Publications by authors named "Krishnarajah Nirantharakumar"

125 Publications

The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.

Endocrinol Diabetes Metab 2021 Dec 3:e00309. Epub 2021 Dec 3.

Department of Diabetes Medicine, University Hospitals of Birmingham, Birmingham, UK.

Introduction: To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes.

Methods: Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality.

Results: Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95-2.03, p = 0.093) and 1.18 (95% CI 0.90-1.54, p = 0.226) in DM+C and DM-C, respectively.

Conclusions: Those with COVID-19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study.
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http://dx.doi.org/10.1002/edm2.309DOI Listing
December 2021

THE IMPACT OF ATRIAL FIBRILLATION ON OUTCOMES OF PERIPHERAL ARTERIAL DISEASE: ANALYSIS OF ROUTINELY COLLECTED PRIMARY CARE DATA.

Am J Med 2021 Nov 15. Epub 2021 Nov 15.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK.

Background: The combination of peripheral arterial disease and atrial fibrillation is linked with high risk of mortality and stroke. This study aims to investigate the impact of atrial fibrillation on patients with diagnosed peripheral arterial disease.

Methods: This is a retrospective study using The Health Improvement Network (THIN) database, which contains prospectively collected data from participating primary care practices. Patients with a new diagnosis of peripheral arterial disease between 01/08/1995 and 01/05/2017 were identified in the database alongside relevant demographic information, clinical history and medications. Every patient in the dataset with peripheral arterial disease and baseline atrial fibrillation (case), was matched to a patient without atrial fibrillation (control) with similar characteristics using propensity score matching. Cox-regression analysis was performed and hazard ratios (HR) calculated for the outcomes of death, stroke, ischaemic heart disease, heart failure and major amputation.

Results: Prevalence of atrial fibrillation in this cohort was 10.2%. All patients with peripheral arterial disease and atrial fibrillation (n=5685) were matched with 5685 patients without atrial fibrillation but otherwise similar characteristics. After multivariate analysis, atrial fibrillation was independently associated with mortality (HR: 1.18, 95% Confidence Interval (CI) 1.12- 1.26, p< 0.01), cerebrovascular events (HR: 1.35, 95%CI 1.17- 1.57, p< 0.01) and heart failure (HR: 1.87, 95%CI 1.62- 2.15, p< 0.01) but not with ischaemic heart disease or limb loss.

Conclusion: In peripheral arterial disease patients, atrial fibrillation is a risk factor for mortality, stroke and heart failure. This emphasizes the need for proactive surveillance and holistic management of these patients.
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http://dx.doi.org/10.1016/j.amjmed.2021.10.021DOI Listing
November 2021

The links between Sleep Duration, Obesity and Type 2 Diabetes Mellitus.

J Endocrinol 2021 Nov 1. Epub 2021 Nov 1.

A Tahrani, Institute of metabolism and systems research, University of Birmingham, Birmingham, United Kingdom of Great Britain and Northern Ireland.

Global rates of obesity and Type 2 diabetes mellitus (T2DM) are increasing globally concomitant with a rising prevalence of sleep deprivation and sleep disorders. Understanding the links between sleep, obesity and T2DM might offer an opportunity to develop better prevention and treatment strategies for these epidemics. Experimental studies have shown that sleep restriction is associated with changes in energy homeostasis, insulin resistance and β-cell function. Epidemiological cohort studies established short sleep duration as a risk factor for developing obesity and T2DM. In addition, small studies suggested that short sleep duration was associated less weight loss following lifestyle interventions or bariatric surgery. In this article, we review the epidemiological evidence linking sleep duration to obesity and T2DM and plausible mechanisms. In addition, we review the impact of changes in sleep duration on obesity and T2DM.
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http://dx.doi.org/10.1530/JOE-21-0155DOI Listing
November 2021

Protocol for the development of a core outcome set for studies of pregnant women with pre-existing multimorbidity.

BMJ Open 2021 10 29;11(10):e044919. Epub 2021 Oct 29.

School of Medicine, Medical Science and Nutrition, University of Aberdeen, Aberdeen, UK.

Introduction: Increasingly more pregnant women are living with pre-existing multimorbidity (≥two long-term physical or mental health conditions). This may adversely affect maternal and offspring outcomes. This study aims to develop a core outcome set (COS) for maternal and offspring outcomes in pregnant women with pre-existing multimorbidity. It is intended for use in observational and interventional studies in all pregnancy settings.

Methods And Analysis: We propose a four stage study design: (1) systematic literature search, (2) focus groups, (3) Delphi surveys and (4) consensus group meeting. The study will be conducted from June 2021 to August 2022. First, an initial list of outcomes will be identified through a systematic literature search of reported outcomes in studies of pregnant women with multimorbidity. We will search the Cochrane library, Medline, EMBASE and CINAHL. This will be supplemented with relevant outcomes from published COS for pregnancies and childbirth in general, and multimorbidity. Second, focus groups will be conducted among (1) women with lived experience of managing pre-existing multimorbidity in pregnancy (and/or their partners) and (2) their healthcare/social care professionals to identify outcomes important to them. Third, these initial lists of outcomes will be prioritised through a three-round online Delphi survey using predefined score criteria for consensus. Participants will be invited to suggest additional outcomes that were not included in the initial list. Finally, a consensus meeting using the nominal group technique will be held to agree on the final COS. The stakeholders will include (1) women (and/or their partners) with lived experience of managing multimorbidity in pregnancy, (2) healthcare/social care professionals involved in their care and (3) researchers in this field.

Ethics And Dissemination: This study has been approved by the University of Birmingham's ethical review committee. The final COS will be disseminated through peer-reviewed publication and conferences and to all stakeholders.
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http://dx.doi.org/10.1136/bmjopen-2020-044919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559099PMC
October 2021

A systematic review and meta-analysis of interventions to preserve insulin-secreting β-cell function in people newly diagnosed with type 1 diabetes: Results from intervention studies aimed at improving glucose control.

