Risk of adverse events following the initiation of antihypertensives in older people with complex health needs: a self-controlled case series in the United Kingdom.

BACKGROUND: We assessed the risk of adverse events-severe acute kidney injury (AKI), falls and fractures-associated with use of antihypertensives in older patients with complex health needs (CHN). SETTING: UK primary care linked to inpatient and mortality records. METHODS: The source population comprised patients aged >65, with ≥1 year of registration and unexposed to antihypertensives in the year before study start. We identified three cohorts of patients with CHN, namely, unplanned hospitalisations, frailty (electronic frailty index deficit count ≥3) and polypharmacy (prescription of ≥10 medicines). Patients in any of these cohorts were included in the CHN cohort. We conducted self-controlled case series for each cohort and outcome (AKI, falls, fractures). Incidence rate ratios (IRRs) were estimated by dividing event rates (i) during overall antihypertensive exposed patient-time over unexposed patient-time; and (ii) in the first 30 days after treatment initiation over unexposed patient-time. RESULTS: Among 42,483 patients in the CHN cohort, 7,240, 5,164 and 450 individuals had falls, fractures or AKI, respectively. We observed an increased risk for AKI associated with exposure to antihypertensives across all cohorts (CHN: IRR 2.36 [95% CI: 1.68-3.31]). In the 30 days post-antihypertensive treatment initiation, a 35-50% increased risk for falls was found across all cohorts and increased fracture risk in the frailty cohort (IRR 1.38 [1.03-1.84]). No increased risk for falls/fractures was associated with continuation of antihypertensive treatment or overall use. CONCLUSION: Treatment with antihypertensives in older patients was associated with increased risk of AKI and transiently elevated risk of falls in the 30 days after starting antihypertensive therapy.

Characterising complex health needs and the use of preventive therapies in the older population: a population-based cohort analysis of UK primary care and hospital linked data.

BACKGROUND: While several definitions exist for multimorbidity, frailty or polypharmacy, it is yet unclear to what extent single healthcare markers capture the complexity of health-related needs in older people in the community. We aimed to identify and characterise older people with complex health needs based on healthcare resource use (unplanned hospitalisations or polypharmacy) or frailty using large population-based linked records. METHODS: In this cohort study, data was extracted from UK primary care records (CPRD GOLD), with linked Hospital Episode Statistics inpatient data. People aged > 65 on 1st January 2010, registered in CPRD for ≥ 1 year were included. We identified complex health needs as the top quintile of unplanned hospitalisations, number of prescribed medicines, and electronic frailty index. We characterised all three cohorts, and quantified point-prevalence and incidence rates of preventive medicines use. RESULTS: Overall, 90,597, 110,225 and 116,076 individuals were included in the hospitalisation, frailty, and polypharmacy cohorts respectively; 28,259 (5.9%) were in all three cohorts, while 277,332 (58.3%) were not in any (background population). Frailty and polypharmacy cohorts had the highest bi-directional overlap. Most comorbidities such as diabetes and chronic kidney disease were more common in the frailty and polypharmacy cohorts compared to the hospitalisation cohort. Generally, prevalence of preventive medicines use was highest in the polypharmacy cohort compared to the other two cohorts: For instance, one-year point-prevalence of statins was 64.2% in the polypharmacy cohort vs. 60.5% in the frailty cohort. CONCLUSIONS: Three distinct groups of older people with complex health needs were identified. Compared to the hospitalisation cohort, frailty and polypharmacy cohorts had more comorbidities and higher preventive therapies use. Research is needed into the benefit-risk of different definitions of complex health needs and use of preventive therapies in the older population.

Association between outpatient follow-up and incidence of revision after knee and hip replacements: a population-based cohort study.

