Publications

@article{Okoth2023,

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.},

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pubstate = {published},

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}

@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.},

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pubstate = {published},

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@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.},

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pubstate = {published},

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@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.},

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pubstate = {published},

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@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.},

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pubstate = {published},

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@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}

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@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.]},

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pubstate = {published},

tppubtype = {article}

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@article{Subramanian2022,

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.},

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pubstate = {published},

tppubtype = {article}

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@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.},

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@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.},

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@article{nokey,

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.},

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@article{Lee2022,

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},

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pubstate = {published},

tppubtype = {article}

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@article{nokey,

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{nokey,

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{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{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{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{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{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{Gokhale2022,

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{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{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{Subramanian2022c,

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{Gooden2022,

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{Adderley2022,

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{Gokhale2022b,

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 = {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{Gooden2022b,

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{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{Okoth2022,

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{Lee2022b,

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 = {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{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{Haider2021,

title = {Disease burden of diabetes, diabetic retinopathy and their future projections in the UK: Cross-sectional analyses of a primary care database},

author = {Sajjad Haider and Rasiah Thayakaran and Anuradha Subramanian and Konstantinos A. Toulis and David Moore and Malcolm James Price and Krishnarajah Nirantharakumar},

doi = {10.1136/BMJOPEN-2021-050058},

issn = {20446055},

year  = {2021},

date = {2021-01-01},

journal = {BMJ Open},

volume = {11},

issue = {7},

publisher = {BMJ Publishing Group},

abstract = {Objectives To estimate the current disease burden, trends and future projections for diabetes mellitus (DM) and diabetic retinopathy (DR) in the IQVIA Medical Research Data (IMRD). Participants/design/setting We performed a cross-sectional study of patients aged 12 and above to determine the prevalence of DM and DR from the IMRD database (primary care database) in January 2017, involving a total population of 1 80 824 patients with DM. We also carried out a series of cross-sectional studies to investigate prevalence trends, and then applied a double exponential smoothing model to forecast the future burden of DM and DR in the UK. Results The crude DM prevalence in 2017 was 5.2%. The DR, sight-threatening retinopathy (STR) and diabetic maculopathy prevalence figures in 2017 were 33.78%, 12.28% and 7.86%, respectively, in our IMRD cross-sectional study. There were upward trends in the prevalence of DM, DR and STR, most marked and accelerating in STR in type 1 DM but slowing in type 2 DM, and in the overall prevalence of DR. Conclusion Our results suggest differential rising trends in the prevalence of DM and DR. Preventive strategies, as well as treatment services planning, can be based on these projected prevalence estimates. Improvements that are necessary for the optimisation of care pathways, and preparations to meet demand and capacity challenges, can also be based on this information. The limitations of the study can be overcome by a future collaborative study linking DR screening and hospital eye services data.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kumarendran2021,

title = {Polycystic ovary syndrome, combined oral contraceptives, and the risk of dysglycemia: A population-based cohort study with a nested pharmacoepidemiological case-control study},

author = {Balachandran Kumarendran and Michael W. O’reilly and Anuradhaa Subramanian and Dana Šsumilo and Konstantinos Toulis and Krishna M. Gokhale and Chandrika N. Wijeratne and Arri Coomarasamy and Abd A. Tahrani and Laurent Azoulay and Wiebke Arlt and Krishnarajah Nirantharakumar},

doi = {10.2337/DC21-0437},

issn = {19355548},

year  = {2021},

date = {2021-01-01},

journal = {Diabetes Care},

volume = {44},

issue = {12},

pages = {2758-2766},

publisher = {American Diabetes Association Inc.},

abstract = {OBJECTIVE Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by androgen excess and irregular menses; androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptive pills (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COCP use and risk of dysglycemia (prediabetes and type 2 diabetes) in women with PCOS. RESEARCH DESIGN AND METHODS Using a large U.K. primary care database (The Health Improvement Network [THIN]; 3.7 million patients from 787 practices), we carried out a retrospective population-based cohort study to determine dysglycemia risk (64,051 women with PCOS and 123,545 matched control subjects), as well as a nested pharma-coepidemiological case-control study to investigate COCP use in relation to dys-glycemia risk (2,407 women with PCOS with [case subjects] and without [control subjects] a diagnosis of dysglycemia during follow-up). Cox models were used to estimate the unadjusted and adjusted hazard ratio, and conditional logistic regression was used to obtain adjusted odds ratios (aORs). RESULTS The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78–1.97, P < 0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with increased rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP use had a reduced dysglycemia risk (aOR 0.72, 95% CI 0.59–0.87). CONCLUSIONS In this study, limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow for exclusion of the impact of prescription-by-indication bias, women with PCOS exposed to COCPs had a reduced risk of dysglycemia across all BMI subgroups. Future prospective studies should be considered for further understanding of these observations and potential causality.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chandan2021,

