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 ≥50 years 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.

Treatment groups in clinical practice may not be comparable as patient characteristics differ according to the need for the prescribed medication, known as confounding. We assessed comparability of two common osteoporosis treatments, denosumab and oral bisphosphonate, in 280 288 postmenopausal women using electronic health records from UK Clinical Practice Research Datalink (CPRD) and Danish National Registries (DNR). We evaluated comparability of recorded patient characteristics with three propensity score (PS) methods, matching, stratification, and weighting. We assessed residual confounding from unrecorded patient characteristics via negative control outcomes (NCO), events known not to be associated with treatment such as delirium. We found that achieving comparability of osteoporosis treatment groups depended on the study population, PS method, and definition of residual confounding. Weighting and stratification performed the best in DNR and CPRD, respectively. Using a stricter threshold based on statistical significance for the NCO suggested the treatment groups were not comparable, except for PS stratification in DNR. Applying clinically significant thresholds of treatment effect size showed comparability using weighting in CPRD and all PS methods in DNR. Studies should consider more than one PS method to test robustness and identify the largest number of NCO to give the greatest flexibility in detecting residual confounding.

The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia.

BACKGROUND: Although vaccines have proved effective to prevent severe COVID-19, their effect on preventing long-term symptoms is not yet fully understood. We aimed to evaluate the overall effect of vaccination to prevent long COVID symptoms and assess comparative effectiveness of the most used vaccines (ChAdOx1 and BNT162b2). METHODS: We conducted a staggered cohort study using primary care records from the UK (Clinical Practice Research Datalink [CPRD] GOLD and AURUM), Catalonia, Spain (Information System for Research in Primary Care [SIDIAP]), and national health insurance claims from Estonia (CORIVA database). All adults who were registered for at least 180 days as of Jan 4, 2021 (the UK), Feb 20, 2021 (Spain), and Jan 28, 2021 (Estonia) comprised the source population. Vaccination status was used as a time-varying exposure, staggered by vaccine rollout period. Vaccinated people were further classified by vaccine brand according to their first dose received. The primary outcome definition of long COVID was defined as having at least one of 25 WHO-listed symptoms between 90 and 365 days after the date of a PCR-positive test or clinical diagnosis of COVID-19, with no history of that symptom 180 days before SARS-Cov-2 infection. Propensity score overlap weighting was applied separately for each cohort to minimise confounding. Sub-distribution hazard ratios (sHRs) were calculated to estimate vaccine effectiveness against long COVID, and empirically calibrated using negative control outcomes. Random effects meta-analyses across staggered cohorts were conducted to pool overall effect estimates. FINDINGS: A total of 1 618 395 (CPRD GOLD), 5 729 800 (CPRD AURUM), 2 744 821 (SIDIAP), and 77 603 (CORIVA) vaccinated people and 1 640 371 (CPRD GOLD), 5 860 564 (CPRD AURUM), 2 588 518 (SIDIAP), and 302 267 (CORIVA) unvaccinated people were included. Compared with unvaccinated people, overall HRs for long COVID symptoms in people vaccinated with a first dose of any COVID-19 vaccine were 0·54 (95% CI 0·44-0·67) in CPRD GOLD, 0·48 (0·34-0·68) in CPRD AURUM, 0·71 (0·55-0·91) in SIDIAP, and 0·59 (0·40-0·87) in CORIVA. A slightly stronger preventative effect was seen for the first dose of BNT162b2 than for ChAdOx1 (sHR 0·85 [0·60-1·20] in CPRD GOLD and 0·84 [0·74-0·94] in CPRD AURUM). INTERPRETATION: Vaccination against COVID-19 consistently reduced the risk of long COVID symptoms, which highlights the importance of vaccination to prevent persistent COVID-19 symptoms, particularly in adults. FUNDING: National Institute for Health and Care Research.

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.

An Evaluation of Different Strategies for Sampling Controls in an Online Case-Crossover Study of Acute Flares in Knee Osteoarthritis.

