IQVIA Medical Research Research Articles

Risk of osteoporotic fractures in menopausal women with common mental health diagnoses prescribed SSRIs/SNRIs: cohort and self-controlled case series analyses

SummaryIn a population-based cohort study of menopausal women with common mental health diagnoses, SSRIs/SNRIs were associated with a 32% increased risk of osteoporotic fractures. The risk of osteoporotic fractures was particularly increased for longer periods of treatment with SSRIs/SNRIs (> 5 years) and in younger menopausal women (< 50 years old).PurposeTo investigate the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and the risk of osteoporotic fractures (OF) in menopausal women with common mental health diagnoses (CMHD).MethodsWe conducted the study with two designs (cohort and self-controlled case series [SCCS]), using the IQVIA Medical Research Database (IMRD) UK. The source population comprised women aged ≥ 50 years and women with a record indicating menopause (< 50 years). All women had a recorded CMHD. For the cohort analysis, the risk of OFs was estimated by comparing women prescribed SSRIs/SNRIs (exposed) to those not exposed. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CIs). For the SCCS, women acted as their own controls; periods of exposure to SSRIs/SNRIs were compared to periods of non-exposure using conditional Poisson regression to estimate incidence rate ratios (IRR) with 95% CIs.ResultsWe identified 292,848 women, of whom 35,222 experienced OFs within a median follow-up of 6.01 years. We found strong evidence of an association between SSRIs/SNRIs and the risk of OFs (adjusted HR = 1.32, 95% CI:1.29–1.35). Compared to periods of no exposure, SSRIs/SNRIs increased the risk of OFs during the first 30 days (IRR = 1.38, 95% CI:1.26–1.51), during the first 90 days (IRR = 1.58, 95% CI: 1.48–1.69), and the remaining exposure (IRR = 1.42, 95% CI:1.37–1.48).ConclusionsIn a population of menopausal women with CMHDs, the prescribing of SSRIs/SNRIs antidepressants was associated with a higher risk of OFs. Careful assessment of osteoporosis risk needs to be considered when treating menopausal women with SSRIs/SNRIs antidepressants.

The prescribing of opioids for chronic noncancer pain in the menopausal and postmenopausal population: a drug utilisation study in the United Kingdom.

Opioid use for chronic noncancer pain (CNCP) is consistently higher in menopausal/postmenopausal women than in younger women or men, elevating their risk of opioid-related adverse health outcomes. Since pain severity increases with hormonal changes accompanying menopause, these women should be a focus of opioid stewardship efforts. To examine opioid prescribing trends for CNCP in menopausal/postmenopausal women diagnosed with a musculoskeletal condition. Population-based drug utilisation study using IQVIA Medical Research Data UK. Annual opioid prescribing incidence, prevalence, and average duration of use were calculated for a cohort of women aged 50-79 with musculoskeletal conditions newly diagnosed between 2010-2021. Specific results were stratified by age, pain indication, and Townsend score. From 2010 to 2021, incident prescribing rates of opioids increased in women aged 50-54 (161.4 [95% CI 149.7-174.0] per 1000 PYAR in 2010 to 239.6 [95% CI 211.7-271.2] per 1000 PYAR in 2021); these women discontinued opioid use faster (~1 year) than older age groups (~2 years). Overall, opioid prescribing prevalence decreased from 23% in 2010 to 14% in 2021, and average opioid use duration decreased from 3 years to 1 year (2010 - post-2017) in women aged 50-79. The overall observed decrease in prevalence and average duration of opioid use is encouraging. Incident prescriptions are rising in women aged 50-54 and those with fibromyalgia while remaining steady in women aged 55-79. Understanding the impact of menopause/post-menopause on opioid use trends is important for effective opioid stewardship.

Quantitative Measurement of the Direct Public Health Impact of Medicines Withdrawals in Europe: Development of a Modelling Method and Proof-of-Concept Study to Estimate the Morbidity and Mortality Prevented by Regulatory Action.