BACKGROUND: Follow-up visits 5 or 7 years after surgery were recommended for people having primary hip or knee replacement. The benefits of this practice to patients and the healthcare system, however, have not yet been specifically examined. The aim of this study was to investigate the association between long-term follow-up outpatient hospital visits and revision rates for patients who undergo primary knee or hip replacement surgery. METHODS: Cohorts were identified for patients undergoing knee or hip replacement surgery using medical records from primary care practices within the UK Clinical Practice Research Datalink (CPRD) GOLD dataset linked to hospital records from the English Hospital Episodes Statistics (HES) data. Two groups of patients were compared in terms of revision and mortality rates: those with at least one long-term (between five and 10 years since primary surgery) follow-up visit at the orthopaedic department ('Follow-up' group), and those without ('No follow-up' group). RESULTS: A total of 9856 (4349 in the Follow-up group) patients with knee replacement and 10,837 (4870 in the Follow-up group) with hip replacement were included in the analysis. For knee replacement, the incidence of revision was 3.6% for those followed-up and 0.6% for those not followed-up. An adjusted regression model confirmed the difference in the hazard ratio (HR) for revision was statistically significant (HR: 5.65 [95% CI 3.62 to 8.81]). Mortality at 4 years was lower for the Follow-up (17%) compared to the No follow-up group (21%), but this difference was not statistically significant (HR: 0.95 [0.84 to 1.07]). For hip replacement, the incidence of revision rates were 3.2 and 1.4% for the follow-up and not follow-up groups, respectively, the difference being statistically significant (HR: 2.34 [1.71 to 3.20]). Mortality was lower for the Follow-up (15%) compared to the No follow-up group (21%), but the difference was not statistically significant (HR: 0.91 [0.81 to 1.02]). CONCLUSION: Patients attending follow-up orthopaedic consultations show a higher risk of revision surgery compared to those who are not followed-up. A cause for this difference could not be identified in this study but a likely explanation is that surgeons play an effective role as ultimate arbitrators when identifying patients to be included in long-term follow-up lists.

One- and 2-year incidence of osteoporotic fracture: a multi-cohort observational study using routinely collected real-world data.

We estimated and characterized the imminent fracture risk (1-2 years) of high-risk fracture patients through a multinational (UK, Spain, Denmark) cohort study. Older individuals with newly diagnosed osteoporosis and individuals who had a fracture while on treatment with a bisphosphonate were at a high risk of imminent fracture. PURPOSE: To characterize and estimate 1- to 2-year fracture risk in high-risk fracture patients. METHODS: Multi-cohort study in (database/study period) UK (CPRD/1995-2017), Spain (SIDIAP/2006-2016) and Denmark (DHR/1995-2016) including individuals ≥ 50 years old in NDO (newly diagnosed osteoporosis), OFx (incident osteoporotic fracture), BP (incident oral bisphosphonates use) or FWOT (fracture while on treatment with bisphosphonates). Outcomes (ICD-10/READ): hip, clinical spine, non-hip, non-spine and hip/humerus/distal forearm fracture. FOLLOW-UP: from cohort entry until death, migration/transfer or end of the study. STATISTICS: baseline characteristics and incidence rate (IR per 1000 persons). RESULTS (1-YEAR IR): NDO included 69,899 (UK), 37,901 (Spain) and 158,191 (Denmark) individuals. Spanish-IR was lowest for hip (4.7), clinical spine (2.5) and major osteoporotic fracture (MOF) (17.3) and highest in Denmark (74.2, 26.0 and 120.1, respectively). OFx included 83,514 (UK), 51,044 (Spain) and 509,551 (Denmark) individuals. IR in Denmark was highest for hip (24.1) and MOF (47.2), in Spain was highest for the clinical spine (9.4) and lowest for hip (9.5) and in the UK was lowest for the clinical spine (2.8) and MOF (20.7). BP included 148,507 (UK), 52,037 (Spain) and 204,010 (Denmark) individuals. Spanish-IR was lowest for hip (5.0) and MOF (21.1) and highest in Denmark (20.3 and 48.6, respectively). FWOT included 28,930 (UK), 1,865 (Spain) and 31,882 (Denmark) individuals. Clinical spine-IR was highest for Spain (12.0). Hip-IR was lowest for Spain (7.6) and highest for Denmark (33.6). Comparing young subjects, those who have FWOT started with an increased fracture rate. CONCLUSION: OFx and FWOT individuals experience higher re-fracture incidence rates than those with osteoporosis with or without treatment.

