Socio-demographic variation in diagnosis of and prescribing for common mental illnesses among children and young people during the COVID-19 pandemic: time series analysis of primary care electronic health records.

BACKGROUND: The impact of the COVID-19 pandemic on the mental health of children and young people (CYP) has been widely reported. Primary care electronic health records were utilised to examine trends in the diagnosing, recording and treating of these common mental disorders by ethnicity and social deprivation in Greater Manchester, England. METHODS: Time-series analyses conducted using Greater Manchester Care Record (GMCR) data examined all diagnosed episodes of anxiety disorders and depression and prescribing of anxiolytics and antidepressants among patients aged 6-24 years. The 41-month observation period was split into three epochs: Pre-pandemic (1/2019-2/2020); Pandemic Phase 1 (3/2020-6/2021); Pandemic Phase 2 (7/2021-5/2022). Rate ratios for all CYP specific to sex, age, ethnicity, and neighbourhood-level Indices of Multiple Deprivation (IMD) quintile were modelled using negative binomial regression. RESULTS: Depression and anxiety disorder rates were highest in females, CYP aged 19-24, and White and 'Other' ethnic groups. During Pandemic Phase 1, rates for these diagnoses fell in all demographic subgroups and then rose to similar levels as those recorded pre-pandemic. In Pandemic Phase 2, rates in Black and Mixed-ethnicity females rose to a significantly greater degree (by 54% and 62%, respectively) than those in White females. Prescribing rates increased throughout the study period, with significantly greater rises observed in non-White females and males. The temporal trends were mostly homogeneous across deprivation quintiles. CONCLUSION: The observed fluctuations in frequency of recorded common mental illness diagnoses likely reflect service accessibility and patients' differential propensities to consult as well as changing levels of distress and psychopathology in the population. However, psychotropic medication prescribing increased throughout the observation period, possibly indicating a sustained decline in mental health among CYP, and also clinicians' responses to problems presented. The comparatively greater increases in frequencies of diagnosis recording and medication prescribing among ethnic minority groups warrants further investigation.

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.

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.

Risk factors for nonfatal self-harm and suicide among adolescents: two nested case-control studies conducted in the UK Clinical Practice Research Datalink.

BACKGROUND: The characteristics of adolescents who die by suicide have hitherto been examined in uncontrolled study designs, thereby precluding examination of risk factors. The degree to which antecedents of nonfatal self-harm and suicide at young age differ remains unknown. METHOD: We delineated two nested case-control studies of patients aged 10-19 years using the Clinical Practice Research Datalink with interlinked hospital and national mortality records. Cases were adolescents who between 1st January 2003 and 31st December 2018 had died from suicide (N = 324) - study 1; experienced their first self-harm episode (N = 56,008) - study 2. In both studies, cases were matched on sex, age and practice-level deprivation quintile to 25 controls. By fitting conditional logistic regression, we examined how risks varied according to psychiatric diagnoses, prescribed psychotropic medication, patterns of clinical contact and area-level deprivation. RESULTS: Suicides occurred more often among boys (66%), but self-harm was more common in girls (68%). Most individuals who self-harmed or died from suicide presented to their GP at least once in the preceding year (85% and 75% respectively). Only a third of cases had one of the examined diagnostic categories recorded. Depression was most strongly associated with elevated risks for both outcomes (self-harm: OR 7.9; 95% CI 7.8-8.2; suicide: OR 7.4; 95% CI 5.5-9.9). Except for autism spectrum disorder, all other diagnostic categories were linked with similar risk elevations for self-harm as for suicide. Whilst self-harm risk rose incrementally with increasing levels of area-level deprivation, suicide risks did not. CONCLUSIONS: We observed few marked differences in risk factor profiles for nonfatal self-harm versus suicide. As most adolescents who had harmed themselves or died by suicide were known to services in the preceding year, their underlying pathology may not be adequately identified and treated. Our findings highlight the need for a multiagency approach to treatment and prevention.

Temporal trends in annual incidence rates for psychiatric disorders and self-harm among children and adolescents in the UK, 2003-2018.