title = {The risk of COVID-19 in survivors of domestic violence and abuse},

author = {Joht Singh Chandan and Anuradhaa Subramanian and Jaidev Kaur Chandan and Krishna M. Gokhale and Alecs Vitoc and Julie Taylor and Caroline Bradbury-Jones and Siddhartha Bandyopadhyay and Krishnarajah Nirantharakumar},

doi = {10.1186/S12916-021-02119-W},

issn = {17417015},

year  = {2021},

date = {2021-01-01},

journal = {BMC Medicine},

volume = {19},

issue = {1},

publisher = {BioMed Central Ltd},

abstract = {A ‘shadow pandemic’ of domestic violence and abuse (DVA) has emerged secondary to strict public health measures containing the spread of SARS-CoV-2. Many countries have implemented policies to allow the free movement of DVA survivors in attempts to minimise their exposure to abusive environments. Although these policies are well received, as a result there is a possibility of increased COVID-19 transmission within this vulnerable group who are not currently prioritised for vaccination. Therefore, we aimed to compare the risk of developing suspected or confirmed COVID-19 in women (aged over 16 years) exposed to DVA against age-sex-matched unexposed controls, following adjustment for known COVID-19 risk factors. A population-based retrospective open cohort study was undertaken between the 31 January 2020 and 28 February 2021 using ‘The Health Improvement Network’ database. We identified 10,462 eligible women exposed to DVA who were matched to 41,467 similarly aged unexposed women. Following adjustment for key covariates, women exposed to DVA were at an increased risk (aHR 1.57; 95% CI 1.29–1.90) of suspected/confirmed COVID-19 compared to unexposed women. These findings support previous calls for positive policy action improving DVA surveillance and prioritising survivors for COVID-19 vaccination.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zemedikun2021,

title = {Burden of chronic diseases associated with periodontal diseases: A retrospective cohort study using UK primary care data},

author = {Dawit T. Zemedikun and Joht Singh Chandan and Devan Raindi and Amarkumar Dhirajlal Rajgor and Krishna Margadhmane Gokhale and Tom Thomas and Marie Falahee and Paola De Pablo and Janet M. Lord and Karim Raza and Krishnarajah Nirantharakumar},

doi = {10.1136/BMJOPEN-2020-048296},

issn = {20446055},

year  = {2021},

date = {2021-01-01},

journal = {BMJ Open},

volume = {11},

issue = {12},

publisher = {BMJ Publishing Group},

abstract = {Objectives To identify the association between periodontal diseases (gingivitis and periodontitis) and chronic diseases including cardiovascular disease, cardiometabolic disease, autoimmune disease and mental ill health. Design Retrospective cohort. Setting IQVIA Medical Research Data-UK between 1 January 1995 and 1 January 2019. Participants 64 379 adult patients with a general practitioner recorded diagnosis of periodontal disease (exposed patients) were matched to 251 161 unexposed patients by age, sex, deprivation and registration date. Main outcome measures Logistic regression models accounting for covariates of clinical importance were undertaken to estimate the adjusted OR (aOR) of having chronic diseases at baseline in the exposed compared with the unexposed group. Incidence rates for each outcome of interest were then provided followed by the calculation of adjusted HRs using cox regression modelling to describe the risk of outcome development in each group. Results The average age at cohort entry was 45 years and the median follow-up was 3.4 years. At study entry, the exposed cohort had an increased likelihood of having a diagnosis of cardiovascular disease (aOR 1.43; 95% CI 1.38 to 1.48), cardiometabolic disease (aOR 1.16; 95% CI 1.13 to 1.19), autoimmune disease (aOR 1.33; 95% CI 1.28 to 1.37) and mental ill health (aOR 1.79; 95% CI 1.75 to 1.83) compared with the unexposed group. During the follow-up of individuals without pre-existing outcomes of interest, the exposed group had an increased risk of developing cardiovascular disease (HR 1.18; 95% CI 1.13 to 1.23), cardiometabolic disease (HR 1.07; 95% CI 1.03 to 1.10), autoimmune disease (HR 1.33; 95% CI 1.26 to 1.40) and mental ill health (HR 1.37; 95% CI 1.33 to 1.42) compared with the unexposed group. Conclusions In this cohort, periodontal diseases appeared to be associated with an increased risk of developing cardiovascular, cardiometabolic, autoimmune diseases and mental ill health. Periodontal diseases are very common; therefore, an increased risk of other chronic diseases represent a substantial public health burden.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{King2021,