Diabet Med 2021 Oct 22:e14730. Epub 2021 Oct 22.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

Aims: Type 1 diabetes is characterised by the destruction of pancreatic β-cells. Significant levels of β-cells remain at diagnosis. Preserving these cells improves glucose control and protects from long-term complications. We undertook a systematic review and meta-analyses of all randomised controlled trials (RCTs) of interventions to preserve β-cell function in people newly diagnosed with type 1 diabetes. This paper reports the results of interventions for improving glucose control to assess whether they preserve β-cell function.

Methods: Searches for RCTs in MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov and WHO International Clinical Trials Registry. Eligible studies included newly diagnosed patients with type 1 diabetes, any intervention to improve glucose control and at least 1 month of follow-up. Data were extracted using a pre-defined data-extraction sheet with 10% of extractions checked by a second reviewer.

Results: Twenty-eight studies with 1662 participants were grouped by intervention into six subgroups (alternative insulins, subcutaneous and intravenous insulin delivery, intensive therapy, glucose sensing, adjuncts). Only three studies demonstrated an improvement in glucose control as well as β-cell function. These interventions included intensive insulin therapy and use of an alternative insulin.

Conclusions: This is the largest comprehensive review of RCTs in this area. It demonstrates a lack of robust evidence that interventions to improve glucose control preserve β-cell function in new onset type 1 diabetes, although analysis was hampered by low-quality evidence and inconsistent reporting of studies. Development of guidelines to support the design of trials in this field is a priority.
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http://dx.doi.org/10.1111/dme.14730DOI Listing
October 2021

Prognostic Models for Predicting Remission of Diabetes Following Bariatric Surgery: A Systematic Review and Meta-analysis.

Diabetes Care 2021 Nov;44(11):2626-2641

Department of Diabetes and Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, U.K.

Background: Remission of type 2 diabetes following bariatric surgery is well established, but identifying patients who will go into remission is challenging.

Purpose: To perform a systematic review of currently available diabetes remission prediction models, compare their performance, and evaluate their applicability in clinical settings.

Data Sources: A comprehensive systematic literature search of MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) was undertaken. The search was restricted to studies published in the last 15 years and in the English language.

Study Selection: All studies developing or validating a prediction model for diabetes remission in adults after bariatric surgery were included.

Data Extraction: The search identified 4,165 references, of which 38 were included for data extraction. We identified 16 model development and 22 validation studies.

Data Synthesis: Of the 16 model development studies, 11 developed scoring systems and 5 proposed logistic regression models. In model development studies, 10 models showed excellent discrimination with area under the receiver operating characteristic curve ≥0.800. Two of these prediction models, ABCD and DiaRem, were widely externally validated in different populations, in a variety of bariatric procedures, and for both short- and long-term diabetes remission. Newer prediction models showed excellent discrimination in test studies, but external validation was limited.

Limitations: While the key messages were consistent, a large proportion of the studies were conducted in small cohorts of patients with short duration of follow-up.

Conclusions: Among the prediction models identified, the ABCD and DiaRem models were the most widely validated and showed acceptable to excellent discrimination. More studies validating newer models and focusing on long-term diabetes remission are needed.
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http://dx.doi.org/10.2337/dc21-0166DOI Listing
November 2021

The Risk of Later Diagnosis of Inflammatory Bowel Disease in Patients With Dermatological Disorders Associated With Inflammatory Bowel Disease.

Inflamm Bowel Dis 2021 10;27(11):1731-1739

Sandwell and West Birmingham Hospitals NHS Trust, West Bromwich, United Kingdom.

Background: Dermatological conditions such as erythema nodosum (EN), pyoderma gangrenosum, Sweet's syndrome, and aphthous stomatitis can occur with inflammatory bowel disease (IBD) and are considered dermatological extraintestinal manifestations (D-EIMs). Rarely, they may precede IBD. Other common conditions such as psoriasis have also been associated with IBD. This study examined the risk of a subsequent IBD diagnosis in patients presenting with a D-EIM.

Methods: A retrospective cohort study compared patients with D-EIMs and age-/sex-matched patients without D-EIMs. Hazard ratios (HRs) were adjusted for age, sex, body mass index, deprivation, comorbidity, smoking, loperamide use, anemia, and lower gastrointestinal symptoms. Logistic regression was used to produce a prediction model for the diagnosis of IBD within 3 years of EN diagnosis.

Results: We matched 7447 patients with D-EIMs (74% female; median age 38 years (interquartile ratio [IQR], 24-65 years) to 29,297 patients without D-EIMs. We observed 131 (1.8%) subsequent IBD diagnoses in patients with D-EIMs compared with 65 (0.2%) in those without D-EIMs. Median time to IBD diagnosis was 205 days (IQR, 44-661 days) in those with D-EIMs and 1594 days (IQR, 693-2841 days) in those without D-EIMs. The adjusted HR for a later diagnosis of IBD was 6.16 (95% confidence interval [CI], 4.53-8.37; P < 0.001), for ulcerative colitis the HR was 3.30 (95% CI, 1.98-5.53; P < 0.001), and for Crohn's disease the HR was 8.54 (95% CI, 5.74-12.70; P < 0.001). Patients with psoriasis had a 34% increased risk of a subsequent IBD diagnosis compared with the matched control patients (HR, 1.34; 95% CI, 1.20-1.51; P < 0.001). We included 4043 patients with an incident EN diagnosis in the prediction model cohort, with 87 patients (2.2%) diagnosed with IBD within 3 years. The model had a bias-corrected c-statistic of 0.82 (95% CI, 0.78-0.86).

Conclusions: Patients with D-EIMs have a 6-fold increased risk of a later diagnosis of IBD. Younger age, smoking, low body mass index, anemia, and lower gastrointestinal symptoms were associated with an increased risk of diagnosis of IBD within 3 years in patients with EN.
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http://dx.doi.org/10.1093/ibd/izaa344DOI Listing
October 2021

Polycystic Ovary Syndrome, Combined Oral Contraceptives, and the Risk of Dysglycemia: A Population-Based Cohort Study With a Nested Pharmacoepidemiological Case-Control Study.