Primary care consultations and pain medicine prescriptions: a comparison between patients with and without chronic pain after total knee replacement.

BACKGROUND: Approximately 20% of patients experience chronic pain after total knee replacement (TKR). The impact of chronic pain after TKR on primary care services in the UK is currently unknown. The aim of this study was to compare primary care consultations and pain medicine prescriptions between patients with and without chronic pain after TKR. METHODS: Data from 5,055 patients who received TKR between 2009 and 2016 with anonymised linked data from the Clinical Practice Research Datalink Gold (CPRD) and English Hospital Episode Statistics (HES) Patient Reported Outcome Measures (PROMs) programme were analysed. The exposure time was from 10 years pre-operative to eight years post-operative. Patients with a score ≤ 14 on the Oxford Knee Score pain component scale at 6 months post-operative were classified as having chronic pain after TKR. Primary care consultations and prescribed pain medicines were quantified, and costs calculated based on national cost data. RESULTS: 721 patients (14%) had chronic pain after TKR. The prevalence and costs of primary care consultations and pain medicine prescriptions per year were consistently higher for patients with chronic pain after TKR compared with those without chronic pain after TKR; these differences were observed both before and after surgery. There was a substantial and sustained increase in the cost of opioid prescriptions after surgery for patients with chronic pain after TKR, peaking at seven years post-operative. CONCLUSIONS: Increased primary care consultations and pain medicine prescriptions associated with chronic pain after TKR represent a considerable financial cost to primary care services. Evaluation of interventions to reduce the risk of developing this pain condition and improve the early management of pain after TKR are needed to improve outcomes for patients and reduce costs to healthcare services.

Higher prevalence of non-skeletal comorbidity related to X-linked hypophosphataemia: a UK parallel cohort study using CPRD.

OBJECTIVES: X-Linked hypophosphataemic rickets (XLH) is a rare multi-systemic disease of mineral homeostasis that has a prominent skeletal phenotype. The aim of this study was to describe additional comorbidities in XLH patients compared with general population controls. METHODS: The Clinical Practice Research Datalink (CPRD) GOLD was used to identify a cohort of XLH patients (1995-2016), along with a non-XLH cohort matched (1 : 4) on age, sex and GP practice. Using the CALIBER portal, phenotyping algorithms were used to identify the first diagnosis (and associated age) of 273 comorbid conditions during patient follow-up. Fifteen major disease categories were used and the proportion of patients having ≥1 diagnosis was compared between cohorts for each category and condition. Main analyses were repeated according to the Index of Multiple Deprivation (IMD). RESULTS: There were 64 and 256 patients in the XLH and non-XLH cohorts, respectively. There was increased prevalence of endocrine [OR 3.46 (95% CI: 1.44, 8.31)] and neurological [OR 3.01 (95% CI: 1.41, 6.44)] disorders among XLH patients. Across all specific comorbidities, four were at least twice as likely to be present in XLH cases, but only depression met the Bonferroni threshold: OR 2.95 (95% CI: 1.47, 5.92). Distribution of IMD among XLH cases indicated greater deprivation than the general population. CONCLUSION: We describe a higher risk of mental illness in XLH patients compared with matched controls, and greater than expected deprivation. These findings may have implications for clinical practice guidelines and decisions around health and social care provision for these patients.

Atopic eczema and fracture risk in adults: A population-based cohort study.