Objective: To evaluate bias and precision of exposure-outcome effect estimates from three control sampling strategies in a case-crossover study. Methods: Online case-crossover study investigating eight physical activity-related triggers for acute flares in knee osteoarthritis. Exposures were measured in hazard periods (≤24 hours before self-declared flare onset). Control period exposure was measured in three ways: (1) four scheduled questionnaires over 13-weeks, (2) "usual" physical activity levels ascertained at baseline, (3) over three days before flare onset. Derived odds ratios, 95% confidence intervals and standard errors were compared. Results: Of 744 participants (mean age 62.1 [SD 10.2] years; 61% female), 493 reported 714 flares. Selecting controls from scheduled questionnaires, independent of hazard periods, yielded predominantly odds ratios in the expected direction (exposure "a lot" versus exposure "not at all", range: 0.57-3.22). When controls were sampled at baseline (range: 0.01-1.42) or immediately before a flare (range: 0.30-1.27) most odds ratio estimates were inverted. Standard errors of the log odds ratios were smallest when controls were sampled from scheduled questionnaires (range: 0.264-0.473) compared to controls sampled at baseline (range: 0.267-0.589) or immediately before a flare (range: 0.319-0.621). Conclusion: Our findings are sensitive to control sample selection. Under certain conditions, different patterns could be attributed to over reporting and social desirability bias, where people may want to present themselves more positively about their "usual" physical activity levels, at baseline. Exposure measurement at the time of a flare may be less precise and more susceptible to recall bias due to systematically reporting exposures differently during a flare, compared to control measurement independent of flares.

Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.

AIMS: Most adults presenting in primary care with chest pain symptoms will not receive a diagnosis ('unattributed' chest pain) but are at increased risk of cardiovascular events. To assess within patients with unattributed chest pain, risk factors for cardiovascular events and whether those at greatest risk of cardiovascular disease can be ascertained by an existing general population risk prediction model or by development of a new model. METHODS AND RESULTS: The study used UK primary care electronic health records from the Clinical Practice Research Datalink linked to admitted hospitalizations. Study population was patients aged 18 plus with recorded unattributed chest pain 2002-2018. Cardiovascular risk prediction models were developed with external validation and comparison of performance to QRISK3, a general population risk prediction model. There were 374 917 patients with unattributed chest pain in the development data set. The strongest risk factors for cardiovascular disease included diabetes, atrial fibrillation, and hypertension. Risk was increased in males, patients of Asian ethnicity, those in more deprived areas, obese patients, and smokers. The final developed model had good predictive performance (external validation c-statistic 0.81, calibration slope 1.02). A model using a subset of key risk factors for cardiovascular disease gave nearly identical performance. QRISK3 underestimated cardiovascular risk. CONCLUSION: Patients presenting with unattributed chest pain are at increased risk of cardiovascular events. It is feasible to accurately estimate individual risk using routinely recorded information in the primary care record, focusing on a small number of risk factors. Patients at highest risk could be targeted for preventative measures.

It is known that patients with chest pain without a recognized cause are at increased risk of future cardiovascular events (for example, heart disease) and so this study aimed to find out whether those patients at greatest risk could be determined using information in their health records. It is possible to accurately estimate a person's risk of future cardiovascular events using the information entered into their health records, and this risk can be estimated using only a small number of factors.Patients at highest risk could now be targeted for management to help prevent future cardiovascular events.

Diabetes as a risk factor for the onset of frozen shoulder: a systematic review and meta-analysis.