Diabetes Care 2021 Oct 14. Epub 2021 Oct 14.

Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham, U.K.

Objective: Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by androgen excess and irregular menses; androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptive pills (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COCP use and risk of dysglycemia (prediabetes and type 2 diabetes) in women with PCOS.

Research Design And Methods: Using a large U.K. primary care database (The Health Improvement Network [THIN]; 3.7 million patients from 787 practices), we carried out a retrospective population-based cohort study to determine dysglycemia risk (64,051 women with PCOS and 123,545 matched control subjects), as well as a nested pharmacoepidemiological case-control study to investigate COCP use in relation to dysglycemia risk (2,407 women with PCOS with [case subjects] and without [control subjects] a diagnosis of dysglycemia during follow-up). Cox models were used to estimate the unadjusted and adjusted hazard ratio, and conditional logistic regression was used to obtain adjusted odds ratios (aORs).

Results: The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78-1.97, < 0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with increased rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP use had a reduced dysglycemia risk (aOR 0.72, 95% CI 0.59-0.87).

Conclusions: In this study, limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow for exclusion of the impact of prescription-by-indication bias, women with PCOS exposed to COCPs had a reduced risk of dysglycemia across all BMI subgroups. Future prospective studies should be considered for further understanding of these observations and potential causality.
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http://dx.doi.org/10.2337/dc21-0437DOI Listing
October 2021

An informatics consult approach for generating clinical evidence for treatment decisions.

BMC Med Inform Decis Mak 2021 10 12;21(1):281. Epub 2021 Oct 12.

Institute of Health Informatics, University College London, London, UK.

Background: An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis.

Methods: We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems.

Results: We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39-1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49-0.76) and ischaemic stroke (HR = 0.27, CI 0.08-0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results.

Conclusion: We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on 'patients like me'. We identify the key challenges in offering such an Informatics Consult as a service.
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http://dx.doi.org/10.1186/s12911-021-01638-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506488PMC
October 2021

wEight chanGes, caRdio-mEtabolic risks and morTality in patients with hyperthyroidism (EGRET): a protocol for a CPRD-HES linked cohort study.

BMJ Open 2021 10 1;11(10):e055219. Epub 2021 Oct 1.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

Introduction: Hyperthyroidism is a common condition affecting up to 3% of the UK population. Treatment improves symptoms and reduces the risk of atrial fibrillation and stroke that contribute to increased mortality. The most common symptom is weight loss, which is reversed during treatment. However, the weight regain may be excessive, contributing to increased risk of obesity. Current treatment options include antithyroid drugs, radioiodine and thyroidectomy. Whether there are differences in either weight change or the long-term cardiometabolic risk between the three treatments is unclear.

Methods And Analysis: The study will establish the natural history of weight change in hyperthyroidism, investigate the risk of obesity and risks of cardiometabolic conditions and death relative to the treatment. The data on patients diagnosed with hyperthyroidism between 1 January 1996 and 31 December 2015 will come from Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office of National Statistics Death Registry. The weight changes will be modelled using a flexible joint modelling, accounting for mortality. Obesity prevalence in the general population will be sourced from Health Survey for England and compared with the post-treatment prevalence of obesity in patients with hyperthyroidism. The incidence and time-to-event of major adverse cardiovascular events, other cardiometabolic outcomes and mortality will be compared between the treatments using the inverse propensity weighting model. Incidence rate ratios of outcomes will be modelled with Poisson regression. Time to event will be analysed using Cox proportional hazards model. A competing risks approach will be adopted to estimate comparative incidences to allow for the impact of mortality.

Ethics And Dissemination: The study will bring new knowledge on the risk of developing obesity, cardiometabolic morbidity and mortality following treatment for hyperthyroidism to inform clinical practice and public health policies. The results will be disseminated via open-access peer-reviewed publications and directly to the patients and public groups (Independent Scientific Advisory Committee protocol approval #20_000185).
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http://dx.doi.org/10.1136/bmjopen-2021-055219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488707PMC
October 2021

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

Psychol Med 2021 Oct 1:1-10. Epub 2021 Oct 1.

Institute for Mental Health, College of Life and Environmental Sciences, University of Birmingham, BirminghamB15 2TT,UK.

Background: Cannabis use is a global public health issue associated with increased risks of developing mental health disorders, especially in young people. We aimed to investigate the relationships between cannabis exposure and risks of receiving mental illness diagnoses or treatment as outcomes.

Methods: A population based, retrospective, open cohort study using patients recorded in 'IQVIA medical research data', a UK primary care database. Read codes were used to confirm patients with recorded exposure to cannabis use who were matched up to two unexposed patients. We examined the risk of developing three categories of mental ill health: depression, anxiety or serious mental illness (SMI).

Results: At study entry, the exposed cohort had an increased likelihood of having experienced mental ill health [odds ratio (OR) 4.13; 95% confidence interval (CI) 3.99-4.27] and mental ill health-related prescription (OR 2.95; 95% CI 2.86-3.05) compared to the unexposed group. During the study period we found that exposure to cannabis was associated with an increased risk of developing any mental disorder [adjusted hazard ratio (aHR) 2.73; 95% CI 2.59-2.88], also noted when examining by subtype of disorder: anxiety (aHR 2.46; 95% CI 2.29-2.64), depression (aHR 2.34; 95% CI 2.20-2.49) and SMI (aHR 6.41; 95% CI 5.42-7.57). These results remained robust in sensitivity analyses.

Conclusion: These findings point to the potential need for a public health approach to the management of people misusing cannabis. However, there is a gross under-recording of cannabis use in GP records, as seen by the prevalence of recorded cannabis exposure substantially lower than self-reported survey records.
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http://dx.doi.org/10.1017/S003329172100386XDOI Listing
October 2021

The risk of COVID-19 in survivors of domestic violence and abuse.