BACKGROUND: Limited evidence suggests increased fracture risk in people with atopic eczema. Any link could have substantial effect; atopic eczema is common, and fractures have associated morbidity and mortality. OBJECTIVE: We sought to examine whether atopic eczema is associated with fracture and whether fracture risk varies with eczema severity. METHODS: We performed a matched cohort study set in primary care (Clinical Practice Research Datalink GOLD 1998-2016) and linked hospital admissions data (Hospital Episode Statistics), including adults (≥18 years old) with atopic eczema matched (by age, sex, general practice, and cohort entry date) with up to 5 individuals without eczema. We estimated hazard ratios (HRs) from stratified Cox regression comparing risk of major osteoporotic (hip, pelvis, spine, wrist, and proximal humerus) fractures individually and any fracture in those with and without atopic eczema. RESULTS: We identified 526,808 people with atopic eczema and 2,569,030 people without atopic eczema. Those with eczema had increased risk of hip (HR, 1.10; 99% CI, 1.06-1.14), pelvic (HR, 1.10; 99% CI, 1.02-1.19), spinal (HR, 1.18; 99% CI, 1.10-1.27), and wrist (HR, 1.07; 99% CI, 1.03,-1.11) fractures. We found no evidence of increased proximal humeral (HR, 1.06; 99% CI, 0.97-1.15) fracture risk. Fracture risk increased with increasing eczema severity, with the strongest associations in people with severe eczema (compared with those without) for spinal (HR, 2.09; 99% CI, 1.66-2.65), pelvic (HR, 1.66; 99% CI, 1.26-2.20), and hip (HR, 1.50; 99% CI, 1.30-1.74) fractures. Associations persisted after oral glucocorticoid adjustment. CONCLUSIONS: People with atopic eczema have increased fracture risk, particularly major osteoporotic fractures.

Association of Tramadol vs Codeine Prescription Dispensation With Mortality and Other Adverse Clinical Outcomes.

Importance: Although tramadol is increasingly used to manage chronic noncancer pain, few safety studies have compared it with other opioids. Objective: To assess the associations of tramadol, compared with codeine, with mortality and other adverse clinical outcomes as used in outpatient settings. Design, Setting, and Participants: Retrospective, population-based, propensity score-matched cohort study using a primary care database with routinely collected medical records and pharmacy dispensations covering more than 80% of the population of Catalonia, Spain (≈6 million people). Patients 18 years or older with 1 or more year of available data and dispensation of tramadol or codeine (2007-2017) were included and followed up to December 31, 2017. Exposures: New prescription dispensation of tramadol or codeine (no dispensation in the previous year). Main Outcomes and Measures: Outcomes studied were all-cause mortality, cardiovascular events, fractures, constipation, delirium, falls, opioid abuse/dependence, and sleep disorders within 1 year after the first dispensation. Absolute rate differences (ARDs) and hazard ratios (HRs) with 95% confidence intervals were calculated using cause-specific Cox models. Results: Of the 1 093 064 patients with a tramadol or codeine dispensation during the study period (326 921 for tramadol, 762 492 for codeine, 3651 for both drugs concomitantly), a total of 368 960 patients (184 480 propensity score-matched pairs) were included after study exclusions and propensity score matching (mean age, 53.1 [SD, 16.1] years; 57.3% women). Compared with codeine, tramadol dispensation was significantly associated with a higher risk of all-cause mortality (incidence, 13.00 vs 5.61 per 1000 person-years; HR, 2.31 [95% CI, 2.08-2.56]; ARD, 7.37 [95% CI, 6.09-8.78] per 1000 person-years), cardiovascular events (incidence, 10.03 vs 8.67 per 1000 person-years; HR, 1.15 [95% CI, 1.05-1.27]; ARD, 1.36 [95% CI, 0.45-2.36] per 1000 person-years), and fractures (incidence, 12.26 vs 8.13 per 1000 person-years; HR, 1.50 [95% CI, 1.37-1.65]; ARD, 4.10 [95% CI, 3.02-5.29] per 1000 person-years). No significant difference was observed for the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders. Conclusions and Relevance: In this population-based cohort study, a new prescription dispensation of tramadol, compared with codeine, was significantly associated with a higher risk of subsequent all-cause mortality, cardiovascular events, and fractures, but there was no significant difference in the risk of constipation, delirium, falls, opioid abuse/dependence, or sleep disorders. The findings should be interpreted cautiously, given the potential for residual confounding.