title = {The Risk of Later Diagnosis of Inflammatory Bowel Disease in Patients with Dermatological Disorders Associated with Inflammatory Bowel Disease},

author = {Dominic King and Joht Singh Chandan and Tom Thomas and Krishnarajah Nirantharakumar and Raoul C. Reulen and Nicola J. Adderley and Nigel Trudgill},

doi = {10.1093/IBD/IZAA344},

issn = {15364844},

year  = {2021},

date = {2021-01-01},

journal = {Inflammatory Bowel Diseases},

volume = {27},

issue = {11},

pages = {1731-1739},

publisher = {Oxford University Press},

abstract = {Background: Dermatological conditions such as erythema nodosum (EN), pyoderma gangrenosum, Sweet's syndrome, and aphthous stomatitis can occur with inflammatory bowel disease (IBD) and are considered dermatological extraintestinal manifestations (D-EIMs). Rarely, they may precede IBD. Other common conditions such as psoriasis have also been associated with IBD. This study examined the risk of a subsequent IBD diagnosis in patients presenting with a D-EIM. Methods: A retrospective cohort study compared patients with D-EIMs and age-/sex-matched patients without D-EIMs. Hazard ratios (HRs) were adjusted for age, sex, body mass index, deprivation, comorbidity, smoking, loperamide use, anemia, and lower gastrointestinal symptoms. Logistic regression was used to produce a prediction model for the diagnosis of IBD within 3 years of EN diagnosis. Results: We matched 7447 patients with D-EIMs (74% female; median age 38 years (interquartile ratio [IQR], 24-65 years) to 29,297 patients without D-EIMs. We observed 131 (1.8%) subsequent IBD diagnoses in patients with D-EIMs compared with 65 (0.2%) in those without D-EIMs. Median time to IBD diagnosis was 205 days (IQR, 44-661 days) in those with D-EIMs and 1594 days (IQR, 693-2841 days) in those without D-EIMs. The adjusted HR for a later diagnosis of IBD was 6.16 (95% confidence interval [CI], 4.53-8.37; P < 0.001), for ulcerative colitis the HR was 3.30 (95% CI, 1.98-5.53; P < 0.001), and for Crohn's disease the HR was 8.54 (95% CI, 5.74-12.70; P < 0.001). Patients with psoriasis had a 34% increased risk of a subsequent IBD diagnosis compared with the matched control patients (HR, 1.34; 95% CI, 1.20-1.51; P < 0.001). We included 4043 patients with an incident EN diagnosis in the prediction model cohort, with 87 patients (2.2%) diagnosed with IBD within 3 years. The model had a bias-corrected c-statistic of 0.82 (95% CI, 0.78-0.86). Conclusions: Patients with D-EIMs have a 6-fold increased risk of a later diagnosis of IBD. Younger age, smoking, low body mass index, anemia, and lower gastrointestinal symptoms were associated with an increased risk of diagnosis of IBD within 3 years in patients with EN.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Subramanian2021,

title = {Increased COVID-19 infections in women with polycystic ovary syndrome: A population-based study},

author = {Anuradhaa Subramanian and Astha Anand and Nicola J. Adderley and Kelvin Okoth and Konstantinos A. Toulis and Krishna Gokhale and Christopher Sainsbury and Michael W. O'Reilly and Wiebke Arlt and Krishnarajah Nirantharakumar},

