS on glycemic control and medications in patients with T2D. Setting and Methods: This was a retrospective, matched, controlled cohort study conducted between January 1, 1990, and January 31, 2018, using IQVIA Medical Research Data, a primary care electronic records database. Adults with body mass index (BMI) ≥30 kg/m2 and T2D who had BS (surgical) were matched for age, sex, BMI, and diabetes duration to two controls (with T2D and no BS). Results: A total of 1126 patients in the surgical group and 2219 patients in the control group were analyzed. Mean (standard deviation) age was 50.0 (9.3) years, 67.6% were women, baseline glycocylated hemoglobin (HbA1C) was 7.8% (1.7 mmol/mol), and diabetes duration was 4.7 years (range, 2.0–8.4 years). Over a median (interquartile range) follow-up of 3.6 years (1.7–5.9 years), a higher proportion of patients in the surgical group achieved an HbA1C of ≤6.0% than the control group (65.8% versus 22.8%). The surgical group showed a decrease in mean HbA1C of 1.5% (95% confidence interval [CI]: 1.4%–1.7%), 1.4% (1.2%–1.5%), and 1.3% (1.1%–1.5%) at 1-, 2-, and 3-year follow-up, respectively, whereas HbA1C increased in the control group. The proportion of patients receiving glucose-lowering medications decreased in the surgical group (92.2% to 66.5%) but increased in the control group (85.3% to 90.2%). Conclusion: BS is associated with significant improvement in glycemic control, achievement of normal HbA1C levels, and reduced need for glucose-lowering therapy in patients with T2D.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Subramanian2022b,

title = {Polycystic ovary syndrome and risk of adverse obstetric outcomes: a retrospective population-based matched cohort study in England},

author = {Anuradhaa Subramanian and Siang Ing Lee and Katherine Phillips and Konstantinos A. Toulis and Punith Kempegowda and Michael W. O’reilly and Nicola J. Adderley and Shakila Thangaratinam and Wiebke Arlt and Krishnarajah Nirantharakumar},

doi = {10.1186/S12916-022-02473-3},

issn = {17417015},

year  = {2022},

date = {2022-01-01},

journal = {BMC Medicine},

volume = {20},

issue = {1},

publisher = {BioMed Central Ltd},

abstract = {Background: Polycystic ovary syndrome (PCOS) affects up to one in five women of childbearing age. Observational studies assessing the association between maternal PCOS and adverse obstetric outcomes have reported varying results, depending on patient population, diagnostic criteria for PCOS and covariates accounted for in their analyses. We aimed to assess the risk of obstetric outcomes among a population-based representative cohort of women with PCOS compared to an age-matched cohort of women without PCOS. Methods: A retrospective cohort study was conducted of pregnancies of women in England aged 15–49 years identified from the Clinical Practice Research Datalink (CPRD) GOLD pregnancy register and linked Hospital Episodes Statistic (HES) data between March 1997 and March 2020. Pregnancies from the register that had a linked HES delivery record were included. Linked CPRD primary care data was used to ascertain maternal PCOS exposure prior to pregnancy. To improve detection of PCOS, in addition to PCOS diagnostic codes, codes for (1) polycystic ovaries or (2) hyperandrogenism and anovulation together were also considered. Sensitivity analysis was limited to only pregnant women with a diagnostic code for PCOS. Primary outcomes ascertained from linked HES data were (1) preterm delivery (gestation < 37 weeks), (2) mode of delivery, (3) high (> 4000 g) or low birthweight (< 2500 g) and (4) stillbirth. Secondary outcomes were (1) very preterm delivery (< 32 weeks), (2) extremely preterm delivery (< 28 weeks), (3) small and (4) large for gestational age. Conditional logistic regression models were performed adjusting for age, ethnicity, deprivation, dysglycaemia, hypertension, thyroid disorders, number of babies born at index pregnancy, and pre-gravid BMI. Multiple imputation was performed for missing outcome data. Results: 27,586 deliveries with maternal PCOS were matched for age (± 1 year) to 110,344 deliveries without PCOS. In the fully adjusted models, maternal PCOS was associated with an increased risk of (1) preterm birth [aOR: 1.11 (95% CI 1.06–1.17)], and (2) emergency caesarean, elective caesarean and instrumental vaginal compared to spontaneous delivery [aOR: 1.10 (1.05–1.15), 1.07 (1.03–1.12) and 1.04 (1.00–1.09), respectively]. There was absence of association with low birthweight, high birthweight and stillbirth. In the sensitivity analysis, the association with preterm birth [aOR: 1.31 (95% CI 1.13–1.52)], emergency caesarean [aOR: 1.15 (95% CI 1.02–1.30)], and elective caesarean [aOR: 1.03 (95% CI 1.02–1.03)] remained. While there was no significant association with any of the secondary outcomes in the primary analysis, in the sensitivity analysis maternal PCOS was associated with increased risk of extremely preterm delivery [aOR: 1.86 (95% CI 1.31–2.65)], and lower risk of small for gestational age babies [aOR: 0.74 (95% CI 0.59–0.94)]. Conclusions: Maternal PCOS was associated with increased risk of preterm and caesarean delivery. Association with low birthweight may be largely mediated by lower gestational age at birth.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Simms-Williams2022,