BMC Med 2021 09 24;19(1):246. Epub 2021 Sep 24.

Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B152TT, UK.

A 'shadow pandemic' of domestic violence and abuse (DVA) has emerged secondary to strict public health measures containing the spread of SARS-CoV-2. Many countries have implemented policies to allow the free movement of DVA survivors in attempts to minimise their exposure to abusive environments. Although these policies are well received, as a result there is a possibility of increased COVID-19 transmission within this vulnerable group who are not currently prioritised for vaccination. Therefore, we aimed to compare the risk of developing suspected or confirmed COVID-19 in women (aged over 16 years) exposed to DVA against age-sex-matched unexposed controls, following adjustment for known COVID-19 risk factors. A population-based retrospective open cohort study was undertaken between the 31 January 2020 and 28 February 2021 using 'The Health Improvement Network' database. We identified 10,462 eligible women exposed to DVA who were matched to 41,467 similarly aged unexposed women. Following adjustment for key covariates, women exposed to DVA were at an increased risk (aHR 1.57; 95% CI 1.29-1.90) of suspected/confirmed COVID-19 compared to unexposed women. These findings support previous calls for positive policy action improving DVA surveillance and prioritising survivors for COVID-19 vaccination.
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http://dx.doi.org/10.1186/s12916-021-02119-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460316PMC
September 2021

Incidence of cardiometabolic diseases in people living with and without HIV in the UK: a population-based matched cohort study.

J Infect Dis 2021 Aug 21. Epub 2021 Aug 21.

Institute for Applied Health Research, University of Birmingham, Birmingham, United Kingdom.

Background: Evidence on the risk of cardiovascular disease (CVD) and CVD risk factors in people with HIV (PWH) is limited. We aimed to identify the risk of composite CVD, individual CVD events and common risk factors.

Methods: This was a nationwide population-based cohort study comparing adult (≥18y) PWH with HIV-negative individuals matched on age, sex, ethnicity and location. The primary outcome was composite CVD comprising stroke, myocardial infarction (MI), peripheral vascular disease (PVD), ischaemic heart disease and heart failure. The secondary outcomes were individual CVD events, hypertension, diabetes, chronic kidney disease (CKD) and all-cause mortality. Cox proportional hazard regression models were used to examine the risk of each outcome.

Results: We identified 9233 PWH and 35721 HIV-negative individuals. An increased risk was found for composite CVD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.28-1.77), stroke (aHR 1.42, 95% CI 1.08-1.86), ischaemic heart disease (aHR 1.55, 95% CI 1.24-1.94), hypertension (aHR 1.37, 95% CI 1.23-1.53), type 2 diabetes (aHR 1.28, 95% CI 1.09-1.50), CKD (aHR 2.42, 95% CI 1.98-2.94) and all-cause mortality (aHR 2.84, 95% CI (2.48-3.25).

Conclusions: PWH have a heightened risk for CVD and common CVD risk factors, reinforcing the importance for regular screening for such conditions.
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http://dx.doi.org/10.1093/infdis/jiab420DOI Listing
August 2021

Impact of Using Risk-Based Stratification on Referral of Patients With Chronic Kidney Disease From Primary Care to Specialist Care in the United Kingdom.

Kidney Int Rep 2021 Aug 1;6(8):2189-2199. Epub 2021 Jun 1.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

Introduction: The externally validated Kidney Failure Risk Equation (KFRE) for predicting risk of end-stage renal disease (ESRD) has been developed, but its potential impact in a population on referrals for patients with chronic kidney disease (CKD) from primary to specialty nephrology care is not known.

Methods: A cross-sectional population-based study of individuals in United Kingdom primary care registered in The Health Improvement Network database was conducted. National Institute of Health and Care Excellence (NICE) 2014 CKD guidelines the 4-variable KFRE set at a >3% risk of ESRD at 5 years were applied to patients identified with CKD stage 3-5 between January 1, 2016, and March 31, 2017.

Results: In all, 39,476 (36.6%) of 107,962 adults with CKD stage 3-5 had a urine albumin:creatinine ratio (ACR) available and entered into the primary analysis. Of that, 7566 (19.2%) patients fulfilled NICE criteria for referral, 2386 (31.5%) of whom had a ≤3% 5-year risk of ESRD. Also 8663 (21.9%) patients had a >3% 5-year risk of ESRD, 3483 (40.2%) of whom did not fulfill NICE criteria; this represents 8.8% of the primary population. By using the KFRE threshold rather than NICE criteria for referral, 5869 patients (14.9% of the primary analysis population) would have been reallocated between primary and specialist care. Imputational analysis was used for missing ACR measurements and showed similar results.

Conclusions: A risk-based referral approach would lead to a substantial reallocation of patients between primary care and specialist nephrology care with only a small increase in numbers eligible, ensuring those at higher risk of progression are identified.
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http://dx.doi.org/10.1016/j.ekir.2021.05.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343777PMC
August 2021

Health-related quality of life, uncertainty and coping strategies in solid organ transplant recipients during shielding for the COVID-19 pandemic.

Transpl Int 2021 11 16;34(11):2122-2137. Epub 2021 Sep 16.

The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK.

Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID-19. Our objective was to investigate health-related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID-19 pandemic. A cross-sectional survey of adult SOT recipients undergoing follow-up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ-5D-5L, Short-form Mishel Uncertainty in Illness Scale (SF-MUIS) and Brief Cope, respectively. Interactions with COVID-19 risk perception, access to health care, demographic and clinical variables were assessed. The survey was completed by 826 of 3839 (21.5%) invited participants. Overall, low levels of uncertainty in illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self-perceived susceptibility to COVID-19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to health care, a perceived high risk of severe COVID-19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies was associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.
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http://dx.doi.org/10.1111/tri.14010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420473PMC
November 2021

Symptoms, complications and management of long COVID: a review.