Coding algorithms for defining Charlson and Elixhauser co-morbidities in Read-coded databases.

BACKGROUND: Comorbidity measures, such as the Charlson Comorbidity Index (CCI) and Elixhauser Method (EM), are frequently used for risk-adjustment by healthcare researchers. This study sought to create CCI and EM lists of Read codes, which are standard terminology used in some large primary care databases. It also aimed to describe and compare the predictive properties of the CCI and EM amongst patients with hip fracture (and matched controls) in a large primary care administrative dataset. METHODS: Two researchers independently screened 111,929 individual Read codes to populate the 17 CCI and 31 EM comorbidity categories. Patients with hip fractures were identified (together with age- and sex-matched controls) from UK primary care practices participating in the Clinical Practice Research Datalink (CPRD). The predictive properties of both comorbidity measures were explored in hip fracture and control populations using logistic regression models fitted with 30- and 365-day mortality as the dependent variables together with tests of equality for Receiver Operating Characteristic (ROC) curves. RESULTS: There were 5832 CCI and 7156 EM comorbidity codes. The EM improved the ability of a logistic regression model (using age and sex as covariables) to predict 30-day mortality (AUROC 0.744 versus 0.686). The EM alone also outperformed the CCI (0.696 versus 0.601). Capturing comorbidities over a prolonged period only modestly improved the predictive value of either index: EM 1-year look-back 0.645 versus 5-year 0.676 versus complete record 0.695 and CCI 0.574 versus 0.591 versus 0.605. CONCLUSIONS: The comorbidity code lists may be used by future researchers to calculate CCI and EM using records from Read coded databases. The EM is preferable to the CCI but only marginal gains should be expected from incorporating comorbidities over a period longer than 1 year.

Increased Risk of Musculoskeletal Disorders and Mental Health Problems in Retired Professional Jockeys: A Cross-Sectional Study.

To examine the prevalence of chronic disease and mental health problems in retired professional, male jockeys compared to an age-matched reference population. A cross-sectional study comparing data from a cohort of retired professional jockeys with an age-matched general population sample. Male participants (age range: 50-89 years old) were used to compare health outcomes of self-reported physician-diagnosed conditions: heart disease, stroke, diabetes, hypertension, osteoporosis, osteoarthritis, depression and anxiety between study populations. Conditional logistic regression models were used to estimate associations between study groups and health outcome. In total, 810 participants (135 retired professional male jockeys and 675 participants from the reference population) were included, with an average age of 64.7±9.9 years old. Increased odds of having osteoporosis (OR=6.5, 95%CI 2.1-20.5), osteoarthritis (OR=7.5, 95%CI 4.6-12.2), anxiety (OR=2.8, 95%CI 1.3-5.9) and depression (OR=2.6, 95%CI 1.3-5.7) were seen in the retired professional jockeys. No differences were found for the remaining health outcomes. Retired professional jockeys had increased odds of musculoskeletal disease and mental health problems compared to the general population. Understanding the prevalence of chronic disease and mental health problems in retired professional jockeys will help inform screening and intervention strategies for jockeys.

The effect of smoking on outcomes following primary total hip and knee arthroplasty: a population-based cohort study of 117,024 patients.