title = {Preventing unscheduled hospitalisations from asthma: A retrospective cohort study using routine primary and secondary care data in the UK (The PUSH-Asthma Study) - protocol paper},

author = {Nikita Simms-Williams and Prasad Nagakumar and Rasiah Thayakaran and Nicola Adderley and Richard Hotham and Adel Mansur and Krishnarajah Nirantharakumar and Shamil Haroon},

doi = {10.1136/BMJOPEN-2021-058356},

issn = {20446055},

year  = {2022},

date = {2022-01-01},

journal = {BMJ Open},

volume = {12},

issue = {8},

publisher = {BMJ Publishing Group},

abstract = {Introduction Asthma is the most common chronic respiratory disease in children and adults. Asthma results in significant disease-related morbidity, healthcare costs and, in some cases, death. Despite efforts through implementation of national guidelines to improve asthma care, the UK has one of the highest asthma-related morbidity and mortality rates in the western world. New approaches are necessary to prevent asthma attacks in children and adults. The objectives of this study are to assess the association between demographic and clinical factors and asthma-related hospital admissions in children and adults, describe the epidemiology of asthma phenotypes among hospital attenders, and externally validate existing asthma risk prediction models. Methods and analysis This is a retrospective cohort study of children and adults with asthma. Data will be extracted from the Clinical Practice Research Datalink (CPRD) Aurum database, which holds anonymised primary care data for over 13 million actively registered patients and covers approximately 19% of the UK population. The primary outcome will be asthma-related hospital admissions. The secondary outcomes will be prescriptions of short courses of oral corticosteroids (as a surrogate measure for asthma exacerbations), a composite outcome measure including hospital admissions and prescriptions of short courses of oral corticosteroids and delivery of asthma care management following hospital discharge. The primary analysis will use a Poisson regression model to assess the association between demographic and clinical risk factors and the primary and secondary outcomes. Latent class analysis will be used to identify distinct subgroups, which will further our knowledge on potential phenotypes of asthma among patients at high risk of asthma-related hospital admissions. A Concordance statistic (C-statistic) and logistic regression model will also be used to externally validate existing risk prediction models for asthma-related hospitalisations to allow for the optimal model to be identified and evaluated provide evidence for potential use of the optimal performing risk prediction model in primary care. Ethics and dissemination This study was approved by the CPRD Independent Scientific Advisory Committee (reference number: 21_000512). Findings from this study will be published in a peer-reviewed journal and disseminated at national and international conferences.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{umilo2022,

title = {Long term impact of prophylactic antibiotic use before incision versus after cord clamping on children born by caesarean section: longitudinal study of UK electronic health records},

author = {Dana Šumilo and Krishnarajah Nirantharakumar and Brian H. Willis and Gavin M. Rudge and James Martin and Krishna Gokhale and Rasiah Thayakaran and Nicola J. Adderley and Joht Singh Chandan and Kelvin Okoth and Isobel M. Harris and Ruth Hewston and Magdalena Skrybant and Jonathan J. Deeks and Peter Brocklehurst},

