Indirect effects of the COVID-19 pandemic on diagnosing, monitoring, and prescribing in people with diabetes and strategies for diabetes service recovery internationally.

The COVID-19 pandemic has caused major disruptions in clinical services for people with chronic long-term conditions. In this narrative review, we assess the indirect impacts of the COVID-19 pandemic on diabetes services globally and the resulting adverse effects on rates of diagnosing, monitoring, and prescribing in people with type 2 diabetes. We summarise potential practical approaches that could address these issues and improve clinical services and outcomes for people living with diabetes during the recovery phase of the pandemic.

Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study.

OBJECTIVE: To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia. DESIGN: Population based matched cohort study. SETTING: Linked primary care, hospital and mortality data from Clinical Practice Research Datalink (CPRD), England. POPULATION: Adults (≥50 years) with a diagnosis of dementia between 1 January 1998 and 31 May 2018 (n=173 910, 63.0% women). Each new antipsychotic user (n=35 339, 62.5% women) was matched with up to 15 non-users using incidence density sampling. MAIN OUTCOME MEASURES: The main outcomes were stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury, stratified by periods of antipsychotic use, with absolute risks calculated using cumulative incidence in antipsychotic users versus matched comparators. An unrelated (negative control) outcome of appendicitis and cholecystitis combined was also investigated to detect potential unmeasured confounding. RESULTS: Compared with non-use, any antipsychotic use was associated with increased risks of all outcomes, except ventricular arrhythmia. Current use (90 days after a prescription) was associated with elevated risks of pneumonia (hazard ratio 2.19, 95% confidence interval (CI) 2.10 to 2.28), acute kidney injury (1.72, 1.61 to 1.84), venous thromboembolism (1.62, 1.46 to 1.80), stroke (1.61, 1.52 to 1.71), fracture (1.43, 1.35 to 1.52), myocardial infarction (1.28, 1.15 to 1.42), and heart failure (1.27, 1.18 to 1.37). No increased risks were observed for the negative control outcome (appendicitis and cholecystitis). In the 90 days after drug initiation, the cumulative incidence of pneumonia among antipsychotic users was 4.48% (4.26% to 4.71%) versus 1.49% (1.45% to 1.53%) in the matched cohort of non-users (difference 2.99%, 95% CI 2.77% to 3.22%). CONCLUSIONS: Antipsychotic use compared with non-use in adults with dementia was associated with increased risks of stroke, venous thromboembolism, myocardial infarction, heart failure, fracture, pneumonia, and acute kidney injury, but not ventricular arrhythmia. The range of adverse outcomes was wider than previously highlighted in regulatory alerts, with the highest risks soon after initiation of treatment.

Survival Outcomes in Older Women with Oestrogen-Receptor-Positive Early-Stage Breast Cancer: Primary Endocrine Therapy vs. Surgery by Comorbidity and Frailty Levels.

Primary endocrine therapy (PET) offers non-surgical treatment for older women with early-stage breast cancer who are unsuitable for surgery due to frailty or comorbidity. This research assessed all-cause and breast cancer-specific mortality of PET vs. surgery in older women (≥70 years) with oestrogen-receptor-positive early-stage breast cancer by frailty and comorbidity levels. This study used UK secondary data to analyse older female patients from 2000 to 2016. Patients were censored until 31 May 2019 and grouped by the Charlson comorbidity index (CCI) and hospital frailty risk score (HFRS). Cox regression models compared all-cause and breast cancer-specific mortality between PET and surgery within each group, adjusting for patient preferences and covariates. Sensitivity analyses accounted for competing risks. There were 23,109 patients included. The hazard ratio (HR) comparing PET to surgery for overall survival decreased significantly from 2.1 (95%CI: 2.0, 2.2) to 1.2 (95%CI: 1.1, 1.5) with increasing HFRS and from 2.1 (95%CI: 2.0, 2.2) to 1.4 (95%CI 1.2, 1.7) with rising CCI. However, there was no difference in BCSM for frail older women (HR: 1.2; 0.9, 1.9). There were no differences in competing risk profiles between other causes of death and breast cancer-specific mortality with PET versus surgery, with a subdistribution hazard ratio of 1.1 (0.9, 1.4) for high-level HFRS (p = 0.261) and CCI (p = 0.093). Given limited survival gains from surgery for older patients, PET shows potential as an effective option for frail older women with early-stage breast cancer. Despite surgery outperforming PET, surgery loses its edge as frailty increases, with negligible differences in the very frail.

