Clinical Practice Research Datalink Research Articles

Foot and ankle problems in children and young people: a population-based cohort study.

The aim of this research was to describe the epidemiology, presentation and healthcare use in primary care for foot and ankle problems in children and young people (CYP) across England. We undertook a population-based cohort study using data from the Clinical Practice Research Datalink Aurum database, a database of anonymised electronic health records from general practices across England. Data was accessed for allCYP aged 0-18 years presenting to their general practitioner between January 2015 and December 2021 with a foot and/or ankle problem. Consultation rates were calculated and used to estimate numbers of consultations in an average practice. Hierarchical Poisson regression estimated relative rates of consultations across sociodemographic groups and logistic regression evaluated factors associated with repeat consultations. A total of 416,137 patients had 687,753 foot and ankle events, of which the majority were categorised as "musculoskeletal" (34%) and "unspecified pain" (21%). Rates peaked at 601 consultations per 10,000 patient-years among males aged 10-14 years in 2018. An average practice might observe 132 (95% CI 110 to 155) consultations annually. Odds for repeat consultations were higher among those with pre-existing diagnoses including juvenile arthritis (OR 1.73, 95% CI 1.48 to 2.03). Conclusions: Consultations for foot and ankleproblems were high among CYP, particularly males aged 10 to 14 years. These data can inform service provision to ensure CYP access appropriate health professionals for accurate diagnosis and treatment. What is Known: • Foot and ankle problems can have considerable impact on health-related quality of life in children and young people (CYP). • There is limited data describing the nature and frequency of foot and ankle problems in CYP. What is New: • Foot and ankle consultations were higher in English general practice among CYP aged 10 to 14 years compared to other age groups, and higher among males compared to females. • The high proportion of unspecified diagnoses and repeat consultations suggests there is need for greater integration between general practice and allied health professionals in community-based healthcare settings.

Dipeptidyl Peptidase-4 Inhibitors and the Risk of Gallbladder and Bile Duct Disease Among Patients with Type 2 Diabetes: A Population-Based Cohort Study.

The use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be associated with an increased risk of gallbladder and bile duct disease among patients with type 2 diabetes. We conducted a population-based cohort study using an active comparator, new-user design. We used data from the United Kingdom Clinical Practice Research Datalink to identify patients newly treated with either a DPP-4 inhibitor or sodium-glucose cotransporter-2 (SGLT-2) inhibitor between January 2013 and December 2020. We fitted Cox proportional hazards models with propensity score fine stratification weighting to estimate the hazard ratio (HR) and its 95% confidence interval (CI) for incident gallbladder and bile duct disease associated with DPP-4 inhibitors compared to SGLT-2 inhibitors. DPP-4 inhibitors were associated with a 46% increased risk of gallbladder and bile duct disease (4.3 vs. 3.0 events per 1000 person-years, HR 1.46, 95% CI 1.17-1.83). At 6 months and 1 year, 745 and 948 patients, respectively, would need to be treated with DPP-4 inhibitors for one patient to experience a gallbladder or bile duct disease. In this population-based cohort study, the use of DPP-4 inhibitors, when compared with SGLT-2 inhibitors, was associated with a moderately increased risk of gallbladder and bile duct disease among patients with type 2 diabetes. This outcome was still quite rare with a high number needed to harm at 6 months and 1 year.

Risk equations for prosthetic joint infections (PJIs) in UK: a retrospective study using the Clinical Practice Research Datalink (CPRD) AURUM and GOLD databases

BackgroundProsthetic joint infections (PJIs) are a serious negative outcome of arthroplasty with incidence of about 1%. Risk of PJI could depend on local treatment policies and guidelines; no UK-specific risk...

