Publications

@article{Riley2021,

title = {Social deprivation and incident diabetes-related foot disease in patients with type 2 diabetes: A population-based cohort study},

author = {Jenny Riley and Christina Antza and Punith Kempegowda and Anuradhaa Subramanian and Joht Singh Chandan and Krishna Gokhale and Neil Thomas and Christopher Sainsbury and Abd A. Tahrani and Krishnarajah Nirantharakumar},

doi = {10.2337/DC20-1027},

issn = {19355548},

year  = {2021},

date = {2021-01-01},

journal = {Diabetes Care},

volume = {44},

issue = {3},

pages = {731-739},

publisher = {American Diabetes Association Inc.},

abstract = {OBJECTIVE To investigate the relationship between social deprivation and incident diabetes-related foot disease (DFD) in newly diagnosed patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A population-based open retrospective cohort study using The Health Improvement Network (1 January 2005 to 31 December 2019) was conducted. Patients with type 2 diabetes free of DFD at baseline were stratified by Townsend deprivation index, and risk of developing DFD was calculated. DFD was defined as a composite of foot ulcer (FU), Charcot arthropathy, lower-limb amputation (LLA), peripheral neuropathy (PN), peripheral vascular disease (PVD), and gangrene. RESULTS A total of 176,359 patients were eligible (56% men; mean age 62.9 [SD 13.1] years). After excluding 26,094 patients with DFD before/within 15 months of type 2 diabetes diagnosis, DFD incidentally developed in 12.1% of the study population over 3.27 years (interquartile range 1.41–5.96). Patients in the most deprived Townsend quintile had increased risk of DFD compared with those in the least deprived (adjusted hazard ratio [aHR] 1.22; 95% CI 1.16–1.29) after adjusting for sex, age at type 2 diabetes diagnosis, ethnicity, smoking, BMI, HbA1c, cardiovascular disease, hypertension, retinopathy, estimated glomerular filtration rate, insulin, glucose/lipid-lowering medication, and baseline foot risk. Patients in the most deprived Townsend quintile had higher risk of PN (aHR 1.18; 95% CI 1.11–1.25), FU (aHR 1.44; 95% CI 1.17–1.77), PVD (aHR 1.40; 95% CI 1.28–1.53), LLA (aHR 1.75; 95% CI 1.08–2.83), and gangrene (aHR 8.49; 95% CI 1.01– 71.58) compared with those in the least. CONCLUSIONS Social deprivation is an independent risk factor for the development of DFD, PN, FU, PVD, LLA, and gangrene in newly diagnosed patients with type 2 diabetes. Considering thehighindividual andeconomic burdens of DFD, strategies targetingpatients insocially deprived areas are needed to reduce health inequalities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zemedikun2021b,

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

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

doi = {10.1093/RHEUMATOLOGY/KEAB148},

issn = {14620332},

year  = {2021},

date = {2021-01-01},

journal = {Rheumatology (United Kingdom)},

volume = {60},

issue = {12},

pages = {5567-5575},

publisher = {Oxford University Press},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

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

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

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

issn = {18791379},

year  = {2021},

date = {2021-01-01},

journal = {Journal of Psychiatric Research},

volume = {137},

pages = {419-425},

publisher = {Elsevier Ltd},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wang2021,

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

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

doi = {10.1210/CLINEM/DGAB067},

issn = {19457197},

year  = {2021},

date = {2021-01-01},

journal = {Journal of Clinical Endocrinology and Metabolism},

volume = {106},

issue = {5},

pages = {1255-1268},

publisher = {Endocrine Society},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sainsbury2021,

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

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

doi = {10.1111/DOM.14203},

issn = {14631326},

year  = {2021},

date = {2021-01-01},

journal = {Diabetes, Obesity and Metabolism},

volume = {23},

issue = {1},

pages = {263-269},

publisher = {Blackwell Publishing Ltd},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

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@article{Gokhale2021,

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

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

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

issn = {15737284},

year  = {2021},

date = {2021-01-01},

journal = {European Journal of Epidemiology},

volume = {36},

issue = {2},

pages = {165-178},

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

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

keywords = {},

pubstate = {published},

tppubtype = {article}

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@article{Subramanian2021b,

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

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

doi = {10.1111/CEA.13741},

issn = {13652222},

year  = {2021},

date = {2021-01-01},

journal = {Clinical and Experimental Allergy},

volume = {51},

issue = {1},

pages = {144-147},

publisher = {Blackwell Publishing Ltd},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chandan2021d,

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

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

doi = {10.1177/0886260519888515},

issn = {15526518},

year  = {2021},

date = {2021-01-01},

journal = {Journal of Interpersonal Violence},

volume = {36},

issue = {21-22},

pages = {NP12279-NP12298},

publisher = {SAGE Publications Inc.},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Braithwaite2020,

title = {Trends in Optic Neuritis Incidence and Prevalence in the UK and Association with Systemic and Neurologic Disease},

author = {Tasanee Braithwaite and Anuradhaa Subramanian and Axel Petzold and James Galloway and Nicola J. Adderley and Susan P. Mollan and Gordon T. Plant and Krishnarajah Nirantharakumar and Alastair K. Denniston},

doi = {10.1001/JAMANEUROL.2020.3502},

issn = {21686157},

year  = {2020},

date = {2020-01-01},

journal = {JAMA Neurology},

volume = {77},

issue = {12},

pages = {1514-1523},

publisher = {American Medical Association},

abstract = {Importance: Epidemiologic data on optic neuritis (ON) incidence and associations with immune-mediated inflammatory diseases (IMIDs) are sparse. Objective: To estimate 22-year trends in ON prevalence and incidence and association with IMIDs in the United Kingdom. Design, Setting, and Participants: This cohort study analyzed data from The Health Improvement Network from January 1, 1995, to September 1, 2019. The study included 10937511 patients 1 year or older with 75.2 million person-years' follow-up. Annual ON incidence rates were estimated yearly (January 1, 1997, to December 31, 2018), and annual ON prevalence was estimated by performing sequential cross-sectional studies on data collected on January 1 each year for the same period. Data for 1995, 1996, and 2019 were excluded as incomplete. Risk factors for ON were explored in a cohort analysis from January 1, 1997, to December 31, 2018. Matched case-control and retrospective cohort studies were performed using data from January 1, 1995, to September 1, 2019, to explore the odds of antecedent diagnosis and hazard of incident diagnosis of 66 IMIDs in patients compared with controls. Exposures: Optic neuritis. Main Outcomes and Measures: Annual point prevalence and incidence rates of ON, adjusted incident rate ratios (IRRs) for risk factors, and adjusted odds ratios (ORs) and adjusted hazard ratios (HRs) for 66 IMIDs. Results: A total of 10937511 patients (median [IQR] age at cohort entry, 32.6 [18.0-50.4] years; 5 571 282 [50.9%] female) were studied. A total of 1962 of 2826 patients (69.4%) with incident ON were female and 1192 of 1290 92.4%) were White, with a mean (SD) age of 35.6 (15.6) years. Overall incidence across 22 years was stable at 3.7 (95% CI, 3.6-3.9) per 100000 person-years. Annual point prevalence (per 100000 population) increased with database maturity, from 69.3 (95% CI, 57.2-81.3) in 1997 to 114.8 (95% CI, 111.0-118.6) in 2018. The highest risk of incident ON was associated with female sex, obesity, reproductive age, smoking, and residence at higher latitude, with significantly lower risk in South Asian or mixed race/ethnicity compared with White people. Patients with ON had significantly higher odds of prior multiple sclerosis (MS) (OR, 98.22; 95% CI, 65.40-147.52), syphilis (OR, 5.76; 95% CI, 1.39-23.96), Mycoplasma (OR, 3.90; 95% CI, 1.09-13.93), vasculitis (OR, 3.70; 95% CI, 1.68-8.15), sarcoidosis (OR, 2.50; 95% CI, 1.21-5.18), Epstein-Barr virus (OR, 2.29; 95% CI, 1.80-2.92), Crohn disease (OR, 1.97; 95% CI, 1.13-3.43), and psoriasis (OR, 1.28; 95% CI, 1.03-1.58). Patients with ON had a significantly higher hazard of incident MS (HR, 284.97; 95% CI, 167.85-483.81), Behçet disease (HR, 17.39; 95% CI, 1.55-195.53), sarcoidosis (HR, 14.80; 95% CI, 4.86-45.08), vasculitis (HR, 4.89; 95% CI, 1.82-13.10), Sjögren syndrome (HR, 3.48; 95% CI, 1.38-8.76), and herpetic infection (HR, 1.68; 95% CI, 1.24-2.28). Conclusions and Relevance: The UK incidence of ON is stable. Even though predominantly associated with MS, ON has numerous other associations with IMIDs. Although individually rare, together these associations outnumber MS-associated ON and typically require urgent management to preserve sight},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Crowe2020,

title = {Comorbidity phenotypes and risk of mortality in patients with ischaemic heart disease in the UK},

author = {Francesca Crowe and Dawit T. Zemedikun and Kelvin Okoth and Nicola Jaime Adderley and Gavin Rudge and Mark Sheldon and Krishnarajah Nirantharakumar and Tom Marshall},

doi = {10.1136/HEARTJNL-2019-316091},

issn = {1468201X},

year  = {2020},

date = {2020-01-01},

journal = {Heart},

publisher = {BMJ Publishing Group},

abstract = {Objectives: The objective of this study is to use latent class analysis of up to 20 comorbidities in patients with a diagnosis of ischaemic heart disease (IHD) to identify clusters of comorbidities and to examine the associations between these clusters and mortality. Methods: Longitudinal analysis of electronic health records in the health improvement network (THIN), a UK primary care database including 92 186 men and women aged ≥18 years with IHD and a median of 2 (IQR 1-3) comorbidities. Results: Latent class analysis revealed five clusters with half categorised as a low-burden comorbidity group. After a median follow-up of 3.2 (IQR 1.4-5.8) years, 17 645 patients died. Compared with the low-burden comorbidity group, two groups of patients with a high-burden of comorbidities had the highest adjusted HR for mortality: those with vascular and musculoskeletal conditions, HR 2.38 (95% CI 2.28 to 2.49) and those with respiratory and musculoskeletal conditions, HR 2.62 (95% CI 2.45 to 2.79). Hazards of mortality in two other groups of patients characterised by cardiometabolic and mental health comorbidities were also higher than the low-burden comorbidity group; HR 1.46 (95% CI 1.39 to 1.52) and 1.55 (95% CI 1.46 to 1.64), respectively. Conclusions: This analysis has identified five distinct comorbidity clusters in patients with IHD that were differentially associated with risk of mortality. These analyses should be replicated in other large datasets, and this 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{Chandan2020,

title = {Exploration of trends in the incidence and prevalence of childhood maltreatment and domestic abuse recording in UK primary care: a retrospective cohort study using 'the health improvement network' database},