Risk of Falls and Fractures in Individuals With Cataract, Age-Related Macular Degeneration, or Glaucoma.

Importance: Three leading disease causes of age-related visual loss are cataract, age-related macular degeneration (AMD), and glaucoma. Although all 3 eye diseases have been implicated with falls and fracture risk, evidence is mixed, with the contribution of different eye diseases being uncertain. Objective: To examine whether people with cataract, AMD, or glaucoma have higher risks of falls or fractures than those without. Design, Setting, and Participants: This cohort study was a population-based study in England using routinely collected electronic health records from the Clinical Practice Research Datalink (CPRD) GOLD and Aurum primary care databases with linked hospitalization and mortality records from 2007 to 2020. Participants were people with cataract, AMD, or glaucoma matched to comparators (1:5) by age, sex, and general practice. Data were analyzed from May 2021 to June 2023. Exposures: For each eye disease, we estimated the risk of falls or fractures using separate multivariable Cox proportional hazards regression models. Main Outcomes: Two primary outcomes were incident falls and incident fractures derived from general practice, hospital, and mortality records. Secondary outcomes were incident fractures of specific body sites. Results: A total of 410 476 people with cataract, 75 622 with AMD, and 90 177 with glaucoma were matched (1:5) to 2 034 194 (no cataract), 375 548 (no AMD), and 448 179 (no glaucoma) comparators. The mean (SD) age was 73.8 (11.0) years, 79.4 (9.4) years, and 69.8 (13.1) years for participants with cataract, AMD, or glaucoma, respectively. Compared with comparators, there was an increased risk of falls in those with cataract (adjusted hazard ratio [HR], 1.36; 95% CI, 1.35-1.38), AMD (HR, 1.25; 95% CI, 1.23-1.27), and glaucoma (HR, 1.38; 95% CI, 1.35-1.41). Likewise for fractures, there were increased risks in all eye diseases, with an HR of 1.28 (95% CI, 1.27-1.30) in the cataract cohort, an HR of 1.18 (95% CI, 1.15-1.21) for AMD, and an HR of 1.31 (95% CI, 1.27-1.35) for glaucoma. Site-specific fracture analyses revealed increases in almost all body sites (including hip, spine, forearm, skull or facial bones, pelvis, ribs or sternum, and lower leg fractures) compared with matched comparators. Conclusions and Relevance: The results of this study support recognition that people with 1 or more of these eye diseases are at increased risk of both falls and fractures. They may benefit from improved advice, access, and referrals to falls prevention services.

Clinical risk associated with COVID-19 among 86000 patients with congenital heart disease.

OBJECTIVE: To determine the magnitude of any excess risk of mortality and hospitalisation due to COVID-19 infection in patients with congenital heart disease (CHD) in the UK healthcare system. METHODS: Matched case-control study within the Clinical Practice Research Datalink study of anonymised general practice records in the National Health Service in England. Patients with CHD were stratified for disease severity according to the European Society of Cardiology guidelines. Presence of a positive COVID-19 test, hospitalisation with a diagnosis of COVID-19 and COVID-19-related mortality were compared in case and control groups. RESULTS: 86 441 patients with CHD and 335 839 controls were studied. Of patients with a positive COVID-19 test, patients with CHD were more likely than controls to be hospitalised (22.4% vs 14.5%; OR=1.77 (95% CI 1.60 to 1.96); p=2.11e-28) and suffer COVID-19-related death (6.1% vs 3.8%; OR=1.60 (95% CI 1.35 to 1.89); p=7.00e-08). The excess risk of COVID-19 hospitalisation and death rose with increasing physiological severity of CHD (presence of pulmonary vascular disease and/or cyanosis), rather than anatomical complexity. CONCLUSIONS: In this study of the COVID-19 pandemic experience, using population health records in over 86000 patients with CHD in England, patients with CHD with COVID-19 were at around 50-75% higher risk of hospitalisation and mortality compared with matched controls with COVID-19. We provide the first primary care-derived estimates for COVID-19 hospitalisation and case-fatality rates in patients with CHD. Some factors predictive of worse COVID-19 outcome in general populations (such as non-white ethnic group), and other CHD-specific comorbidities (such as pulmonary hypertension), influenced outcomes among patients with CHD.

Changes to healthcare utilisation and symptoms for common mental health problems over the first 21 months of the COVID-19 pandemic: parallel analyses of electronic health records and survey data in England.