Removing medicines from market may benefit public health by preventing adverse drug reactions (ADRs), which should be quantified. This study's aim was to identify a model to quantify the impact of medicines' marketing authorisation (MA) withdrawal and revocation in terms of preventing morbidity and mortality. MA withdrawals and revocations for safety reasons in France, Germany and/or the United Kingdom between July 2012 and December 2016 were identified for prescription medicines. Annual exposure was estimated for each medicine, using IQVIA Medical Research Data (IMRD)-France, IMRD-Germany and IMRD-UK primary care electronic health record databases. European Medicines Agency records provided reasons for regulatory action for each medicine. Absolute risks of ADRs which led to MA withdrawal were estimated for patients exposed to each medicine by systematic review of quantitative research. Public health impact, expressed as annual number of ADRs avoided, was estimated by modelling exposure and ADR risk. Four MA withdrawals and two revocations met study inclusion criteria. Each product's usage decreased following MA withdrawal or revocation. Absolute risk for ADRs was 0.1%-41.25%. To estimate impact of each withdrawal or revocation, its average annual exposure within each IMRD population was multiplied by the absolute risk to give the crude number of ADRs prevented annually due to regulatory action. This model quantifies the public health impact of MA withdrawal and revocation in terms of serious morbidity, resulting from eliminated or reduced usage of medicines. This method can be applied to products in other settings to quantify the impact of other pharmacovigilance actions.

Memantine attenuates the development of osteoarthritis by blocking NMDA receptor mediated calcium overload and chondrocyte senescence

BackgroundMemantine, which is an FDA-proven drug for the treatment of dementia, exerts its function by blocking the function of NMDA (N-methyl-D-aspartate) receptor, a calcium-permeable ion channel that reduces cytotoxic calcium overload. Chondrocyte senescence is a crucial cellular event that contributes to articular cartilage degeneration during osteoarthritis (OA) development. To date, the effects of memantine and its downstream NMDA receptor on chondrocyte senescence and OA have been rarely reported. MethodsThe protein levels of NMDA receptor and its agonistic ligand, glutamate, were compared between normal and OA chondrocytes. The quantity of intracellular calcium ions and the level of mitochondrial damage were evaluated using specific fluorescent probes and transmission electron microscopy (TEM), respectively. Chondrocyte senescence was evaluated by senescence-associated β-galactosidase (SA-β-Gal) staining and p16INK4a analysis. The function of NMDA receptor in chondrocyte senescence and OA was tested via agonists activation and gene knockdown experiments. The therapeutic effects of memantine on OA were examined both in vitro and in vivo. Additionally, to verify the findings from animal samples, a propensity score-matched cohort study was conducted using data from a United Kingdom primary care database (i.e., IQVIA Medical Research Database [IMRD]) to compare the risk of OA-related joint replacement involved in memantine initiators versus active comparators (i.e., acetylcholinesterase [AchE] initiators) in patients with dementia. ResultsThe protein expression of NMDA receptor and the secretion of glutamate were both significantly increased in OA chondrocytes. NMDA receptor activation was found to stimulate chondrocyte calcium overload, which further led to mitochondrial fragmentation and chondrocyte senescence. Blocking the NMDA receptor with memantine and N-methyl-D-aspartate receptor subunit 1(NR1, the gene encoding NMDA receptor) knockdown resulted in reduced calcium influx, mitochondrial fragmentation, as well as cellular senescence in OA chondrocytes. Intra-articular injection of memantine in OA mice also exhibited protective effects against cartilage degeneration. Moreover, in the 1:5 propensity score-matched cohort study consisting of 6218 patients (n = 1435 in the memantine cohort; n = 4783 in the AchE cohort), the memantine initiator was associated with a lower risk of OA-related joint replacement than AchE initiators (Hazard ratio = 0.56, 95 % confidence interval: 0.34 to 0.99). ConclusionNMDA receptor plays an important role in inflammatory-induced cytotoxic calcium overload in chondrocytes, while memantine can effectively block the NMDA receptor to reduce chondrocyte senescence and retard the development of OA. The translational potential of this articleAs a clinically licensed drug used for the treatment of dementia, memantine has shown promising therapeutic effects on OA. Mechanistically, it functions by blocking NMDA receptor from mediating chondrocyte senescence. The protective effects of memantine against OA were verified not only by in vivo and in vitro experiments but also via a propensity score-matched human cohort study. These findings presented robust evidence for repurposing memantine for the treatment of OA.

Prevalence of cardiovascular drug-related adverse drug reactions consultations in UK primary care: A cross-sectional study.