Accuracy of the recording of pneumonia events in English electronic healthcare record data in patients with chronic obstructive pulmonary disease

BackgroundIn primary care, identifying pneumonia events in people with chronic obstructive pulmonary disease (COPD) may be challenging due to similarities in symptoms with COPD exacerbations and lack of diagnostic testing. This study explored the accuracy of pneumonia diagnosis coded in primary care by comparing diagnosis in primary care with diagnosis in hospital.MethodsA study population of people with COPD in England was created using the Clinical Practice Research Datalink Aurum database linked with Hospital Episode Statistics inpatient data. Pneumonia codes only, and pneumonia code with associated clinical and/or treatment codes (chest x-ray, symptoms, antibiotics, sputum and blood culture) were used to determine pneumonia events in primary care. Events that were followed by hospitalisation within 7 days were used to estimate the positive predictive value (PPV) of pneumonia coding in primary care, using primary diagnosis of pneumonia in secondary care as the gold standard. The PPV of primary care recording of hospitalised pneumonia was also calculated.ResultsTwo hundred seventy-four thousand one hundred fifty-six COPD patients were eligible for inclusion, of whom 7,560 had an eligible pneumonia event in primary care diagnosed between 2015–2019 which was not ‘hospital-acquired’ and was diagnosed and entered on the same day. Of the 2,094 events which were followed by hospitalisation within 7 days, 1,208 had a primary diagnosis of pneumonia in hospital, representing a PPV of pneumonia coding in primary care of 57.7% (95% CI 55.6%-59.8%). Another 284 (13.6%) were diagnosed as a COPD exacerbation and 114 (5.4%) were diagnosed as another respiratory disease. Use of additional pneumonia clinical and treatment codes had a modest effect on the PPV but substantially lowered the number of events. Of the 33,603 eligible pneumonia events identified in secondary care, only 11,445 were recorded in primary care within 42 days, representing a sensitivity of 34.1% (95% CI 33.6%-34.6%).ConclusionsUse of primary care pneumonia codes and associated clinical and treatment codes to determine pneumonia is not recommended due to significant levels of misdiagnosis and many hospitalised events failing to be recorded in primary care.

Factors associated with non-fatal heart failure and atrial fibrillation or flutter within the first 30 days post COPD exacerbation: a nested case-control study

BackgroundAn immediate, temporal risk of heart failure and arrhythmias after a Chronic Obstructive Pulmonary Disease (COPD) exacerbation has been demonstrated, particularly in the first month post-exacerbation. However, the clinical profile of patients who develop heart failure (HF) or atrial fibrillation/flutter (AF) following exacerbation is unclear. Therefore we examined factors associated with people being hospitalized for HF or AF, respectively, following a COPD exacerbation.MethodsWe conducted two nested case-control studies, using primary care electronic healthcare records from the Clinical Practice Research Datalink Aurum linked to Hospital Episode Statistics, Office for National Statistics for mortality, and socioeconomic data (2014-2020). Cases had hospitalization for HF or AF within 30 days of a COPD exacerbation, with controls matched by GP practice (HF 2:1;AF 3:1). We used conditional logistic regression to explore demographic and clinical factors associated with HF and AF hospitalization.ResultsOdds of HF hospitalization (1,569 cases, 3,138 controls) increased with age, type II diabetes, obesity, HF and arrhythmia history, exacerbation severity (hospitalization), most cardiovascular medications, GOLD airflow obstruction, MRC dyspnea score, and chronic kidney disease. Strongest associations were for severe exacerbations (adjusted odds ratio (aOR)=6.25, 95%CI 5.10-7.66), prior HF (aOR=2.57, 95%CI 1.73-3.83), age≥80 years (aOR=2.41, 95%CI 1.88-3.09), and prior diuretics prescription (aOR=2.81, 95%CI 2.29-3.45).Odds of AF hospitalization (841 cases, 2,523 controls) increased with age, male sex, severe exacerbation, arrhythmia and pulmonary hypertension history and most cardiovascular medications. Strongest associations were for severe exacerbations (aOR=5.78, 95%CI 4.45-7.50), age≥80 years (aOR=3.15, 95%CI 2.26-4.40), arrhythmia (aOR=3.55, 95%CI 2.53-4.98), pulmonary hypertension (aOR=3.05, 95%CI 1.21-7.68), and prescription of anticoagulants (aOR=3.81, 95%CI 2.57-5.64), positive inotropes (aOR=2.29, 95%CI 1.41-3.74) and anti-arrhythmic drugs (aOR=2.14, 95%CI 1.10-4.15).ConclusionsCardiopulmonary factors were associated with hospitalization for HF in the 30 days following a COPD exacerbation, while only cardiovascular-related factors and exacerbation severity were associated with AF hospitalization. Understanding factors will help target people for prevention.