Background and purpose - Smoking is a modifiable risk factor that may adversely affect postoperative outcomes. Healthcare providers are increasingly denying smokers access to total hip and knee arthroplasty (THA and TKA) until they stop smoking. Evidence supporting this is unclear. We assessed the effect of smoking on outcomes following arthroplasty.Patients and methods - We identified THAs and TKAs from the Clinical Practice Research Datalink, which were linked with datasets from Hospital Episode Statistics and the Office for National Statistics to identify outcomes. The effect of smoking on postoperative outcomes (complications, medications, revision, mortality, patient-reported outcome measures [PROMs]) was assessed using adjusted regression models.Results - We studied 60,812 THAs and 56,212 TKAs (11% smokers, 33% ex-smokers, 57% non-smokers). Following THA, smokers had an increased risk of lower respiratory tract infection (LRTI) and myocardial infarction compared with non-smokers and ex-smokers. Following TKA, smokers had an increased risk of LRTI compared with non-smokers. Compared with non-smokers (THA relative risk ratio [RRR] = 0.65; 95% CI = 0.61-0.69; TKA RRR = 0.82; CI = 0.78-0.86) and ex-smokers (THR RRR = 0.90; CI = 0.84-0.95), smokers had increased opioid usage 1-year postoperatively. Similar patterns were observed for weak opioids, paracetamol, and gabapentinoids. 1-year mortality rates were higher in smokers compared with non-smokers (THA hazard ratio [HR] = 0.37, CI = 0.29-0.49; TKA HR = 0.52, CI = 0.34-0.81) and ex-smokers (THA HR = 0.53, CI = 0.40-0.70). Long-term revision rates were not increased in smokers. Smokers had improvement in PROMs compared with preoperatively, with no clinically important difference in postoperative PROMs between smokers, non-smokers, and ex-smokers.Interpretation - Smoking is associated with more medical complications, higher analgesia usage, and increased mortality following arthroplasty. Most adverse outcomes were reduced in ex-smokers, therefore smoking cessation should be encouraged before arthroplasty.

Evaluating Patients' Expectations From a Novel Patient-Centered Perspective Predicts Knee Arthroplasty Outcome.

BACKGROUND: One-in-five patients are dissatisfied following knee arthroplasty and <50% have fulfilled expectations. The relationship between knee-arthroplasty expectations and surgical outcome remains unclear. PURPOSE: Are expectations regarding the impact of pain on postoperative life predictive of one-year outcome? Does the impact of pain on preoperative quality of life (QOL) influence this relationship? METHODS: Longitudinal cohort of 1044 uni-compartmental (43%) or total knee-arthroplasty (57%) (UKA or TKA) patients, aged mean 69 ± 9 years. Preoperatively, patients reported the impact of pain on QOL and expected impact of pain on life one-year post-arthroplasty. One-year postoperative outcomes: non-return to desired activity, surgical dissatisfaction, not achieving Oxford Knee Score minimal important change (OKS

Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial.

BACKGROUND: For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS: In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS: Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79­1·02] during years 5­9 and 0·75 [0·62­0·90] in later years; breast cancer mortality RR 0·97 [0·79­1·18] during years 5­9 and 0·71 [0·58­0·88] in later years). The cumulative risk of recurrence during years 5­14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5­14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89­1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13­3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83­1·36), ischaemic heart disease 0·76 (0·60­0·95, p=0·02), and endometrial cancer 1·74 (1·30­2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5­14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION: For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING: Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.

Observational methods for COVID-19 vaccine effectiveness research: an empirical evaluation and target trial emulation.

BACKGROUND: There are scarce data on best practices to control for confounding in observational studies assessing vaccine effectiveness to prevent COVID-19. We compared the performance of three well-established methods [overlap weighting, inverse probability treatment weighting and propensity score (PS) matching] to minimize confounding when comparing vaccinated and unvaccinated people. Subsequently, we conducted a target trial emulation to study the ability of these methods to replicate COVID-19 vaccine trials. METHODS: We included all individuals aged ≥75 from primary care records from the UK [Clinical Practice Research Datalink (CPRD) AURUM], who were not infected with or vaccinated against SARS-CoV-2 as of 4 January 2021. Vaccination status was then defined based on first COVID-19 vaccine dose exposure between 4 January 2021 and 28 January 2021. Lasso regression was used to calculate PS. Location, age, prior observation time, regional vaccination rates, testing effort and COVID-19 incidence rates at index date were forced into the PS. Following PS weighting and matching, the three methods were compared for remaining covariate imbalance and residual confounding. Last, a target trial emulation comparing COVID-19 at 3 and 12 weeks after first vaccine dose vs unvaccinated was conducted. RESULTS: Vaccinated and unvaccinated cohorts comprised 583 813 and 332 315 individuals for weighting, respectively, and 459 000 individuals in the matched cohorts. Overlap weighting performed best in terms of minimizing confounding and systematic error. Overlap weighting successfully replicated estimates from clinical trials for vaccine effectiveness for ChAdOx1 (57%) and BNT162b2 (75%) at 12 weeks. CONCLUSION: Overlap weighting performed best in our setting. Our results based on overlap weighting replicate previous pivotal trials for the two first COVID-19 vaccines approved in Europe.