OBJECTIVE: Summarise longitudinal observational studies to determine whether diabetes (types 1 and 2) is a risk factor for frozen shoulder. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase, AMED, PsycINFO, Web of Science Core Collection, CINAHL, Epistemonikos, Trip, PEDro, OpenGrey and The Grey Literature Report were searched on January 2019 and updated in June 2021. Reference screening and emailing professional contacts were also used. ELIGIBILITY CRITERIA: Longitudinal observational studies that estimated the association between diabetes and developing frozen shoulder. DATA EXTRACTION AND SYNTHESIS: Data extraction was completed by one reviewer and independently checked by another using a predefined extraction sheet. Risk of bias was judged using the Quality In Prognosis Studies tool. For studies providing sufficient data, random-effects meta-analysis was used to derive summary estimates of the association between diabetes and the onset of frozen shoulder. RESULTS: A meta-analysis of six case-control studies including 5388 people estimated the odds of developing frozen shoulder for people with diabetes to be 3.69 (95% CI 2.99 to 4.56) times the odds for people without diabetes. Two cohort studies were identified, both suggesting diabetes was associated with frozen shoulder, with HRs of 1.32 (95% CI 1.22 to 1.42) and 1.67 (95% CI 1.46 to 1.91). Risk of bias was judged as high in seven studies and moderate in one study. CONCLUSION: People with diabetes are more likely to develop frozen shoulder. Risk of unmeasured confounding was the main limitation of this systematic review. High-quality studies are needed to confirm the strength of, and understand reasons for, the association. PROSPERO REGISTRATION NUMBER: CRD42019122963.

The effectiveness of corticosteroid injection versus night splints for carpal tunnel syndrome: 24-month follow-up of a randomized trial.

OBJECTIVES: This follow-up study of the INSTinCTS (INjection vs SplinTing in Carpal Tunnel Syndrome) trial compared the effects of corticosteroid injection (CSI) and night splinting (NS) for the initial management of mild-to-moderate CTS on symptoms, resource use and carpal tunnel surgery, over 24 months. METHODS: Adults with mild-to-moderate CTS were randomized 1:1 to a local corticosteroid injection or a night splint worn for 6 weeks. Outcomes at 12 and 24 months included the Boston Carpal Tunnel Questionnaire (BCTQ), hand/wrist pain intensity numeric rating scale (NRS), the number of patients referred for and undergoing CTS surgery, and healthcare utilization. A cost-utility analysis was conducted. RESULTS: One hundred and sixteen participants received a CSI and 118 a NS. The response rate at 24 months was 73% in the CSI arm and 71% in the NS arm. By 24 months, a greater proportion of the CSI group had been referred for (28% vs 20%) and undergone (22% vs 16%) CTS surgery compared with the NS group. There were no statistically significant between-group differences in BCTQ score or pain NRS at 12 or 24 months. CSI was more costly [mean difference £68.59 (95% CI: -120.84, 291.24)] with fewer quality-adjusted life-years than NS over 24 months [mean difference -0.022 (95% CI: -0.093, 0.045)]. CONCLUSION: Over 24 months, surgical intervention rates were low in both groups, but less frequent in the NS group. While there were no differences in the clinical effectiveness of CSI and NS, initial treatment with CSI may not be cost-effective in the long-term compared with NS.

Identifying Long-Term Trajectories of Foot Pain Severity and Potential Prognostic Factors: A Population-Based Cohort Study.

OBJECTIVES: To identify distinct foot pain trajectories over 7 years and examine their associations with potential prognostic factors. METHODS: Adults ages ≥50 years and registered with 4 general practices in North Staffordshire, UK were mailed a baseline health survey. Those reporting current or recent foot pain were invited to attend a research assessment clinic. Follow-up was by repeated postal surveys at 18, 36, 54, and 84 months. Distinct trajectories of foot pain were explored using latent class growth analysis (LCGA). Subsequently, identified trajectories were combined into most and least progressive groups, and covariate-adjusted associations with a range of prognostic factors were examined. RESULTS: Of 560 adults with foot pain attending baseline research clinics, 425 (76%) provided data at baseline and 2 or more follow-up time points. LCGA for foot pain severity (0-10 numerical rating scale) identified a 4-trajectory model: "mild, improving" (37%); "moderate, improving" (33%); "moderate-severe, persistent" (24%); and "severe, persistent" (6%). Compared with individuals in more favorable (improving) pain trajectories, those in less favorable (persistent) pain trajectories were more likely to be obese, have routine/manual and intermediate occupations, have poorer physical and mental health, have catastrophizing beliefs, have greater foot-specific functional limitation, and have self-assessed hallux valgus at baseline. CONCLUSIONS: Four distinct trajectories of foot pain were identified over a 7-year period, with one-third of individuals classified as having pain that is persistently moderate-severe and severe in intensity. The effect of intervening to target modifiable prognostic factors such as obesity and hallux valgus on long-term outcomes in people with foot pain requires investigation.