doi = {10.1530/EJE-20-1163},

issn = {1479683X},

year  = {2021},

date = {2021-01-01},

journal = {European Journal of Endocrinology},

volume = {184},

issue = {5},

pages = {637-645},

publisher = {BioScientifica Ltd.},

abstract = {Objective: Several recent observational studies have linked metabolic comorbidities to an increased risk from COVID- 19. Here we investigated whether women with PCOS are at an increased risk of COVID-19 infection. Design: Population-based closed cohort study between 31 January 2020 and 22 July 2020 in the setting of a UK primary care database (The Health Improvement Network, THIN). Methods: The main outcome was the incidence of COVID-19 coded as suspected o r confirmed by the primary care provider. We used Cox proportional hazards regression model with stepwise inclusion of explanatory variables (age, BMI, impaired glucose regulation, androgen excess, anovul ation, vitamin D deficiency, hypertension, and cardiovascular disease) to provide unadjusted and adjusted hazard risks (HR) of COVID-19 infection among women with PCOS compared to women without PCOS. Results: We identified 21 292 women with a coded diagnosis of PCO/PCOS an d randomly selected 78 310 aged and general practice matched control women. The crude COVID-19 inci dence was 18.1 and 11.9 per 1000 person-years among women with and without PCOS, respectively. Age-adjusted Cox regression analysis suggested a 51% higher risk of COVID-19 among women with PCOS compared to women without PCO S (HR: 1.51 (95% CI: 1.27-1.80), P < 0.001). After adjusting for age and BMI, HR reduced to 1.36 (1.14-1.63) ]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bhachu2021,

title = {Impact of Using Risk-Based Stratification on Referral of Patients With Chronic Kidney Disease From Primary Care to Specialist Care in the United Kingdom},

author = {Harjeet K. Bhachu and Paul Cockwell and Anuradhaa Subramanian and Nicola J. Adderley and Krishna Gokhale and Anthony Fenton and Derek Kyte and Krishnarajah Nirantharakumar and Melanie Calvert},

doi = {10.1016/J.EKIR.2021.05.031},

issn = {24680249},

year  = {2021},

date = {2021-01-01},

journal = {Kidney International Reports},

volume = {6},

issue = {8},

pages = {2189-2199},

publisher = {Elsevier Inc.},

abstract = {Introduction: The externally validated Kidney Failure Risk Equation (KFRE) for predicting risk of end-stage renal disease (ESRD) has been developed, but its potential impact in a population on referrals for patients with chronic kidney disease (CKD) from primary to specialty nephrology care is not known. Methods: A cross-sectional population-based study of individuals in United Kingdom primary care registered in The Health Improvement Network database was conducted. National Institute of Health and Care Excellence (NICE) 2014 CKD guidelines versus the 4-variable KFRE set at a >3% risk of ESRD at 5 years were applied to patients identified with CKD stage 3-5 between January 1, 2016, and March 31, 2017. Results: In all, 39,476 (36.6%) of 107,962 adults with CKD stage 3-5 had a urine albumin:creatinine ratio (ACR) available and entered into the primary analysis. Of that, 7566 (19.2%) patients fulfilled NICE criteria for referral, 2386 (31.5%) of whom had a ≤3% 5-year risk of ESRD. Also 8663 (21.9%) patients had a >3% 5-year risk of ESRD, 3483 (40.2%) of whom did not fulfill NICE criteria; this represents 8.8% of the primary population. By using the KFRE threshold rather than NICE criteria for referral, 5869 patients (14.9% of the primary analysis population) would have been reallocated between primary and specialist care. Imputational analysis was used for missing ACR measurements and showed similar results. Conclusions: A risk-based referral approach would lead to a substantial reallocation of patients between primary care and specialist nephrology care with only a small increase in numbers eligible, ensuring those at higher risk of progression are identified.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Parretti2021,

title = {Post-bariatric surgery nutritional follow-up in primary care: a population-based cohort study},

author = {Helen M. Parretti and Anuradhaa Subramanian and Nicola J. Adderley and Sally Abbott and Abd A. Tahrani and Krishnarajah Nirantharakumar},

doi = {10.3399/BJGP20X714161},

issn = {14785242},

year  = {2021},

date = {2021-01-01},

journal = {British Journal of General Practice},

volume = {71},

issue = {707},

pages = {E441-E449},

publisher = {Royal College of General Practitioners},

abstract = {Background Bariatric surgery is the most effective treatment for severe obesity. However, without recommended follow-up it has long-term risks. Aim To investigate whether nutritional and weight monitoring in primary care meets current clinical guidance, after patients are discharged from specialist bariatric care. Design and setting Retrospective cohort study in primary care practices contributing to IQVIA Medical Research Data in the UK (1 January 2000 to 17 January 2018). Method Participants were adults who had had bariatric surgery with a minimum of 3 years’ follow-up post-surgery, as this study focused on patients discharged from specialist care (at 2 years post-surgery). Outcomes were the annual proportion of patients from 2 years post-surgery with a record of recommended nutritional screening blood tests, weight measurement, and prescription of nutritional supplements, and the proportions with nutritional deficiencies based on blood tests. Results A total of 3137 participants were included in the study, and median follow-up post-surgery was 5.7 (4.2–7.6) years. Between 45% and 59% of these patients had an annual weight measurement. The greatest proportions of patients with a record of annual nutritional blood tests were for tests routinely conducted in primary care, for example, recorded haemoglobin measurement varied between 44.9% (n = 629/1400) and 61.2% (n = 653/1067). Annual proportions of blood tests specific to bariatric surgery were low, for example, recorded copper measurement varied between 1.2% (n = 10/818) and 1.5% (n = 16/1067) where recommended. Results indicated that the most common deficiency was anaemia. Annual proportions of patients with prescriptions for recommended nutritional supplements were low. Conclusion This study suggests that patients who have bariatric surgery are not receiving the recommended nutritional monitoring after discharge from specialist care. GPs and patients should be supported to engage with follow-up care. Future research should aim to understand the reasons underpinning these findings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Almulhem2021,