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

doi = {10.1136/BMJOPEN-2020-036949},

issn = {20446055},

year  = {2020},

date = {2020-01-01},

journal = {BMJ open},

volume = {10},

issue = {6},

pages = {e036949},

publisher = {NLM (Medline)},

abstract = {OBJECTIVES: Describe the epidemiology of childhood maltreatment and domestic abuse (in women). DESIGN: Analysis of longitudinal records between 1 January 1995 to 31 December 2018. SETTING: UK primary care database: 'The Health Improvement Network' (THIN). PARTICIPANTS: 11 831 850 eligible patients from 787 contributing practices. Childhood maltreatment and domestic abuse (women only) were defined as the presence of a recorded Read code. OUTCOME MEASURES: The incidence rate (IR) and prevalence of childhood maltreatment (in children aged 0-18 years) and domestic abuse (in women aged over 18) between 1996 and 2017. An adjusted incidence rate ratio (aIRR) is given to examine the differences in IRs based on sex, ethnicity and deprivation. RESULTS: The age and gender breakdown of THIN has been previously reported to be representative of the UK population, however, there is substantial missing information on deprivation quintiles (<20%) and ethnicity (approximately 50%). The IR (IR 60.1; 95% CI 54.3 to 66.0 per 100 000 child years) and prevalence (416.1; 95% CI 401.3 to 430.9 per 100 000 child population) of childhood maltreatment rose until 2017. The aIRR was greater in patients from the most deprived backgrounds (aIRR 5.14; 95% CI 4.57 to 5.77 compared with least deprived) and from an ethnic minority community (eg, black aIRR 1.25; 1.04 to 1.49 compared with white). When examining domestic abuse in women, in 2017, the IR was 34.5 (31.4 to 37.7) per 100 000 adult years and prevalence 368.7 (358.7 to 378.7) per 100 000 adult population. Similarly, the IR was highest in the lowest socioeconomic class (aIRR 2.30; 2.71 to 3.30) and in ethnic minorities (South Asian aIRR 2.14; 1.92 to 2.39 and black aIRR 1.64; 1.42 to 1.89). CONCLUSION: Despite recent improvements in recording, there is still a substantial under-recording of maltreatment and abuse within UK primary care records, compared with currently existing sources of childhood maltreatment and domestic abuse data. Approaches must be implemented to improve recording and detection of childhood maltreatment and domestic abuse within medical records.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vusirikala2020,

title = {Impact of obesity and metabolic health status in the development of non-alcoholic fatty liver disease (NAFLD): A United Kingdom population-based cohort study using the health improvement network (THIN)},

author = {A. Vusirikala and T. Thomas and N. Bhala and A. A. Tahrani and A. A. Tahrani and A. A. Tahrani and G. N. Thomas and K. Nirantharakumar and K. Nirantharakumar},

doi = {10.1186/S12902-020-00582-9},

issn = {14726823},

year  = {2020},

date = {2020-01-01},

journal = {BMC Endocrine Disorders},

volume = {20},

issue = {1},

publisher = {BioMed Central Ltd},

abstract = {Background: With the obesity epidemic reaching crisis levels, there has been attention around those who may be resilient to the effects of obesity, termed metabolically healthy obesity (MHO), who initially present without associated metabolic abnormalities. Few longitudinal studies have explored the relationship between MHO and non-alcoholic fatty liver disease (NAFLD), which we address using over 4 million primary care patient records. Methods: A retrospective population-based longitudinal cohort was conducted using The Health Improvement Network (THIN) database incorporating adults with no history of NAFLD or alcohol excess at baseline. Individuals were classified according to BMI category and metabolic abnormalities (diabetes, hypertension and dyslipidaemia). Diagnosis of NAFLD during follow-up was the primary outcome measure. NAFLD was identified by Read codes. Results: During a median follow-up period of 4.7 years, 12,867 (0.3%) incident cases of NAFLD were recorded in the cohort of 4,121,049 individuals. Compared to individuals with normal weight and no metabolic abnormalities, equivalent individuals who were overweight, or obese were at significantly greater risk of incident NAFLD (Adjusted HR 3.32 (95%CI 2.98-3.49), and 6.92 (6.40-7.48, respectively). Metabolic risk factors further increased risk, including in those with normal weight and 1 (2.27, 1.97-2.61) or = < 2 (2.39, 1.99-2.87) metabolic abnormalities. Conclusions: MHO individuals are at greater risk of developing NAFLD compared to those with normal weight. This finding supports that the MHO phenotype is a temporary state, and weight must be considered a risk factor even before other risk factors develop. Being normal weight with metabolic abnormalities was also associated with risk of NAFLD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tresoldi2020,

title = {Increased Infection Risk in Addison's Disease and Congenital Adrenal Hyperplasia},

author = {Alberto S. Tresoldi and Dana Sumilo and Mary Perrins and Konstantinos A. Toulis and Alessandro Prete and Narendra Reddy and John A. H. Wass and Wiebke Arlt and Krishnarajah Nirantharakumar},

doi = {10.1210/CLINEM/DGZ006},

issn = {19457197},

year  = {2020},

date = {2020-01-01},

journal = {Journal of Clinical Endocrinology and Metabolism},

volume = {105},

issue = {2},

publisher = {Endocrine Society},

abstract = {Context: Mortality and infection-related hospital admissions are increased in patients with primary adrenal insufficiency (PAI). However, the risk of primary care-managed infections in patients with PAI is unknown. Objective: To estimate infection risk in PAI due to Addison's disease (AD) and congenital adrenal hyperplasia (CAH) in a primary care setting. Design: Retrospective cohort study using UK data collected from 1995 to 2018. Main outcome measures: Incidence of lower respiratory tract infections (LRTIs), urinary tract infections (UTIs), gastrointestinal infections (GIIs), and prescription counts of antimicrobials in adult PAI patients compared to unexposed controls. Results: A diagnosis of PAI was established in 1580 AD patients (mean age 51.7 years) and 602 CAH patients (mean age 35.4 years). All AD patients and 42% of CAH patients were prescribed glucocorticoids, most frequently hydrocortisone in AD (82%) and prednisolone in CAH (50%). AD and CAH patients exposed to glucocorticoids, but not CAH patients without glucocorticoid treatment, had a significantly increased risk of LRTIs (adjusted incidence rate ratio AD 2.11 [95% confidence interval (CI) 1.64-2.69], CAH 3.23 [95% CI 1.21-8.61]), UTIs (AD 1.51 [95% CI 1.29-1.77], CAH 2.20 [95% CI 1.43-3.34]), and GIIs (AD 3.80 [95% CI 2.99-4.84], CAH 1.93 [95% CI 1.06-3.52]). This was mirrored by increased prescription of antibiotics (AD 1.73 [95% CI 1.69-1.77], CAH 1.77 [95% CI 1.66-1.89]) and antifungals (AD 1.89 [95% CI 1.74-2.05], CAH 1.91 [95% CI 1.50-2.43]). Conclusions: There is an increased risk of infections and antimicrobial use in PAI in the primary care setting at least partially linked to glucocorticoid treatment. Future studies will need to address whether more physiological glucocorticoid replacement modes could reduce this risk.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Thomas2020,

title = {Epidemiology, morbidity and mortality in Behçet's disease: A cohort study using the Health Improvement Network (THIN)},

author = {Tom Thomas and Joht Singh Chandan and Anuradhaa Subramanian and Krishna Gokhale and George Gkoutos and Lorraine Harper and Christopher Buckley and Priyanka Chandratre and Karim Raza and Deva Situnayake and Krishnarajah Nirantharakumar},

doi = {10.1093/RHEUMATOLOGY/KEAA010},

issn = {14620332},

year  = {2020},

date = {2020-01-01},

journal = {Rheumatology (United Kingdom)},

volume = {59},

issue = {10},

pages = {2785-2795},

publisher = {Oxford University Press},

abstract = {The epidemiology of Behçet's disease (BD) has not been well characterized in the UK. Evidence on the risk of cardiovascular disease, thromboembolic disease and mortality in patients with BD compared with the general population is scarce. Methods: We used a large UK primary care database to investigate the epidemiology of BD. A retrospective matched cohort study was used to assess the following outcomes: risk of cardiovascular, thromboembolic disease and mortality. Controls were selected at a 1:4 ratio (age and gender matched). Cox proportional hazard models were used to derive adjusted hazard ratios (aHR). Results: The prevalence of BD was 14.61 (95% CI 13.35-15.88) per 100 000 population in 2017. A total of 1281 patients with BD were compared with 5124 age- and gender-matched controls. There was significantly increased risk of ischaemic heart disease [aHR 3.09 (1.28-7.44)], venous thrombosis [aHR 4.80 (2.42-9.54)] and mortality [aHR 1.40 (1.07-1.84)] in patients with BD compared with corresponding controls. Patients with BD were at higher risk of pulmonary embolism compared with corresponding controls at baseline [adjusted odds ratio 4.64 (2.66-8.09), P < 0.0001]. The majority of patients with pulmonary embolism and a diagnosis of BD had pulmonary embolism preceding the diagnosis of BD, not after (87.5%; n = 28/32). Conclusion: BD has a higher prevalence than previously thought. Physicians should be aware of the increased risk of developing ischaemic heart disease, stroke/transient ischaemic attack and deep venous thrombosis in patients with BD at an earlier age compared with the general population. Risk of embolism in patients with BD might vary across the disease course.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{King2020,

title = {Changing patterns in the epidemiology and outcomes of inflammatory bowel disease in the United Kingdom: 2000-2018},

author = {Dominic King and Raoul C. Reulen and Tom Thomas and Joht Singh Chandan and Rasiah Thayakaran and Anuradhaa Subramanian and Krishna Gokhale and Neeraj Bhala and Krishnarajah Nirantharakumar and Nicola J. Adderley and Nigel Trudgill},

doi = {10.1111/APT.15701},

issn = {13652036},

year  = {2020},

date = {2020-01-01},

journal = {Alimentary Pharmacology and Therapeutics},

volume = {51},

issue = {10},

pages = {922-934},

publisher = {Blackwell Publishing Ltd},

abstract = {Background: Data regarding incidence, prevalence and long-term outcomes of inflammatory bowel diseases in the UK are limited or outdated. Aims: To investigate incidence and prevalence of Crohn's disease and ulcerative colitis and risk of colorectal cancer and all-cause mortality in these diseases. Methods: Inflammatory bowel disease cases between 2000 and 2018 were identified from a national primary care database. Inflammatory bowel disease prevalence was forecast until 2025. The association between inflammatory bowel disease and colorectal cancer and all-cause mortality was investigated using age/sex-matched retrospective cohort studies. Hazard ratios were adjusted for age, sex, deprivation, comorbidity, smoking status and body mass index. Results: Ulcerative colitis prevalence increased from 390 to 570 per 100 000 population from 2000 to 2017. Prevalence of Crohn's disease increased from 220 to 400 per 100 000. In 2017 male Crohn's disease prevalence was 0.35% (95% confidence interval 0.34-0.36); female prevalence was 0.44% (0.43-0.45). Prevalence of inflammatory bowel disease is predicted to be 1.1% by 2025. Incidence of ulcerative colitis and Crohn's disease was 23.2 (22.8-23.6) and 14.3 (14.0-14.7) per 100 000 person-years respectively. Subjects with ulcerative colitis were more likely to develop colorectal cancer than controls (adjusted Hazard Ratio 1.40 [1.23-1.59]). Colorectal cancer rates remained stable in inflammatory bowel diseases over time. Ulcerative colitis and Crohn's disease were associated with increased risk of all-cause mortality (1.17 [1.14-1.21] and 1.42 [1.36-1.48] respectively). Conclusions: The UK prevalence of inflammatory bowel disease is greater than previous reports suggest and we predict an 11% increase in prevalence by the year 2025. Mortality risk in inflammatory bowel disease and colorectal cancer risk in ulcerative colitis are increased compared to matched controls.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Adderley2020,

title = {Obstructive sleep apnea, a risk factor for cardiovascular and microvascular disease in patients with type 2 diabetes: Findings from a population-based cohort study},

author = {Nicola J. Adderley and Anuradhaa Subramanian and Konstantinos Toulis and Krishna Gokhale and Thomas Taverner and Wasim Hanif and Shamil Haroon and G. Neil Thomas and Christopher Sainsbury and Abd A. Tahrani and Krishnarajah Nirantharakumar},

doi = {10.2337/DC19-2116},

issn = {19355548},

year  = {2020},

date = {2020-01-01},

journal = {Diabetes Care},

volume = {43},

issue = {8},

pages = {1868-1877},

publisher = {American Diabetes Association Inc.},

abstract = {OBJECTIVE: To determine the risk of cardiovascular disease (CVD), microvascular complications, and mortality in patients with type 2 diabetes who subsequently develop obstructive sleep apnea (OSA) compared with patients with type 2 diabetes without a diagnosis of OSA. RESEARCH DESIGN AND METHODS This age-, sex-, BMI-, and diabetes duration–matched cohort study used data from a U.K. primary care database from 1 January 2005 to 17 January 2018. Participants aged ≥16 years with type 2 diabetes were included. Exposed participants were those who developed OSA after their diabetes diagnosis; unexposed participants were those without diagnosed OSA. Outcomes were composite CVD (ischemic heart disease [IHD], stroke/transient ischemic attack [TIA], heart failure [HF]), peripheral vascular disease (PVD), atrial fibrillation (AF), peripheral neuropathy (PN), diabetes-related foot disease (DFD), referable retinopathy, chronic kidney disease (CKD), and all-cause mortality. The same outcomes were explored in patients with preexisting OSA before a diagnosis of type 2 diabetes versus diabetes without diagnosed OSA. RESULTS A total of 3,667 exposed participants and 10,450 matched control participants were included. Adjusted hazard ratios for the outcomes were as follows: composite CVD 1.54 (95% CI 1.32, 1.79), IHD 1.55 (1.26, 1.90), HF 1.67 (1.35, 2.06), stroke/TIA 1.57 (1.27, 1.94), PVD 1.10 (0.91, 1.32), AF 1.53 (1.28, 1.83), PN 1.32 (1.14, 1.51), DFD 1.42 (1.16, 1.74), referable retinopathy 0.99 (0.82, 1.21), CKD (stage 3–5) 1.18 (1.02, 1.36), albuminuria 1.11 (1.01, 1.22), and all-cause mortality 1.24 (1.10, 1.40). In the prevalent OSA cohort, the results were similar, but some associations were not observed. CONCLUSIONS Patients with type 2 diabetes who develop OSA are at increased risk of CVD, AF, PN, DFD, CKD, and all-cause mortality compared with patients without diagnosed OSA. Patients with type 2 diabetes who develop OSA are a high-risk population, and strategies to detect OSA and prevent cardiovascular and microvascular complications should be implemented.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chandan2020b,