Background: Few studies have investigated the effect of the COVID-19 pandemic on mental health beyond 2020. This study quantifies changes to healthcare utilisation and symptoms for common mental health problems over the pandemic's first 21 months. Methods: Parallel cohort studies using primary care database and survey data for adults (≥16 years) in England from January 2015 to December 2021: 16,551,842 from the Clinical Practice Research Datalink (CPRD) and 40,699 from the UK Household Longitudinal Survey (UKHLS). Interrupted time-series models estimated changes in monthly prevalence of presentations and prescribed medications for anxiety and depression (CPRD); and self-reported psychological distress (UKHLS). The pandemic period was divided into five phases: 1st Wave (April-May 2020); post-1st Wave (June-September 2020); 2nd Wave (October 2020-February 2021); post 2nd Wave (March-May 2021); 3rd Wave (June-December 2021). Findings: Primary care presentations for depression or anxiety dropped during the first wave (4.6 fewer monthly appointments per 1000 patients, 4.4-4.8) and remained lower than expected throughout follow-up. Self-reported psychological distress exceeded expected levels during the first (Prevalence Ratio = 1.378, 95% CI 1.289-1.459) and second waves (PR = 1.285, 1.189-1.377), returning towards expected levels during the third wave (PR = 1.038, 0.929-1.154). Increases in psychological distress and declines in presentations were greater for women. The decrease in primary care presentations for depression and anxiety exceeded that for physical health conditions (rheumatoid arthritis, diabetes, urinary tract infections). Anxiety and depression prescriptions returned to pre-pandemic levels during the second wave due to increased repeat prescriptions. Interpretation: Despite periods of distress during the pandemic, we did not find an enduring effect on common mental health problems. The fall in primary care presentations for anxiety or depression suggests changing healthcare utilisation for mental distress and a potential treatment gap. Funding: National Institute for Health and Care Research (NIHR).

Non-fatal overdose risk associated with prescribing opioid agonists concurrently with other medication: Cohort study conducted using linked primary care, secondary care and mortality records.

BACKGROUND AND AIMS: An apparently protective effect of opioid agonist treatment (OAT) on all-cause and cause-specific mortality risk has been widely reported. Non-fatal overdose (NFO) often precedes subsequent drug-poisoning deaths. We hypothesized that benzodiazepines, gabapentinoids, antipsychotics, antidepressants, Z-drugs or opioids increase the NFO risk when co-prescribed with OAT. DESIGN: We conducted a cohort study using the Clinical Practice Research Datalink GOLD and Aurum databases. The cohort was linked to Hospital Episode Statistics admitted patient care data (HES-APC), neighbourhood- and practice-level Index of Multiple Deprivation quintiles and mortality records from the Office for National Statistics. SETTING: Primary care in England. PARTICIPANTS: We studied patients with opioid use disorder, aged 18-64 years, who were prescribed OAT (15155 methadone and 5743 buprenorphine recipients) between Jan 1, 1998, and Dec 31, 2017. MEASUREMENTS: The main outcome examined was NFO risk during co-prescription of OAT with benzodiazepines, antipsychotics, gabapentinoids, antidepressants, Z-drugs or opioids. Overdose was defined according to International Classification of Diseases codes from the HES-APC data set. Negative binomial regression models were used to estimate weighted rate ratios (wRR) for NFO during co-prescription of OAT and benzodiazepines, antipsychotics, gabapentinoids, antidepressants, Z-drugs or opioids with periods of exclusive OAT usage. FINDINGS: Among 20 898 patients observed over 83 856 person-years, we found an elevated overdose risk that resulted in hospital admission during co-prescription of OAT with benzodiazepines [wRR: 1.45; 95% confidence interval (CI) = 1.26-1.67], gabapentinoids (wRR = 2.22; 95% CI = 1.77-2.79), Z-drugs (wRR = 1.60; 95% CI = 1.31-1.96), antipsychotics (wRR = 1.85; 95% CI = 1.53-2.25) and opioids (wRR = 1.28; 95% CI = 1.02-1.60). The risk ratio for antidepressant co-prescriptions was below unity (wRR = 0.90; 95% CI = 0.79-1.02) but this result was not statistically significant. CONCLUSION: Elevated risk of non-fatal overdose among opioid agonist treatment recipients is associated with concurrent use of medication prescribed for other reasons.

Temporal trends in eating disorder and self-harm incidence rates among adolescents and young adults in the UK in the 2 years since onset of the COVID-19 pandemic: a population-based study.