Adverse drug reactions (ADRs) represent a significant barrier to achieve optimal treatment outcomes. Cardiovascular drugs, including antihypertensive drugs, lipid-lowering drugs, and antithrombotic drugs, are among the most prescribed medications in the primary care setting. To estimate the prevalence of cardiovascular drug-related ADRs consultations in United Kingdom (UK) primary care and identify risk factors of these ADRs. This was a cross-sectional study of cardiovascular drug users between 2000-2019 using UK IQVIA Medical Research Data. ADRs consultations were identified using database screening method employing standardised designated codes. The overall and annual age-standardised prevalence was estimated using direct standardisation method using 2019 mid-year UK population. Risk factors of ADRs consultations were estimated using logistic regression model stratified by therapeutic areas. The standardised prevalence of consultations related to cardiovascular drugs ADRs was 10.60 (95% CI. 10.46, 10.75) per 1000 patients. Patients aged 70-79 years had the highest occurrence of ADRs consultations. The most frequently drug classes implicated in the ADRs consultations were statins (n = 9,993 events, 27.09%), beta-blockers (n = 8,538 events, 23.15%), ACEIs/ARBs (n = 8,345 events, 22.62%), and aspirin (n = 6,482 events, 17.57%). Risk factors of ADRs consultations were previous history of cardiovascular diseases, e.g., myocardial infarction and stroke; advanced age, comorbidities; diabetes and dyslipidaemia; and polypharmacy. The burden of cardiovascular drug-related ADRs consultations in primary care was considerable. Statins, beta-blockers, ACEIs/ARBs, and aspirin were the most frequently implicated drug classes. Closer clinical monitoring should be performed for patients affected by the ADRs to mitigate the risk of suboptimal treatment outcomes.

Severe mental illness as a risk factor for recorded diagnosis of osteoporosis and fragility fractures in people aged ≥50 years: retrospective cohort study using UK primary care data.

Severe mental illness (SMI) has been associated with reduced bone density and increased risk of fractures, although some studies have shown inconsistent results. To examine the association between SMI and recorded diagnosis of osteoporosis and fragility fracture in people aged ≥50 years. Population-based cohort study set in UK primary care. Anonymised primary care data (IQVIA Medical Research Database) were used. Patients with a diagnosis of SMI aged 50-99 years (2000-2018) were matched to individuals without SMI. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Analyses were stratified by sex and age, accounting for social deprivation, year, smoking, alcohol, and body mass index. In total, 444 480 people were included (SMI n = 50 006; unexposed n = 394 474). In men, diagnosis of SMI increased the likelihood of an osteoporosis diagnosis, with differences mainly observed among the youngest (aged 50-54 years: HR 2.12, 95% CI = 1.61 to 2.79) and the oldest (aged 85-99 years: HR 2.15, 95% CI = 1.05 to 4.37), and SMI increased the risk of fragility fractures across all ages. In women, SMI increased the risk of an osteoporosis diagnosis only in those aged 50-54 years (HR 1.16, 95% CI = 1.01 to 1.34), but increased the risk of fragility fractures across all ages. There were more than twice as many men with SMI with fragility fracture records than with an osteoporosis diagnosis: fragility fracture:osteoporosis = 2.10, compared with fragility fracture:osteoporosis = 1.89 in men without SMI. The fragility fracture:osteoporosis ratio was 1.56 in women with SMI versus 1.11 in women without SMI. SMI is associated with an increased likelihood of fragility fractures and osteoporosis underdiagnosis. Interventions should be considered to mitigate the increased risk of fractures in people with SMI.

The first 100 days after childbirth: cross-sectional study of maternal clinical events and health needs from primary care.

The first 100 days after childbirth are important for women recovering from pregnancy and birth. To describe the most common clinical events or health needs documented in women's primary care records in the first 100 days after childbirth. Cross-sectional study using electronic health records from UK primary care data. Primary care records were examined from childbirth up to 100 days after childbirth for women aged 16-49 years who had given birth to a single live infant between 2006 and 2016 using IQVIA Medical Research Data. The most common clinical events or health needs based on documented symptoms, diagnoses, and medications were identified. How these varied by patient characteristic was explored. In total, 925 712 contacts were identified during the 100 days following 309 573 births. Women were most likely to use primary care to have a postnatal visit or check (60.6%, n = 187 455), for monitoring (such as a blood pressure reading) (49.9%, n = 154 328), and to access contraception (49.7%, n = 153 876). Younger women were more likely to have contacts for preventive care compared with older women, but were less likely to have contacts for ongoing mental and physical symptoms or conditions and pre-existing conditions. The highest peak in contacts occurred 42 days after birth, and related to a postnatal check or visit, monitoring a patient, and recording lifestyle factors (such as smoking status). Primary care services should seek to match the needs of new mothers, taking account of a high volume of contacts, for a broad range of planned and responsive care following childbirth.

Could primary care records be used to identify women at risk of perinatal anxiety? A mixed-methods study.