title = {Increased cardiometabolic and mortality risk following childhood maltreatment in the United Kingdom},

author = {Joht Singh Chandan and Kelvin Okoth and Krishna Margadhamane Gokhale and Siddhartha Bandyopadhyay and Julie Taylor and Krishnarajah Nirantharakumar},

doi = {10.1161/JAHA.119.015855},

issn = {20479980},

year  = {2020},

date = {2020-01-01},

journal = {Journal of the American Heart Association},

volume = {9},

issue = {10},

publisher = {American Heart Association Inc.},

abstract = {BACKGROUND: Childhood maltreatment remains a significant public health issue associated with a number of poor health outcomes. This study explores the association between childhood maltreatment and the subsequent development of cardiometabolic disease and all-cause mortality. METHODS AND RESULTS: Using a UK primary care database between January 1, 1995 and December 31, 2018, we conducted a population-based open retrospective cohort study. We matched 80 657 adult patients with a historic recording of childhood maltreatment or maltreatment-related concerns (exposed group) to 161 314 unexposed patients. Outcomes of interest were the development of cardiovascular disease, hypertension, type 2 diabetes mellitus, and risk of all-cause mortality. During the study period there were 243 new diagnoses of cardiovascular disease (incidence rate 8.3 per 10 000 person-years) in the exposed group compared with 254 in the unexposed group (incidence rate 4.6 per 10 000 person-years). Following adjustment for key covariates, this translated to an adjusted incidence rate ratio of 1.71 (95% CI 1.42–2.06). Additionally, the exposed group had an increased risk of hypertension (adjusted incidence rate ratio 1.42; 95% CI, 1.26–1.59), type 2 diabetes mellitus (adjusted incidence rate ratio 2.13; 95% CI, 1.86–2.45) and all-cause mortality (adjusted incidence rate ratio 1.75; 95% CI, 1.52–2.02) during the study period compared with the unexposed group. CONCLUSIONS: Considering the high prevalence of exposure to childhood maltreatment, we have demonstrated the substantial associated burden of preventable cardiometabolic disease. There is a clear need to ensure that public health approaches are implemented to prevent the adverse consequences following exposure to childhood maltreatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chandan2020c,

title = {Risk of Cardiometabolic Disease and All-Cause Mortality in Female Survivors of Domestic Abuse},

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

doi = {10.1161/JAHA.119.014580},

issn = {20479980},

year  = {2020},

date = {2020-01-01},

journal = {Journal of the American Heart Association},

volume = {9},

issue = {4},

publisher = {American Heart Association Inc.},

abstract = {Background: Domestic abuse (DA) against women is a global public health problem. Although the possible health burden could be substantial, the associations between DA and subsequent cardiometabolic disease (cardiovascular disease, hypertension, and type 2 diabetes mellitus) and all-cause mortality are poorly understood. Methods and Results: This retrospective cohort study consisted of UK-based primary care patients between January 1, 1995, to December 1, 2017. Overall, 18 547 women exposed to DA were matched to 72 231 unexposed women by age and lifestyle factors. The main outcomes, presented as adjusted incidence rate ratios (IRRs), were the risk of developing cardiovascular disease, hypertension, type 2 diabetes mellitus, and all-cause mortality. In total, 181 exposed women experienced a cardiovascular disease event compared with 644 of the unexposed control group, relating to an increased adjusted IRR of 1.31 (95% CI, 1.11–1.55; P=0.001). There was also an increased risk of subsequent type 2 diabetes mellitus (adjusted IRR: 1.51; 95% CI, 1.30–1.76; P<0.001) and all-cause mortality (adjusted IRR: 1.44; 95% CI, 1.24–1.67; P<0.001) following exposure to DA. This observation was not seen with hypertension (adjusted IRR: 0.99; 95% CI, 0.88–1.12; P=0.873). Conclusions: There is an increased risk of subsequent cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality in female survivors of DA. However, there is no association with the development of hypertension in this group, in keeping with previous literature. Considering the high prevalence of DA, clinicians should be made aware of the disproportionally increased risk and thus are encouraged to manage modifiable risk factors actively in this group.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chandan2020d,

title = {The association between exposure to childhood maltreatment and the subsequent development of functional somatic and visceral pain syndromes},

author = {Joht Singh Chandan and Deepiksana Keerthy and Dawit Tefra Zemedikun and Kelvin Okoth and Krishna Margadhamane Gokhale and Karim Raza and Siddhartha Bandyopadhyay and Julie Taylor and Krishnarajah Nirantharakumar},

doi = {10.1016/J.ECLINM.2020.100392},

issn = {25895370},

year  = {2020},

date = {2020-01-01},

journal = {EClinicalMedicine},

volume = {23},

publisher = {Lancet Publishing Group},

abstract = {Background: Childhood maltreatment is a global public health issue linked to a vast mortality and morbidity burden. This study builds on current literature to explore the risk of developing central sensitivity syndromes (CSS) (consisting of somatic and visceral pain syndromes) subsequent to childhood maltreatment exposure. Methods: A retrospective population based open cohort study using the UK primary care database, ‘The Health Improvement Network,’ between 1st January 1995-31st December 2018. 80,657 adult patients who had experienced childhood maltreatment or maltreatment related concerns (exposed patients) were matched to 161,314 unexposed patients by age and sex. Outcomes of interest were the development of CSS: either somatic (Fibromyalgia, chronic fatigue syndrome, temporomandibular joint disorder, chronic lower back pain, chronic headache, myofascial pain syndrome and restless leg syndrome) or visceral (Interstitial cystitis, vulvodynia, chronic prostatitis and irritable bowel syndrome) in nature. Effect sizes are presented as adjusted incidence rate ratios (aIRR) with confidence intervals (CI). Models were adjusted for the following covariates at cohort entry: age, sex, deprivation, anxiety, depression and serious mental ill health. Results: The average age at cohort entry was 23.4 years and the median follow was 2.2 years. There was an increased risk of developing fibromyalgia (aIRR 2.06; 95% CI 1.71–2.48), chronic fatigue syndrome (1.47; 1.08–2.00), chronic lower back pain (1.99; 1.68–2.35), restless leg syndrome (1.82; 1.41–2.35) and irritable bowel syndrome (1.15; 1.08–1.22) when compared to the unexposed group, whereas no statistical association was seen with the development of temporomandibular joint disorder (1.00; 0.88–1.13), chronic headache (1.04; 0.59–1.86), interstitial cystitis (1.19; 0.51–2.74), vulvodynia (0.65; 0.34–1.26), chronic prostatitis (0.34; 0.07–1.77) and myofascial pain syndrome (0.88; 0.36–2.14). Outcome numbers were low, most likely, due to the rarity of visceral conditions (aside from irritable bowel syndrome). The association between a history of childhood maltreatment and CSS were mainly observed in somatic CSS. Interpretation: The debilitating effects of CSS carry a substantial physical, psychological and economic burden to both the individuals who are diagnosed with them and the health services who serve them. Primary prevention approaches targeting childhood maltreatment as well as secondary preventative approaches should be considered to minimise the associated burden of CSS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Singh2020,

title = {Impact of bariatric surgery on cardiovascular outcomes and mortality: a population-based cohort study},

author = {P. Singh and A. Subramanian and N. Adderley and K. Gokhale and R. Singhal and S. Bellary and K. Nirantharakumar and A. A. Tahrani},

doi = {10.1002/BJS.11433},

issn = {13652168},

year  = {2020},

date = {2020-01-01},

journal = {British Journal of Surgery},

volume = {107},

issue = {4},

pages = {432-442},

publisher = {John Wiley and Sons Ltd},

abstract = {Background: Cohort studies have shown that bariatric surgery may reduce the incidence of and mortality from cardiovascular disease (CVD), but studies using real-world data are limited. This study examined the impact of bariatric surgery on incident CVD, hypertension and atrial fibrillation, and all-cause mortality. Methods: A retrospective, matched, controlled cohort study of The Health Improvement Network primary care database (from 1 January 1990 to 31 January 2018) was performed (approximately 6 per cent of the UK population). Adults with a BMI of 30 kg/m2 or above who did not have gastric cancer were included as the exposed group. Each exposed patient, who had undergone bariatric surgery, was matched for age, sex, BMI and presence of type 2 diabetes mellitus (T2DM) with two controls who had not had bariatric surgery. Results: A total of 5170 exposed and 9995 control participants were included; their mean(s.d.) age was 45·3(10·5) years and 21·5 per cent (3265 of 15 165 participants) had T2DM. Median follow-up was 3·9 (i.q.r. 1·8– 6·4) years. Mean(s.d.) percentage weight loss was 20·0(13·2) and 0·8(9·5) per cent in exposed and control groups respectively. Overall, bariatric surgery was not associated with a significantly lower CVD risk (adjusted hazard ratio (HR) 0·80; 95 per cent c.i. 0·62 to 1·02; P = 0·074). Only in the gastric bypass group was a significant impact on CVD observed (HR 0·53, 0·34 to 0·81; P = 0·003). Bariatric surgery was associated with significant reduction in all-cause mortality (adjusted HR 0·70, 0·55 to 0·89; P = 0·004), hypertension (adjusted HR 0·41, 0·34 to 0·50; P < 0·001) and heart failure (adjusted HR 0·57, 0·34 to 0·96; P = 0·033). Outcomes were similar in patients with and those without T2DM (exposed versus controls), except for incident atrial fibrillation, which was reduced in the T2DM group. Conclusion: Bariatric surgery is associated with a reduced risk of hypertension, heart failure and mortality, compared with routine care. Gastric bypass was associated with reduced risk of CVD compared to routine care.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chandan2020e,

title = {Female survivors of intimate partner violence and risk of depression, anxiety and serious mental illness},