BACKGROUND: There has been growing concern in the UK over recent years that a perceived mental health crisis is affecting children and adolescents, although published epidemiological evidence is limited. METHODS: Two population-based UK primary care cohorts were delineated in the Aurum and GOLD datasets of the Clinical Practice Research Datalink (CPRD). We included data from 9,133,246 individuals aged 1-20 who contributed 117,682,651 person-years of observation time. Sex- and age-stratified annual incidence rates were estimated for attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) (age groups: 1-5, 6-9, 10-12, 13-16, 17-19), depression, anxiety disorders (6-9, 10-12, 13-16, 17-19), eating disorders and self-harm (10-12, 13-16, 17-19) during 2003-2018. We fitted negative binomial regressions to estimate incidence rate ratios (IRRs) to examine change in incidence between the first (2003) and final year (2018) year of observation and to examine sex-specific incidence. RESULTS: The results indicated that the overall incidence has increased substantially in both boys and girls in between 2003 and 2018 for anxiety disorders (IRR 3.51 95% CI 3.18-3.89), depression (2.37; 2.03-2.77), ASD (2.36; 1.72-3.26), ADHD (2.3; 1.73-3.25), and self-harm (2.25; 1.82-2.79). The incidence for eating disorders also increased (IRR 1.3 95% CI 1.06-1.61), but less sharply. The incidence of anxiety disorders, depression, self-harm and eating disorders was in absolute terms higher in girls, whereas the opposite was true for the incidence of ADHD and ASD, which were higher among boys. The largest relative increases in incidence were observed for neurodevelopmental disorders, particularly among girls diagnosed with ADHD or ASD. However, in absolute terms, the incidence was much higher for depression and anxiety disorders. CONCLUSION: The number of young people seeking help for psychological distress appears to have increased in recent years. Changes to diagnostic criteria, reduced stigma, and increased awareness may partly explain our results, but we cannot rule out true increases in incidence occurring in the population. Whatever the explanation, the marked rise in demand for healthcare services means that it may be more challenging for affected young people to promptly access the care and support that they need.

Prevalence of comorbid mental and physical illnesses and risks for self-harm and premature death among primary care patients diagnosed with fatigue syndromes.

BACKGROUND: Fatigue syndromes (FSs) affect large numbers of individuals, yet evidence from epidemiological studies on adverse outcomes, such as premature death, is limited. METHODS: Cohort study involving 385 general practices in England that contributed to the Clinical Practice Research Datalink (CPRD) with linked inpatient Hospital Episode Statistics (HES) and Office for National Statistics (ONS) cause of death information. A total of 10 477 patients aged 15 years and above, diagnosed with a FS during 2000-2014, were individually matched with up to 20 comparator patients without a history of having a FS. Prevalence ratios (PRs) were estimated to compare the FS and comparison cohorts on clinical characteristics. Adjusted hazard ratios (HRs) for subsequent adverse outcomes were estimated from stratified Cox regression models. RESULTS: Among patients diagnosed with FSs, we found elevated baseline prevalence of: any psychiatric illness (PR 1.77; 95% CI 1.72-1.82), anxiety disorders (PR 1.92; 1.85-1.99), depression (PR 1.89; 1.83-1.96), psychotropic prescriptions (PR 1.68; 1.64-1.72) and comorbid physical illness (PR 1.28; 1.23-1.32). We found no significant differences in risks for: all-cause mortality (HR 0.99; 0.91-1.09), natural death (HR 0.99; 0.90-1.09), unnatural death (HR 1.00; 0.59-1.72) or suicide (HR 1.68; 0.78-3.63). We did, however, observe a significantly elevated non-fatal self-harm risk: HR 1.83; 1.56-2.15. CONCLUSIONS: The absence of elevated premature mortality risk is reassuring. The raised prevalence of mental illness and increased non-fatal self-harm risk indicate a need for enhanced assessment and management of psychopathology associated with fatigue syndromes.

Temporal trends in incidence of hospital-treated self-harm among adolescents in Denmark: national register-based study.

BACKGROUND: Studies conducted in the UK and in Ireland have reported increased rates of self-harm in adolescent females from around the time of the 2008 economic recession and through periods of subsequent national austerity programme implementation. It is not known if incidence rates have increased similarly in other Western European countries during this period. METHODS: Data from interlinked national administrative registers were extracted for individuals born in Denmark during 1981-2006. We estimated gender- and age-specific incidence rates (IRs) per 10,000 person-years at risk for hospital-treated non-fatal self-harm during 2000-2016 at ages 10-19 years. RESULTS: Incidence of self-harm peaked in 2007 (IR 25.1) and then decreased consistently year on year to 13.8 in 2016. This pattern was found in all age groups, in both males and females and in each parental income tertile. During the last 6 years of the observation period, 2011-2016, girls aged 13-16 had the highest incidence rates whereas, among boys, incidence was highest among 17-19 year olds throughout. CONCLUSIONS: The temporal increases in incidence rates of self-harm among adolescents observed in some Western European countries experiencing major economic recession were not observed in Denmark. Restrictions to sales of analgesics, access to dedicated suicide prevention clinics, higher levels of social spending and a stronger welfare system may have protected potentially vulnerable adolescents from the increases seen in other countries. A better understanding of the specific mechanisms behind the temporal patterns in self-harm incidence in Denmark is needed to help inform suicide prevention in other nations.