Perinatal anxiety (PNA) occurs throughout the antenatal period or up to 1 year after childbirth, with a prevalence of 21%. To investigate if primary care records could be used to identify women at 'higher risk' of PNA. Mixed-methods approach using quantitative and qualitative methods. Quantitative data analysis used Clinical Practice Research Datalink and IQVIA Medical Research Data to identify risk factors for PNA. Interviews explored the lived experiences of women with PNA about predisposing factors for PNA and acceptability of being informed of risk; and perspectives of primary healthcare professionals and Voluntary, Community, and Social Enterprise practitioners about risk communication. Interviews were conducted online, digitally recorded with consent, transcribed, and anonymised prior to analysis. Data were thematically analysed. Patient and clinical advisory groups informed each stage of the research. Women reflected on both positive and negative impacts of being identified at higher risk of PNA, a lack of understanding of how primary care records are used, and who has access to them. All interview participants suggested predisposing factors that would not be coded in primary care records. Quantitative analysis demonstrated that some predisposing factors for PNA can be identified in a woman's primary care records. Initial analysis suggests associations between PNA and infant health and healthcare use. While identification of higher risk of PNA may be acceptable, some factors that may contribute to PNA are not coded in primary care records. Identifying and managing PNA is needed to improve infant health.

Trends in clinical workload in UK primary care 2005-2019: a retrospective cohort study.

Substantial increases in UK consulting rates, mean consultation duration, and clinical workload were observed between 2007 and 2014. To the authors' knowledge, no analysis of more recent trends in clinical workload has been published to date. This study updates and builds on previous research, identifying underlying changes in population morbidity levels affecting demand for primary health care. To describe the changes in clinical workload in UK primary care since 2005. Retrospective cohort study using GP primary care electronic health records data from 824 UK general practices. Over 500 million anonymised electronic health records were obtained from IQVIA Medical Research Data to examine consulting rates with GPs and practice nurses together with the duration of these consultations to determine total patient-level workload per person-year. Age-standardised mean GP direct (face-to-face and telephone) consulting rates fell steadily by 2.0% a year from 2014 to 2019. Between 2005 and 2019 mean GP direct consulting rates fell by 5.8% overall whereas mean workload per person-year increased by 25.8%, owing in part to a 36.9% increase in mean consultation duration. Indirect GP workload almost tripled over the 15 years, contributing to a 48.3% increase in overall clinical workload per person-year. The proportion of the study population with ≥3 serious chronic conditions increased from 9.7% to 16.1%, accounting for over a third of total clinical workload in 2019. Findings show sustained increases in consulting rates, consultation duration, and clinical workload until 2014. From 2015, however, rising demand for health care and a larger administrative workload have led to capacity constraints as the system nears saturation.

Effect of statin treatment on the risk of cancer in patients with heart failure: A target trial emulation study.

A recent observational study suggested statins could reduce cancer diagnosis in patients with heart failure (HF). The findings need to be validated using robust epidemiological methods. This study aimed to evaluate the effect of statin treatment on the risk of cancer in patients with HF. We conducted two target trial emulations using primary care data from IQVIA Medical Research Database-UK (2000 to 2019) with a clone-censor-weight design. The first emulated trial addressed the treatment initiation effect: initiating within 1 year versus not initiating a statin after the HF diagnosis. The second emulated trial addressed the cumulative exposure effect: continuing a statin for ≤3 years, 3-6 years, and >6 years after initiation. The study outcomes were any incident cancer and site-specific cancer diagnoses. Weighted pooled logistic regression models were used to estimate 10-year risk ratios (RR). 95% confidence intervals (CIs) were estimated using non-parametric bootstrapping. The first emulated trial showed that, compared to no statin, statins did not reduce the cancer risk in patients with HF (RR, 1.05; 95% CI, 0.94-1.15). The second emulated trial showed that, compared to treatment ≤3 years, statins with longer durations did not reduce the cancer risk (3-6 years: RR, 0.94; 95% CI, 0.70-1.33. >6 years: RR, 0.97; 95% CI, 0.79-1.26). No significant risk difference was observed on any site-specific cancer diagnoses. The results from the target trial emulations suggest that statin treatment is not associated with cancer risk in patients with HF.

Association of sildenafil use with age-related macular degeneration: a retrospective cohort study

ObjectiveDespite significant advances in clinical care and understanding of the underlying pathophysiology, age-related macular degeneration (AMD)—a major cause of global blindness—lacks effective treatment to prevent the irreversible degeneration of photoreceptors...

Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease: A Cohort Study.