doi = {10.1136/BMJ-2021-069704},

issn = {17561833},

year  = {2022},

date = {2022-01-01},

journal = {BMJ (Clinical research ed.)},

volume = {377},

pages = {e069704},

publisher = {NLM (Medline)},

abstract = {OBJECTIVE: To investigate the impact on child health up to age 5 years of a policy to use antibiotic prophylaxis for caesarean section before incision compared with after cord clamping. DESIGN: Observational controlled interrupted time series study. SETTING: UK primary and secondary care. PARTICIPANTS: 515 945 children born in 2006-18 with linked maternal records and registered with general practices contributing to two UK primary care databases (The Health Improvement Network and Clinical Practice Research Datalink), and 7 147 884 children with linked maternal records in the Hospital Episode Statistics database covering England, of which 3 945 351 were linked to hospitals that reported the year of policy change to administer prophylactic antibiotics for caesarean section before incision rather than after cord clamping. INTERVENTION: Fetal exposure to antibiotics shortly before birth (using pre-incision antibiotic policy as proxy) compared with no exposure. MAIN OUTCOME MEASURES: The primary outcomes were incidence rate ratios of asthma and eczema in children born by caesarean section when pre-incision prophylactic antibiotics were recommended compared with those born when antibiotics were administered post-cord clamping, adjusted for temporal changes in the incidence rates in children born vaginally. RESULTS: Prophylactic antibiotics administered before incision for caesarean section compared with after cord clamping were not associated with a significantly higher risk of asthma (incidence rate ratio 0.91, 95% confidence interval 0.78 to 1.05) or eczema (0.98, 0.94 to 1.03), including asthma and eczema resulting in hospital admission (1.05, 0.99 to 1.11 and 0.96, 0.71 to 1.29, respectively), up to age 5 years. CONCLUSIONS: This study found no evidence of an association between pre-incision prophylactic antibiotic use and risk of asthma and eczema in early childhood in children born by caesarean section.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Thayakaran2022,

title = {Cluster analysis of patients with granulomatosis with polyangiitis (GPA) based on clinical presentation symptoms: a UK population-based cohort study},

author = {Rasiah Thayakaran and Ruchika Goel and Nicola J. Adderley and Joht Singh Chandan and Dawit Zemedikun and Krishnarajah Nirantharakumar and Lorraine Harper},

doi = {10.1186/S13075-022-02885-9},

issn = {14786362},

year  = {2022},

date = {2022-01-01},

journal = {Arthritis Research and Therapy},

volume = {24},

issue = {1},

publisher = {BioMed Central Ltd},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{umilo2022b,

title = {Long-term impact of pre-incision antibiotics on children born by caesarean section: a longitudinal study based on UK electronic health records},

author = {Dana Šumilo and Krishnarajah Nirantharakumar and Brian H. Willis and Gavin M. Rudge and James Martin and Krishna Gokhale and Rasiah Thayakaran and Nicola J. Adderley and Joht Singh Chandan and Kelvin Okoth and Isobel M. Harris and Ruth Hewston and Magdalena Skrybant and Jonathan J. Deeks and Peter Brocklehurst},

doi = {10.3310/ZYZC8514},

issn = {20464924},

year  = {2022},

date = {2022-01-01},

journal = {Health Technology Assessment},

volume = {26},

issue = {30},

pages = {vii-63},

publisher = {NIHR Journals Library},

abstract = {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 postcord 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lee2022b,

title = {Epidemiology of pre-existing multimorbidity in pregnant women in the UK in 2018: a population-based cross-sectional study},

author = {Siang Ing Lee and Amaya Azcoaga-Lorenzo and Utkarsh Agrawal and Jonathan I. Kennedy and Adeniyi Francis Fagbamigbe and Holly Hope and Anuradhaa Subramanian and Astha Anand and Beck Taylor and Catherine Nelson-Piercy and Christine Damase-Michel and Christopher Yau and Francesca Crowe and Gillian Santorelli and Kelly Ann Eastwood and Zoe Vowles and Maria Loane and Ngawai Moss and Peter Brocklehurst and Rachel Plachcinski and Shakila Thangaratinam and Mairead Black and Dermot O’Reilly and Kathryn M. Abel and Sinead Brophy and Krishnarajah Nirantharakumar and Colin McCowan},