Keratinocyte-Releasable Factors Stimulate the Expression of Granulocyte Colony-Stimulating Factor in Human Dermal Fibroblasts.

Interaction between keratinocytes and fibroblasts plays a critical role in maintaining skin integrity under both normal and pathological conditions. We have previously demonstrated that keratinocyte-releasable factors influence the expression of key extracellular matrix components, such as collagen and matrix metalloproteinases in dermal fibroblasts. In this study, we utilized DNA microarray analysis to examine the effects of keratinocyte-releasable factors on the expression of several cytokines in human dermal fibroblasts. The results revealed significantly higher granulocyte colony-stimulating factor (G-CSF) expression in fibroblasts co-cultured with keratinocytes relative to mono-cultured cells, which was verified by RT-PCR and western blot. G-CSF is an important hematopoietic factor also thought to play a beneficial role in wound healing through stimulating keratinocyte proliferation. To partially characterize the keratinocyte-releasable factors responsible for stimulating G-CSF production, keratinocyte-conditioned medium (KCM) was subjected to thermal treatment and ammonium sulfate precipitation before treating fibroblasts. The results showed that keratinocyte-releasable G-CSF-stimulating factors remain stable at 56°C and upon 50% ammonium sulfate precipitation. Knowing that keratinocytes release IL-1, which stimulates G-CSF expression in various immune cells, several experiments were conducted to ask whether this might also be the case for fibroblasts. The results showed that the addition of recombinant IL-1 markedly increased G-CSF expression in fibroblasts; however, IL-1 receptor antagonist only partially abrogated KCM-stimulated G-CSF expression, indicating the role of additional keratinocyte-releasable factors. These findings underline the importance of cross-talk between keratinocytes and fibroblasts, suggesting that communication between these cells in vivo modulates the production of cytokines required for cutaneous wound healing and maintenance. J. Cell. Biochem. 118: 308-317, 2017. © 2016 Wiley Periodicals, Inc.

Examining trends in type 2 diabetes incidence, prevalence and mortality in the UK between 2004 and 2014.

AIMS: Contemporary data describing type 2 diabetes prevalence, incidence and mortality are limited. We aimed to (1) estimate annual incidence and prevalence rates of type 2 diabetes in the UK between 2004 and 2014, (2) examine relationships between observed rates with age, gender, socio-economic status and geographic region, and (3) assess how temporal changes in incidence and all-cause mortality rates influence changes in prevalence. METHODS: Type 2 diabetes patients aged ≥16 years between January 2004 and December 2014 were identified using the Clinical Practice Research Datalink (CPRD). Up to 5 individuals without diabetes were matched to diabetes patients based on age, gender and the general practice. Annual incidence, prevalence and mortality rates were calculated per 10 000 person-years at risk (95% CI). Survival models compared mortality rates in patients with and without type 2 diabetes. RESULTS: Prevalence rates of type 2 diabetes increased from 3.21% (3.19; 3.22) in 2004 to 5.26% (5.24; 5.29) in 2014. Incidence rates remained stable, overall, throughout the study period. Higher incidence and prevalence rates were related to male gender and deprivation. Individuals with type 2 diabetes were associated with higher risk of mortality (Hazard ratio 1.26 [1.20; 1.32]). Mortality rates declined in patients with and without diabetes throughout the study period. The incidence and prevalence of type 2 diabetes in patients aged 16 to 34 years increased over time. CONCLUSIONS: The rising prevalence of type 2 diabetes in the UK over the last decade is probably explained by patients living longer rather than by increasing incidence of type 2 diabetes.

Premature Death Among Primary Care Patients With a History of Self-Harm.

PURPOSE: Self-harm is a public health problem that requires a better understanding of mortality risk. We undertook a study to examine premature mortality in a nationally representative cohort of primary care patients who had harmed themselves. METHODS: During 2001-2013, a total of 385 general practices in England contributed data to the Clinical Practice Research Datalink with linkage to Office for National Statistics mortality records. We identified 30,017 persons aged 15 to 64 years with a recorded episode of self-harm. We estimated the relative risks of all-cause and cause-specific natural and unnatural mortality using a comparison cohort of 600,258 individuals matched on age, sex, and general practice. RESULTS: We found an elevated risk of dying prematurely from any cause among the self-harm cohort, especially in the first year of follow-up (adjusted hazard ratio for that year, 3.6; 95% CI, 3.1-4.2). In particular, suicide risk was especially high during the first year (adjusted hazard ratio, 54.4; 95% CI, 34.3-86.3); although it declined sharply, it remained much higher than that in the comparison cohort. Large elevations of risk throughout the follow-up period were also observed for accidental, alcohol-related, and drug poisoning deaths. At 10 years of follow-up, cumulative incidence values were 6.5% (95% CI, 6.0%-7.1%) for all-cause mortality and 1.3% (95% CI, 1.2%-1.5%) for suicide. CONCLUSIONS: Primary care patients who have harmed themselves are at greatly increased risk of dying prematurely by natural and unnatural causes, and especially within a year of a first episode. These individuals visit clinicians at a relatively high frequency, which presents a clear opportunity for preventive action. Primary care patients with myriad comorbidities, including self-harming behavior, mental disorder, addictions, and physical illnesses, will require concerted, multipronged, multidisciplinary collaborative care approaches.