Repurposing phosphodiesterase type 5 inhibitors (PDE5Is) as drugs for Alzheimer disease (AD) risk reduction has shown promise based on animal studies. However, evidence in humans remains inconclusive. Therefore, we conducted a cohort study to evaluate the association between PDE5I initiation compared with nonuse and the risk of developing AD in men with erectile dysfunction (ED). Using electronic health records from IQVIA Medical Research Data UK (formerly known as the THIN database), we identified men aged ≥40 years with a new diagnosis of ED between 2000 and 2017. Individuals with a previous diagnosis of dementia, cognitive impairment, confusion, or prescription for dementia symptoms were excluded. The occurrence of incident AD was identified using diagnostic read codes. To minimize immortal-time bias, PDE5I initiation was treated as a time-varying exposure variable. Potential confounders were adjusted using inverse probability of treatment weighting based on propensity scores. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) with 95% CIs. A secondary analysis explored the association between AD and the cumulative number of PDE5I prescriptions. Sensitivity analyses included lag (delay) periods of 1 and 3 years after cohort entry to address the prodromal stage of AD. The study included 269,725 men, with 1,119 newly diagnosed with AD during a median follow-up of 5.1 (interquartile range 2.9-8.9) years. The adjusted HR in PDE5I initiators compared with nonuse was 0.82 (95% CI 0.72-0.93). The associated risk of AD decreased in individuals issued >20 prescriptions: HR 0.56 (95% CI 0.43-0.73) for 21-50 prescriptions and HR 0.65 (95% CI 0.49-0.87) for >50 prescriptions. Sensitivity analysis with a 1-year lag period supported the primary findings (HR 0.82, 95% CI 0.72-0.94), but the results differed with the inclusion of a 3-year lag period (HR 0.93, 95% CI 0.80-1.08). PDE5I initiation in men with ED was associated with a lower risk of AD, particularly in those most frequently issued prescriptions. The differences between primary and sensitivity analyses highlight the need to explore the optimal lag period. To enhance the generalizability of our findings, a randomized controlled trial including both sexes and exploring various PDE5I doses would be beneficial to confirm the association between PDE5I and AD.

Prevalence of potentially inappropriate medications among newly treated patients with type 2 diabetes in UK primary care.

The aim of this study was to estimate the prevalence of potentially inappropriate prescriptions (PIPs) in patients starting their first noninsulin antidiabetic treatment (NIAD) using two explicit process measures of the appropriateness of prescribing in UK primary care, stratified by age and polypharmacy status. A descriptive cohort study between 2016 and 2019 was conducted to assess PIPs in patients aged ≥45 years at the start of their first NIAD, stratified by age and polypharmacy status. The American Geriatrics Society Beers criteria 2015 was used for older (≥65 years) patients and the Prescribing Optimally in Middle-age People's Treatments criteria was used for middle-aged (45-64 years) patients. Prevalence of overall PIPs and individual PIPs criteria was reported using the IQVIA Medical Research Data incorporating THIN, a Cegedim Database of anonymized electronic health records in the UK. Among 28 604 patients initiating NIADs, 18 494 (64.7%) received polypharmacy. In older and middle-aged patients with polypharmacy, 39.6% and 22.7%, respectively, received ≥1 PIP. At the individual PIP level, long-term proton pump inhibitors (PPI) use was the most frequent PIP among older adults, and strong opioid without laxatives was the most frequent PIP in middle-aged patients with polypharmacy (11.1% and 4.1%, respectively). This study revealed that patients starting NIAD treatment receiving polypharmacy have the potential for pharmacotherapy optimization.

2022 Association between severe mental illness and risk of osteoporosis and fragility fractures: analysis of UK primary care data