doi = {10.1186/S12884-022-04442-3},

issn = {14712393},

year  = {2022},

date = {2022-01-01},

journal = {BMC Pregnancy and Childbirth},

volume = {22},

issue = {1},

publisher = {BioMed Central Ltd},

abstract = {Background: Although maternal death is rare in the United Kingdom, 90% of these women had multiple health/social problems. This study aims to estimate the prevalence of pre-existing multimorbidity (two or more long-term physical or mental health conditions) in pregnant women in the United Kingdom (England, Northern Ireland, Wales and Scotland). Study design: Pregnant women aged 15–49 years with a conception date 1/1/2018 to 31/12/2018 were included in this population-based cross-sectional study, using routine healthcare datasets from primary care: Clinical Practice Research Datalink (CPRD, United Kingdom},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Umar2022,

title = {The association between inflammatory bowel disease and mental ill health: a retrospective cohort study using data from UK primary care},

author = {Nosheen Umar and Dominic King and Joht Singh Chandan and Neeraj Bhala and Krish Nirantharakumar and Nicola Adderley and Dawit T. Zemedikun and Phil Harvey and Nigel Trudgill},

doi = {10.1111/APT.17110},

issn = {13652036},

year  = {2022},

date = {2022-01-01},

journal = {Alimentary Pharmacology and Therapeutics},

volume = {56},

issue = {5},

pages = {814-822},

publisher = {John Wiley and Sons Inc},

abstract = {Background: Patients with active inflammatory bowel disease (IBD) and mental illnesses experience worse IBD outcomes. Aim: To describe the incidence of mental illnesses, including deliberate self-harm, in IBD patients. Methods: A population-based retrospective cohort study using IQVIA medical research data of a primary care database covering the whole UK, between January 1995 and January 2021. IBD patients of all ages were matched 4:1 by demographics and primary care practice to unexposed controls. Following exclusion of patients with mental ill health at study entry, adjusted hazard ratios (HR) of developing depression, anxiety, deliberate self-harm, severe mental illness and insomnia were calculated using a Cox proportional hazards model. Results: We included 48,799 incident IBD patients: 28,352 with ulcerative colitis and 20,447 with Crohn's disease. Incidence rate ratios of mental illness were higher in IBD patients than controls (all p < 0.001): deliberate self-harm 1.31 (95% CI 1.16–1.47), anxiety 1.17 (1.11–1.24), depression 1.36 (1.31–1.42) and insomnia 1.62 (1.54–1.69). Patients with Crohn's disease were more likely to develop deliberate self-harm HR 1.51 (95% CI 1.28–1.78), anxiety 1.38 (1.16–1.65), depression 1.36 (1.26–1.47) and insomnia 1.74 (1.62–1.86). Patients with IBD are at increased risk of deliberate self-harm (HR 1.20 [1.07–1.35]). The incidence rate ratios of mental illnesses were particularly high during the first year following IBD diagnosis: anxiety 1.28 (1.13–1.46), depression 1.62 (1.48–1.77) and insomnia 1.99 (1.78–2.21). Conclusion: Deliberate self-harm, depression, anxiety and insomnia were more frequent among patients with IBD. IBD is independently associated with an increased risk of deliberate self-harm.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Subramanian2022c,

title = {Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension},

author = {Anuradhaa Subramanian and Diana Han and Tasanee Braithwaite and Rasiah Thayakaran and Dawit T. Zemedikun and Krishna M. Gokhale and Wen Hwa Lee and Jesse Coker and Pearse A. Keane and Alastair K. Denniston and Krishnarajah Nirantharakumar and Laurent Azoulay and Nicola J. Adderley},

doi = {10.1111/BCP.15366},

issn = {13652125},

year  = {2022},

date = {2022-01-01},

journal = {British Journal of Clinical Pharmacology},

volume = {88},

issue = {9},

pages = {4199-4210},

publisher = {John Wiley and Sons Inc},

abstract = {Aims: Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK. Methods: In this study, 53 832 and 43 106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD. Results: During a median follow-up of 2 years (interquartile range 1–5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2–2.6) and 2.2 (2.0–2.4) per 1000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90–1.27] and 0.87 [0.71–1.07], respectively). Conclusion: We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Alshehri2022,

title = {Risk of incident obstructive sleep apnoea in patients with type 1 diabetes: a population-based retrospective cohort study},

author = {Ziyad Alshehri and Anuradhaa Subramanian and Nicola J. Adderley and Krishna M. Gokhale and Muhammad Ali Karamat and Clare J. Ray and Prem Kumar and Krishnarajah Nirantharakumar and Abd A. Tahrani},