title = {Cardio-metabolic outcomes in South Asians compared to White Europeans in the United Kingdom: a matched controlled population-based cohort study},

author = {Munerah Almulhem and Joht Singh Chandan and Krishna Gokhale and Nicola J. Adderley and Rasiah Thayakaran and Kamlesh Khunti and Abd A. Tahrani and Wasim Hanif and Krishnarajah Nirantharakumar},

doi = {10.1186/S12872-021-02133-Z},

issn = {14712261},

year  = {2021},

date = {2021-01-01},

journal = {BMC Cardiovascular Disorders},

volume = {21},

issue = {1},

publisher = {BioMed Central Ltd},

abstract = {Background: There appears to be an inequality in the risk of cardio-metabolic disease between those from a South Asian (SA) background when compared to those of White Europeans (WE) descendance, however, this association has not been explored in a large European cohort. This population-based open retrospective cohort explores the incidence of cardio-metabolic disease in those without pre-existing cardiometabolic disease taken from a large UK primary care database from 1st January 2007 to 31st December 2017. Methods: A retrospective open cohort matched population-based study using The Health Improvement Network (THIN) database. The outcomes of this study were the incidences of cardio-metabolic events (type 2 diabetes mellitus, hypertension, ischemic heart disease, stroke, heart failure, and atrial fibrillation). Results: A total of 94,870 SA patients were matched with 189,740 WE patients. SA were at an increased risk of developing: T2DM (adjusted hazard ratio (aHR) 3.1; 95% CI 2.97–3.23); HTN (1.34; 95% CI: 1.29–1.39); ischaemic heart disease (IHD) (1.81; 95% CI: 1.68–1.93) and heart failure (HF) (1.11; 95% CI: 1.003–1.24). However, they were at a lower risk of atrial fibrillation (AF) (0.53; 95% CI: 0.48–0.59) when compared to WE. Of those of SA origin, the Bangladeshi community were at the greatest risk of T2DM, HTN, IHD and HF, but were at the lowest risk of AF in when compared to Indians and Pakistanis. Conclusion: Considering the high risk of cardio-metabolic diseases in the SA cohort, differential public health measures should be considered in these patients to reduce their risk of disease, which may be furthered tailored depending on their country of origin.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Goel2021,

title = {Cardiovascular and Renal Morbidity in Takayasu Arteritis: A Population-Based Retrospective Cohort Study From the United Kingdom},

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

doi = {10.1002/ART.41529},

issn = {23265205},

year  = {2021},

date = {2021-01-01},

journal = {Arthritis and Rheumatology},

volume = {73},

issue = {3},

pages = {504-511},

publisher = {John Wiley and Sons Inc},

abstract = {Objective: Cardiovascular disease (CVD) is a major complication and cause of mortality in Takayasu arteritis (TAK), but population-based controlled studies from the UK are lacking. We undertook the present study to investigate the frequency of morbidity and mortality related to CVD, as well as to cerebrovascular and kidney disease, among patients with TAK in the UK. Methods: Yearly cohort and cross-sectional studies were performed from 2000 to 2017 to estimate annual incidence and prevalence, respectively, of TAK. Using a UK primary care database (IQVIA Medical Research Data), an open retrospective matched cohort study was conducted to estimate risk of hypertension, diabetes, cardiovascular morbidity, chronic kidney disease (CKD), and all-cause mortality in TAK. Risk (adjusted hazard ratio [HR]) of the assessed comorbidities among patients with TAK compared to age- and sex-matched controls was estimated. Changes in medication prescription over time were examined in both groups. Results: One hundred forty-two patients with TAK (median age 53.4 years [interquartile range 33.8–70.7]) and 1,371 matched controls were included. The annual incidence and prevalence of TAK were 0.8 per million and 7.5 per million respectively. All-cause mortality was increased in TAK (adjusted HR 1.88 [95% confidence interval 1.29–2.76]). Patients with TAK had an increased risk of developing ischemic heart disease, stroke/transient ischemic attack, combined CVD, and peripheral vascular disease compared to controls, but no increase in risk of hypertension, CKD, heart failure, or diabetes. Only ~50% of patients with TAK requiring secondary CVD prevention were prescribed statins or antiplatelet agents within 1 year after study entry. Conclusion: Cardiovascular morbidity was increased among patients with TAK receiving primary care services in the UK. Treatment with statins and antiplatelet agents in these patients was suboptimal.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Singh2021,