Incidence and Progression of Hallux Valgus: A Prospective Cohort Study.

OBJECTIVE: Hallux valgus is a common and disabling condition. The objective of the present study was to identify factors associated with hallux valgus incidence and progression. METHODS: Participants were from a population-based prospective cohort study, the Clinical Assessment Study of the Foot. All adults ages ≥50 years who were registered at 4 general practices in North Staffordshire, UK, were invited to take part in a postal survey at baseline and at 7-year follow-up, which included health questionnaires and self-assessment of hallux valgus using line drawings. RESULTS: Complete baseline and follow-up data were available for 1,482 participants (739 women and 743 men, mean ± SD age 62.9 ± 8.1 years), of whom 450 (30.4%) had hallux valgus in at least 1 foot at baseline. Incident hallux valgus was identified in 207 (20.1%) participants (349 [15.4%] feet) and was associated with baseline age, poorer physical health, foot pain, and wearing shoes with a very narrow toe-box shape between the ages of 20 and 29 years. Hallux valgus progression was identified in 497 (33.6%) participants (719 [24.3%] feet) but was not associated with any baseline factors. CONCLUSION: Incident hallux valgus develops in 1 in 5 adults ages ≥50 years over a 7-year period and is related to age, poorer physical health, foot pain, and previous use of constrictive footwear. Progression occurs in 1 in 3 adults. These findings suggest that changes in first metatarsophalangeal joint alignment may still occur beyond the age of 50 years.

Long-Term Cardiovascular Risk and Management of Patients Recorded in Primary Care With Unattributed Chest Pain: An Electronic Health Record Study.

Background Most adults presenting with chest pain will not receive a diagnosis and be recorded with unattributed chest pain. The objective was to assess if they have increased risk of cardiovascular disease compared with those with noncoronary chest pain and determine whether investigations and interventions are targeted at those at highest risk. Methods and Results We used records from general practices in England linked to hospitalization and mortality information. The study population included patients aged 18 years or over with a new record of chest pain with a noncoronary cause or unattributed between 2002 and 2018, and no cardiovascular disease recorded up to 6 months (diagnostic window) afterward. We compared risk of a future cardiovascular event by type of chest pain, adjusting for cardiovascular risk factors and alternative explanations for chest pain. We determined prevalence of cardiac diagnostic investigations and preventative medication during the diagnostic window in patients with estimated cardiovascular risk ≥10%. There were 375 240 patients with unattributed chest pain (245 329 noncoronary chest pain). There was an increased risk of cardiovascular events for patients with unattributed chest pain, highest in the first year (hazard ratio, 1.25 [95% CI, 1.21-1.29]), persistent up to 10 years. Patients with unattributed chest pain had consistently increased risk of myocardial infarction over time but no increased risk of stroke. Thirty percent of patients at higher risk were prescribed lipid-lowering medication. Conclusions Patients presenting to primary care with unattributed chest pain are at increased risk of cardiovascular events. Primary prevention to reduce cardiovascular events appears suboptimal in those at higher risk.

Identification of Radiographic Foot Osteoarthritis: Sensitivity of Views and Features Using the La Trobe Radiographic Atlas.

OBJECTIVE: To compare the sensitivity of alternative case finding approaches for the identification of foot osteoarthritis (OA) based on the La Trobe radiographic atlas. METHODS: This was a cross-sectional study of 533 adults age ≥50 years with foot pain in the past year. Weightbearing dorsoplantar (DP) and lateral radiographs were taken of both feet. The La Trobe radiographic atlas was used to document the presence of osteophytes (OPs) and joint space narrowing (JSN). The prevalence of OA in each joint was documented using both views and features in combination (as recommended in the original atlas), and by using a single view (DP or lateral only) and a single feature (OP or JSN only). RESULTS: Compared to the recommended case definition based on OPs and JSN using both views, a DP-only view identified between 15% and 77% of OA cases, while a lateral-only view identified between 28% and 97% of OA cases. Compared to the recommended case definition of using both features, using only OPs identified between 46% and 94% of OA cases, while using only JSN identified between 19% and 76% of OA cases. CONCLUSION: Applying the La Trobe radiographic atlas but using only 1 radiograph view (DP or lateral) or 1 feature (OP or JSN) in isolation misses a substantial number of OA cases, and the sensitivity of these approaches varies considerably between different foot joints. These findings indicate that, where possible, the atlas should be administered according to the original description to avoid under-ascertainment of radiographic foot OA.