doi = {10.1007/S00125-022-05714-5},

issn = {14320428},

year  = {2022},

date = {2022-01-01},

journal = {Diabetologia},

volume = {65},

issue = {8},

pages = {1353-1363},

publisher = {Springer Science and Business Media Deutschland GmbH},

abstract = {Aims/hypothesis: People with type 2 diabetes are at increased risk of developing obstructive sleep apnoea. However, it is not known whether people with type 1 diabetes are also at an increased risk of obstructive sleep apnoea. This study aimed to examine whether people with type 1 diabetes are at increased risk of incident obstructive sleep apnoea compared with a matched cohort without type 1 diabetes. Methods: We used a UK primary care database, The Health Improvement Network (THIN), to perform a retrospective cohort study between January 1995 and January 2018 comparing sleep apnoea incidence between patients with type 1 diabetes (exposed) and without type 1 diabetes (unexposed) (matched for age, sex, BMI and general practice). The outcome was incidence of obstructive sleep apnoea. Baseline covariates and characteristics were assessed at the start of the study based on the most recent value recorded prior to the index date. The Cox proportional hazards regression model was used to estimate unadjusted and adjusted hazard ratios, based on a complete-case analysis. Results: In total, 34,147 exposed and 129,500 matched unexposed patients were included. The median follow-up time was 5.43 years ((IQR 2.19–10.11), and the mean BMI was 25.82 kg/m2 (SD 4.33). The adjusted HR for incident obstructive sleep apnoea in patients with type 1 diabetes vs those without type 1 diabetes was 1.53 (95% CI 1.25, 1.86; p<0.001). Predictors of incident obstructive sleep apnoea in patients with type 1 diabetes were older age, male sex, obesity, being prescribed antihypertensive or lipid-lowering drugs, atrial fibrillation and depression. Conclusions/interpretation: Individuals with type 1 diabetes are at increased risk of obstructive sleep apnoea compared with people without diabetes. Clinicians should suspect obstructive sleep apnoea in patients with type 1 diabetes if they are old, have obesity, are male, have atrial fibrillation or depression, or if they are taking lipid-lowering or antihypertensive drugs. Graphical abstract: [Figure not available: see fulltext.]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Benson2022,

title = {Analysis of the relationship between sex and prescriptions for guideline-recommended therapy in peripheral arterial disease, in relation to 1-year all-cause mortality: A primary care cohort study},

author = {Ruth A. Benson and Kelvin Okoth and Deepiksana Keerthy and Krishna Gokhale and Nicola J. Adderley and Krishnarajah Nirantharakumar and Daniel S. Lasserson},

doi = {10.1136/BMJOPEN-2021-055952},

issn = {20446055},

year  = {2022},

date = {2022-01-01},

journal = {BMJ Open},

volume = {12},

issue = {3},

publisher = {BMJ Publishing Group},

abstract = {Objectives To explore population patterns of sex-based incidence and prevalence of peripheral arterial disease (PAD), guideline-directed best medical therapy prescriptions and its relationship with all-cause mortality at 1 year. Design A retrospective cohort study. Setting Anonymised electronic primary care from 787 practices in the UK, or approximately 6.2% of the UK population. Participants All registered patients over 40 with a documented diagnosis of peripheral arterial disease. Outcome measure Population incidence and prevalence of PAD by sex. Patterns of guideline-directed therapy, and correlation with all-cause mortality at 1 year (defined as death due to any outcome) in patients with and without an existing diagnosis of cardiovascular disease. Covariates included Charlson comorbidity, sex, age, body mass index, Townsend score of deprivation, smoking status, diabetes, hypertension, statin and antiplatelet prescription. Results Sequential cross-sectional studies from 2010 to 2017 found annual PAD prevalence (12.7-14.3 vs 25.6 per 1000 in men) and incidence were lower in women (11.6-12.4 vs 22.7-26.8 per 10 000 person years in men). Cox proportional hazards models created for PAD patients with and without cardiovascular disease over one full year analysed 25 121 men and 13 480 women, finding that following adjustment for age, women were still less likely to be on a statin (OR 0.69; 95% CI 0.66 to 0.72; p<0.001) or antiplatelet (OR: 0.87; 95% CI 0.83 to 0.90; p<0.001). Once fully adjusted for guideline recommended medical therapy, all-cause mortality was similar between women and men (adjusted HR (aHR) 0.95, 95% CI 0.87 to 1.03},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chandan2021,