The epidemiology of self-harm in a UK-wide primary care patient cohort, 2001-2013.

BACKGROUND: Most of the research conducted on people who harm themselves has been undertaken in secondary healthcare settings. Little is known about the frequency of self-harm in primary care patient populations. This is the first study to describe the epidemiology of self-harm presentations to primary care using broadly representative national data from across the United Kingdom (UK). METHODS: Using the Clinical Practice Research Datalink (CPRD), we calculated directly standardised rates of incidence and annual presentation during 2001-2013. Rates were compared by gender and age and across the nations of the UK, and also by degree of socioeconomic deprivation measured ecologically at general practice level. RESULTS: We found significantly elevated rates in females vs. males for incidence (rate ratio - RR, 1.45, 95 % confidence interval - CI, 1.42-1.47) and for annual presentation (RR 1.56, CI 1.54-1.58). An increasing trend over time in incidence was apparent for males (P < 0.001) but not females (P = 0.08), and both genders exhibited rising temporal trends in presentation rates (P < 0.001). We observed a decreasing gradient of risk with increasing age and markedly elevated risk for females in the youngest age group (aged 15-24 years vs. all other females: RR 3.75, CI 3.67-3.83). Increasing presentation rates over time were observed for males across all age bands (P < 0.001). We found higher rates when comparing Northern Ireland, Scotland, and Wales with England, and increasing rates of presentation over time for all four nations. We also observed higher rates with increasing levels of deprivation - most vs. least deprived male patients: RR 2.17, CI 2.10-2.25. CONCLUSIONS: Incorporating data from primary care yields a more comprehensive quantification of the health burden of self-harm. These novel findings may be useful in informing public health programmes and the targeting of high-risk groups toward the ultimate goal of lowering risk of self-harm repetition and premature death in this population.

Primary care contact, clinical management and suicide risk following discharge from inpatient mental health care.

BACKGROUND: Evidence is sparse regarding service usage and the clinical management of people recently discharged from inpatient psychiatric care who die by suicide. AIM: To improve understanding of how people discharged from inpatient mental health care are supported by primary care during this high-risk transition. DESIGN & SETTING: A nested case-control study utilising interlinked primary and secondary care records in England for people who died within a year of discharge between 2001 and 2019, matched on age, sex, practice-level deprivation and region with up to 20 living discharged people. METHOD: We described patterns of consultation, prescription of psychotropic medication and continuity of care for people who died by suicide and those who survived. Mutually adjusted relative risk estimates were generated for a range of primary care and clinical variables. RESULTS: Over 40% of patients who died within 2 weeks and 80% who died later had at least one primary care consultation. Evidence of discharge communication from hospital was infrequent. Within-practice continuity of care was relatively high. Those who died by suicide were less likely to consult within two weeks of discharge, AOR 0.61 (0.42-0.89), more likely to consult in the week before death, AOR 1.71 (1.36-2.15), to be prescribed multiple types of psychotropic medication, (AOR 1.73, 1.28-2.33), to experience readmission and have a diagnosis outside of the 'Severe Mental Illness' definition. CONCLUSION: Primary care clinicians have opportunities to intervene and should prioritise patients experiencing transition from inpatient care. Clear communication and liaison between services is essential to provide timely support.

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.

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.

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.

The role of accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study.

Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (HbA1c). To explore potential effects, we used MR methods to assess effects of accelerometer-derived sleep traits (duration, mid-point least active 5-h, mid-point most active 10-h, sleep fragmentation, and efficiency) on HbA1c/glucose in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 146,806). Cross-trait linkage disequilibrium score regression was applied to determine genetic correlations across accelerometer-derived, self-reported sleep traits, and HbA1c/glucose. We found no causal effect of any accelerometer-derived sleep trait on HbA1c or glucose. Similar MR results for self-reported sleep traits in the UKB sub-sample with accelerometer-derived measures suggested our results were not explained by selection bias. Phenotypic and genetic correlation analyses suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different types of exposure. These findings suggested accelerometer-derived sleep traits do not affect HbA1c. Accelerometer-derived measures of sleep duration and quality might not simply be 'objective' measures of self-reported sleep duration and insomnia, but rather captured different sleep characteristics.

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.

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.