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

doi = {10.1192/BJP.2019.124},

issn = {14721465},

year  = {2020},

date = {2020-01-01},

journal = {British Journal of Psychiatry},

volume = {217},

issue = {4},

pages = {562-567},

publisher = {Cambridge University Press},

abstract = {Background Internationally, intimate partner violence (IPV) cohorts have demonstrated associations with depression and anxiety. However, this association has not yet been described in a UK population, nor has the association with serious mental illness (SMI).Aims To explore the relationship between IPV exposure and mental illness in a UK population.Method We designed a retrospective cohort study whereby we matched 18 547 women exposed to IPV to 74 188 unexposed women. Outcomes of interest (anxiety, depression and SMI) were identified through clinical codes.Results At baseline, 9174 (49.5%) women in the exposed group had some form of mental illness compared with 17 768 (24.0%) in the unexposed group, described as an adjusted odds ratio of 2.62 (95% CI 2.52-2.72). Excluding those with mental illness at baseline, 1254 exposed women (incidence rate 46.62 per 1000 person-years) went on to present with any type of mental illness compared with 3119 unexposed women (incidence rate 14.93 per 1000 person-years), with an aIRR of 2.77 (95% CI 2.58-2.97). Anxiety (aIRR 1.99, 95% CI 1.80-2.20), depression (aIRR 3.05, 95% CI 2.81-3.31) and SMI (aIRR 3.08, 95% CI 2.19-4.32) were all associated with exposure to IPV.Conclusions IPV remains a significant public health issue in the UK. We have demonstrated the significant recorded mental health burden associated with IPV in primary care, at both baseline and following exposure. Clinicians must be aware of this association to reduce mental illness diagnostic delay and improve management of psychological outcomes in this group of patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bhachu2019,

title = {Cross-sectional observation study to investigate the impact of risk-based stratification on care pathways for patients with chronic kidney disease: Protocol paper},

author = {Harjeet Kaur Bhachu and Paul Cockwell and Anuradhaa Subramanian and Krishnarajah Nirantharakumar and Derek Kyte and Melanie Calvert},

doi = {10.1136/BMJOPEN-2018-027315},

issn = {20446055},

year  = {2019},

date = {2019-01-01},

journal = {BMJ Open},

volume = {9},

issue = {6},

publisher = {BMJ Publishing Group},

abstract = {Introduction Chronic kidney disease (CKD) management in the UK is usually primary care based, with National Institute for Health and Care Excellence (NICE) guidelines defining criteria for referral to secondary care nephrology services. Estimated glomerular filtration rate (EGFR) is commonly used to guide timing of referrals and preparation of patients approaching renal replacement therapy. However, EGFR lacks sensitivity for progression to end-stage renal failure; as a consequence, the international guideline group, Kidney Disease: Improving Global Outcomes has recommended the use of a risk calculator. The validated Kidney Failure Risk Equation may enable increased precision for the management of patients with CKD; however, there is little evidence to date for the implication of its use in routine clinical practice. This study will aim to determine the impact of the Kidney Failure Risk Equation on the redesignation of patients with CKD in the UK for referral to secondary care, compared with NICE CKD guidance. Method and analysis This is a cross-sectional population-based observational study using The Health Improvement Network database to identify the impact of risk-based designation for referral into secondary care for patients with CKD in the UK. Adult patients registered in primary care and active in the database within the period 1 January 2016 to 31 March 2017 with confirmed CKD will be analysed. The proportion of patients who meet defined risk thresholds will be cross-referenced with the current NICE guideline recommendations for referral into secondary care along with an evaluation of urinary albumin-creatinine ratio monitoring. Ethics and dissemination Approval was granted by The Health Improvement Network Scientific Review Committee (Reference number: 18THIN061). Study outcomes will inform national and international guidelines including the next version of the NICE CKD guideline. Dissemination of findings will also be through publication in a peer-reviewed journal, presentation at conferences and inclusion in the core resources of the Think Kidneys programme.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chandan2019,

title = {The burden of mental ill health associated with childhood maltreatment in the UK, using The Health Improvement Network database: a population-based retrospective cohort study},

author = {Joht S. Chandan and Tom Thomas and Krishna M. Gokhale and Siddhartha Bandyopadhyay and Julie Taylor and Krishnarajah Nirantharakumar},

doi = {10.1016/S2215-0366(19)30369-4},

issn = {22150374},

year  = {2019},

date = {2019-01-01},

journal = {The Lancet Psychiatry},

volume = {6},

issue = {11},

pages = {926-934},

publisher = {Elsevier Ltd},

abstract = {Background: Childhood maltreatment is a global public health, human rights, and moral issue that is associated with a substantial mental health burden. We aimed to assess the association between childhood maltreatment and the development of mental ill health and the initiation of new prescriptions for mental ill health. Methods: In this population-based, retrospective, open cohort study, we used a dataset from individuals in The Health Improvement Network (THIN) database. THIN database comprises UK electronic medical records taken from 787 general practices throughout the UK. We used read codes in these records to identify exposed patients (those with a read code identifying officially confirmed childhood maltreatment or a maltreatment-related concern) and up to two unexposed patients (those without such read codes) from the same general practice, who were matched by age and sex. We evaluated the risk of developing depression, anxiety, or serious mental illness (a composite mental ill health outcome) or initiation of a prescription drug used to treat mental ill health, and the odds ratio of these events at baseline, in the exposed versus unexposed patients. Findings: The first possible date for cohort entry (the study start date) was Jan 1, 1995, and patients could enter the cohort until the study end date, Dec 31, 2018. During the study period, 11 831 850 patients were eligible to participate. Of these patients, we identified 217 758 (1·8%) patients with any recorded childhood maltreatment. These patients were matched to 423 410 unexposed control patients with no recorded exposure to childhood maltreatment. The exposed group were followed up for a median of 1·8 years (IQR 0·6–4·3) versus 3·2 years (1·3–6·1) in the unexposed group. During the study period, 11 665 (5·9%) new diagnoses of mental ill health were made in the exposed group, giving an incidence rate of 16·8 events per 1000 person-years versus 15 301 (3·7%) new recorded diagnoses at an incidence rate of 8·3 events per 1000 person-years in the unexposed cohort, giving an adjusted IRR of 2·14 (95% CI 2·08–2·19). 30 911 (14·8%) patients in the exposed group received a new prescription for any type of mental ill health (incidence rate 46·5 events per 1000 person-years) versus 36 390 (8·9%) patients in the unexposed group (20·5 per 1000 person-years) resulting in an adjusted IRR of 2·44 (95% CI 2·40–2·48). Interpretation: Childhood maltreatment is thought to affect one in three children globally; therefore, a doubled risk of developing mental ill health among these individuals represents a substantial contribution to the mental ill health burden in the UK. It is imperative that public health approaches, including those aimed at preventing and detecting childhood maltreatment and its associated negative consequences, are implemented to prevent mental ill health. Funding: None.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Thomas2019,

title = {The Risk of Inflammatory Bowel Disease in Subjects Presenting with Perianal Abscess: Findings from the THIN Database},

author = {Tom Thomas and Joht S. Chandan and Philip R. Harvey and Neeraj Bhala and Subrata Ghosh and Krishnarajah Nirantharakumar and Nigel J. Trudgill},

doi = {10.1093/ECCO-JCC/JJY210},

issn = {18764479},

year  = {2019},

date = {2019-01-01},

journal = {Journal of Crohn's and Colitis},

volume = {13},

issue = {5},

pages = {600-606},

publisher = {Oxford University Press},

abstract = {Background: Perianal abscess [PA] is associated with inflammatory bowel disease [IBD]. The incidence of IBD after a diagnosis of PA and potential predictors of a future diagnosis of IBD are unknown. Methods: The Health Improvement Network [THIN] is a primary care database representative of the UK population. Incident cases of PA were identified between 1995 and 2017. Subjects with PA were matched to controls within the same general practice. The primary outcome was a subsequent diagnosis of Crohn's Disease [CD] or ulcerative colitis [UC]. A Cox regression model was used to assess potential predictors of a new diagnosis of CD or UC following PA. Results: The risk of CD was higher in the PA cohort compared with controls; adjusted hazard ratio [HR] 7.51 (95% confidence interval [CI] 4.86-11.62), p < 0.0001. The risk of UC was also higher in the PA cohort compared with controls; adjusted HR 2.03 [1.38-2.99], p < 0.0001. Anaemia in men (HR 2.82 [1.34-5.92]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Taverner2019,

title = {Circulating folate concentrations and risk of peripheral neuropathy and mortality: A retrospective cohort study in the U.K},

author = {Tom Taverner and Francesca L. Crowe and G. Neil Thomas and Krishna Gokhale and Rasiah Thayakaran and Krishnarajah Nirantharakumar and Yusuf A. Rajabally},

doi = {10.3390/NU11102443},

issn = {20726643},

year  = {2019},

date = {2019-01-01},

journal = {Nutrients},

volume = {11},

issue = {10},

publisher = {MDPI AG},

abstract = {Background: Folate deficiency may increase the risk of peripheral neuropathy but there is a paucity of data from large prospective studies examining this association. Methods: Longitudinal analysis of electronic health records in The Health Improvement Network (THIN), a U.K. primary care database including 594,338 patients aged 18–70 years with a folate measurement and without a history of peripheral neuropathy. Results: After a mean follow-up of 3.71 (standard deviation (SD) = 3.14) years, 1949 patients were diagnosed with peripheral neuropathy and 20,679 patients died. In those <40 years, compared to patients with folate ≥13.6 nmol/L, those with folate <6.8 (deficient) and 6.8–13.5 nmol/L (insufficient) had a hazard ratio (HR) for peripheral neuropathy of 1.83 (95% confidence intervals (CI) = 1.16–2.91) and 1.48 (95% CI = 1.04–2.08), respectively. There was no significant association between folate and peripheral neuropathy among those aged 41–70 years. Compared to patients with folate ≥ 13.6 nmol/L, folate <6.8 nmol/L was associated with a greater risk of death among all ages. Conclusion: Folate deficiency and insufficiency was associated with a greater risk of peripheral neuropathy among younger patients. This investigation should be replicated in other large datasets and it may be important to monitor peripheral neuropathy incidence after the introduction of mandatory folic acid fortification of flour in the U.K.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Harvey2019,

title = {Outcomes following feeding gastrostomy (FG) insertion in patients with learning disability: A retrospective cohort study using the health improvement network (THIN) database},

author = {Philip R. Harvey and Tom Thomas and Joht Singh Chandan and Neeraj Bhala and Krishnarajah Nirantharakumar and Nigel J. Trudgill},

doi = {10.1136/BMJOPEN-2018-026714},

issn = {20446055},

year  = {2019},

date = {2019-01-01},

journal = {BMJ Open},

volume = {9},

issue = {6},

publisher = {BMJ Publishing Group},

abstract = {Objectives To measure the rates of lower respiratory tract infection (LRTI) and mortality following feeding gastrostomy (FG) placement in patients with learning disability (LD). Following this to compare these rates between those having LRTI prior to FG placement and those with no recent LRTI. Design Retrospective cohort study. Setting and participants The study population included patients with LD undergoing FG placement in the ' The Health Improvement Network' database. Patients with LRTI in the year prior (LYP) to their FG placement were compared with patients without a history of LRTI in the year prior (non-LYP) to FG placement. FG placement and LD were identified using Read codes previously developed by an expert panel. Main outcome measures Incidence rate ratio (IRR) of developing LRTI and mortality following FG, comparing patients with LRTI in the year prior to FG placement to patients without a history of LRTI. Results 214 patients with LD had a FG inserted including 743.4 person years follow-up. 53.7% were males and the median age was 27.6 (IQR 19.6 to 38.6) years. 27.1% were in the LYP patients. 18.7% had a LRTI in the year following FG, with an estimated incidence rate of 254 per 1000-person years. Over the study period the incidence rate of LRTI in LYP patients was 369 per 1000-person years, in non-LYP patients this was 91 per 1000-person years (adjusted IRR 4.21 (95% CI 2.68 to 6.63) p<0.001). 27.1% of patients died during study follow-up. Incidence rate of death was 80 and 45 per 1000-person year for LYP and non-LYP patients, respectively (adjusted IRR 1.80 (1.00 to 3.23) p=0.05). Conclusion In LD patients, no clinically meaningful reduction in LRTI incidence was observed following FG placement. Mortality and LRTI were higher in patients with at least one LRTI in the year preceding FG placement, compared with those without a preceding LRTI.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Subramanian2019,

title = {Risk of incident obstructive sleep apnea among patients with type 2 diabetes},

author = {Anuradhaa Subramanian and Nicola J. Adderley and Alexander Tracy and Tom Taverner and Wasim Hanif and Konstantinos A. Toulis and G. Neil Thomas and Abd A. Tahrani and Krishnarajah Nirantharakumar},

doi = {10.2337/DC18-2004},

issn = {19355548},

year  = {2019},

date = {2019-01-01},

journal = {Diabetes Care},

volume = {42},

issue = {5},

pages = {954-963},

publisher = {American Diabetes Association Inc.},

abstract = {OBJECTIVE This study compared the incidence of obstructive sleep apnea (OSA) in patients with and without type 2 diabetes and investigated risk factors for OSA in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A retrospective cohort study was performed to compare OSA incidence between adult patients with and without type 2 diabetes matched for age, sex, and BMI. Patients with a prevalent OSA diagnosis were excluded. The study cohort was derived from The Health Improvement Network (THIN), a U.K. primary care database, from 1 January 2005 to 31 December 2017. RESULTS There were 3,110 (0.88%) and 5,968 (0.46%) incident OSA cases identified in the 360,250 exposed and 1,296,489 unexposed patient cohorts, respectively. Adjusted incidence rate ratio (aIRR) of OSA in patients with type 2 diabetes compared with those without was 1.48 (95% CI 1.42–1.55; P < 0.001). In a multivariate regression analysis of patients with type 2 diabetes, significant predictors of OSA were diabetes-related foot disease (1.23 [1.06–1.42]; P = 0.005), being prescribed insulin in the last 60 days (1.58 [1.42–1.75]; P < 0.001), male sex (2.27 [2.09–2.46]; P < 0.001), being overweight (2.02 [1.54–2.64]; P < 0.001) or obese (8.29 [6.42–10.69]; P < 0.001), heart failure (1.41 [1.18–1.70]; P < 0.001), ischemic heart disease (1.22 [1.11–1.34]; P < 0.001), atrial fibrillation (1.23 [1.04–1.46]; P = 0.015), hypertension (1.32 [1.23–1.43]; P < 0.001), and depression (1.75 [1.61–1.91]; P < 0.001). CONCLUSIONS When considered alongside previous evidence, this study indicates that the association between type 2 diabetes and OSA is bidirectional. In addition to known predictors of OSA, diabetes-related foot disease and insulin treatment were identified as risk factors in patients with type 2 diabetes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tracy2019,