Fluoroquinolones and the risk of severe hypoglycaemia among sulphonylurea users: Population-based cohort study.

Fluoroquinolone-related hypoglycaemia is rare but may become clinically relevant in individuals at high baseline hypoglycaemic risk, such as patients with diabetes using sulphonylureas. Our population-based cohort study assessed whether fluoroquinolones are associated with an increased risk of severe hypoglycaemia compared with amoxicillin among patients treated with sulphonylureas. Using the UK's Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data, we assembled a base cohort of patients who initiated second-generation sulphonylureas (1998-2020). The study cohort included patients initiating either fluoroquinolones or amoxicillin while on sulphonylureas. Using an intent-to-treat exposure definition, we assessed the 30-day risk of severe hypoglycaemia (hospitalization with or death because of hypoglycaemia) associated with fluoroquinolones compared with amoxicillin. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of severe hypoglycaemia after 1:5 matching on previous sulphonylurea use and propensity scores. Secondary analyses were stratified by demographics and glycated haemoglobin. Overall, 143 417 patients initiated fluoroquinolones (n = 13 123) or amoxicillin (n = 130 294) while on sulphonylureas. Compared with amoxicillin, fluoroquinolones were not associated with the risk of severe hypoglycaemia (HR, 1.17; 95% CI, 0.91-1.50). Fluoroquinolones were associated with an increased risk in patients <65 years (HR, 2.90; 95% CI, 1.41-5.97) but not in those ≥65 years (HR, 1.03; 95% CI, 0.79-1.35) in stratified analyses. There was no evidence of effect modification by sex or glycated haemoglobin. In patients using second-generation sulphonylureas, fluoroquinolones were not associated with an increased risk of severe hypoglycaemia compared with amoxicillin. An increased risk among younger adults is possible.

Risk factors for asthma-related hospital and intensive care admissions in children, adolescents and adults: a cohort study using primary and secondary care data

BackgroundAsthma remains a common cause of hospital admissions across the life course. We estimated the contribution of key risk factors to asthma-related hospital and intensive care unit (ICU) admissions in...

Incidence, prevalence and mortality of idiopathic pulmonary fibrosis in England from 2008 to 2018: a cohort study

BackgroundOwing to discrepancies in methodologies and how idiopathic pulmonary fibrosis (IPF) is diagnosed it is challenging to establish a consistent understanding of the disease burden In the UK, over 10...

Risk of bleeding amongst warfarin and direct oral anticoagulant users prescribed immediate antibiotics for respiratory tract infection: Cohort study.

Incidence of bleeding amongst warfarin and direct oral anticoagulant (DOAC) users is greater following a respiratory tract infection (RTI). It is unclear whether immediate antibiotics modify this association. We estimated the risk of bleeding amongst warfarin and DOAC users with RTI by antibiotic treatment. This retrospective cohort study used data from the Clinical Practice Research Datalink (CPRD) GOLD for adults in England prescribed warfarin or a DOAC, who sought primary care for an RTI between 1st January 2011 and 31st December 2019. Outcomes were major bleeding (hospital admission for intracranial or gastrointestinal bleeding), and non-major bleeding (hospital admission or General Practice consult for epistaxis, haemoptysis, or haematuria). Cox models derived hazard ratios (HRs) and 95% confidence intervals (CIs) for each outcome, adjusting for confounders using inverse probability of treatment weighting. Of 14 817 warfarin and DOAC users consulting for an RTI, 8768 (59%) were prescribed immediate antibiotics and 6049 (41%) were not. Approximately 49% were female, and median age was 76 years. Antibiotics were associated with reduced risk of major bleeding (adjusted HR 0.38, 95% CI 0.25 to 0.58). This was consistent across several sensitivity analyses. Antibiotics were also associated with a reduced risk of non-major bleeding (adjusted HR 0.78, 95% CI 0.61 to 0.99). Immediate antibiotics were associated with reduced risk of bleeding amongst warfarin and DOAC users with an RTI. Further work is needed to understand mechanisms and confirm whether a lower threshold for antibiotic use for RTI in this population may be beneficial.

Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events: population based cohort study

ObjectiveTo determine whether the combined use of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is associated with a decreased risk of major adverse cardiovascular events and serious...

P021 Uptake, safety, and effectiveness of pneumococcal vaccination in adults with immune mediated inflammatory diseases: a UK wide study using data from the Clinical Practice Research Datalink

Abstract Background/Aims The safety and effectiveness of pneumococcal vaccine in people with immune mediated inflammatory diseases (IMIDs) is not known, which may contribute to suboptimal uptake. We investigated UK wide pneumococcal vaccine uptake in adults with IMIDs, the association between pneumococcal vaccination and disease flares, and the effectiveness of pneumococcal vaccine in preventing pneumonia in this at-risk population. Methods Adults with incident rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and spondyloarthritis (SpA) prior to 31st August 2018 in the Clinical Practice Research Datalink (CPRD) Gold were included. The study was approved by CPRD research data governance (Reference 21_000614). We calculated the proportion of patients vaccinated against pneumococcal pneumonia. To investigate the association between vaccination and IMID flare, we employed a self-controlled case series analysis, adjusted for season. The study period was up-to six-month before and six-month after the date of pneumococcal vaccination. This period was partitioned into induction (14 days pre-vaccination) and exposed periods (up-to 90 days post vaccination) with the remaining time considered unexposed. Incidence rate ratios (IRR) and 95% CI were calculated. We conducted a multivariable nested case-control study to assess vaccine effectiveness. Cases were patients hospitalised with pneumonia and were matched to up to ten controls for age and sex. Multivariable conditional logistic regression was used to calculate odds ratio (OR) and 95% CI. Results We included 32,277 IMID patients: 14,151 with RA, 13,631 with IBD, 3,804 with SpA and 691 with SLE. Overall uptake of pneumococcal vaccination was 50% (95% CI 49.4% -50.5%). Vaccination uptake was significantly lower in the under 45-year-olds, in patients with IBD and in those without additional indication for vaccination at 29.7%, 38.4%, 42.7% respectively. In the safety study, data for 1001, 854, 424 vaccinated patients with primary care consultations for joint pain, AIRD flare, and IBD flare respectively were included. Vaccination against pneumococcal pneumonia was not associated with AIRD flare (IRR (95% CI) 1.07 (0.93-1.22)), primary care consultations for joint pain (IRR (95% CI) 0.95 (0.83-1.10)), and IBD flare (IRR (95% CI) 0.82 (0.64-1.06)) in the 90-days post vaccination. The vaccine effectiveness study included 25,707 patients, either with (n = 2,771) or without (n = 22,936) a hospitalisation record for pneumonia after IMID diagnosis. Patients hospitalised for pneumonia compared with their matched controls, had higher odds of current smoking, deprivation, corticosteroid prescriptions, additional indication for vaccination, primary care consultations, hospital admissions and prescriptions. In the multivariable adjusted model, pneumococcal vaccination was associated with reduced odds of hospitalisation for pneumonia (OR (95% CI) 0.88 (0.78-0.98). Conclusion The uptake of pneumococcal vaccine is low in IMID patients. Pneumococcal vaccination is not associated with IMID flare and is protective against pneumonia. These findings call for promotion of pneumococcal vaccination in IMID by health professionals. Disclosure G. Nakafero: None. M.J. Grainge: None. C.D. Mallen: Grants/research support; NIHR, MRC, Versus Arthritis and BMS. T. Card: None. J.S. Nguyen Van-Tam: Consultancies; CSL Seqirus and Moderna. Royalties; AstraZeneca and Sanofi Pasteur. A. Abhishek: Consultancies; NGM Bio, Limbic and Inflazome.. Royalties; UpToDate, Springer, Cadilla Pharmaceuticals.. Grants/research support; AstraZeneca and Oxford Immunotech..