J R Soc Med 2021 09 15;114(9):428-442. Epub 2021 Jul 15.

Institute of Applied Health Research, 1724University of Birmingham, Birmingham, UK.

Globally, there are now over 160 million confirmed cases of COVID-19 and more than 3 million deaths. While the majority of infected individuals recover, a significant proportion continue to experience symptoms and complications after their acute illness. Patients with 'long COVID' experience a wide range of physical and mental/psychological symptoms. Pooled prevalence data showed the 10 most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhoea. Other common symptoms were cognitive impairment, memory loss, anxiety and sleep disorders. Beyond symptoms and complications, people with long COVID often reported impaired quality of life, mental health and employment issues. These individuals may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health and social services support. Resilient healthcare systems are needed to ensure efficient and effective responses to future health challenges.
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http://dx.doi.org/10.1177/01410768211032850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450986PMC
September 2021

Disease burden of diabetes, diabetic retinopathy and their future projections in the UK: cross-sectional analyses of a primary care database.

BMJ Open 2021 07 12;11(7):e050058. Epub 2021 Jul 12.

Institute Of Applied Health Research, University of Birmingham, Birmingham, UK

Objectives: To estimate the current disease burden, trends and future projections for diabetes mellitus (DM) and diabetic retinopathy (DR) in the IQVIA Medical Research Data (IMRD).

Participants/design/setting: We performed a cross-sectional study of patients aged 12 and above to determine the prevalence of DM and DR from the IMRD database (primary care database) in January 2017, involving a total population of 1 80 824 patients with DM. We also carried out a series of cross-sectional studies to investigate prevalence trends, and then applied a double exponential smoothing model to forecast the future burden of DM and DR in the UK.

Results: The crude DM prevalence in 2017 was 5.2%. The DR, sight-threatening retinopathy (STR) and diabetic maculopathy prevalence figures in 2017 were 33.78%, 12.28% and 7.86%, respectively, in our IMRD cross-sectional study. There were upward trends in the prevalence of DM, DR and STR, most marked and accelerating in STR in type 1 DM but slowing in type 2 DM, and in the overall prevalence of DR.

Conclusion: Our results suggest differential rising trends in the prevalence of DM and DR. Preventive strategies, as well as treatment services planning, can be based on these projected prevalence estimates. Improvements that are necessary for the optimisation of care pathways, and preparations to meet demand and capacity challenges, can also be based on this information. The limitations of the study can be overcome by a future collaborative study linking DR screening and hospital eye services data.
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http://dx.doi.org/10.1136/bmjopen-2021-050058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276304PMC
July 2021

Trends in the pharmacological management of atrial fibrillation in UK general practice 2008-2018.

Heart 2021 Jul 5. Epub 2021 Jul 5.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK

Objective: The pharmacological management of atrial fibrillation (AF) comprises anticoagulation, for stroke prophylaxis, and rate or rhythm control drugs to alleviate symptoms and prevent heart failure. The aim of this study was to investigate trends in the proportion of patients with AF prescribed pharmacological therapies in the UK between 2008 and 2018.

Methods: Eleven sequential cross-sectional analyses were performed yearly from 2008 to 2018. Data were derived from an anonymised UK primary care database. Outcomes were the proportion of patients with AF prescribed anticoagulants, rhythm and rate control drugs in the whole cohort, those at high risk of stroke and those with coexisting heart failure.

Results: Between 2008 and 2018, the proportion of patients prescribed anticoagulants increased from 45.3% (95% CI 45.0% to 45.7%) to 71.1% (95% CI 70.7% to 71.5%) driven by increased prescription of non-vitamin K antagonist anticoagulants. The proportion of patients prescribed rate control drugs remained constant between 2008 and 2018 (69.3% (95% CI 68.9% to 69.6%) to 71.6% (95% CI 71.2% to 71.9%)). The proportion of patients prescribed rhythm control therapy by general practitioners (GPs) decreased from 9.5% (95% CI 9.3% to 9.7%) to 5.4% (95% CI 5.2% to 5.6%).

Conclusions: There has been an increase in the proportion of patients with AF appropriately prescribed anticoagulants following National Institute for Health and Care Excellence and European Society of Cardiology guidelines, which correlates with improvements in mortality and stroke outcomes. Beta-blockers appear increasingly favoured over digoxin for rate control. There has been a steady decline in GP prescribing rates for rhythm control drugs, possibly related to concerns over efficacy and safety and increased availability of AF ablation.
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http://dx.doi.org/10.1136/heartjnl-2021-319338DOI Listing
July 2021

Cardio-metabolic outcomes in South Asians compared to White Europeans in the United Kingdom: a matched controlled population-based cohort study.

BMC Cardiovasc Disord 2021 06 30;21(1):320. Epub 2021 Jun 30.

Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B152TT, UK.

Background: There appears to be an inequality in the risk of cardio-metabolic disease between those from a South Asian (SA) background when compared to those of White Europeans (WE) descendance, however, this association has not been explored in a large European cohort. This population-based open retrospective cohort explores the incidence of cardio-metabolic disease in those without pre-existing cardiometabolic disease taken from a large UK primary care database from 1st January 2007 to 31st December 2017.

Methods: A retrospective open cohort matched population-based study using The Health Improvement Network (THIN) database. The outcomes of this study were the incidences of cardio-metabolic events (type 2 diabetes mellitus, hypertension, ischemic heart disease, stroke, heart failure, and atrial fibrillation).

Results: A total of 94,870 SA patients were matched with 189,740 WE patients. SA were at an increased risk of developing: T2DM (adjusted hazard ratio (aHR) 3.1; 95% CI 2.97-3.23); HTN (1.34; 95% CI: 1.29-1.39); ischaemic heart disease (IHD) (1.81; 95% CI: 1.68-1.93) and heart failure (HF) (1.11; 95% CI: 1.003-1.24). However, they were at a lower risk of atrial fibrillation (AF) (0.53; 95% CI: 0.48-0.59) when compared to WE. Of those of SA origin, the Bangladeshi community were at the greatest risk of T2DM, HTN, IHD and HF, but were at the lowest risk of AF in when compared to Indians and Pakistanis.