Longitudinal trajectories of frailty are associated with short-term mortality in older people: a joint latent class models analysis using 2 UK primary care databases.

OBJECTIVES: Frailty is a dynamic health state that changes over time. Our hypothesis was that there are identifiable subgroups of the older population that have specific patterns of deterioration. The objective of this study was to evaluate the application of joint latent class model in identifying trajectories of frailty progression over time and their group-specific risk of death in older people. STUDY DESIGN AND SETTING: The primary care records of UK patients, aged over 65 as of January 1, 2010, included in the Clinical Practice Research Datalink: GOLD and AURUM databases, were analyzed and linked to mortality data. The electronic frailty index (eFI) scores were calculated at baseline and annually in subsequent years (2010-2013). Joint latent class model was used to divide the population into clusters with different trajectories and associated mortality hazard ratios. The model was built in GOLD and validated in AURUM. RESULTS: Five trajectory clusters were identified and characterized based on baseline and speed of progression: low-slow, low-moderate, low-rapid, high-slow, and high-rapid. The high-rapid cluster had the highest average starting eFI score; 7.9, while the low-rapid cluster had the steepest rate of eFI progression; 1.7. Taking the low-slow cluster as reference, low-rapid and high-rapid had the highest hazard ratios: 3.73 (95% CI 3.71, 3.76) and 3.63 (3.57-3.69), respectively. Good validation was found in the AURUM population. CONCLUSION: Our research found that there are vulnerable subgroups of the older population who are currently frail or have rapid frailty progression. Such groups may be targeted for greater healthcare monitoring.

Trends in incidence, prevalence, and survival of breast cancer in the United Kingdom from 2000 to 2021.

Breast cancer is the most frequently diagnosed cancer in females globally. However, we know relatively little about trends in males. This study describes United Kingdom (UK) secular trends in breast cancer from 2000 to 2021 for both sexes. We describe a population-based cohort study using UK primary care Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases. There were 5,848,436 eligible females and 5,539,681 males aged 18+ years, with ≥ one year of prior data availability in the study period. We estimated crude breast cancer incidence rates (IR), prevalence and survival probability at one-, five- and 10-years after diagnosis using the Kaplan-Meier method. Analyses were further stratified by age. Crude IR of breast cancer from 2000 to 2021 was 194.4 per 100,000 person-years for females and 1.16 for males. Crude prevalence in 2021 was 2.1% for females and 0.009% for males. Both sexes have seen around a 2.5-fold increase in prevalence across time. Incidence increased with age for both sexes, peaking in females aged 60-69 years and males 90+ . There was a drop in incidence for females aged 70-79 years. From 2003-2019, incidence increased > twofold in younger females (aged 18-29: IR 2.12 in 2003 vs. 4.58 in 2018); decreased in females aged 50-69 years; and further declined from 2015 onwards in females aged 70-89 years. Survival probability for females after one-, five-, and ten-years after diagnosis was 95.1%, 80.2%, and 68.4%, and for males 92.9%, 69.0%, and 51.3%. Survival probability at one-year increased by 2.08% points, and survival at five years increased by 5.39% from 2000-2004 to 2015-2019 for females, particularly those aged 50-70 years. For males, there were no clear time-trends for short-term and long-term survival probability. Changes in incidence of breast cancer in females largely reflect the success of screening programmes, as rates rise and fall in synchronicity with ages of eligibility for such programmes. Overall survival from breast cancer for females has improved from 2000 to 2021, again reflecting the success of screening programmes, early diagnosis, and improvements in treatments. Male breast cancer patients have worse survival outcomes compared to females, highlighting the need to develop male-specific diagnosis and treatment strategies to improve long-term survival in line with females.