P051 Trends in consultations for musculoskeletal pain in children and young people presenting to United Kingdom primary care: an electronic health record study

Abstract Background/Aims Musculoskeletal pain in childhood increases the risk of such pain in adulthood but there is an absence of management guidance for this group, not helped by a lack of evidence on the extent and nature of pain in children. The aim was to determine the extent and patterns of consultations for musculoskeletal pain in children and young people (CYP) presenting to UK primary care. Methods Data were obtained from an anonymised nationally representative UK primary care electronic health record database (Clinical Practice Research Datalink, CPRD). The study population was patients aged 8-18 years between 2005-2021 with consultations for musculoskeletal pain. Consultation prevalence was calculated per 10,000 registered population for each calendar year, and by age (8-11, 12-15 and 16-18 years), gender and body site (prevalence presented for 2019 prior to COVID-19 pandemic). Results 1.12 million children and young people (48% female; median age 14 years) were recorded with musculoskeletal pain, with an annual consultation prevalence of over 9% (932/10,000, 95% CI 928-937). Consultation prevalence increased until 2015, stabilised until 2019, and was lower during 2020 due to the COVID-19 pandemic, but climbed slightly in 2021. Consultation prevalence in 2019 was highest for those aged 12-15 years (1105/10,000 vs 8-11 years 736/10,000 and 16-18 years 984/10,000) and for females. Age and gender differences were observed by body site with foot/ankle the most common site of pain in younger children (ages 8-11: females 277/10,000, males 229/10,000,), back the most common site in older females (ages 16- 18: 247/10,000) and knee the most common site in older males (ages 16-18: 178/10,000). Conclusion Musculoskeletal pain in CYP is common with almost one in ten consulting primary care annually, but pain sites vary by age and gender. Understanding the extent and nature of musculoskeletal pain in CYP presenting to primary care can help inform targeted and effective care, and underpin much needed intervention studies, potentially reducing risk of continued pain into adulthood. Disclosure K.J. Mason: None. K.P. Jordan: None. J. Bailey: None. A. Jöud: None. S. Jowett: None. J. Protheroe: None. F. Mughal: None. K.I.E. Snell: None. M. Thomas: None. K.M. Dunn: None.

P100 Clinical Indications Associated with New Opioid Use for Pain Management in the United Kingdom: Using National Primary Care Data

Abstract Background/Aims Prescription opioids for non-cancer pain in the UK have increased over the past two decades, alongside associated harms. There is an increasing recognition that policies to address opioid prescribing need to be tailored according to individual patient needs with specific indications and disease systems. This study aimed to evaluate clinical indications associated with new opioid initiation in non-cancer pain using UK large-scale data. Methods National primary care electronic health records from 01/01/2006 to 31/20/2021 were used from the Clinical Research Practice Datalink. Codelists for opioid-related conditions based on literature and experts in pain management, primary care, rheumatology, and pharmacy were applied to a one-year period before first opioid prescription for surgical indications (given the acute nature) and five-years prior for chronic conditions. Descriptive statistics were used for data analysis, accounting for overlapping indications. Results A total of 3,031,950 new opioid users were identified. Opioids were initiated more commonly in women (60.7%), people in age groups: 45-64 (40.0%) and ≥65 years (37.0%). Nine systems associated with opioid-initiation were identified. The most common were musculoskeletal (74.0%), respiratory (53.1%), infections (25.7%), trauma/injury (16.1%), neurology (16.0%), gastrointestinal (4.2%) within five years prior to the opioid prescription date and post-surgical within one-year prior (3.8%). Musculoskeletal conditions most frequently associated with opioid use were osteoarthritis (n = 1,536,338, 50.7%), low back pain (1,094,163, 36.1%), other non-inflammatory musculoskeletal conditions 344,3412 (11.4%), rheumatoid arthritis 63,365 (2.1%) and fibromyalgia 56,038 (1.9%). Post-surgical indications were associated with 3.8% of all prescriptions, with orthopaedic surgeries being the most common: 42.1% of all post-surgical indications, including total knee replacements (n = 31,944; 27.6%) and total hip replacements (n = 17,863; 14.5%). Conclusion This is the first study in the UK evaluating large scale national data to assess indications associated with opioid initiation. Almost three quarters of the new prescriptions of opioids for non-cancer pain were in people with a diagnosis of a musculoskeletal condition. Orthopaedic surgeries contributed to a third of all post-surgical indications. These findings could help inform prioritisation of targeted interventions in opioid de-prescribing, clinical vigilance, and policy development to support non-pharmacological interventions in patients with musculoskeletal conditions. Disclosure M. Lyon: None. C. Ramirez Medina: None. E. Davies: None. M. Jani: None.