Conclusion: Considering the high risk of cardio-metabolic diseases in the SA cohort, differential public health measures should be considered in these patients to reduce their risk of disease, which may be furthered tailored depending on their country of origin.
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http://dx.doi.org/10.1186/s12872-021-02133-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244230PMC
June 2021

Examining variation in the measurement of multimorbidity in research: a systematic review of 566 studies.

Lancet Public Health 2021 08 22;6(8):e587-e597. Epub 2021 Jun 22.

Usher Institute, University of Edinburgh Medical School, Edinburgh, UK. Electronic address:

Background: A systematic understanding of how multimorbidity has been constructed and measured is unavailable. This review aimed to examine the definition and measurement of multimorbidity in peer-reviewed studies internationally.

Methods: We systematically reviewed studies on multimorbidity, via a search of nine bibliographic databases (Ovid [PsycINFO, Embase, Global Health, and MEDLINE], Web of Science, the Cochrane Library, CINAHL Plus, Scopus, and ProQuest Dissertations & Theses Global), from inception to Jan 21, 2020. Reference lists and tracked citations of retrieved articles were hand-searched. Eligible studies were full-text articles measuring multimorbidity for any purpose in community, primary care, care home, or hospital populations receiving a non-specialist service. Abstracts, qualitative research, and case series were excluded. Two reviewers independently reviewed the retrieved studies with conflicts resolved by discussion or a third reviewer, and a single researcher extracted data from published papers. To assess our objectives of how multimorbidity has been measured and examine variation in the chronic conditions included (in terms of number and type), we used descriptive analysis (frequencies, cross-tabulation, and negative binomial regression) to summarise the characteristics of multimorbidity studies and measures (study setting, source of morbidity data, study population, primary study purpose, and multimorbidity measure type). This systematic review is registered with PROSPERO, CRD420201724090.

Findings: 566 studies were included in our review, of which 206 (36·4%) did not report a reference definition for multimorbidity and 73 (12·9%) did not report the conditions their measure included. The number of conditions included in measures ranged from two to 285 (median 17 [IQR 11-23). 452 (79·9%) studies reported types of condition within a single multimorbidity measure; most included at least one cardiovascular condition (441 [97·6%] of 452 studies), metabolic and endocrine condition (440 [97·3%]), respiratory condition (422 [93·4%]), musculoskeletal condition (396 [87·6%]), or mental health condition (355 [78·5%]) in their measure of multimorbidity. Chronic infections (123 [27·2%]), haematological conditions (110 [24·3%]), ear, nose, and throat conditions (107 [23·7%]), skin conditions (70 [15·5%]), oral conditions (19 [4·2%]), and congenital conditions (14 [3·1%]) were uncommonly included. Only eight individual conditions were included by more than half of studies in the multimorbidity measure used (diabetes, stroke, cancer, chronic obstructive pulmonary disease, hypertension, coronary heart disease, chronic kidney disease, and heart failure), with individual mental health conditions under-represented. Of the 566 studies, 419 were rated to be of moderate risk of bias, 107 of high risk of bias, and 40 of low risk of bias according to the Effective Public Health Practice Project quality assessment tool.

Interpretation: Measurement of multimorbidity is poorly reported and highly variable. Consistent reporting of measure definitions should be required by journals, and consensus studies are needed to define core and study-dependent conditions to include in measures of multimorbidity.

Funding: Health Data Research UK.
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http://dx.doi.org/10.1016/S2468-2667(21)00107-9DOI Listing
August 2021

Diet and physical activity in pregnancy to prevent gestational diabetes: a protocol for an individual participant data (IPD) meta-analysis on the differential effects of interventions with economic evaluation.

BMJ Open 2021 06 11;11(6):e048119. Epub 2021 Jun 11.

WHO Collaborating Centre for Global Women's Health, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.

Introduction: Mothers with gestational diabetes mellitus (GDM) are at increased risk of pregnancy-related complications and developing type 2 diabetes after delivery. Diet and physical activity-based interventions may prevent GDM, but variations in populations, interventions and outcomes in primary trials have limited the translation of available evidence into practice. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to assess the differential effects and cost-effectiveness of diet and physical activity-based interventions in preventing GDM and its complications.

Methods: The International Weight Management in Pregnancy Collaborative Network database is a living repository of IPD from randomised trials on diet and physical activity in pregnancy identified through a systematic literature search. We shall update our existing search on MEDLINE, Embase, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment Database without language restriction to identify relevant trials until March 2021. Primary researchers will be invited to join the Network and share their IPD. Trials including women with GDM at baseline will be excluded. We shall perform a one and two stage random-effect meta-analysis for each intervention type (all interventions, diet-based, physical activity-based and mixed approach) to obtain summary intervention effects on GDM with 95% CIs and summary treatment-covariate interactions. Heterogeneity will be summarised using I and tau statistics with 95% prediction intervals. Publication and availability bias will be assessed by examining small study effects. Study quality of included trials will be assessed by the Cochrane Risk of Bias tool, and the Grading of Recommendations, Assessment, Development and Evaluations approach will be used to grade the evidence in the results. A model-based economic analysis will be carried out to assess the cost-effectiveness of interventions to prevent GDM and its complications compared with usual care.

Ethics And Dissemination: Ethics approval is not required. The study is registered on the International Prospective Register of Systematic Reviews (CRD42020212884). Results will be submitted for publication in peer-reviewed journals.
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http://dx.doi.org/10.1136/bmjopen-2020-048119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202105PMC
June 2021

Reply.

Arthritis Rheumatol 2021 11 22;73(11):2145-2146. Epub 2021 Sep 22.