BACKGROUND: Self-harm and eating disorders share multiple risk factors, with onset typically during adolescence or early adulthood. We aimed to examine the incidence rates of these psychopathologies among young people in the UK in the 2 years following onset of the COVID-19 pandemic. METHODS: We conducted a population-based study using the primary care electronic health records of patients aged 10-24 years in the UK Clinical Practice Research Datalink (CPRD). The observation period was from Jan 1, 2010, to March 31, 2022. We calculated the monthly incidence rates of eating disorders and self-harm according to the first record of each outcome. On the basis of antecedent trends between January, 2010, and February, 2020, negative binomial regression models were fitted to predict monthly incidence rates after the pandemic began in March, 2020. Percentage differences between observed and expected incidence were calculated to indicate changes since the onset of the pandemic, with stratification by sex, age, and deprivation quintile. FINDINGS: The primary care health records of 9 184 712 patients aged 10-24 years (4 836 226 [52·7%] female patients and 4 348 486 [47·3%] male patients; n=1881 general practices) were included for analysis. The incidence rates of eating disorders and self-harm among girls were higher than expected between March 1, 2020, and March 31, 2022. The observed incidence of eating disorders was 42·4% (95% CI 25·7-61·3) higher than expected for girls aged 13-16 years, and 32·0% (13·3-53·8) higher than expected for girls aged 17-19 years, whereas other age groups showed little difference between observed and expected incidence. Similarly, the increase in self-harm incidence was driven by girls aged 13-16 years, for whom the observed incidence was 38·4% (20·7-58·5) higher than expected. By contrast, among boys in all age groups, the incidence rates of eating disorders and self-harm were lower than, or close to, the expected rates. Among boys, the observed incidence of eating disorders was 22·8% (9·2-34·4) lower than expected, and the observed incidence of self-harm was 11·5% (3·6-18·7) lower than expected. The estimated increases in eating disorder and self-harm incidence among girls aged 13-16 years were largely attributable to increases within less deprived communities. INTERPRETATION: Although causes are uncertain, increased incidence of eating disorder diagnoses and self-harm among teenage girls in the UK during the first 2 years of the COVID-19 pandemic highlight an urgent need for intervention. Early identification of mental health difficulties by primary care clinicians is necessary. Timely access to treatments and sufficient support from general practitioners and mental health services needs to be available to manage presenting problems and to prevent exacerbations of conditions. FUNDING: National Institute for Health and Care Research.

Validation of a miniaturized handheld arterial pressure monitor for guiding full and partial REBOA use during resuscitation.

PURPOSE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a well-validated method for the control of noncompressible truncal hemorrhage. In lower resource or battlefield settings, the need for arterial line setup and monitoring is problematic and potentially prohibitive. We sought to evaluate the accuracy and precision of a miniaturized portable device (Centurion COMPASS®) versus standard arterial pressure monitoring using standard ER-REBOA and partial REBOA (pREBOA) as a high-fidelity and space-/time-conserving alternative. METHODS: A total of 40 swine underwent a four-phase validation/precision study (each phase using five ER-REBOAs and five pREBOAs). Phases I/II evaluated accuracy with full and pREBOA in uninjured animals. Phases III/IV duplicated the previous phases but in a severe hemorrhagic shock model. Carotid and femoral pressures were monitored with both intra-arterial pressure systems and the COMPASS® device. The vascular flow was measured by aortic flow probes. Correlation and Bland-Altman analysis were performed. RESULTS: There was a strong correlation in accuracy testing of proximal and distal COMPASS® devices compared to standard intra-arterial pressure monitoring (r = 0.94, 0.8; p < 0.005) as well as during precision testing (r = 0.98, 0.89 p < 0.005) in the uninjured phases. Similar accuracy and reliability were demonstrated in hemorrhagic shock, with a strong correlation for the proximal and distal COMPASS® devices (r = 0.98, 0.97; p < 0.005), as well as during precision testing (r = 0.99, 0.95; p < 0.005) in both full and pREBOA scenarios. Bland-Altman analysis showed extremely low bias between the COMPASS® and arterial line for both proximal (bias = 1.9) and distal (bias = 0.8) pressure measurements. CONCLUSION: The COMPASS® provides accurate and precise pressure measurements during standard and partial REBOA in both uninjured and shock conditions. This device may help extend and enhance capability in any low-resource/battlefield settings, or even eliminate the need for standard intra-arterial invasive pressure monitoring and external setup.