Collateral effects of the COVID-19 pandemic on endocrine treatments for breast and prostate cancer in the UK: a cohort study.

Background: The COVID-19 pandemic affected cancer screening, diagnosis and treatments. Many surgeries were substituted with bridging therapies during the initial lockdown, yet consideration of treatment side effects and their management was not a priority. Objectives: To examine how the changing social restrictions imposed by the pandemic affected incidence and trends of endocrine treatment prescriptions in newly diagnosed (incident) breast and prostate cancer patients and, secondarily, endocrine treatment-related outcomes (including bisphosphonate prescriptions, osteopenia and osteoporosis), in UK clinical practice from March 2020 to June 2022. Design: Population-based cohort study using UK primary care Clinical Practice Research Datalink GOLD database. Methods: There were 13,701 newly diagnosed breast cancer patients and 12,221 prostate cancer patients with ⩾1-year data availability since diagnosis between January 2017 and June 2022. Incidence rates (IR) and incidence rate ratios (IRR) were calculated across multiple time periods before and after lockdown to examine the impact of changing social restrictions on endocrine treatments and treatment-related outcomes, including osteopenia, osteoporosis and bisphosphonate prescriptions. Results: In breast cancer patients, aromatase inhibitor (AI) prescriptions increased during lockdown versus pre-pandemic [IRR: 1.22 (95% confidence interval (CI): 1.11-1.34)], followed by a decrease post-first lockdown [IRR: 0.79 (95% CI: 0.69-0.89)]. In prostate cancer patients, first-generation antiandrogen prescriptions increased versus pre-pandemic [IRR: 1.23 (95% CI: 1.08-1.4)]. For breast cancer patients on AIs, diagnoses of osteopenia, osteoporosis and bisphosphonate prescriptions were reduced across all lockdown periods versus pre-pandemic (IRR range: 0.31-0.62). Conclusion: During the first 2 years of the pandemic, newly diagnosed breast and prostate cancer patients were prescribed more endocrine treatments compared to pre-pandemic due to restrictions on hospital procedures replacing surgeries with bridging therapies. But breast cancer patients had fewer diagnoses of osteopenia and osteoporosis and bisphosphonate prescriptions. These patients should be followed up in the coming years for signs of bone thinning. Evidence of poorer management of treatment-related side effects will help assess resource allocation for patients at high risk for bone-related complications.

Effects of the COVID-19 pandemic on hormone treatments for breast and prostate cancer in the UK: implications for bone health The COVID-19 pandemic has had a big impact on health, going beyond just causing illness. One area it has influenced is how patients with breast cancer or prostate cancer are treated. Surgeries and radiotherapies were delayed from the first lockdown as hospitals reduced non-covid related procedures. Some patients with breast or prostate cancer were instead given some medications to help stop their cancers from growing until they were able to have surgery or radiotherapy. These medications (called endocrine treatments) have important side effects, such as conditions that affect the bones. Patients on these medications should be monitored by doctors for signs of bone thinning and should, in some cases, be given other medications to help stop this happening. This study used doctors' records from more than 5 million people to find out whether the pandemic affected the number of endocrine medications being prescribed in patients with breast or prostate cancer, and also looked at the number of these patients that were diagnosed with conditions that affect their bones and whether they were given medications that could protect their bone health. We found that during the first lockdown, patients with breast cancer or prostate cancer had more of some types of endocrine treatments compared to before the lockdown. However, they had fewer diagnoses of conditions related to bone health and fewer medications to protect their bones. It is possible that appointments and tests that are usually carried out to diagnose conditions relating to bone health were not performed in the months after the first lockdown, and so these conditions were underdiagnosed. The use of medications to protect their bones was also reduced, likely because this was not considered a priority during the pandemic. This highlights that such patients should be followed up in the coming years for signs of bone thinning, given the relatively poorer management of these side effects in these people after the pandemic.