Abstract Introduction Severe Mental Illness (SMI), particularly schizophrenia, has been associated with reduced bone mineral density and increased risk of fractures, although some studies have shown inconsistent results. We aimed to examine the effect of SMI on recorded diagnosis of osteoporosis and fragility fracture in older people in the UK, accounting for age, sex, social deprivation and lifestyle factors (smoking, alcohol and Body Mass Index (BMI)). Methods We used de-identified data provided as part of routine primary care (IQVIA Medical Research Database). Patients with a diagnosis of SMI (schizophrenia, bipolar disorder, other psychosis) aged 50-99y between 1/1/2000-31/12/2018 were matched 1:8 to age- and sex-adjusted controls without SMI, using Exposure Density Sampling (EDS). We estimated Hazard Ratios (HR) and 95% Confidence Intervals (95%CI) based on Cox Proportional Hazards model. We stratified the analysis by sex, accounting for age, social deprivation, year (model 1), and the above plus smoking, alcohol, and BMI (model 2). We imputed missing lifestyle data using Multiple Imputation. Results In total 444,480 people aged ≥50 years were included in the analysis (SMI N=50,006; controls N=394,474). In men, prior diagnosis of SMI increased the risk of osteoporosis diagnosis by 64% (HR 1.64; 95%CI 1.44-1.88) and the risk of fragility fractures by 87% (HR 1.87; 95%CI 1.70-2.06) in model 1. SMI also increased osteoporosis risk by 49% (HR=1.49; 95%CI 1.30-1.71) and fragility fracture risk by 82% (HR=1.82; 95%CI 1.65-2.00) in model 2 in men. In contrast, prior diagnosis of SMI had no significant effect on recorded osteoporosis risk in women. Prior SMI in women increased fragility fracture risk by 53% (HR 1.53; 95%CI 1.45-1.61) in model 1 and by 51% (HR=1.51; 95%CI 1.43-1.58) in model 2. Conclusions SMI is associated with increased risk of osteoporosis in men, and fragility fractures in both men and women, with a greater effect in men.

Weight Loss Induced by Antiobesity Medications and All-Cause Mortality Among Patients With Knee or Hip Osteoarthritis.

The current guidelines recommend weight loss for patients with overweight or obesity and knee or hip osteoarthritis (OA); however, there is a paucity of data on the relation of weight loss to death among patients with OA. We aimed to examine the relation of the rate of weight loss induced by antiobesity medications over one year to all-cause mortality among patients with overweight or obesity and knee or hip OA. Using the IQVIA Medical Research Database, we identified people with overweight or obesity and knee or hip OA. We emulated analyses of a hypothetical target trial to assess the effect of slow-to-moderate (2%-10%) or fast (≥10%) weight loss induced by the initiation of antiobesity medications within one year on all-cause mortality and secondary outcomes over five years' follow-up. Among 6,524 participants, the five-year all-cause mortality rates were 5.3%, 4.0%, and 5.4% for weight gain or stable, slow-to-moderate weight loss, and fast weight loss arms, respectively. Compared with the weight gain or stable arm, hazard ratios of all-cause mortality were 0.72 (95% confidence interval [CI] 0.56-0.92) for the slow-to-moderate weight loss arm and 0.99 (95% CI 0.67-1.44) for the fast weight loss arm. We found dose-response protective effects of weight loss on incident hypertension, type 2 diabetes, and venous thromboembolism but a slightly higher risk of cardiovascular disease, albeit not statistically significant, in the fast rate of weight loss arm than in the weight gain or stable arm and no significant relations of weight loss to the risk of cancer. In this population-based study, a slow-to-moderate, but not fast, rate of weight loss induced by antiobesity medications is associated with a lower risk of all-cause mortality in people with overweight or obesity and knee or hip OA.

Estimating life expectancy and years of life lost for autistic people in the UK: a matched cohort study

Previous research has shown that people who have been diagnosed autistic are more likely to die prematurely than the general population. However, statistics on premature mortality in autistic people have often been misinterpreted. In this study we aimed to estimate the life expectancy and years of life lost experienced by autistic people living in the UK. We studied people in the IQVIA Medical Research Database with an autism diagnosis between January 1, 1989 and January 16, 2019. For each participant diagnosed autistic, we included ten comparison participants without an autism diagnosis, matched by age, sex, and primary care practice. We calculated age- and sex-standardised mortality ratios comparing people diagnosed autistic to the reference group. We used Poisson regression to estimate age-specific mortality rates, and life tables to estimate life expectancy at age 18 and years of life lost. We analysed the data separately by sex, and for people with and without a record of intellectual disability. We discuss the findings in the light of the prevalence of recorded diagnosis of autism in primary care compared to community estimates. From a cohort of nearly 10 million people, we identified 17,130 participants diagnosed autistic without an intellectual disability (matched with 171,300 comparison participants), and 6450 participants diagnosed autistic with an intellectual disability (matched with 64,500 comparison participants). The apparent estimates indicated that people diagnosed with autism but not intellectual disability had 1.71 (95% CI: 1.39-2.11) times the mortality rate of people without these diagnoses. People diagnosed with autism and intellectual disability had 2.83 (95% CI: 2.33-3.43) times the mortality rate of people without these diagnoses. Likewise, the apparent reduction in life expectancy for people diagnosed with autism but not intellectual disability was 6.14 years (95% CI: 2.84-9.07) for men and 6.45 years (95% CI: 1.37-11.58 years) for women. The apparent reduction in life expectancy for people diagnosed with autism and intellectual disability was 7.28 years (95% CI: 3.78-10.27) for men and 14.59 years (95% CI: 9.45-19.02 years) for women. However, these findings are likely to be subject to exposure misclassification biases: very few autistic adults and older-adults have been diagnosed, meaning that we could only study a fraction of the total autistic population. Those who have been diagnosed may well be those with greater support needs and more co-occurring health conditions than autistic people on average. The findings indicate that there is a group of autistic people who experience premature mortality, which is of significant concern. There is an urgent need for investigation into the reasons behind this. However, our estimates suggest that the widely reported statistic that autistic people live 16-years less on average is likely incorrect. Nine out of 10 autistic people may have been undiagnosed across the time-period studied. Hence, the results of our study do not generalise to all autistic people. Diagnosed autistic adults, and particularly older adults, are likely those with greater-than-average support needs. Therefore, we may have over-estimated the reduction in life expectancy experienced by autistic people on average. The larger reduction in life expectancy for women diagnosed with autism and intellectual disability vs. men may in part reflect disproportionate underdiagnosis of autism and/or intellectual disability in women. Dunhill Medical Trust, Medical Research Council, National Institute for Health and Care Research, and the Royal College of Psychiatrists.