title = {Cardiovascular, thromboembolic and renal outcomes in IgA vasculitis (Henoch-Schönlein purpura): A retrospective cohort study using routinely collected primary care data},

author = {Alexander Tracy and Anuradhaa Subramanian and Nicola J. Adderley and Paul Cockwell and Charles Ferro and Simon Ball and Lorraine Harper and Krishnarajah Nirantharakumar},

doi = {10.1136/ANNRHEUMDIS-2018-214142},

issn = {14682060},

year  = {2019},

date = {2019-01-01},

journal = {Annals of the Rheumatic Diseases},

volume = {78},

issue = {2},

pages = {261-269},

publisher = {BMJ Publishing Group},

abstract = {Background IgA vasculitis (IgAV, Henoch-Schönlein purpura) is a small-vessel vasculitis most common in children but also occurring in adults. Case series have suggested that IgAV may be associated with cardiovascular disease and venous thromboembolism, but this has not been evaluated in population-based studies. Renal disease and hypertension are possible complications of the disease with unknown incidence. Methods Using a large UK primary care database, we conducted an open retrospective matched cohort study of cardiovascular, venous thrombotic and renal outcomes in adult-onset and childhood-onset IgAV. Control participants were selected at a 2:1 ratio, matched for age and sex. Adjusted HRs (aHRs) were calculated using Cox proportional hazards models. Results 2828 patients with adult-onset IgAV and 10 405 patients with childhood-onset IgAV were compared with age-matched and sex-matched controls. There was significantly increased risk of hypertension (adult-onset aHR 1.42, 95% CI 1.19 to 1.70, p < 0.001; childhood-onset aHR 1.52, 95% CI 1.22 to 1.89, p < 0.001) and stage G3-G5 chronic kidney disease (adult-onset aHR 1.54, 95% CI 1.23 to 1.93, p < 0.001; childhood-onset aHR 1.89, 95% CI 1.16 to 3.07},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Krishna2019,

title = {Allergic diseases and long-term risk of autoimmune disorders: Longitudinal cohort study and cluster analysis},

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

doi = {10.1183/13993003.00476-2019},

issn = {13993003},

year  = {2019},

date = {2019-01-01},

journal = {European Respiratory Journal},

volume = {54},

issue = {5},

publisher = {European Respiratory Society},

abstract = {Introduction: The association between allergic diseases and autoimmune disorders is not well established. Our objective was to determine incidence rates of autoimmune disorders in allergic rhinitis/conjunctivitis (ARC), atopic eczema and asthma, and to investigate for co-occurring patterns. Methods: This was a retrospective cohort study (1990–2018) employing data extracted from The Health Improvement Network (UK primary care database). The exposure group comprised ARC, atopic eczema and asthma (all ages). For each exposed patient, up to two randomly selected age- and sex-matched controls with no documented allergic disease were used. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters. Results: 782320, 1393570 and 1049868 patients with ARC, atopic eczema and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sjögren’s syndrome, vitiligo, rheumatoid arthritis, psoriasis, pernicious anaemia, inflammatory bowel disease, coeliac disease and autoimmune thyroiditis were uniformly higher in the three allergic diseases compared with controls. Specifically, aIRRs of SLE (1.45) and Sjögren’s syndrome (1.88) were higher in ARC; aIRRs of SLE (1.44), Sjögren’s syndrome (1.61) and myasthenia (1.56) were higher in asthma; and aIRRs of SLE (1.86), Sjögren’s syndrome (1.48), vitiligo (1.54) and psoriasis (2.41) were higher in atopic eczema. There was no significant effect of the three allergic diseases on multiple sclerosis or of ARC and atopic eczema on myasthenia. Using ARM, allergic diseases clustered with multiple autoimmune disorders. Three age- and sex-related clusters were identified, with a relatively complex pattern in females ≥55 years old. Conclusions: The long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lavrentaki2019,

title = {Increased risk of non-alcoholic fatty liver disease in women with gestational diabetes mellitus: A population-based cohort study, systematic review and meta-analysis},

author = {Aikaterini Lavrentaki and Tom Thomas and Anuradhaa Subramanian and George Valsamakis and Neil Thomas and Konstantinos A. Toulis and Jingya Wang and Barbara Daly and Ponnusamy Saravanan and Dana Sumilo and George Mastorakos and Abd A. Tahrani and Krishnarajah Nirantharakumar},

doi = {10.1016/J.JDIACOMP.2019.06.006},

issn = {1873460X},

year  = {2019},

date = {2019-01-01},

journal = {Journal of Diabetes and its Complications},

volume = {33},

issue = {10},

publisher = {Elsevier Inc.},

abstract = {Aims: Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the leading causes of liver transplantation in the West. This study seeks to examine whether women with gestational diabetes mellitus (GDM) are at increased risk of developing NAFLD compared to women without GDM. Methods: We conducted a population-based retrospective matched-controlled cohort study utilising The Health Improvement Network (THIN), a large primary care database representative of the United Kingdom population, between 01/01/1990 to 31/05/2016 followed by systematic review of available literature. The study population included 9640 women with GDM and 31,296 controls without GDM, matched for age, body mass index (BMI) and time of pregnancy. All study participants were free from NAFLD diagnosis at study entry. Patients with GDM and patients developing NAFLD were identified by clinical codes. Results: The median (range) follow-up duration was similar in women with and without GDM (2.95 (1.21–6.01) vs 2.85 (1.14–5.75) years respectively). Unadjusted incidence rate ratio (IRR) for NAFLD development in women with vs without GDM was 3.28 (95% CI 2.14–5.02), which remained significant after adjustment for wide range of potential confounders (IRR 2.70; 95% CI 1.744–4.19). The risk of NAFLD in GDM remained high (IRR 2.46: 95% CI 1.51–4.00) despite women being censored after they developed type 2 diabetes. The meta-analysis of 3 studies (including the current study) showed increased NAFLD risk in women with vs without GDM (OR 2.60; 95% CI 1.90–3.57},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Thayakaran2019,

title = {Impact of glycaemic control on fracture risk in 5368 people with newly diagnosed Type 1 diabetes: a time-dependent analysis},

author = {R. Thayakaran and M. Perrins and K. M. Gokhale and S. Kumaran and P. Narendran and M. J. Price and K. Nirantharakumar and K. A. Toulis},

doi = {10.1111/DME.13945},

issn = {14645491},

year  = {2019},

date = {2019-01-01},

journal = {Diabetic Medicine},

volume = {36},

issue = {8},

pages = {1013-1019},

publisher = {Blackwell Publishing Ltd},

abstract = {Aims: To assess whether glycaemic control is associated with a lifelong increased risk of fracture in people with newly diagnosed Type 1 diabetes. Methods: People with newly diagnosed Type 1 diabetes between 1 January 1995 and 10 May 2016 were identified in The Health Improvement Network database. Longitudinal HbA1c measurements from diagnosis to fracture or study end or loss to follow-up were collected. A Cox proportional hazards model with HbA1c included as a time-dependent variable was fitted to these data. Results: Some 5368 people with newly diagnosed Type 1 diabetes were included. The estimated adjusted hazard ratio (aHR) for HbA1c was statistically significant [aHR 1.007; 95% confidence interval (CI) 1.002–1.011 (mmol/mol) and aHR 1.07; 95% CI 1.03–1.12 (%)]. An incremental higher risk of fracture was observed with increasing levels of HbA1c. Conclusions: In people with newly diagnosed Type 1 diabetes, higher HbA1c is associated with an increased risk for fractures.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chandan2019b,

title = {Intimate partner violence and temporomandibular joint disorder},

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

doi = {10.1016/J.JDENT.2019.01.008},

issn = {03005712},

year  = {2019},

date = {2019-01-01},

journal = {Journal of Dentistry},

volume = {82},

pages = {98-100},

publisher = {Elsevier Ltd},

abstract = {Objective: To assess the relationship between Intimate partner violence (IPV) (a highly prevalent form of domestic abuse) with the subsequent development of temporomandibular joint disorder (TMD). Methods: A retrospective open cohort study using a UK primary care database was undertaken. 18,547 women exposed to IPV were matched by age to 74,188 unexposed women. Defined through clinical codes the outcome of interest was TMD, and adjusted incidence rates (aIRR) were used to describe the relationship after considering covariates of interest. Results: 94 individuals in the exposed group were clinically coded with TMD during the study period translating to an incidence rate (IR) or 1.59 per 1000 person years. This was in comparison to 342 outcomes in the unexposed group (IR 1.21 per 1000 person years). The unadjusted IRR was 1.31 (95% CI 1.04–1.65; p < 0.020) and after adjustment for important covariates increased to 1.45 (95% CI 1.14–1.84; p < 0.002). Conclusion: Our results suggest that the development of TMD may be associated with exposure to IPV in women. Clinical significance: In the first cohort to do so, we have identified a moderate association between Intimate partner violence exposure and subsequent development of TMD. This highlights an opportunity for screening of abuse in individuals presenting with TMD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Adderley2019,

title = {Association between Idiopathic Intracranial Hypertension and Risk of Cardiovascular Diseases in Women in the United Kingdom},

author = {Nicola J. Adderley and Anuradhaa Subramanian and Krishnarajah Nirantharakumar and Andreas Yiangou and Krishna M. Gokhale and Susan P. Mollan and Alexandra J. Sinclair},

doi = {10.1001/JAMANEUROL.2019.1812},

issn = {21686149},

year  = {2019},

date = {2019-01-01},

journal = {JAMA Neurology},

volume = {76},

issue = {9},

pages = {1088-1098},

publisher = {American Medical Association},

abstract = {Importance: Cardiovascular disease (CVD) risk has not been previously evaluated in a large matched cohort study in idiopathic intracranial hypertension (IIH). Objectives: To estimate the risk of composite cardiovascular events, heart failure, ischemic heart disease, stroke/transient ischemic attack (TIA), type 2 diabetes, and hypertension in women with idiopathic intracranial hypertension and compare it with the risk in women, matched on body mass index (BMI) and age, without the condition; and to evaluate the prevalence and incidence of IIH. Design, Setting, and Participants: This population-based matched controlled cohort study used 28 years of data, from January 1, 1990, to January 17, 2018, from The Health Improvement Network (THIN), an anonymized, nationally representative electronic medical records database in the United Kingdom. All female patients aged 16 years or older were eligible for inclusion. Female patients with IIH (n = 2760) were included and randomly matched with up to 10 control patients (n = 27125) by BMI and age. Main Outcomes and Measures: Adjusted hazard ratios (aHRs) of cardiovascular outcomes were calculated using Cox regression models. The primary outcome was a composite of any CVD (heart failure, ischemic heart disease, and stroke/TIA), and the secondary outcomes were each CVD outcome, type 2 diabetes, and hypertension. Results: In total, 2760 women with IIH and 27125 women without IIH were included. Age and BMI were similar between the 2 groups, with a median (interquartile range) age of 32.1 (25.6-42.0) years in the exposed group and 32.1 (25.7-42.1) years in the control group; in the exposed group 1728 women (62.6%) were obese, and in the control group 16514 women (60.9%) were obese. Higher absolute risks for all cardiovascular outcomes were observed in women with IIH compared with control patients. The aHRs were as follows: composite cardiovascular events, 2.10 (95% CI, 1.61-2.74; P <.001); heart failure, 1.97 (95% CI, 1.16-3.37; P =.01); ischemic heart disease, 1.94 (95% CI, 1.27-2.94; P =.002); stroke/TIA, 2.27 (95% CI, 1.61-3.21; P <.001); type 2 diabetes, 1.30 (95% CI, 1.07-1.57; P =.009); and hypertension, 1.55 (95% CI, 1.30-1.84; P <.001). The incidence of IIH in female patients more than tripled between 2005 and 2017, from 2.5 to 9.3 per 100000 person-years. Similarly, IIH prevalence increased in the same period, from 26 to 79 per 100000 women. Incidence increased markedly with BMI higher than 30. Conclusions and Relevance: Idiopathic intracranial hypertension in women appeared to be associated with a 2-fold increase in CVD risk; change in patient care to modify risk factors for CVD may reduce long-term morbidity for women with IIH and warrants further evaluation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Adderley2019b,