title = {The Impact of Bariatric Surgery on Incident Microvascular Complications in Patients With Type 2 Diabetes: A Matched Controlled Population-Based Retrospective Cohort Study},

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

doi = {10.2337/DC20-0571},

issn = {19355548},

year  = {2021},

date = {2021-01-01},

journal = {Diabetes care},

volume = {44},

issue = {1},

pages = {116-124},

publisher = {NLM (Medline)},

abstract = {OBJECTIVE: To assess the impact of bariatric surgery (BS) on incident microvascular complications of diabetes-related foot disease (DFD), sight-threatening diabetic retinopathy (STDR), and chronic kidney disease (CKD) in patients with type 2 diabetes and obesity. RESEARCH DESIGN AND METHODS: A retrospective matched, controlled population-based cohort study was conducted of adults with type 2 diabetes between 1 January 1990 and 31 January 2018 using IQVIA Medical Research Data (IMRD), a database of primary care electronic records. Each patient with type 2 diabetes who subsequently had BS (surgical group) was matched on the index date with up to two patients with type 2 diabetes who did not have BS (nonsurgical group) within the same general practice by age, sex, preindex BMI, and diabetes duration. RESULTS: Included were 1,126 surgical and 2,219 nonsurgical participants. In the study population 2,261 (68%) were women. Mean (SD) age was 49.87 (9.3) years vs. 50.12 (9.3) years and BMI was 46.76 (7.96) kg/m2 vs. 46.14 (7.49) kg/m2 in the surgical versus nonsurgical group, respectively. In the surgical group, 22.1%, 22.7%, 52.2%, and 1.1% of patients had gastric band, sleeve gastrectomy, Roux-en-Y gastric bypass (RYGB), and duodenal switch, respectively. Over a median follow-up of 3.9 years (interquartile range 1.8-6.4), BS was associated with reduction in incident combined microvascular complications (adjusted hazard ratio 0.53, 95% CI 0.43-0.66, P < 0.001), DFD (0.61, 0.50-0.75, P < 0.001), STDR (0.66, 0.44-1.00},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{King2021b,

title = {Achalasia Is Associated With Atopy in Patients Younger Than 40 Years of Age},

author = {Dominic King and Tom Thomas and Joht Singh Chandan and Nij Bhala and Nicola J. Adderley and Krishnarajah Nirantharakumar and Nigel Trudgill},

doi = {10.14309/AJG.0000000000001006},

issn = {15720241},

year  = {2021},

date = {2021-01-01},

journal = {The American journal of gastroenterology},

volume = {116},

issue = {2},

pages = {416-419},

publisher = {NLM (Medline)},

abstract = {INTRODUCTION: Case reports describe individuals with achalasia features subsequently diagnosed with eosinophilic esophagitis (an atopic disorder). We have examined associations between achalasia and atopic and autoimmune conditions. METHODS: This is a UK cohort study of 2,593 subjects with achalasia matched to 10,402 controls. RESULTS: At diagnosis, achalasia was associated with autoimmune conditions (odds ratio 1.39; 95% confidence interval 1.02-1.90) and atopic conditions (1.40; 1.00-1.95) in those aged younger than 40 years. DISSCUSSION: Our findings support an autoimmune etiology in achalasia but also suggest a possible atopic etiology in younger subjects.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Postpartum haemorrhage and risk of long-term hypertension and cardiovascular disease: An English population-based longitudinal study using linked primary and secondary care databases},

author = {William Parry-Smith and Dana Sˇumilo and Anuradhaa Subramanian and Krishna Gokhale and Kelvin Okoth and Ioannis Gallos and Arri Coomarasamy and Krishnarajah Nirantharakumar},