University of Birmingham and Queen Elizabeth Hospital Birmingham, Birmingham, UK.

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http://dx.doi.org/10.1002/art.41809DOI Listing
November 2021

Reply.

Arthritis Rheumatol 2021 10 18;73(10):1948-1950. Epub 2021 Aug 18.

University of Birmingham and Queen Elizabeth Hospital, Birmingham, UK.

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http://dx.doi.org/10.1002/art.41789DOI Listing
October 2021

Postpartum haemorrhage and risk of long-term hypertension and cardiovascular disease: an English population-based longitudinal study using linked primary and secondary care databases.

BMJ Open 2021 05 5;11(5):e041566. Epub 2021 May 5.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

Objective: To investigate the long-term risk of developing hypertension and cardiovascular disease (CVD) among those women who suffered a postpartum haemorrhage (PPH) compared with those women who did not.

Design: Population-based longitudinal open cohort study.

Setting: English primary care (The Health Improvement Network (THIN)) and secondary care (Hospital Episode Statistics (HES)) databases.

Population: Women exposed to PPH during the study period matched for age and date of delivery, and unexposed.

Methods: We conducted an open cohort study using linked primary care THIN and HES Databases, from 1 January 1997 to 31 January 2018. A total of 42 327 women were included: 14 109 of them exposed to PPH during the study period and 28 218 matched for age and date of delivery, and unexposed to PPH. HRs for cardiovascular outcomes among women who had and did not have PPH were estimated after controlling for covariates using multivariate Cox regression models.

Outcome Measures: Risk of hypertensive disease, ischaemic heart disease, heart failure, stroke or transient ischaemic attack.

Results: During a median follow-up of over 4 years, there was no significant difference in the risk of hypertensive disease after adjustment for covariates (adjusted HR (aHR): 1.03 (95% CI: 0.87 to 1.22); p=0.71). We also did not observe a statistically significant difference in the risk of composite CVD (ischaemic heart disease, heart failure, stroke or transient ischaemic attack) between the exposed and the unexposed cohort (aHR: 0.86 (95% CI: 0.52 to 1.43; p=0.57).

Conclusion: Over a median follow-up of 4 years, we did not observe an association between PPH and hypertension or CVD.
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http://dx.doi.org/10.1136/bmjopen-2020-041566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103369PMC
May 2021

Post-bariatric surgery nutritional follow-up in primary care: a population-based cohort study.

Br J Gen Pract 2021 06 27;71(707):e441-e449. Epub 2021 May 27.

Institute of Applied Health Research, University of Birmingham, Birmingham; CEDAM, Birmingham Health Partners, Birmingham; Department of Diabetes, Endocrinology and Weight Management, University Hospitals Birmingham NHS Foundation Trust, Birmingham; Midlands Health Data Research UK.

Background: Bariatric surgery is the most effective treatment for severe obesity. However, without recommended follow-up it has long-term risks.

Aim: To investigate whether nutritional and weight monitoring in primary care meets current clinical guidance, after patients are discharged from specialist bariatric care.

Design And Setting: Retrospective cohort study in primary care practices contributing to IQVIA Medical Research Data in the UK (1 January 2000 to 17 January 2018).

Method: Participants were adults who had had bariatric surgery with a minimum of 3 years' follow-up post-surgery, as this study focused on patients discharged from specialist care (at 2 years post-surgery). Outcomes were the annual proportion of patients from 2 years post-surgery with a record of recommended nutritional screening blood tests, weight measurement, and prescription of nutritional supplements, and the proportions with nutritional deficiencies based on blood tests.

Results: A total of 3137 participants were included in the study, and median follow-up post-surgery was 5.7 (4.2-7.6) years. Between 45% and 59% of these patients had an annual weight measurement. The greatest proportions of patients with a record of annual nutritional blood tests were for tests routinely conducted in primary care, for example, recorded haemoglobin measurement varied between 44.9% ( = 629/1400) and 61.2% ( = 653/1067). Annual proportions of blood tests specific to bariatric surgery were low, for example, recorded copper measurement varied between 1.2% ( = 10/818) and 1.5% ( = 16/1067) where recommended. Results indicated that the most common deficiency was anaemia. Annual proportions of patients with prescriptions for recommended nutritional supplements were low.

Conclusion: This study suggests that patients who have bariatric surgery are not receiving the recommended nutritional monitoring after discharge from specialist care. GPs and patients should be supported to engage with follow-up care. Future research should aim to understand the reasons underpinning these findings.
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http://dx.doi.org/10.3399/bjgp20X714161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041293PMC
June 2021

Incident atrial fibrillation in patients with differentiated thyroid cancer: a meta-analysis.

Endocr Relat Cancer 2021 Apr 29;28(5):325-335. Epub 2021 Apr 29.

Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece.

Differentiated thyroid cancer (DTC) represents the most common form of thyroid neoplasms and is becoming increasingly prevalent. Evidence suggests a possible relationship between DTC diagnosis and subsequent atrial fibrillation (AF). If confirmed, this may present an alarming health risk (AF) in an otherwise condition with a relatively good prognosis (DTC). The aim of this systematic review and meta-analysis is to provide for the first time a pooled estimate of AF incidence in DTC patients in comparison to healthy controls. A detailed search in electronic databases, clinical trial registries and grey literature was performed to identify studies reporting the incidence of AF in DTC patients. Newcastle-Ottawa quality assessment scale was used to assess study quality. We used a random effects (RE) generalized linear mixed model (GLMM) in pooling of individual studies and also calculated a prediction interval for the estimate of a new study. Six observational studies met the eligibility criteria, which included totally 187,754 patients with DTC and 199,770 healthy controls. The median follow-up period was 4.3 to 18.8 years; the incidence rate of AF was 4.86 (95% CI, 3.29 to 7.17, I2 = 96%) cases per 1000 person-years, while the incidence rate ratio was 1.54 (95% CI, 1.44 to 1.65, I2 = 0%, 95% PI, 1.33 to 1.78).This is the first meta-analysis to confirm that patients with DTC are at a high risk for developing AF, which may be attributed to a state of iatrogenic hyperthyroidism due to long-term thyrotropin suppression therapy.
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http://dx.doi.org/10.1530/ERC-20-0496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111325PMC
April 2021

Impact of diabetes specialist nurses on inpatient care: A systematic review.