Financial Vulnerability of American College of Surgeons-Verified Trauma Centers: A Statewide Analysis.

BACKGROUND: Although trauma centers represent an integral part of healthcare in the US, characterization of their financial vulnerability has not been reported. We sought to characterize the financial health and vulnerability among California trauma centers and identify factors associated with high and low vulnerability. STUDY DESIGN: The RAND Hospital Data financial dataset was used to evaluate all American College of Surgeons (ACS)-verified trauma centers in California. Financial vulnerability of each center was calculated using 6 metrics to calculate a composite Financial Vulnerability Score (FVS). Tertiles of the FVS were generated to classify trauma centers as high, medium, or low financial vulnerability. Hospital characteristics were also analyzed and compared. RESULTS: Forty-seven ACS trauma centers were identified. Nine were Level I, 27 were Level II, and 8 were Level III. Level I centers encompassed the greatest proportion of the high FVS tier (44%), whereas Level II and III centers were the most likely to be in the middle and lower tiers, respectively (44%; 63%). Lower FVS centers had greater asset:liability ratios, operating margins, and days cash on hand compared with the 2 higher tiers, whereas high FVS centers showed a greater proportion of uncompensated care, outpatient share rates, outpatient surgeries, and longer days in net accounts. Lower FVS centers were more likely to be teaching hospitals and members of a larger corporate entity. CONCLUSION: Many ACS trauma centers are at moderate/high risk for financial vulnerability and disparate impacts of stressor events, and the FVS may represent a novel metric that could be used at the local or statewide level.

Non-fatal overdose risk during and after opioid agonist treatment: A primary care cohort study with linked hospitalisation and mortality records.

Background: The initiation and cessation of opioid agonist treatment (OAT) have both been associated with elevated risk of fatal overdose. We examined risk of non-fatal overdose during OAT initiation and cessation and specifically between methadone versus buprenorphine recipients. Methods: We utilised primary care electronic health records from the Clinical Practice Research Datalink to delineate a study cohort of adults aged 18-64 who were prescribed OAT between Jan 1, 1998 and Dec 31, 2017. These records were linked to hospitalisation, mortality records and patient neighbourhood and practice-level Index of Multiple Deprivation quintiles. With inverse probability treatment weights applied and negative binomial regression models we estimated incidence rate ratios for hospital admissions among patients who experienced multiple overdoses. Findings: A total of 20898 patients were prescribed methadone or buprenorphine over 83856 person-years of follow-up. Compared with periods in treatment, patients not in treatment were 51% more likely to experience a non-fatal overdose that required hospitalisation (weighted rate ratio, wRR 1·51; 95% CI 1·42, 1·60), especially during the four weeks of OAT initiation (5·59; 5·31, 5·89) and following cessation (13·39; 12·78, 14·03). The wRR of overdose during (0·37; 0·34, 0·39) and after treatment (0·36; 0·34, 0·38) favoured buprenorphine compared to methadone. Interpretation: OAT is associated with decreased non-fatal overdose risk. Buprenorphine may act more protectively than methadone, especially during the first four weeks of treatment. Funding: National Institute for Health and Care Research (NIHR) Greater Manchester Patient Safety Translational Research Centre (PSTRC-2016-003).

Management of anxiety disorders among children and adolescents in UK primary care: A cohort study.

BACKGROUND: Anxiety disorders are common in childhood and adolescence but evidence-based guidance on their management is limited in the UK. In the absence of guidelines, we examined what treatment young people with anxiety disorders receive in primary care in the year following diagnosis. METHOD: We delineated a cohort of individuals diagnosed with anxiety disorders aged 10-18 using the Clinical Practice Research Datalink (CPRD). We estimated the annual prevalence of antidepressant and anxiolytic prescribing and referrals to mental health services in the year following diagnosis between 2003 and 2019 via Poisson models, adjusted for age, gender, and practice-level deprivation. RESULTS: 34,490 out of 52,358 (66 %) individuals were not prescribed or referred in the year following diagnosis. Those registered to practices in the most deprived compared to the least deprived areas were less likely to be referred (PR 0.80, 95%CI 0.76-0.84) and prescribed antidepressants (PR 0.77, 95%CI 0.72-0.82). Referrals increased 2003-2008 (22-28 %) and then declined until 2019 (28-21 %). Antidepressant prescribing decreased substantially between 2003 and 2005 (18-11 %) and then increased slightly between 2006 and 2019 (11-13 %). Anxiolytic prescribing declined between 2003 and 2019 (10-2 %). LIMITATIONS: Prescriptions in the CPRD are not coupled with information about indication. Some prescriptions may therefore have been incorrectly attributed to the treatment of anxiety disorders. CONCLUSION: The continued use of antidepressants necessitates the development of evidence-based guidance. The lower likelihood of being prescribed medication and/or referred among young people in more deprived practice populations, where incidence of anxiety disorder and other mental illnesses is higher, must also be investigated and rectified.