Radiographic validation of a self-report instrument for hallux valgus.

BACKGROUND: Hallux valgus (HV) is a common condition causing substantial morbidity. Radiographic assessment is the gold standard for grading severity but is not always feasible in clinical/research settings. HV line-drawings, consisting of five drawings for each foot depicting a sequential increase in HV angle of 15°, have been clinically validated for self-reporting severity. We aimed to undertake radiographic validation of this self-report instrument. METHODS: Adults aged ≥50 from four GP practices were sent a health survey. Responders self-reported HV severity for each foot using the line-drawing instrument. Those reporting foot pain in the last year had radiographs taken at a research clinic from which intermetatarsal, hallux abductus and hallux interphalangeal abductus angles were calculated. Ten feet were randomly selected for each HV line-drawing grade for both feet. Associations between self-reported HV line drawings and radiographic measurements were assessed using Spearman's ρ correlation coefficients, mean radiographic angle measurement (95% confidence interval) and one-way analysis of variance. RESULTS: Increasing HV line-drawing grade was positively correlated with radiographic measurements for intermetatarsal and hallux abductus angles (Spearman's ρ = 0.602, p < 0.001; 0.821, p < 0.001, respectively). Hallux interphalangeal abductus angle showed an inverse correlation with increasing line-drawing grade (-0.204, p = 0.053). Differences in radiographic measures between HV line drawing grades were significant for intermetatarsal (F = 13.98, p < 0.001) hallux abductus (F = 38.90, p < 0.001) but not hallux interphalangeal abductus angle (F = 2.21, p = 0.075). CONCLUSION: Grading HV severity by self-reported HV line-drawings provides a valid representation of deformity determined from radiographic measurements and is a useful screening/self-reporting tool.

Diabetes as a Prognostic Factor in Frozen Shoulder: A Systematic Review.

OBJECTIVE: To summarize evidence from longitudinal observational studies to determine whether diabetes (types 1 and 2) is associated with the course of symptoms in people with frozen shoulder. DATA SOURCES: A systematic literature search of 11 bibliographic databases (published through June 2021), reference screening, and emailing professional contacts. STUDY SELECTION: Studies were selected if they had a longitudinal observational design that included people diagnosed with frozen shoulder at baseline and compared outcomes at follow-up (>2wk) among those with and without diabetes at baseline. DATA EXTRACTION: Data extraction was completed by 1 reviewer using a predefined extraction sheet and was checked by another reviewer. Two reviewers independently judged risk of bias using the Quality in Prognostic Factor Studies tool. DATA SYNTHESIS: A narrative synthesis, including inspection of forest plots and use of the prognostic factor Grading of Recommendations, Assessment, Development and Evaluations framework. Twenty-eight studies satisfied the inclusion criteria. Seven studies were judged to be at a moderate risk of bias and 21 at a high risk of bias. Diabetes was associated with worse multidimensional clinical scores (moderate certainty in evidence), worse pain (low certainty in evidence), and worse range of motion (very low certainty in evidence). CONCLUSIONS: This review provides preliminary evidence to suggest that people with diabetes may experience worse outcomes from frozen shoulder than those without diabetes. If high-quality studies can confirm the findings of this review, then clinicians should monitor patients with frozen shoulder with diabetes more closely and offer further treatment if pain or lack of function persists long-term.

Identification of patterns of foot and ankle pain in the community: Cross-sectional findings from the clinical assessment study of the foot.