title = {Temporal variation in the diagnosis of resolved atrial fibrillation and the influence of performance targets on clinical coding: Cohort study},

author = {Nicola Adderley and Krishnarajah Nirantharakumar and Tom Marshall},

doi = {10.1136/BMJOPEN-2019-030454},

issn = {20446055},

year  = {2019},

date = {2019-01-01},

journal = {BMJ Open},

volume = {9},

issue = {11},

publisher = {BMJ Publishing Group},

abstract = {Objectives To investigate whether the introduction of performance targets for anticoagulation in atrial fibrillation (AF) was associated with a change in use of the resolved AF' code. Design Retrospective cohort studies. Setting Data from The Health Improvement Network, a UK database of electronic patient records, from 2000 to 2016. Participants 250 788 adult patients aged ≥18 years with a diagnosis of AF, including 14 757 with an incident diagnosis of resolved AF'. Main outcome measures Annual and monthly incidence of resolved AF' from 2000 to 2016. Among patients with resolved AF', for each year we calculated median duration of the preceding AF diagnosis and the proportion prescribed anticoagulants prior to resolved AF'. Results Incidence of resolved AF' increased from 5.7 to 26.3 per 1000 person-years between 2005 and the introduction of AF performance targets in 2006. Compared with the years prior to the introduction of the performance targets, incidence has remained higher in every year since their implementation. Since 2007, monthly incidence has been highest between January and March. Between 2005 and 2006, median duration between AF and resolved AF' diagnoses increased from 276 days (9 months) to 1343 days (3 years 8 months). Among resolved AF' patients with CHA 2 DS 2-VASc score ≥1, 81.9% (95% CI 81.1 to 82.6) had no current anticoagulant prescription, and 62.3% (95% CI 61.4 to 63.2) had no record of any anticoagulant prescription. Conclusion The introduction of AF performance targets was followed by a large increase in use of the resolved AF' code, particularly in the months immediately before practices make their anticoagulant performance target submissions. Although most AF patients are prescribed anticoagulants, few patients diagnosed with resolved AF' are prescribed anticoagulants and most have never been prescribed them. Untreated patients are much more likely to be coded as having resolved AF'.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mittal2019,

title = {Cancer as a risk factor for urinary tract calculi: a retrospective cohort study using ‘The Health Improvement Network’: Cancer and urinary tract calculi},

author = {Ankush Mittal and Motaz Elmahdy Hassan and Joht Singh Chandan and Brian H. Willis and Krishnarajah Nirantharakumar and Kesvapilla Subramonian},

doi = {10.1007/S00240-019-01127-Z},

issn = {21947236},

year  = {2019},

date = {2019-01-01},

journal = {Urolithiasis},

volume = {47},

issue = {6},

pages = {541-547},

publisher = {Springer Verlag},

abstract = {Purpose: Urolithiasis is a common condition that poses significant morbidity to patients. There are similarities in the development of certain cancers and urinary tract calculi (UTC), however, little is known about their temporal relationship. This study aims to identify if cancer is a risk factor for the development of UTC. Methods: A population-based retrospective cohort study was conducted for the period 1st January 1990 to 1st May 2016. 124,901 exposed patients identified using clinical codes with newly diagnosed cancer were matched to 476,203 unexposed controls by age, gender, BMI, and general practice. The main outcome measure was the risk of developing UTC described by hazard ratios. Results: There were 512 incident UTC events in the cancer group compared to 1787 in the unexposed controls. This translated to an adjusted hazard ratio of 1.26 (95% CI 1.14–1.39; p < 0.001). A sub-analysis assessing cancer-specific effects demonstrated increased risks for 10 out of 12 common cancers, most significantly in bladder, colorectal and prostate cancer. Conclusion: This study demonstrated a 26% increased risk of UTC in cancer patients suggesting wider recognition of this risk amongst clinicians could improve diagnosis and prevention of UTC, as well as encourage further research exploring this association.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kumarendran2019,

title = {Increased risk of obstructive sleep apnoea in women with polycystic ovary syndrome: A population-based cohort study},

author = {Balachandran Kumarendran and Dana Sumilo and Michael W. O’Reilly and Konstantinos A. Toulis and Krishna M. Gokhale and Chandrika N. Wijeyaratne and Arri Coomarasamy and Wiebke Arlt and Abd A. Tahrani and Krishnarajah Nirantharakumar},

doi = {10.1530/EJE-18-0693},

issn = {1479683X},

year  = {2019},

date = {2019-01-01},

journal = {European Journal of Endocrinology},

volume = {180},

issue = {4},

pages = {265-272},

publisher = {BioScientifica Ltd.},

abstract = {Objective: Obesity is very common in patients with obstructive sleep apnoea (OSA) and polycystic ovary syndrome (PCOS). Longitudinal studies assessing OSA risk in PCOS and examining the role of obesity are lacking. Our objective was to assess the risk of OSA in women with vs without PCOS and to examine the role of obesity in the observed findings. Design: Population-based retrospective cohort study utilizing The Health Improvement Network (THIN), UK. Methods: 76 978 women with PCOS and 143 077 age-, BMI- and location-matched women without PCOS between January 2000 and May 2017 were identified. Hazard ratio (HR) for OSA among women with and without PCOS were calculated after controlling for confounding variables using multivariate Cox models. Results: Median patient age was 30 (IQR: 25–35) years; median follow-up was 3.5 (IQR: 1.4–7.1) years. We found 298 OSA cases in PCOS women vs 222 in controls, with incidence rates for OSA of 8.1 and 3.3 per 10 000 person years, respectively. Women with PCOS were at increased risk of developing OSA (adjusted HR = 2.26, 95% CI: 1.89–2.69, P < 0.001), with similar HRs for normal weight, overweight and obese PCOS women. Conclusions: Women with PCOS are at increased risk of developing OSA compared to control women irrespective of obesity. Considering the significant metabolic morbidity associated with OSA, clinicians should have a low threshold to test for OSA in women with PCOS. Whether OSA treatment has an impact on PCOS symptoms and outcomes needs to be examined.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Toulis2019,

title = {Risk of incident circulatory disease in patients treated for differentiated thyroid carcinoma with no history of cardiovascular disease},

author = {Konstantinos A. Toulis and David Viola and George Gkoutos and Deepiksana Keerthy and Kristien Boelaert and Krishnarajah Nirantharakumar},

doi = {10.1111/CEN.13990},

issn = {13652265},

year  = {2019},

date = {2019-01-01},

journal = {Clinical Endocrinology},

volume = {91},

issue = {2},

pages = {323-330},

publisher = {Blackwell Publishing Ltd},

abstract = {Context: The incidence of differentiated thyroid cancer (DTC) is increasing, yet the prognosis is favourable and long-term survival is expected. Exogenous TSH suppression has been used for many years to prevent DTC recurrence and may be associated with increased risks of circulatory diseases. Design: Risks of circulatory disease in patients treated for DTC were compared to randomly matched patients without DTC (controls) up to a 1:5 ratio using age, sex, body mass index (BMI) and smoking as the matching parameters in a population-based, open cohort study using The Health Improvement Network. Patients: A total of 3009 patients treated for DTC with no pre-existing cardiovascular disease were identified and matched to 11 303 controls, followed up to median of 5 years. Results: A total of 1259 incident circulatory events were recorded during the observation period. No difference in the risk of ischaemic heart disease (IHD) (adjusted hazards ratio [aHR]: 1.04, 95% CI: 0.80-1.36) or heart failure (HF) (aHR: 1.27, 95% CI: 0.89-1.81) was detected. The risk of atrial fibrillation (AF) and stroke was significantly higher in patients with DTC (aHR: 1.71, 95% CI: 1.36-2.15 and aHR: 1.34, 95% CI: 1.05-1.72, respectively). In a sensitivity analysis limited to newly diagnosed patients with DTC, only the risk of AF was consistently elevated (aHR: 1.86, 95% CI: 1.33-2.60). Conclusions: The increased risk of AF in patients who have undergone treatment for DTC but without pre-existing CVD may warrant periodic screening for this arrhythmia. Whereas no evidence of increased risk of IHD or HF was observed, the increased risk of stroke/TIA warrants further investigation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Crowe2019,

title = {Non-linear associations of 25-hydroxyvitamin D concentrations with risk of cardiovascular disease and all-cause mortality: Results from The Health Improvement Network (THIN) database},

author = {Francesca L. Crowe and Rasiah Thayakaran and Neil Gittoes and Martin Hewison and G. Neil Thomas and Robert Scragg and Krishnarajah Nirantharakumar},

doi = {10.1016/J.JSBMB.2019.105480},

issn = {18791220},

year  = {2019},

date = {2019-01-01},

journal = {Journal of Steroid Biochemistry and Molecular Biology},

volume = {195},

publisher = {Elsevier Ltd},

abstract = {Background: There is increasing evidence that vitamin D supplementation may only be beneficial in people with vitamin D deficiency, and the lack of sufficient people with very low vitamin D levels could explain the lack of protection against cardiovascular disease (CVD) reported in recent clinical trials of vitamin D supplementation. The aim of this study was to assess associations of low to moderate circulating concentrations of 25-hydroxyvitamin D (25(OH)D with risk of incident CVD and all-cause mortality, as well as the risk of ischaemic heart disease (IHD), cerebrovascular disease, and heart failure separately. Methods and Results: Longitudinal analysis of electronic health records in The Health Improvement Network (THIN), a UK primary care database. The analysis included 180,263 patients age 18 years and older without a history of CVD and with circulating concentrations of 25(OH)D. After a mean follow-up of 2.2 (SD 1.7) years, there were 3747 patients diagnosed with CVD and 3912 patients died. Compared to patients in the highest quintile of 25(OHD) (≥ 67.5 nmol/L), those in the lowest 25(OH)D quintile (<23.1 nmol/L) had a hazard ratio (HR) of 1.24 (95% CI 1.12–1.38, P < 0.001) for CVD and 1.71 (1.55–1.88, P < 0.001) for mortality. The HR for both outcomes associated with 25(OH)D concentration was non-linear, being significantly increased in patients with 25(OH)D <35 nmol/L, and highest in those with 25(OH)D <25 nmol/L, although increased for mortality at 25(OH)D ≥100 nmol/L. The increased CVD HR in the lowest 25(OH)D quintile was more from IHD (1.35, 95% CI 1.13–1.60) and heart failure (1.38, 95% CI 1.08–1.77), than from cerebrovascular disease (1.13, 95% CI 0.97–1.31). Conclusion: Low 25(OH)D are associated with highest risk of CVD and mortality, and are consistent with accumulating evidence that increased risk of these diseases occurs primarily in people with vitamin D deficiency.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Thayakaran2019b,

title = {Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: Longitudinal study},

author = {Rasiah Thayakaran and Nicola J. Adderley and Christopher Sainsbury and Barbara Torlinska and Kristien Boelaert and Dana Šumilo and Malcolm Price and G. Neil Thomas and Konstantinos A. Toulis and Krishnarajah Nirantharakumar},