Incidence of nonvalvular atrial fibrillation and oral anticoagulant prescribing in England, 2009 to 2019: A cohort study.

BACKGROUND: Atrial fibrillation (AF) is an important risk factor for ischaemic stroke, and AF incidence is expected to increase. Guidelines recommend using oral anticoagulants (OACs) to prevent the development of stroke. However, studies have reported the frequent underuse of OACs in AF patients. The objective of this study is to describe nonvalvular atrial fibrillation (NVAF) incidence in England and assess the clinical and socioeconomic factors associated with the underprescribing of OACs. METHODS AND FINDINGS: We conducted a population-based retrospective cohort study using the UK Clinical Practice Research Datalink (CPRD) database to identify patients with NVAF aged ≥18 years and registered in English general practices between 2009 and 2019. Annual incidence rate of NVAF by age, deprivation quintile, and region was estimated. OAC prescribing status was explored for patients at risk for stroke and classified into the following: OAC, aspirin only, or no treatment. We used a multivariable multinomial logistic regression model to estimate relative risk ratios (RRRs) and 95% confidence intervals (CIs) of the factors associated with OAC or aspirin-only prescribing compared to no treatment in patients with NVAF who are recommended to take OAC. The multivariable regression was adjusted for age, sex, comorbidities, socioeconomic status, baseline treatment, frailty, bleeding risk factors, and takes into account clustering by general practice. Between 2009 and 2019, 12,517,191 patients met the criteria for being at risk of developing NVAF. After a median follow-up of 4.6 years, 192,265 patients had an incident NVAF contributing a total of 647,876 person-years (PYR) of follow-up. The overall age-adjusted incidence of NVAF per 10,000 PYR increased from 20.8 (95% CI: 20.4; 21.1) in 2009 to 25.5 (25.1; 25.9) in 2019. Higher incidence rates were observed for older ages and males. Among NVAF patients eligible for anticoagulation, OAC prescribing rose from 59.8% (95% CI: 59.0; 60.6) in 2009 to 83.2% (95% CI: 83.0; 83.4) in 2019. Several conditions were associated with lower risk of OAC prescribing: dementia [RRR 0.52 (0.47; 0.59)], liver disease 0.58 (0.50; 0.67), malignancy 0.74 (0.72; 0.77), and history of falls 0.82 (0.78; 0.85). Compared to white ethnicity, patients from black and other ethnic minorities were less likely to receive OAC; 0.78 (0.65; 0.94) and 0.76 (0.64; 0.91), respectively. Patients living in the most deprived areas were less likely to receive OAC 0.85 (0.79; 0.91) than patients living in the least deprived areas. Practices located in the East of England were associated with higher risk of prescribing aspirin only over no treatment than practices in London (RRR 1.22; 95% CI 1.02 to 1.45). The main limitation of this study is that these findings depends on accurate recording of conditions by health professionals and the inevitable residual confounding due to lack of data on certain factors that could be associated with under-prescribing of OACs. CONCLUSIONS: The incidence of NVAF increased between 2009 and 2015, before plateauing. Underprescribing of OACs in NVAF is associated with a range of comorbidities, ethnicity, and socioeconomic factors, demonstrating the need for initiatives to reduce inequalities in the care for AF patients.

Assessing the Causal Role of Sleep Traits on Glycated Hemoglobin: A Mendelian Randomization Study.