P177 The prevalence and incidence of psoriasis and psoriatic arthritis in England from 2009-2019: an observational study using primary care data

Abstract Background/Aims Psoriasis (PsO) and psoriatic arthritis (PsA) greatly impact quality of life and result in substantial personal and societal costs. Complete and up-to-date data on the prevalence and incidence of these conditions and whether these change over time and vary by age is important for healthcare service planning so that specialist care and funding can be appropriately allocated. Objective to determine the prevalence and incidence of PsO and PsA in males and females from 2009-2019 across all age groups in England. Methods We used Clinical Practice Research Datalink AURUM, a primary care electronic health record database, including 20% of the English population. The codes used to identify patients with PsO and PsA were selected by rheumatologists and dermatologists and cross-checked with published code lists from other studies. All included patients must have data for at least 1 year before their diagnosis. The annual incidence and point prevalence were calculated from 2009-2019 and stratified by age/sex. The study period ended in 2019 to avoid COVID-19 pandemic affecting results. Results The prevalence of PsO and PsA in males and females has increased annually, peaking in 2019 (PsO males 2.41% [95% confidence interval (CI) 2.40, 2.42]; PsO females 2.60% [95% CI 2.59-2.61]; PsA males 0.20% [95% CI 0.20-0.20]; PsA females 0.21% [95% CI 0.21- 0.22]), as illustrated in Table 1. In 2019, the prevalence of PsO and PsA was highest in the over 65 years age group; PsO 4.25% [95% CI 4.22-4.28] and PsA 0.38% [95% CI 0.37-0.38]. The annual incidence (per 100,000 person years) of PsO has gradually decreased in males (from 168 [164-171] in 2009 to 148 [145-151] in 2019) but in females it has been stable with a slight annual decrease (from 180 [177-184] in 2009 to 173 [170-176]) in 2019. The annual incidence for PsA has increased in both males and females; 13 (12-14) in 2009 and 15 (14-16) in 2019 for males and 12 (11-13) in 2009 and 18 (17-19) in 2019 for females. Conclusion The increasing prevalence of PsO and PsA highlights the importance of organising healthcare services to meet this need, particularly in the elderly population. Disclosure A. Vivekanantham: None. E. Burn: None. M. Pineda Moncusi: None. S. Khalid: None. D. Prieto Alhambra: Consultancies; DP-A’s research group has received consultancy or speaker fees from Astellas, Amgen, AstraZeneca, and UCB Biopharma. Grants/research support; DP-A’s research group has received research grants from the European Medicines Agency; the Innovative Medicines Initiative; and Amgen, Chiesi, and UCB Biopharma. L.C. Coates: Grants/research support; LCC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Novartis and Pfizer; worked as a paid consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene.

The long-term impact of vaginal surgical mesh devices on pain clinic and psychological service referrals, anti-inflammatory testing and pelvic scans in UK primary care: A cohort study with the Clinical Practice Research Datalink.

To examine long-term complications in women with stress urinary incontinence (SUI) and pelvic organ prolapse (POP), with and without surgical mesh implants. Longitudinal open cohort study from 1 April 2006 (or 1 April 2012) to 30 November 2018. The Clinical Practice Research Datalink (CPRD) Gold database, which is linked to Hospital Episodes Statistics (HES) inpatient data, the HES Diagnostic Imaging Dataset (DID), Office for National Statistics mortality data and Index of Multiple Deprivation socio-economic status data. Women aged ≥18 years with a diagnostic SUI/POP Read code. Rates are estimated using negative binomial regression. Rates of referrals for: psychological and pain services; urinalysis, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) testing; and pelvic ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) scans. A cohort of 220 544 women were eligible for inclusion; 74% (n = 162 687) had SUI, 37% (n = 82 123) had POP and 11% (n = 24 266) had both. Rates of psychological referrals and CT scans were lower in women with SUI mesh surgery, but this was offset by higher rates of CRP testing in women with SUI or POP mesh, MRI scans in women with SUI mesh, and urinalysis testing and referrals to pain clinics for women with POP mesh. Our results suggest a higher burden of morbidity in women with SUI/POP mesh surgery, and that these women may require ongoing follow-up in the primary care setting.