Diabet Med 2021 Sep 18;38(9):e14573. Epub 2021 May 18.

Institute of Applied Health Sciences, University of Birmingham, Birmingham, UK.

Background: People with diabetes have longer hospital stays and poorer clinical outcomes. Diabetes inpatient specialist nurses have been introduced to improve care.

Aims: To assess the evidence for the benefit of diabetes specialist nurses in the inpatient setting.

Methods: A systematic search of MEDLINE (ovid), Embase (ovid), CINAHL (EBSCO) and Web of Science core collection from January 1998 to September 2019 was performed using key terms for diabetes specialist nurses and hospital setting. Studies measuring patient care using any standardised or validated outcome measures after introduction of a dedicated diabetes specialist nurse or nursing team were eligible for inclusion and findings reported by narrative synthesis.

Results: There were 10 studies which met the inclusion criteria. One was a randomised controlled study and the remaining nine studies were before and after studies with three of them using a time series analysis methodology. The majority reported length of stay (LOS) and showed a reduction in median LOS by between 0.5 and 3 days. Reductions in bed occupancy ranged from 39% to 47%. There was a paucity of evidence for outcomes related to patient care with some measures limited to single studies. These included a 52% reduction in total drug errors, improved patient knowledge, higher patient satisfaction and improved glycaemic control post-discharge. There was no reduction of mortality observed.

Conclusions: These studies suggest a reduction in LOS and improved clinical care for patients with diabetes after the introduction of diabetes inpatient specialist nurses. Future research should examine a range of benefits associated with diabetes inpatient specialist nurse delivered services, including reduction of inpatient complications such as infections and cardiovascular events.
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http://dx.doi.org/10.1111/dme.14573DOI Listing
September 2021

Postpartum haemorrhage and risk of mental ill health: A population-based longitudinal study using linked primary and secondary care databases.

J Psychiatr Res 2021 05 18;137:419-425. Epub 2021 Mar 18.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

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, p = 0·239) and anxiety (adjusted HR: 0·99, 95%CI: 0·90-1·09). PPH is associated with a significant increase in the risk of developing postnatal depression and PTSD in the first year after delivery. Active monitoring for mental illness should form an integral part of the follow-up in women who suffered a PPH.
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http://dx.doi.org/10.1016/j.jpsychires.2021.03.022DOI Listing
May 2021

Epidemiology of Scleritis in the United Kingdom From 1997 to 2018: Population-Based Analysis of 11 Million Patients and Association Between Scleritis and Infectious and Immune-Mediated Inflammatory Disease.

Arthritis Rheumatol 2021 07 6;73(7):1267-1276. Epub 2021 Jun 6.

University Hospitals Birmingham NHS Foundation Trust, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK, and NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, Institute of Ophthalmology, University College London, and Health Data Research UK, London, UK.

Objective: To estimate 22-year trends in the prevalence and incidence of scleritis, and the associations of scleritis with infectious and immune-mediated inflammatory diseases (I-IMIDs) in the UK.

Methods: The retrospective cross-sectional and population cohort study (1997-2018) included 10,939,823 patients (2,946 incident scleritis cases) in The Health Improvement Network, a nationally representative primary care records database. The case-control and matched cohort study (1995-2019) included 3,005 incident scleritis cases and 12,020 control patients matched by age, sex, region, and Townsend deprivation index. Data were analyzed using multivariable Poisson regression, multivariable logistic regression, and Cox proportional hazards multivariable models adjusted for age, sex, Townsend deprivation index, race/ethnicity, smoking status, nation within the UK, and body mass index. Incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) were calculated.

Results: Scleritis incidence rates per 100,000 person-years declined from 4.23 (95% CI 2.16-6.31) to 2.79 (95% CI 2.19-3.39) between 1997 and 2018. The prevalence of scleritis per 100,000 person-years was 93.62 (95% CI 90.17-97.07) in 2018 (61,650 UK patients). Among 2,946 patients with incident scleritis, 1,831 (62.2%) were female, the mean ± SD age was 44.9 ± 17.6 years (range 1-93), and 1,257 (88.8%) were White. Higher risk of incident scleritis was associated with female sex (adjusted IRR 1.53 [95% CI 1.43-1.66], P < 0.001), Black race/ethnicity (adjusted IRR 1.52 [95% CI 1.14-2.01], P = 0.004 compared to White race/ethnicity), or South Asian race/ethnicity (adjusted IRR 1.50 [95% CI 1.19-1.90], P < 0.001 compared to White race/ethnicity), and older age (peak adjusted IRR 4.95 [95% CI 3.99-6.14], P < 0.001 for patients ages 51-60 years versus those ages ≤10 years). Compared to controls, scleritis patients had a 2-fold increased risk of a prior I-IMID diagnosis (17 I-IMIDs, P < 0.001) and significantly increased risk of subsequent diagnosis (13 I-IMIDs). The I-IMIDs most strongly associated with scleritis included granulomatosis with polyangiitis, Behçet's disease, and Sjögren's syndrome.

Conclusion: From 1997 through 2018, the UK incidence of scleritis declined from 4.23 to 2.79/100,000 person-years. Incident scleritis was associated with 19 I-IMIDs, providing data for rational investigation and cross-specialty engagement.
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July 2021

Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care.

BMC Infect Dis 2021 Mar 15;21(1):262. Epub 2021 Mar 15.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

Introduction: Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality.

Methods: We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome.

Results: The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality.

Conclusion: Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.
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http://dx.doi.org/10.1186/s12879-021-05951-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957446PMC
March 2021
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