OBJECTIVE: To examine the effects of sleep traits on glycated hemoglobin (HbA1c). RESEARCH DESIGN AND METHODS: This study triangulated evidence across multivariable regression (MVR) and one- (1SMR) and two-sample Mendelian randomization (2SMR) including sensitivity analyses on the effects of five self-reported sleep traits (i.e., insomnia symptoms [difficulty initiating or maintaining sleep], sleep duration, daytime sleepiness, napping, and chronotype) on HbA1c (in SD units) in adults of European ancestry from the UK Biobank (for MVR and 1SMR analyses) (n = 336,999; mean [SD] age 57 [8] years; 54% female) and in the genome-wide association studies from the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC) (for 2SMR analysis) (n = 46,368; 53 [11] years; 52% female). RESULTS: Across MVR, 1SMR, 2SMR, and their sensitivity analyses, we found a higher frequency of insomnia symptoms (usually vs. sometimes or rarely/never) was associated with higher HbA1c (MVR 0.05 SD units [95% CI 0.04-0.06]; 1SMR 0.52 [0.42-0.63]; 2SMR 0.24 [0.11-0.36]). Associations remained, but point estimates were somewhat attenuated after excluding participants with diabetes. For other sleep traits, there was less consistency across methods, with some but not all providing evidence of an effect. CONCLUSIONS: Our results suggest that frequent insomnia symptoms cause higher HbA1c levels and, by implication, that insomnia has a causal role in type 2 diabetes. These findings could have important implications for developing and evaluating strategies that improve sleep habits to reduce hyperglycemia and prevent diabetes.

Suicide and other causes of death among working-age and older adults in the year after discharge from in-patient mental healthcare in England: matched cohort study.

BACKGROUND: Evidence for risk of dying by suicide and other causes following discharge from in-patient psychiatric care throughout adulthood is sparse. AIMS: To estimate risks of all-cause mortality, natural and external-cause deaths, suicide and accidental, alcohol-specific and drug-related deaths in working-age and older adults within a year post-discharge. METHOD: Using interlinked general practice, hospital, and mortality records in the Clinical Practice Research Datalink we delineated a cohort of discharged adults in England, 2001-2018. Each patient was matched to up to 20 general population comparator patients. Cumulative incidence (absolute risks) and hazard ratios (relative risks) were estimated separately for ages 18-64 and ≥65 years with additional stratification by gender and practice-level deprivation. RESULTS: The 1-year cumulative incidence of dying post-discharge was 2.1% among working-age adults (95% CI 2.0-2.3) and 14.1% (95% CI 13.6-14.5) among older adults. Suicide risk was particularly elevated in the first 3 months, with hazard ratios of 191.1 (95% CI 125.0-292.0) among working-age adults and 125.4 (95% CI 52.6-298.9) in older adults. Older patients were vulnerable to dying by natural causes within 3 months post-discharge. Risk of dying by external causes was greater among discharged working-age adults in the least deprived areas. Relative risk of suicide in discharged working-age women relative to their general population peers was double the equivalent male risk elevation. CONCLUSIONS: Recently discharged adults at any age are at increased risk of dying from external and natural causes, indicating the importance of close monitoring and provision of optimal support to all such patients, particularly during the first 3 months post-discharge.

Primary Prevention of Cardiovascular and Heart Failure Events With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Their Combination in Type 2 Diabetes.

OBJECTIVE: To assess associations between current use of sodium-glucose cotransporter 2 inhibitors (SGLT2is), glucagon-like peptide 1 receptor agonists (GLP-1RAs), and their combination and risk for major adverse cardiac and cerebrovascular events (MACCE) and heart failure (HF) in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: In three nested case-control studies involving patients with type 2 diabetes in England and Wales (primary care data from the Clinical Practice Research Datalink and Secure Anonymised Information Linkage Databank with linkage to hospital and mortality records), we matched each patient experiencing an event with up to 20 control subjects. Adjusted odds ratios (ORs) for MACCE and HF among patients receiving SGLT2i or GLP-1RA regimens versus other combinations were estimated using conditional logistic regression and pooled using random-effects meta-analysis. RESULTS: Among 336,334 people with type 2 diabetes and without cardiovascular disease, 18,531 (5.5%) experienced a MACCE. In a cohort of 411,206 with type 2 diabetes and without HF, 17,451 (4.2%) experienced an HF event. Compared with other combination regimens, the adjusted pooled OR and 95% CI for MACCE associated with SGLT2i regimens was 0.82 (0.73, 0.92), with GLP-1RA regimens 0.93 (0.81, 1.06), and with the SGLT2i/GLP-1RA combination 0.70 (0.50, 0.98). Corresponding data for HF were SGLT2i 0.49 (0.42, 0.58), GLP-1RA 0.82 (0.71, 0.95), and SGLT2i/GLP-1RA combination 0.43 (0.28, 0.64). CONCLUSIONS: SGLT2i and SGLT2i/GLP-1RA combination regimens may be beneficial in primary prevention of MACCE and HF and GLP-1RA for HF. These data call for primary prevention trials using these agents and their combination.