title = {Intimate Partner Violence and the Risk of Developing Fibromyalgia and Chronic Fatigue Syndrome},

author = {Joht Singh Chandan and Tom Thomas and Karim Raza and Caroline Bradbury-Jones and Julie Taylor and Siddhartha Bandyopadhyay and Krishnarajah Nirantharakumar},

doi = {10.1177/0886260519888515},

issn = {15526518},

year  = {2021},

date = {2021-01-01},

journal = {Journal of Interpersonal Violence},

volume = {36},

issue = {21-22},

pages = {NP12279-NP12298},

publisher = {SAGE Publications Inc.},

abstract = {Intimate partner violence (IPV) is a global public health issue with a variety of ill health consequences associated with exposure. Due to the stimulation of chronic stress and inflammatory pathways, childhood abuse has been associated with the subsequent development of functional syndromes such as fibromyalgia and chronic fatigue syndrome (CFS). Although IPV in women appears to elicit similar biochemical responses, this association has not been tested thoroughly in IPV survivors. These functional syndromes are complex in etiology and any indication of their risk factors would benefit health care professionals managing this population. Therefore, we aimed to investigate the association between exposure to IPV with functional syndromes: fibromyalgia and CFS. We conducted a retrospective open cohort study using “The Heath Improvement Network” database between January 1, 1995 and December 1, 2017. A total of 18,547 women who were exposed to IPV were each matched by age to four controls who were not exposed (n = 74,188). The main outcome measures were the risk of developing fibromyalgia and CFS. These were presented as adjusted incidence rate ratios (aIRR) with 95% confidence intervals (CIs). We found that 97 women in the exposed group developed fibromyalgia (incidence rate [IR] = 1.63 per 1,000 person-years) compared to 239 women in the unexposed group (IR = 0.83 per 1,000 person-years). Following adjustment, this translated to an IRR of 1.73 (95% CI = [1.36, 2.22]). Similarly, 19 women developed CFS in the exposed group (IR = 0.32 per 1,000 person-years), compared to 53 in the unexposed group (0.18 per 1,000 person-years), which translates to an aIRR of 1.92 (95% CI = [1.11, 3.33]). Therefore, we have identified an association between a history of IPV in women and the development of these functional syndromes, which may provide more information to inform the biopsychosocial pathway precipitating the development of fibromyalgia and CFS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Subramanian2021,

title = {Ethnicity-based differences in the incident risk of allergic diseases and autoimmune disorders: A UK-based retrospective cohort study of 4.4 million participants},

author = {Anuradhaa Subramanian and Nicola J. Adderley and Georgios V. Gkoutos and Krishna Margadhamane Gokhale and Krishnarajah Nirantharakumar and Mamidipudi Thirumala Krishna},

doi = {10.1111/CEA.13741},

issn = {13652222},

year  = {2021},

date = {2021-01-01},

journal = {Clinical and Experimental Allergy},

volume = {51},

issue = {1},

pages = {144-147},

publisher = {Blackwell Publishing Ltd},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gokhale2021,

title = {Data extraction for epidemiological research (DExtER): a novel tool for automated clinical epidemiology studies},

author = {Krishna Margadhamane Gokhale and Joht Singh Chandan and Konstantinos Toulis and Georgios Gkoutos and Peter Tino and Krishnarajah Nirantharakumar},