doi = {10.1136/BMJ.L4892},

issn = {17561833},

year  = {2019},

date = {2019-01-01},

journal = {The BMJ},

volume = {366},

publisher = {BMJ Publishing Group},

abstract = {Objective To explore whether thyroid stimulating hormone (TSH) concentration in patients with a diagnosis of hypothyroidism is associated with increased all cause mortality and a higher risk of cardiovascular disease and fractures. Design Retrospective cohort study. Setting The Health Improvement Network (THIN), a database of electronic patient records from UK primary care. Participants Adult patients with incident hypothyroidism from 1 January 1995 to 31 December 2017. Exposure TSH concentration in patients with hypothyroidism. Main outcome measures Ischaemic heart disease, heart failure, stroke/transient ischaemic attack, atrial fibrillation, any fractures, fragility fractures, and mortality. Longitudinal TSH measurements from diagnosis to outcomes, study end, or loss to follow-up were collected. An extended Cox proportional hazards model with TSH considered as a time varying covariate was fitted for each outcome. Results 162 369 patients with hypothyroidism and 863 072 TSH measurements were included in the analysis. Compared with the reference TSH category (2-2.5 mIU/L), risk of ischaemic heart disease and heart failure increased at high TSH concentrations (>10 mIU/L) (hazard ratio 1.18 (95% confidence interval 1.02 to 1.38; P=0.03) and 1.42 (1.21 to 1.67; P<0.001), respectively). A protective effect for heart failure was seen at low TSH concentrations (hazard ratio 0.79 (0.64 to 0.99; P=0.04) for TSH <0.1 mIU/L and 0.76 (0.62 to 0.92; P=0.006) for 0.1-0.4 mIU/L). Increased mortality was observed in both the lowest and highest TSH categories (hazard ratio 1.18 (1.08 to 1.28; P<0.001), 1.29 (1.22 to 1.36; P<0.001), and 2.21 (2.07 to 2.36; P<0.001) for TSH <0.1 mIU/L, 4-10 mIU/L, and >10 mIU/L. An increase in the risk of fragility fractures was observed in patients in the highest TSH category (>10 mIU/L) (hazard ratio 1.15 (1.01 to 1.31; P=0.03)). Conclusions In patients with a diagnosis of hypothyroidism, no evidence was found to suggest a clinically meaningful difference in the pattern of long term health outcomes (all cause mortality, atrial fibrillation, ischaemic heart disease, heart failure, stroke/transient ischaemic attack, fractures) when TSH concentrations were within recommended normal limits. Evidence was found for adverse health outcomes when TSH concentration is outside this range, particularly above the upper reference value.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ntouva2019,

title = {Hypoglycaemia is associated with increased risk of fractures in patients with type 2 diabetes mellitus: A cohort study},

author = {Antiopi Ntouva and Konstantinos A. Toulis and Deepikshana Keerthy and Nicola J. Adderley and Wasim Hanif and Rasiah Thayakaran and Krishna Gokhale and G. Neil Thomas and Kamlesh Khunti and Abd A. Tahrani and Krishnarajah Nirantharakumar},

doi = {10.1530/EJE-18-0458},

issn = {1479683X},

year  = {2019},

date = {2019-01-01},

journal = {European Journal of Endocrinology},

volume = {180},

issue = {1},

pages = {51-58},

publisher = {BioScientifica Ltd.},

abstract = {Objective: Type 2 diabetes is associated with an increased risk of fracture. Any factor that incrementally increases this risk should be taken into account when individualising treatment. Hypoglycaemia is a common complication of antidiabetes medications and suggested as a risk factor for fractures; yet, its real-life clinical impact is unclear. Design: A population-based, retrospective open cohort study using routinely collected data between 1st of January 1995 and 1st of May 2016 in The Health Improvement Network (THIN) database. Methods: Patients with type 2 diabetes mellitus with documented hypoglycaemic events were compared to randomly matched patients with type 2 diabetes mellitus without documented hypoglycaemic events matched to exposed patients on age, sex, duration of diabetes and BMI. The primary outcome was any incident fracture. Secondary outcome was incident fragility (osteoporotic) fracture. Results: A total of 41 163 patients with type 2 diabetes were included: 14 147 patients in the exposed cohort and 27 016 patients in the unexposed cohort. Patients with a documented hypoglycaemic event were significantly more likely to sustain any fracture compared to patients with no record of hypoglycaemic events: adjusted IRR = 1.20 (95% CI: 1.12–1.30; P < 0.0001). Patients who had a documented hypoglycaemic event were significantly more likely to suffer a fragility fracture compared to controls: adjusted IRR = 1.24 (95% CI: 1.13–1.37; P < 0.0001). Conclusions: Hypoglycaemic events are a significant risk factor for fractures in patients with diabetes mellitus. This observation is clinically relevant when individualising targets for glycaemic control and selecting antidiabetic agents.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort},

author = {Michael W. O’Reilly and Marija Glisic and Balachandran Kumarendran and Anuradhaa Subramanian and Konstantinos N. Manolopoulos and Abd A. Tahrani and Deepi Keerthy and Taulant Muka and Konstantinos A. Toulis and Wasim Hanif and G. Neil Thomas and Oscar H. Franco and Wiebke Arlt and Krishnarajah Nirantharakumar},

doi = {10.1111/CEN.13862},

issn = {13652265},

year  = {2019},

date = {2019-01-01},

journal = {Clinical Endocrinology},

volume = {90},

issue = {1},

pages = {145-154},

publisher = {Blackwell Publishing Ltd},

abstract = {Objective: Previous studies suggest that androgens have a sexually dimorphic impact on metabolic dysfunction. However, the sex-specific link between circulating androgens and risk of type 2 diabetes mellitus (T2DM) has not been examined in a large scale, longitudinal cohort, a task we undertook in this study. Design: A retrospective cohort study in a UK primary care database. Patients: We included men and women with available serum testosterone and sex hormone-binding globulin (SHBG) results. Measurements: We categorized serum concentrations according to clinically relevant cut-off points and calculated crude and adjusted T2DM Incidence Rate Ratios (IRRs and aIRRs). Results: Serum testosterone concentrations were available in 70 541 men and 81 889 women; serum SHBG was available in 15 907 men and 42 034 women. In comparison to a reference cohort with serum testosterone ≥20 nmol/L, men with lower serum testosterone had a significantly increased risk of T2DM, with the highest risk in those with serum testosterone <7 nmol/L (aIRR 2.71, 95% CI 2.34-3.14, P < 0.001). In women, the risk of T2DM started to increase significantly when serum testosterone concentrations exceeded 1.5 nmol/L, with the highest risk in women with serum testosterone ≥3.5 nmol/L (aIRR 1.98, 95% CI 1.55-2.52, P < 0.001). These observations were verified in a continuous rather than categorized analysis. The risk of T2DM increased in men and women with serum SHBG <40 and <50 nmol/L, respectively. Conclusions/Interpretation: In this longitudinal study, we found sexually dimorphic associations between serum testosterone and risk of incident T2DM. Androgen deficiency and excess should be considered important risk factors for diabetes in men and women, respectively.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Harvey2018,

title = {Incidence, morbidity and mortality of patients with achalasia in England: Findings from a study of nationwide hospital and primary care data},

author = {Philip R. Harvey and Tom Thomas and Joht S. Chandan and Jemma Mytton and Ben Coupland and Neeraj Bhala and Felicity Evison and Prashant Patel and Krishnarajah Nirantharakumar and Nigel J. Trudgill},

doi = {10.1136/GUTJNL-2018-316089},

issn = {14683288},

year  = {2018},

date = {2018-01-01},

journal = {Gut},

publisher = {BMJ Publishing Group},

abstract = {Background: Achalasia is an uncommon condition characterised by failed lower oesophageal sphincter relaxation. Data regarding its incidence, prevalence, disease associations and long-term outcomes are very limited. Methods: Hospital Episode Statistics (HES) include demographic and diagnostic data for all English hospital attendances. The Health Improvement Network (THIN) includes the primary care records of 4.5 million UK subjects, representative of national demographics. Both were searched for incident cases between 2006 and 2016 and THIN for prevalent cases. Subjects with achalasia in THIN were compared with age, sex, deprivation tand smoking status matched controls for important comorbidities and mortality. Results: There were 10 509 and 711 new achalasia diagnoses identified in HES and THIN, respectively. The mean incidence per 100 000 people in HES was 1.99 (95% CI 1.87 to 2.11) and 1.53 (1.42 to 1.64) per 100 000 person-years in THIN. The prevalence in THIN was 27.1 (25.4 to 28.9) per 100 000 population. Incidence rate ratios (IRRs) were significantly higher in subjects with achalasia (n=2369) compared with controls (n=3865) for: oesophageal cancer (IRR 5.22 (95% CI: 1.88 to 14.45), p<0.001), aspiration pneumonia (13.38 (1.66 to 107.79)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Toulis2018,

title = {Males with prolactinoma are at increased risk of incident cardiovascular disease},

author = {Konstantinos A. Toulis and Tim Robbins and Narendra Reddy and Kumarendran Balachandran and Krishna Gokhale and Haren Wijesinghe and Kar Keung Cheng and Niki Karavitaki and John Wass and Krishnarajah Nirantharakumar},

doi = {10.1111/CEN.13498},

issn = {13652265},

year  = {2018},

date = {2018-01-01},

journal = {Clinical Endocrinology},

volume = {88},

issue = {1},

pages = {71-76},

publisher = {Blackwell Publishing Ltd},

abstract = {Objective: To investigate whether the risk of incident cardiovascular disease (CVD) is increased in patients with prolactinoma. Design: Population-based, retrospective, open-cohort study using The Health Improvement Network (THIN) database. Patients: A total of 2233 patients with prolactinoma and 10 355 matched controls (1:5 ratio) from UK General Practices contributing to THIN were included. Sex, age, body mass index and smoking status were used as matching parameters. The primary outcome was any incident CVD, defined by Read codes suggesting myocardial infarction, angina pectoris, stroke, transient ischaemic attack or heart failure. Sex-specific-adjusted incidence rate ratios (aIRRs) were calculated with Poisson regression, using clinically relevant parameters as model covariates. Sensitivity analyses were performed to check whether a change in the initial assumptions could have an impact on the findings. Results: During the 6-year observation period, the composite CVD outcome was recorded in 54 patients with prolactinoma and 180 “nonexposed” individuals. The incidence rate was 1.8 and 14.8 per 1000 person-years for the females and males with prolactinoma, respectively. The aIRRs for CVD were estimated at 0.99 [95% confidence interval (CI): 0.61-1.61},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Adderley2018,

title = {Risk of stroke and transient ischaemic attack in patients with a diagnosis of resolved atrial fibrillation: Retrospective cohort studies},

author = {Nicola J. Adderley and Krishnarajah Nirantharakumar and Tom Marshall},

doi = {10.1136/BMJ.K1717},

issn = {17561833},

year  = {2018},

date = {2018-01-01},

journal = {BMJ (Online)},

volume = {361},

publisher = {BMJ Publishing Group},

abstract = {Objectives To determine rates of stroke or transient ischaemic attack (TIA) and all cause mortality in patients with a diagnosis of "resolved" atrial fibrillation compared to patients with unresolved atrial fibrillation and without atrial fibrillation. Design Two retrospective cohort studies. Setting General practices contributing to The Health Improvement Network, 1 January 2000 to 15 May 2016. Participants Adults aged 18 years or more with no previous stroke or TIA: 11 159 with resolved atrial fibrillation, 15 059 controls with atrial fibrillation, and 22 266 controls without atrial fibrillation. Main outcome measures Primary outcome was incidence of stroke or TIA. Secondary outcome was all cause mortality. Results Adjusted incidence rate ratios for stroke or TIA in patients with resolved atrial fibrillation were 0.76 (95% confidence interval 0.67 to 0.85, P<0.001) versus controls with atrial fibrillation and 1.63 (1.46 to 1.83, P<0.001) versus controls without atrial fibrillation. Adjusted incidence rate ratios for mortality in patients with resolved atrial fibrillation were 0.60 (0.56 to 0.65, P<0.001) versus controls with atrial fibrillation and 1.13 (1.06 to 1.21, P<0.001) versus controls without atrial fibrillation. When patients with resolved atrial fibrillation and documented recurrent atrial fibrillation were excluded the adjusted incidence rate ratio for stroke or TIA was 1.45 (1.26 to 1.67, P<0.001) versus controls without atrial fibrillation. Conclusion Patients with resolved atrial fibrillation remain at higher risk of stroke or TIA than patients without atrial fibrillation. The risk is increased even in those in whom recurrent atrial fibrillation is not documented. Guidelines should be updated to advocate continued use of anticoagulants in patients with resolved atrial fibrillation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chandan2018,

title = {The association between idiopathic thrombocytopenic purpura and cardiovascular disease: a retrospective cohort study},