Prognostic factors for colchicine prophylaxis-related adverse events when initiating allopurinol for gout: retrospective cohort study.

Colchicine is commonly used to prevent flares when starting urate-lowering therapy for gout. Patients with gout are frequently concurrently prescribed other medications (such as statins) that may interact with colchicine, increasing the risk of adverse events. The aim of this study was to describe potential prognostic factors for adverse events in patients prescribed colchicine when initiating allopurinol. We conducted a retrospective cohort study in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with colchicine (01/04/1997-30/11/2016) were included. Potential prognostic factors were defined, and the likelihood of adverse events, including diarrhoea, nausea or vomiting, myocardial infarction (MI), neuropathy, myalgia, myopathy, rhabdomyolysis, and bone marrow suppression, were estimated. From 01/04/1997-30/11/2016, 13 945 people with gout initiated allopurinol with colchicine prophylaxis (mean age 63.9 (SD 14.7) years, 78.2% male). One quarter (26%, 95% CI 25% to 27%) were prescribed ≥1 potentially interacting medicines, most commonly statins (21%, 95% CI 20% to 22%). Statins were not associated with increased adverse events, although other drugs were associated with some adverse outcomes. Diarrhoea and MI were associated with more comorbidities and more severe CKD. People were given colchicine prophylaxis despite commonly having preexisting prescriptions for medications with potential to interact with colchicine. Adverse events were more common in people who had more comorbidities and certain potentially interacting medications. Our findings will provide much-needed information about prognostic factors for colchicine-related adverse events that can inform treatment decisions about prophylaxis when initiating allopurinol.

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

To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia. Population based matched cohort study. Linked primary care, hospital and mortality data from Clinical Practice Research Datalink (CPRD), England. 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. 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. 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%). 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.

Outcomes in patients treated with loop diuretics without a diagnosis of heart failure: a retrospective cohort study.

Loop diuretics are commonly prescribed in the community, not always to patients with a recorded diagnosis of heart failure (HF). The rate of HF events in patients prescribed loop diuretics without a diagnosis of HF is unknown. This was a propensity-matched cohort study using data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office of National Statistics in the UK. Patients prescribed a loop diuretic without a diagnosis of HF (loop diuretic group) between 1 January 2010 and 31 December 2015 were compared with patients with HF (HF group)-analysis A, and patients with risk factors for HF (either ischaemic heart disease, or diabetes and hypertension-at-risk group)-analysis B. The primary endpoint was an HF event (a composite of presentation with HF symptoms, HF hospitalisation, HF diagnosis (analysis B only) and all-cause mortality). From a total population of 180 384 patients (78 968 in the loop diuretic group, 28 177 in the HF group and 73 239 in the at-risk group), there were 59 694 patients, 22 352 patients and 57 219 patients in the loop diuretic, HF and at-risk groups, respectively, after exclusion criteria were applied. After propensity matching for age, sex and comorbidities, patients in the loop diuretic group had a similar rate of HF events as those in the HF group (71.9% vs 72.1%; HR=0.92 (95% CI 0.90 to 0.94); p<0.001), and twice as those in the at-risk group (59.2% vs 35.7%; HR=2.04 (95% CI 2.00 to 2.08); p<0.001). Patients prescribed a loop diuretic without a recorded diagnosis of HF experience HF events at a rate comparable with that of patients with a recorded diagnosis of HF; many of these patients may have undiagnosed HF.