doi = {10.1007/S10654-020-00677-6},

issn = {15737284},

year  = {2021},

date = {2021-01-01},

journal = {European Journal of Epidemiology},

volume = {36},

issue = {2},

pages = {165-178},

publisher = {Springer Science and Business Media B.V.},

abstract = {The use of primary care electronic health records for research is abundant. The benefits gained from utilising such records lies in their size, longitudinal data collection and data quality. However, the use of such data to undertake high quality epidemiological studies, can lead to significant challenges particularly in dealing with misclassification, variation in coding and the significant effort required to pre-process the data in a meaningful format for statistical analysis. In this paper, we describe a methodology to aid with the extraction and processing of such databases, delivered by a novel software programme; the “Data extraction for epidemiological research” (DExtER). The basis of DExtER relies on principles of extract, transform and load processes. The tool initially provides the ability for the healthcare dataset to be extracted, then transformed in a format whereby data is normalised, converted and reformatted. DExtER has a user interface designed to obtain data extracts specific to each research question and observational study design. There are facilities to input the requirements for; eligible study period, definition of exposed and unexposed groups, outcome measures and important baseline covariates. To date the tool has been utilised and validated in a multitude of settings. There have been over 35 peer-reviewed publications using the tool, and DExtER has been implemented as a validated public health surveillance tool for obtaining accurate statistics on epidemiology of key morbidities. Future direction of this work will be the application of the framework to linked as well as international datasets and the development of standardised methods for conducting electronic pre-processing and extraction from datasets for research purposes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wang2021,

title = {Association of Metformin with Susceptibility to COVID-19 in People with Type 2 Diabetes},

author = {Jingya Wang and Jennifer M. Cooper and Krishna Gokhale and Dionisio Acosta-Mena and Samir Dhalla and Nathan Byne and Joht Singh Chandan and Astha Anand and Kelvin Okoth and Anuradhaa Subramanian and Mansoor N. Bangash and Thomas Jackson and Dawit Zemedikun and Tom Taverner and Wasim Hanif and Sandip Ghosh and Parth Narendran and Konstantinos A. Toulis and Abd A. Tahrani and Rajendra Surenthirakumaran and Nicola J. Adderley and Shamil Haroon and Kamlesh Khunti and Christopher Sainsbury and G. Neil Thomas and Krishnarajah Nirantharakumar},

doi = {10.1210/CLINEM/DGAB067},

issn = {19457197},

year  = {2021},

date = {2021-01-01},

journal = {Journal of Clinical Endocrinology and Metabolism},

volume = {106},

issue = {5},

pages = {1255-1268},

publisher = {Endocrine Society},

abstract = {Objective: Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes. Research Design and Methods: We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed. Results: There were 29 558 and 10 271 patients in the MF+ and MF-groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding. Conclusion: Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Parry-Smith2021,

title = {Postpartum haemorrhage and risk of mental ill health: A population-based longitudinal study using linked primary and secondary care databases},

author = {William Parry-Smith and Kelvin Okoth and Anuradhaa Subramanian and Krishna Margadhamane Gokhale and Joht Singh Chandan and Clara Humpston and Arri Coomarasamy and Krishnarajah Nirantharakumar and Dana Šumilo},

doi = {10.1016/J.JPSYCHIRES.2021.03.022},

issn = {18791379},

year  = {2021},

date = {2021-01-01},

journal = {Journal of Psychiatric Research},

volume = {137},

pages = {419-425},

publisher = {Elsevier Ltd},

abstract = {There is a gap in the literature investigating the impact of obstetric complications on subsequent mental ill health outcomes. The aim of this study was to establish the association between post-partum haemorrhage (PPH) and mental ill health. We conducted a retrospective open cohort study utilizing linked primary care (The Health Improvement Network (THIN)) and English secondary care (Hospital Episode Statistics (HES)) databases, from January 1, 1990 to January 31, 2018. A total of 42,327 women were included: 14,109 of them were exposed to PPH during the study period and 28,218 unexposed controls were matched for age and date of delivery. Hazard ratios (HRs) for mental illness among women with and without exposure to PPH were estimated after controlling for covariates. Women who had had PPH were at an increased risk of developing postnatal depression (adjusted HR: 1·10, 95%CI: 1·01–1·21) and post–traumatic stress disorder (PTSD) (adjusted HR: 1·17, 95%CI: 0·73–1·89) compared to women unexposed to PPH. When restricting the follow–up to the first year after childbirth, the adjusted HR for PTSD was 3·44 (95% CI 1·31–9·03). No increase in the overall risk was observed for other mental illnesses, including depression (adjusted HR: 0·94, 95%CI: 0·87–1·01), severe mental illness (adjusted HR: 0·65, 95%CI: 0·40–1·08},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sainsbury2021,

title = {Sodium-glucose co-transporter-2 inhibitors and susceptibility to COVID-19: A population-based retrospective cohort study},