author = {J. S. Chandan and T. Thomas and S. Lee and T. Marshall and B. Willis and K. Nirantharakumar and P. Gill},

doi = {10.1111/JTH.13940},

issn = {15387836},

year  = {2018},

date = {2018-01-01},

journal = {Journal of Thrombosis and Haemostasis},

volume = {16},

issue = {3},

pages = {474-480},

publisher = {Blackwell Publishing Ltd},

abstract = {Essentials We estimated the cardiovascular risk of patients with idiopathic thrombocytopenic purpura (ITP). The risk of cardiovascular disease was 38% higher in ITP patients compared with controls. Among the ITP patients, splenectomy was associated with higher cardiovascular disease. Clinicians should consider cardiovascular risk when managing ITP patients. Summary: Background Idiopathic thrombocytopenic purpura (ITP) is classically characterized by a transient or persistent decrease of platelet count. Mortality is higher in the ITP population than the general population, with a possible association with increased cardiovascular disease (CVD). Objectives The objective was to assess the strength of the association between ITP and CVD, with a secondary aim to assess the impact of splenectomy on CVD. Methods A population-based retrospective, open cohort study using clinical codes was performed using data from 6591 patients with ITP and 24 275 randomly matched controls (up to 1:4 ratio matched by age, sex, body mass index and smoking status). The main outcome was the risk of CVD, which included ischemic heart disease, stroke, trans-ischemic attack and heart failure. Adjusted incidence rate ratios were calculated using Poisson regression. Results During a median 6-year observation period there was a CVD diagnosis recorded in 392 (5.9%) ITP patients and 1114 (4.5%) control patients. There was an increased risk of developing CVD in the ITP cohort (incidence rate ratio [IRR], 1.38; 95% confidence interval [CI], 1.23–1.55), which remained robust even after a sensitivity analysis only including incident cases of ITP. Findings suggested that patients who had undergone splenectomy were at even further increased risk of developing CVD when compared with the ITP population who had not undergone splenectomy (adjusted IRR, 1.69; 95% CI, 1.22–2.34). Conclusion There is an increased risk of developing CVD in patients with ITP and even further increased risk for those patients with ITP who underwent splenectomy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nirantharakumar2018,

title = {Clinically meaningful and lasting HbA1c improvement rarely occurs after 5 years of type 1 diabetes: an argument for early, targeted and aggressive intervention following diagnosis},

author = {Krishnarajah Nirantharakumar and Nuredin Mohammed and Konstantinos A. Toulis and G. Neil Thomas and Parth Narendran},

doi = {10.1007/S00125-018-4574-6},

issn = {14320428},

year  = {2018},

date = {2018-01-01},

journal = {Diabetologia},

volume = {61},

issue = {5},

pages = {1064-1070},

publisher = {Springer Verlag},

abstract = {Aims/hypothesis: Our objectives were to explore whether the phenomenon of HbA1c ‘tracking’ occurs in individuals with type 1 diabetes, how long after diagnosis does tracking take to stabilise, and whether there is an effect of sex and age at diagnosis on tracking. Methods: A total of 4525 individuals diagnosed with type 1 diabetes between 1 January 1995 and 1 May 2015 were identified from The Health Improvement Network (THIN) database. Mixed models were applied to assess the variability of HbA1c levels over time with random effects on general practices (primary care units) and individuals within practices. Results: 4525 individuals diagnosed with type 1 diabetes were identified in THIN over the study period. The greatest difference in mean HbA1c measurement (−7.0 [95% CI −8.0, −6.1] mmol/mol [0.6%]) was seen when comparing measurements made immediately after diagnosis (0–1 year since diagnosis) with those at 10 or more years (the reference category). The mean difference in HbA1c for the successive periods compared with 10 or more years after diagnosis declined and was no longer statistically significant after 5 years. In the stratified analysis using sex and age group there was considerable heterogeneity with adult onset type 1 diabetes appearing to track earlier and at a lower mean HbA1c. Conclusions/interpretation: In individuals with type 1 diabetes, glycaemic control measured by HbA1c settles onto a long-term ‘track’ and this occurs on average by 5 years following diagnosis. Age at diagnosis modifies both the rate at which individuals settle into their track and the absolute HbA1c tracking level for the next 10 years.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kumarendran2018,

title = {Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database},

author = {Balachandran Kumarendran and Michael W. O’Reilly and Konstantinos N. Manolopoulos and Konstantinos A. Toulis and Krishna M. Gokhale and Alice J. Sitch and Chandrika N. Wijeyaratne and Arri Coomarasamy and Wiebke Arlt and Krishnarajah Nirantharakumar},

doi = {10.1371/JOURNAL.PMED.1002542},

issn = {15491676},

year  = {2018},

date = {2018-01-01},

journal = {PLoS Medicine},

volume = {15},

issue = {3},

publisher = {Public Library of Science},

abstract = {Background: Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), which affects 10% of women and represents a lifelong metabolic disorder, with increased risk of type 2 diabetes, hypertension, and cardiovascular events. Previous studies have suggested an increased risk of nonalcoholic fatty liver disease (NAFLD) in individuals with PCOS and implicated androgen excess as a potential driver. Methods and findings: We carried out a retrospective longitudinal cohort study utilizing a large primary care database in the United Kingdom, evaluating NAFLD rates in 63,120 women with PCOS and 121,064 age-, body mass index (BMI)-, and location-matched control women registered from January 2000 to May 2016. In 2 independent cohorts, we also determined the rate of NAFLD in women with a measurement of serum testosterone (n = 71,061) and sex hormone-binding globulin (SHBG; n = 49,625). We used multivariate Cox models to estimate the hazard ratio (HR) for NAFLD and found that women with PCOS had an increased rate of NAFLD (HR = 2.23, 95% CI 1.86–2.66, p < 0.001), also after adjusting for BMI or dysglycemia. Serum testosterone >3.0 nmol/L was associated with an increase in NAFLD (HR = 2.30, 95% CI 1.16–4.53},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Toulis2017,

title = {All-cause mortality in patients with diabetes under glucagon-like peptide-1 agonists: A population-based, open cohort study},

author = {K. A. Toulis and W. Hanif and P. Saravanan and B. H. Willis and T. Marshall and B. Kumarendran and K. Gokhale and S. Ghosh and K. K. Cheng and P. Narendran and G. N. Thomas and K. Nirantharakumar},

doi = {10.1016/J.DIABET.2017.02.003},

issn = {18781780},

year  = {2017},

date = {2017-01-01},

journal = {Diabetes and Metabolism},

volume = {43},

issue = {3},

pages = {211-216},

publisher = {Elsevier Masson SAS},

abstract = {Aim The glucagon-like peptide-1 receptor agonist (GLP1a) liraglutide has been described to benefit patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk. However, there are still uncertainties relating to these cardiovascular benefits: whether they also apply to an unselected diabetic population that includes low-risk patients, represent a class-effect, and could be observed in a real-world setting. Methods We conducted a population-based, retrospective open cohort study using data derived from The Health Improvement Network database between Jan 2008 to Sept 2015. Patients with T2DM exposed to GLP1a (n = 8345) were compared to age, gender, body mass index, duration of T2DM and smoking status-matched patients with T2DM unexposed to GLP1a (n = 16,541). Results Patients with diabetes receiving GLP1a were significantly less likely to die from any cause compared to matched control patients with diabetes (adjusted incidence rate ratio [aIRR]: 0.64, 95% CI: 0.56–0.74, P-value < 0.0001). Similar findings were observed in low-risk patients (aIRR: 0.64, 95% CI: 0.53–0.76, P -value = 0.0001). No significant difference in the risk of incident CVD was detected in the low-risk patients (aIRR: 0.93, 95% CI: 0.83–1.12). Subgroup analyses suggested that effect is persistent in the elderly or across glycated haemoglobin categories. Conclusions GLP1a treatment in a real-world setting may confer additional mortality benefit in patients with T2DM irrespective of their baseline CVD risk, age or baseline glycated haemoglobin and was sustained over the observation period.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dafoulas2017,

title = {Type 1 diabetes mellitus and risk of incident epilepsy: a population-based, open-cohort study},

author = {George E. Dafoulas and Konstantinos A. Toulis and Dougall Mccorry and Balachadran Kumarendran and G. Neil Thomas and Brian H. Willis and Krishna Gokhale and George Gkoutos and Parth Narendran and Krishnarajah Nirantharakumar},

doi = {10.1007/S00125-016-4142-X},

issn = {14320428},

year  = {2017},

date = {2017-01-01},

journal = {Diabetologia},

volume = {60},

issue = {2},

pages = {258-261},

publisher = {Springer Verlag},

abstract = {Aims/Hypothesis: The aim of this research was to explore the relationship between incident epilepsy and type 1 diabetes in British participants. Methods: Using The Health Improvement Network database, we conducted a retrospective, open-cohort study. Patients who were newly diagnosed with type 1 diabetes mellitus at the age of ≤40 years were identified and followed-up from 1 January 1990 to 15 September 2015. These patients, identified as not suffering from epilepsy at the time of diagnosis, were randomly matched with up to four individuals without type 1 diabetes mellitus, based on age, sex and participating general practice. A Cox regression analysis was subsequently performed using Townsend deprivation index, cerebral palsy, head injury and learning disabilities as model covariates. Results: The study population consisted of a total of 24,610 individuals (4922 with type 1 diabetes and 19,688 controls). These individuals were followed up for a mean of 5.4 years (approximately 132,000 person-years of follow up). Patients with type 1 diabetes were significantly more likely to be diagnosed with epilepsy during the observation period compared with controls (crude HR [95% CI]: 3.02 [1.95, 4.69]). The incidence rate was estimated to be 132 and 44 per 100,000 person-years in patients and controls, respectively. This finding persisted after adjusting for model covariates (adjusted HR [95% CI]: 3.01 [1.93, 4.68]) and was also robust to sensitivity analysis, excluding adult-onset type 1 diabetes mellitus. Conclusions/Interpretation: Patients with type 1 diabetes are at approximately three-times greater risk of developing epilepsy compared with matched controls without type 1 diabetes. This should be considered when investigating seizure-related disorders in patients with type 1 diabetes mellitus.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Toulis2017b,

title = {All-cause mortality in patients with diabetes under treatment with dapagliflozin: A population-based, open-cohort study in the health improvement network database},

author = {Konstantinos A. Toulis and Brian H. Willis and Tom Marshall and Balachadran Kumarendran and Krishna Gokhale and Sandip Ghosh and G. Neil Thomas and Kar Keung Cheng and Parth Narendran and Wasim Hanif and Krishnarajah Nirantharakumar},

doi = {10.1210/JC.2016-3446},

issn = {19457197},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Clinical Endocrinology and Metabolism},

volume = {102},

issue = {5},

pages = {1719-1725},

publisher = {Endocrine Society},

abstract = {Context: Empagliflozin was found to decrease mortality in patients with type 2 diabetes mellitus (T2DM) and a prior cardiovascular disease (CVD) event. Objectives: To establish whether these benefits can be replicated in a real-world setting, should be expected with the use of dapagliflozin, and apply to T2DM patients at low risk of CVD. Design: General practice, population-based, retrospective cohort study (January 2013 to September 2015). Setting: The Health Improvement Network database. Participants: A total of 22,124 T2DM patients (4444 exposed to dapagliflozin; 17,680 unexposed T2DM patients) matched for age, sex, body mass index, T2DM duration, and smoking. Main Outcome Measures: The primary outcome was all-cause mortality (high and low risk for CVD) in the total study population, expressed as the adjusted incidence rate ratio (aIRR) with 95% confidence intervals (CIs). As a secondary analysis in the low-risk population, all-cause mortality and incident CVD were considered. Results: Patients with T2DM exposed to dapagliflozin were significantly less likely to die of any cause (aIRR: 0.50; 95% CI: 0.33 to 0.75; P = 0.001). Similarly, in low-risk patients, death from any cause was significantly lower in the cohort exposed to dapagliflozin (aIRR: 0.44; 95% CI: 0.25 to 0.78; P = 0.002). The difference in the risk of incident CVD did not reach statistical significance between groups in low-risk patients (aIRR: 0.89; 95% CI: 0.61 to 1.31; P = 0.546). Conclusions: Patients with T2DM who were exposed to dapagliflozin had a lower risk of death from any cause irrespective of baseline CVD status.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}