Impact of COVID-19 restrictions on diabetes health checks and prescribing for people with type 2 diabetes: a UK-wide cohort study involving 618 161 people in primary care.

OBJECTIVE: To compare rates of performing National Institute for Health and Care Excellence-recommended health checks and prescribing in people with type 2 diabetes (T2D), before and after the first COVID-19 peak in March 2020, and to assess whether trends varied by age, sex, ethnicity and deprivation. METHODS: We studied 618 161 people with T2D followed between March and December 2020 from 1744 UK general practices registered with the Clinical Practice Research Datalink. We focused on six health checks: haemoglobin A1c, serum creatinine, cholesterol, urinary albumin excretion, blood pressure and body mass index assessment. Regression models compared observed rates in April 2020 and between March and December 2020 with trend-adjusted expected rates derived from 10-year historical data. RESULTS: In April 2020, in English practices, rates of performing health checks were reduced by 76%-88% when compared with 10-year historical trends, with older people from deprived areas experiencing the greatest reductions. Between May and December 2020, the reduced rates recovered gradually but overall remained 28%-47% lower, with similar findings in other UK nations. Extrapolated to the UK population, there were ~7.4 million fewer care processes undertaken March-December 2020. In England, rates for new medication fell during April with reductions varying from 10% (95% CI: 4% to 16%) for antiplatelet agents to 60% (95% CI: 58% to 62%) for antidiabetic medications. Overall, between March and December 2020, the rate of prescribing new diabetes medications fell by 19% (95% CI: 15% to 22%) and new antihypertensive medication prescribing fell by 22% (95% CI: 18% to 26%), but prescribing of new lipid-lowering or antiplatelet therapy was unchanged. Similar trends were observed across the UK, except for a reduction in new lipid-lowering therapy prescribing in the other UK nations (reduction: 16% (95% CI: 10% to 21%)). Extrapolated to the UK population, between March and December 2020, there were ~31 800 fewer people with T2D prescribed a new type of diabetes medication and ~14 600 fewer prescribed a new type of antihypertensive medication. CONCLUSIONS: Over the coming months, healthcare services will need to manage this backlog of testing and prescribing. We recommend effective communications to ensure patient engagement with diabetes services, monitoring and opportunities for prescribing, and when appropriate use of home monitoring, remote consultations and other innovations in care.

Evaluating the safety of mental health-related prescribing in UK primary care: a cross-sectional study using the Clinical Practice Research Datalink (CPRD).

BACKGROUND: Most patients with mental illness are managed in primary care, yet there is a lack of data exploring potential prescribing safety issues in this setting for this population. OBJECTIVES: Examine the prevalence of, between-practice variation in, and patient and practice-level risk factors for, 18 mental health-related potentially hazardous prescribing indicators and four inadequate medication monitoring indicators in UK primary care. METHOD: Cross-sectional analyses of routinely collected electronic health records from 361 practices contributing to Clinical Practice Research Datalink GOLD database. The proportion of patients 'at risk' (based on an existing diagnosis, medication, age and/or sex) triggering each indicator and composite indicator was calculated. To examine between-practice variation, intraclass correlation coefficient (ICC) and median OR (MOR) were estimated using two-level logistic regression models. The relationship between patient and practice characteristics and risk of triggering composites including 16 of the 18 prescribing indicators and four monitoring indicators were assessed using multilevel logistic regression. RESULTS: 9.4% of patients 'at risk' (151 469 of 1 611 129) triggered at least one potentially hazardous prescribing indicator; between practices this ranged from 3.2% to 24.1% (ICC 0.03, MOR 1.22). For inadequate monitoring, 90.2% of patients 'at risk' (38 671 of 42 879) triggered at least one indicator; between practices this ranged from 33.3% to 100% (ICC 0.26, MOR 2.86). Patients aged 35-44, females and those receiving more than 10 repeat prescriptions were at greatest risk of triggering a prescribing indicator. Patients aged less than 25, females and those with one or no repeat prescription were at greatest risk of triggering a monitoring indicator. CONCLUSION: Potentially hazardous prescribing and inadequate medication monitoring commonly affect patients with mental illness in primary care, with marked between-practice variation for some indicators. These findings support health providers to identify improvement targets and inform development of improvement efforts to reduce medication-related harm.