doi = {10.1136/BMJOPEN-2020-041566},

issn = {20446055},

year  = {2021},

date = {2021-01-01},

journal = {BMJ Open},

volume = {11},

issue = {5},

publisher = {BMJ Publishing Group},

abstract = {Objective To investigate the long-term risk of developing hypertension and cardiovascular disease (CVD) among those women who suffered a postpartum haemorrhage (PPH) compared with those women who did not. Design Population-based longitudinal open cohort study. Setting English primary care (The Health Improvement Network (THIN)) and secondary care (Hospital Episode Statistics (HES)) databases. Population Women exposed to PPH during the study period matched for age and date of delivery, and unexposed. Methods We conducted an open cohort study using linked primary care THIN and HES Databases, from 1 January 1997 to 31 January 2018. A total of 42 327 women were included: 14 109 of them exposed to PPH during the study period and 28 218 matched for age and date of delivery, and unexposed to PPH. HRs for cardiovascular outcomes among women who had and did not have PPH were estimated after controlling for covariates using multivariate Cox regression models. Outcome measures Risk of hypertensive disease, ischaemic heart disease, heart failure, stroke or transient ischaemic attack. Results During a median follow-up of over 4 years, there was no significant difference in the risk of hypertensive disease after adjustment for covariates (adjusted HR (aHR): 1.03 (95% CI: 0.87 to 1.22); p=0.71). We also did not observe a statistically significant difference in the risk of composite CVD (ischaemic heart disease, heart failure, stroke or transient ischaemic attack) between the exposed and the unexposed cohort (aHR: 0.86 (95% CI: 0.52 to 1.43; p=0.57). Conclusion Over a median follow-up of 4 years, we did not observe an association between PPH and hypertension or CVD. © 2021 Author(s). Published by BMJ.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Haroon2021,

title = {Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care},

author = {Shamil Haroon and Anuradhaa Subramanian and Jennifer Cooper and Astha Anand and Krishna Gokhale and Nathan Byne and Samir Dhalla and Dionisio Acosta-Mena and Thomas Taverner and Kelvin Okoth and Jingya Wang and Joht Singh Chandan and Christopher Sainsbury and Dawit Tefra Zemedikun and G. Neil Thomas and Dhruv Parekh and Tom Marshall and Elizabeth Sapey and Nicola J. Adderley and Krishnarajah Nirantharakumar},

doi = {10.1186/S12879-021-05951-W},

issn = {14712334},

year  = {2021},

date = {2021-01-01},

journal = {BMC Infectious Diseases},

volume = {21},

issue = {1},

publisher = {BioMed Central Ltd},

abstract = {Introduction: Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality. Methods: We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome. Results: The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality. Conclusion: Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chandan2021b,

title = {Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19},

author = {Joht Singh Chandan and Dawit Tefra Zemedikun and Rasiah Thayakaran and Nathan Byne and Samir Dhalla and Dionisio Acosta-Mena and Krishna M. Gokhale and Tom Thomas and Christopher Sainsbury and Anuradhaa Subramanian and Jennifer Cooper and Astha Anand and Kelvin O. Okoth and Jingya Wang and Nicola J. Adderley and Thomas Taverner and Alastair K. Denniston and Janet Lord and G. Neil Thomas and Christopher D. Buckley and Karim Raza and Neeraj Bhala and Krishnarajah Nirantharakumar and Shamil Haroon},

doi = {10.1002/ART.41593},

issn = {23265205},

year  = {2021},

date = {2021-01-01},

journal = {Arthritis and Rheumatology},

volume = {73},

issue = {5},

pages = {731-739},

publisher = {John Wiley and Sons Inc},

abstract = {Objective: To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics. Methods: We performed a propensity score–matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality. Results: During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score–matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62–1.10) and 0.79 (95% CI 0.57–1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75–1.27) and 0.85 (95% CI 0.61–1.20), respectively. There was no effect modification by age or sex. Conclusion: No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chandan2021c,

title = {The association between exposure to domestic abuse in women and the development of syndromes indicating central nervous system sensitization: A retrospective cohort study using UK primary care records},

author = {Joht Singh Chandan and Deepiksana Keerthy and Krishna Margadhamane Gokhale and Caroline Bradbury-Jones and Karim Raza and Siddhartha Bandyopadhyay and Julie Taylor and Krishnarajah Nirantharakumar},