Patterns and trends of medicinal poisoning substances: a population-based cohort study of injuries in 0–11 year old children from 1998–2018

BackgroundThere have been sharp increases in antidepressant and opioid prescriptions over the last 10 years, as well as increased over-the-counter medicine availability. However, the impact on childhood medicinal poisonings rates, particularly by socioeconomic deprivation is unclear. This study reports population level medicinal poisoning substance patterns in England among children aged 0–11 years, helping inform safety advice and poisoning prevention interventions.MethodsAn open cohort study of 1,489,620 0–11 year olds was conducted from 1998 to 2018, using the Clinical Practice Research Datalink, to examine inpatient hospital admissions for poisoning. Incidence rates and adjusted incidence rate ratios (aIRR) were calculated for poisoning substance groups by age, sex, socio-economic deprivation and year.Results3,685 medicinal poisoning hospital admissions were identified. The most common substances were paracetamol (33.2%), dependence/withdrawal risk drugs (DWRD - antidepressants, opioids, gabapentinoids, benzodiazepines) (13.5%) and other over-the-counter (OTC) analgesics/anti-common cold drugs (13.0%). Over the study period DWRD poisonings decreased 33% (aIRR 0.67, 95%CI 0.50–0.90 comparing 2013/14-2017/18 to 1998/99-2002/03), while paracetamol poisonings increased 43% (aIRR 1.43, 95%CI 1.20–1.70 for the same periods), with no change in incidence rates for other OTC drugs (aIRR 0.82, 95% CI 0.60–1.12) or all medications combined (aIRR 0.97, 95%CI 0.88–1.07). A gradient in poisonings by area-level socioeconomic deprivation was shown for all medications (aIRR 1.32, 95%CI 1.18–1.47 for most deprived compared to least deprived quintile), and DWRDs (aIRR 2.03, 95%CI 1.42–2.88 for 4th most deprived quintile and aIRR 1.88, 95%CI 1.32–2.66 for 5th most deprived quintile, compared to least deprived quintile), but not for paracetamol or other OTC drug poisonings.ConclusionsPoisonings from DWRDs decreased by 33%, while paracetamol poisonings increased by 43% during the study period. There was a gradient by area-level socioeconomic deprivation in prescribed medication poisonings, including drugs with withdrawal/dependence risk, but not OTC medication poisonings. Households in more socioeconomically deprived areas have the potential to benefit most from measures to improve safe storage of medicines and are likely to require targeted interventions providing education and safety equipment. In addition, universal promotion of the safe storage of OTC and prescribed medicines must be provided by prescribers, community pharmacies and other outlets of such medication.

Evaluating the comparability of osteoporosis treatments using propensity score and negative control outcome methods in UK and Denmark electronic health record databases.

Evidence on the comparative effectiveness of osteoporosis treatments is heterogeneous. This may be attributed to different populations and clinical practice, but also to differing methodologies ensuring comparability of treatment groups before treatment effect estimation and the amount of residual confounding by indication. This study assessed the comparability of denosumab vs oral bisphosphonate (OBP) groups using propensity score (PS) methods and negative control outcome (NCO) analysis. A total of 280 288 women aged ≥50years initiating denosumab or OBP in 2011-2018 were included from the UK Clinical Practice Research Datalink (CPRD) and the Danish National Registries (DNR). Balance of observed covariates was assessed using absolute standardised mean difference (ASMD) before and after PS weighting, matching, and stratification, with ASMD >0.1 indicating imbalance. Residual confounding was assessed using NCOs with ≥100 events. Hazard ratio (HR) and 95% confidence interval (CI) between treatment and NCO was estimated using Cox models. Presence of residual confounding was evaluated with two approaches1: >5% of NCOs with 95% CI excluding 1,2 >5% of NCOs with an upper CI <0.75 or lower CI >1.3. The number of imbalanced covariates before adjustment (CPRD 22/87; DNR 18/83) decreased, with 2-11% imbalance remaining after weighting, matching or stratification. Using approach 1, residual confounding was present for all PS methods in both databases (≥8% of NCOs), except for stratification in DNR (3.8%). Using approach 2, residual confounding was present in CPRD with PS matching (5.3%) and stratification (6.4%), but not with weighting (4.3%). Within DNR, no NCOs had HR estimates with upper or lower CI limits beyond the specified bounds indicating residual confounding for any PS method. Achievement of covariate balance and determination of residual bias were dependent upon several factors including the population under study, PS method, prevalence of NCO, and the threshold indicating residual confounding.