Risk of atopic dermatitis and the atopic march paradigm in children of mothers with atopic illnesses: A birth cohort study from the United Kingdom

Atopic dermatitis (AD) is thought to precede the onset of other allergic illness (OAI) in a temporal progression (ie, atopic march), yet the timing and progression has been questioned. It is also unclear how parental allergic illness impacts the development of these illnesses in offspring. (1) Explore risk of incident AD and (2) timing of allergic disease onset in children of mothers with AD compared with mothers without AD from the United Kingdom. We created a birth cohort of mother-child pairs using IQVIA Medical Research Data database and developed Cox proportional models to examine the above associations (hazard ratio, HR [95% confidence interval, CI]). Among 1,224,243 child-mother pairs, mean child (standard deviation) follow-up time was 10.8 (8.3) years and 50.1% were males (N=600,905). Children were 59% (HR=1.59 [1.57, 1.60]) more likely to have AD if their mothers had AD compared with no AD with mean age of first AD diagnosis at 3.3 (4.8) years. Most children with any diagnosis of AD present with AD first (91.0%); however, in those with asthma, only 67.8% developed AD first. Children born to mothers with AD are more prone to develop AD and some develop OAI first, suggesting that not all follow the same sequential pathway.

Drug-induced orthostatic hypotension: Cluster analysis of co-prescription patterns in older people in UK primary care.

Over 250 medications are reported to cause orthostatic hypotension, associated with serious adverse outcomes in older adults. Studies suggest a harmful cumulative risk of orthostatic hypotension with multiple medication use. However, there is limited evidence on the potential for harm in practice, particularly which drugs is co-prescribed and may increase risk of orthostatic hypotension. Retrospective cohort study and cluster analysis using general practice data from IQVIA Medical Research Data (IMRD) in patients aged ≥50 contributing data between 1 January 2018 and 31 December 2018. Thirteen drug groups known to be associated with orthostatic hypotension by mechanism, were analyzed and clusters generated by sex and age-band. A total of 602 713 individuals aged ≥50 with 283 912 (47%) men and 318 801 (53%) women were included. The most prevalent prescriptions that might contribute to orthostatic hypotension were ACE inhibitors, calcium-channel blockers, beta-blockers, selective serotonin reuptake inhibitors and uroselective alpha-blockers. We identified distinct clusters of cardiovascular system (cardiovascular system) drugs in men and women at all ages. cardiovascular system plus psychoactive drug clusters were common in women at all ages, and in men aged ≤70. cardiovascular system plus uroselective alpha-blockers were identified in men aged ≥70. Distinct clusters of drugs associated with orthostatic hypotension exist in practice, which change over the life course. Our findings highlight potentially harmful drug combinations that may cause cumulative risk of orthostatic hypotension in older people. This may guide clinicians about the potential of synergistic harm and to monitor for orthostatic hypotension if using combinations of cardiovascular system drugs, cardiovascular system plus psychoactive drugs and/or alpha-blockers-particularly in patients aged ≥70 or at high-risk due to comorbidity. Future research should consider quantifying the risk of drug-induced orthostatic hypotension with such drug combinations.