doi = {10.1002/EJP.1750},

issn = {15322149},

year  = {2021},

date = {2021-01-01},

journal = {European Journal of Pain (United Kingdom)},

volume = {25},

issue = {6},

pages = {1283-1291},

publisher = {John Wiley and Sons Inc},

abstract = {Background: Domestic abuse is a global public health issue. The association between the development of central sensitivity syndromes (CSS) and previous exposure to domestic abuse has been poorly understood particularly within European populations. Methods: A retrospective cohort study using the ‘The Health Improvement Network,’ (UK primary care medical records) between 1st January 1995–31st December 2018. 22,604 adult women exposed to domestic abuse were age matched to 44,671 unexposed women. The average age at cohort entry was 36 years and the median follow-up was 2.5 years. The outcomes of interest were the development of a variety of syndromes which demonstrate central nervous system sensitization. Fibromyalgia, chronic fatigue syndrome and temporomandibular joint disorder outcomes have been reported previously. Outcomes were adjusted for the presence of mental ill health. Results: During the study period, women exposed to domestic abuse experienced an increased risk of developing chronic lower back pain (adjusted incidence rate ratio [aIRR] 2.28; 95% CI 1.85–2.80), chronic headaches (aIRR 3.15; 95% CI 1.07–9.23), irritable bowel syndrome (aIRR 1.41; 95% CI 1.25–1.60) and restless legs syndrome (aIRR 1.89; 95% CI 1.44–2.48). However, no positive association was seen with the development of interstitial cystitis (aIRR 0.52; 95% CI 0.14–1.93), vulvodynia (aIRR 0.42; 95% CI 0.14–1.25) and myofascial pain syndrome (aIRR 1.01; 95% CI 0.28–3.61). Conclusion: This study demonstrates the need to consider a past history of domestic abuse in patients presenting with CSS; and also consider preventative approaches in mitigating the risk of developing CSS following exposure to domestic abuse. Significance: Domestic abuse is a global public health issue, with a poorly understood relationship with the development of complex pain syndromes. Using a large UK primary care database, we were able to conduct the first global cohort study to explore this further. We found a strong pain morbidity burden associated with domestic abuse, suggesting the need for urgent public health intervention to not only prevent domestic abuse but also the associated negative pain consequences.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Okoth2021,

title = {Risk of cardiovascular outcomes among women with endometriosis in the United Kingdom: a retrospective matched cohort study},

author = {K. Okoth and J. Wang and D. Zemedikun and G. N. Thomas and K. Nirantharakumar and N. J. Adderley},

doi = {10.1111/1471-0528.16692},

issn = {14710528},

year  = {2021},

date = {2021-01-01},

journal = {BJOG: An International Journal of Obstetrics and Gynaecology},

volume = {128},

issue = {10},

pages = {1598-1609},

publisher = {John Wiley and Sons Inc},

abstract = {Objective: To describe the prevalence and incidence of endometriosis and to estimate the risk of cardiovascular outcomes in women with endometriosis. Design: Population-based cohort study using The Health Improvement Network database. Setting: UK primary care. Population: Women aged 16–50 years were followed from 1995 to 2018. Methods: Adjusted hazard ratios (aHR) for cardiovascular outcomes comparing women with endometriosis with those without endometriosis were estimated using multivariable Cox regression models. Prevalence and incidence of endometriosis were estimated using annual (1998–2017) sequential cross-sectional and cohort studies, respectively. Main outcome measure: The primary outcome was composite cardiovascular disease (CVD) including, ischaemic heart disease (IHD), heart failure (HF) and cerebrovascular disease. Secondary outcomes were arrhythmia, hypertension and all-cause mortality. Results: In all, 56 090 women with endometriosis and 223 669 matched controls without endometriosis were included in the analysis of cardiovascular risk. Compared with women without endometriosis, the aHR for cardiovascular outcomes among women with endometriosis were: composite CVD 1.24 (95% CI 1.13–1.37); IHD 1.40 (95% CI 1.22–1.61); cerebrovascular disease 1.19 (95% CI 1.04–1.36); HF 0.76 (95% CI 0.54–1.07); arrhythmia 1.26 (95% CI 1.11–1.43); hypertension 1.12 (95% CI 1.07–1.17) and all-cause mortality 0.66 (95% CI 0.59–0.74). The incidence of endometriosis was 12.3 per 10 000 person-years in 1998 and 11.5 per 10 000 person-years in 2017. The prevalence of endometriosis increased from 119.7 per 10 000 population in 1998 to 201.3 per 10 000 population in 2017. Conclusion: Endometriosis is associated with an increased risk of cardiovascular outcomes. Young women with endometriosis are a potential target for CVD risk assessment and prevention. Tweetable abstract: Endometriosis is associated with increased risk of cardiovascular outcomes: a UK retrospective matched cohort study.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}