author = {Christopher Sainsbury and Jingya Wang and Krishna Gokhale and Dionisio Acosta-Mena and Samir Dhalla and Nathan Byne and Joht Singh Chandan and Astha Anand and Jennifer Cooper and Kelvin Okoth and Anuradhaa Subramanian and Mansoor N. Bangash and Thomas Taverner and Wasim Hanif and Sandip Ghosh and Parth Narendran and Kar K. Cheng and Tom Marshall and Georgios Gkoutos and Konstantinos Toulis and Neil Thomas and Abd Tahrani and Nicola J. Adderley and Shamil Haroon and Krishnarajah Nirantharakumar},

doi = {10.1111/DOM.14203},

issn = {14631326},

year  = {2021},

date = {2021-01-01},

journal = {Diabetes, Obesity and Metabolism},

volume = {23},

issue = {1},

pages = {263-269},

publisher = {Blackwell Publishing Ltd},

abstract = {Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed in people with type 2 diabetes. We aimed to investigate whether SGLT2 inhibitor prescription is associated with COVID-19, when compared with an active comparator. We performed a propensity-score-matched cohort study with active comparators and a negative control outcome in a large UK-based primary care dataset. Participants prescribed SGLT2 inhibitors (n = 9948) and a comparator group prescribed dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 14 917) were followed up from January 30 to July 27, 2020. The primary outcome was confirmed or clinically suspected COVID-19. The incidence rate of COVID-19 was 19.7/1000 person-years among users of SGLT2 inhibitors and 24.7/1000 person-years among propensity-score-matched users of DPP-4 inhibitors. The adjusted hazard ratio was 0.92 (95% confidence interval 0.66 to 1.29), and there was no evidence of residual confounding in the negative control analysis. We did not observe an increased risk of COVID-19 in primary care amongst those prescribed SGLT2 inhibitors compared to DPP-4 inhibitors, suggesting that clinicians may safely use these agents in the everyday care of people with type 2 diabetes during the COVID-19 pandemic.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zemedikun2021,

title = {Type 2 diabetes mellitus, glycaemic control, associated therapies and risk of rheumatoid arthritis: A retrospective cohort study},

author = {Dawit T. Zemedikun and Krishna Gokhale and Joht Singh Chandan and Jennifer Cooper and Janet M. Lord and Andrew Filer and Marie Falahee and Krishnarajah Nirantharakumar and Karim Raza},

doi = {10.1093/RHEUMATOLOGY/KEAB148},

issn = {14620332},

year  = {2021},

date = {2021-01-01},

journal = {Rheumatology (United Kingdom)},

volume = {60},

issue = {12},

pages = {5567-5575},

publisher = {Oxford University Press},

abstract = {Objective: To compare the incident risk of RA in patients with type 2 diabetes mellitus (T2DM) and to explore the role of glycaemic control and associated therapeutic use in the onset of RA. Methods: This study was a retrospective cohort study using patients derived from the IQVIA Medical Research Data (IMRD-UK) database between 1995 and 2019. A total of 224 551 newly diagnosed patients with T2DM were matched to 449 101 patients without T2DM and followed up to assess their risk of RA. Further analyses investigated the effect of glycaemic control, statin use and anti-diabetic drugs on the relationship between T2DM and RA using a time-dependent Cox regression model. Results: During the study period, the incidence of RA was 8.1 and 10.6 per 10 000 person-years in the exposed and unexposed groups, respectively. The adjusted hazard ratio (aHR) was 0.73 (95% CI 0.67, 0.79). In patients who had not used statins in their lifetime, the aHR was 0.89 (95% CI 0.69, 1.14). When quantifying the effects of glycaemic control, anti-diabetic drugs and statins using time-varying analyses, there was no association with glycaemic control [aHR 1.00 (95% CI 0.99, 1.00)], use of metformin [aHR 1.00 (95% CI 0.82, 1.22)], dipeptidyl peptidase-4 inhibitors [DPP4is; aHR 0.94 (95% CI 0.71, 1.24)] and the development of RA. However, statins demonstrated a protective effect for progression of RA in those with T2DM [aHR 0.76 (95% CI 0.66, 0.88)], with evidence of a duration-response relationship. Conclusion: There is a reduced risk of RA in patients with T2DM that may be attributable to the use of statins.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}