Prevalence of chronic pain or analgesic use in children and young people and its long-term impact on substance misuse, mental illness, and prescription opioid use: a retrospective longitudinal cohort study

Epidemiological studies suggest chronic and recurrent pain affects around a quarter of children, while 8% report intense and frequent pain. The long-term implications of chronic pain in childhood are uncertain. Using electronic health records (EHRs) we used both disease codes and medicines prescription records to investigate the scale of chronic pain and long-term analgesic use in children and young people (CYP), and if chronic pain and/or use of analgesic medicines at an early age is associated with substance misuse, use of prescription opioids, and poor mental health in adulthood. We conducted a cohort study using data from IQVIA Medical Research Data UK. We identified individuals aged 2-24 with exposure to either a diagnostic code indicating chronic pain (diagnosis-exposed), repeat prescription for medicines commonly used to treat pain (prescription-exposed), or both. Follow-up began at 25, and the unexposed population acted as comparators. We calculated hazard ratios (HR) for mental health and substance misuse outcomes, and rate ratios (RR) for opioid prescriptions in adulthood. Additionally, we investigated which diagnoses, if any, were over-represented in the prescription-exposed subgroup. The cohort constituted 853,625 individuals; 146,431 had one or more of the exposures of interest (diagnosis-exposed=115,101, prescription-exposed=20,298, both-exposed=11,032), leaving 707,194 as comparators. Median age at index exposure was 18.7 years (IQR 14.7-22.3). On average during follow-up, the pooled exposed group had, respectively, a 31% and 17% higher risk of adverse mental health and substance misuse outcomes (adjusted HR [95% CI] of 1.31 [1.29-1.32] and 1.17 [1.11-1.24]). Exposed individuals also received prescription opioids at double the rate of unexposed individuals on average during follow-up (adjusted RR 2.01 [95% CI 1.95-2.10]). Outcomes varied between exposure subgroups, with prescription- and both-exposure tending to have worse outcomes. Unlike these two subgroups, in the diagnosis-exposed subgroup we did not detect a greater risk of substance misuse. Chronic pain in CYP is associated with increased prescription opioid use and adverse mental health outcomes in adulthood, as is repeat prescription for analgesic medicines, but only the latter is also associated with substance misuse in adulthood. It is essential to avoid the harms of under-treating pain in CYP while giving due consideration to the risks posed by analgesic medicines. Early recognition of chronic pain in CYP and utilising non-pharmacological management options may help minimise overprescribing, and long-term reliance on dependence-forming-drugs. AL is an NIHR funded academic clinical fellow, and was supported by funding from UCLH Charities while carrying out this work. RS and DS are part of the Advanced Pain Discovery Platform and were supported by a UKRI and Versus Arthritis grant (MR/W002566/1) as part of the Consortium Against Pain Inequality. AW was supported by the Wellcome Trust (220558/Z/20/Z).

Using Repeated Measurements to Predict Cardiovascular Risk in Patients With Type 2 Diabetes Mellitus

The QRISK cardiovascular disease (CVD) risk assessment model is not currently optimized for patients with type 2 diabetes mellitus (T2DM). We aim to identify if the abundantly available repeatedly measured data for patients with T2D improves the predictive capability of QRISK to support the decision-making process regarding CVD prevention in patients with T2DM. We identified patients with T2DM aged 25 to 85, not on statin treatment and without pre-existing CVD from the IQVIA Medical Research Data United Kingdom primary care database and then followed them up until the first diagnosis of CVD, ischemic heart disease, or stroke/transient ischemic attack. We included traditional, nontraditional risk factors and relevant treatments for our analysis. We then undertook a Cox's hazards model accounting for time-dependent covariates to estimate the hazard rates for each risk factor and calculated a 10-year risk score. Models were developed for males and females separately. We tested the performance of our models using validation data and calculated discrimination and calibration statistics. The study included 198,835 (180,143 male with 11,976 outcomes and 90,466 female with 8,258 outcomes) patients. The 10-year predicted survival probabilities for females was 0.87 (0.87 to 0.87), whereas the observed survival estimates from the Kaplan-Meier curve for all female models was 0.87 (0.86 to 0.87). The predicted and observed survival estimates for males were 0.84 (0.84 to 0.84) and 0.84 (0.83 to 0.84) respectively. The Harrell's C-index of all female models and all male models were 0.71 and 0.69 respectively. We found that including time-varying repeated measures, only mildly improved CVD risk prediction for T2DM patients in comparison to the current practice standard. We advocate for further research using time-varying data to identify if the involvement of further covariates may improve the accuracy of currently accepted prediction models.