OBJECTIVES: To investigate patterns of foot and ankle pain locations and symptoms, socio-demographic and comorbid characteristics to examine whether there are distinct foot and ankle pain phenotypes. METHODS: Adults aged ≥50 years registered with four general practices in North Staffordshire were mailed a Health Survey questionnaire. Participants reporting foot pain in the last month indicated foot pain location on a foot manikin. Foot and ankle pain patterns were investigated by latent class analysis. Associations between the classes with foot pain symptoms, socio-demographic and comorbid characteristics were assessed. RESULTS: Four thousand four hundred fifty-five participants with complete foot pain and manikin data were included in this analysis (mean age 65 years [SD 9.8], 49% male). Of those with foot and ankle pain (n = 1356), 90% had pain in more than one region. Six distinct classes of foot and ankle pain were identified: no pain (71%), bilateral forefoot/midfoot pain (4%), bilateral hindfoot pain (5%), left forefoot/midfoot pain (8%), right forefoot/midfoot pain (5%) and bilateral widespread foot and ankle pain (6%). People with bilateral widespread foot and ankle pain were more likely to be female, obese, depressed, anxious, have/had a manual occupation, have comorbidities, lower SF-12 scores and greater foot-specific disability. Age did not differ between classes. CONCLUSIONS: Six distinct classes of foot and ankle pain locations were identified, and those with bilateral widespread foot and ankle pain had distinct characteristics. Further investigation of these individuals is required to determine if they have poorer outcomes over time and whether they would benefit from earlier identification and treatment.

Markers of dementia-related health in primary care electronic health records.

OBJECTIVES: Identifying routinely recorded markers of poor health in patients with dementia may help treatment decisions and evaluation of earlier outcomes in research. Our objective was to determine whether a set of credible markers of dementia-related health could be identified from primary care electronic health records (EHR). METHODS: The study consisted of (i) rapid review of potential measures of dementia-related health used in EHR studies; (ii) consensus exercise to assess feasibility of identifying these markers in UK primary care EHR; (iii) development of UK EHR code lists for markers; (iv) analysis of a regional primary care EHR database to determine further potential markers; (v) consensus exercise to finalise markers and pool into higher domains; (vi) determination of 12-month prevalence of domains in EHR of 2328 patients with dementia compared to matched patients without dementia. RESULTS: Sixty-three markers were identified and mapped to 13 domains: Care; Home Pressures; Severe Neuropsychiatric; Neuropsychiatric; Cognitive Function; Daily Functioning; Safety; Comorbidity; Symptoms; Diet/Nutrition; Imaging; Increased Multimorbidity; Change in Dementia Drug. Comorbidity was the most prevalent recorded domain in dementia (69%). Home Pressures were the least prevalent domain (1%). Ten domains had a statistically significant higher prevalence in dementia patients, one (Comorbidity) was higher in non-dementia patients, and two (Home Pressures, Diet/Nutrition) showed no association with dementia. CONCLUSIONS: EHR captures important markers of dementia-related health. Further research should assess if they indicate dementia progression. These markers could provide the basis for identifying individuals at risk of faster progression and outcome measures for use in research.

Indicators of dementia disease progression in primary care: An electronic health record cohort study.

BACKGROUND AND PURPOSE: The objectives were to assess the feasibility and validity of using markers of dementia-related health as indicators of dementia progression in primary care, by assessing the frequency with which they are recorded and by testing the hypothesis that they are associated with recognised outcomes of dementia. The markers, in 13 domains, were derived previously through literature review, expert consensus, and analysis of regional primary care records. METHODS: The study population consisted of patients with a recorded dementia diagnosis in the Clinical Practice Research Datalink, a UK primary care database linked to secondary care records. Incidence of recorded domains in the 36 months after diagnosis was determined. Associations of recording of domains with future hospital admission, palliative care, and mortality were derived. RESULTS: There were 30,463 people with diagnosed dementia. Incidence of domains ranged from 469/1000 person-years (Increased Multimorbidity) to 11/1000 (Home Pressures). An increasing number of domains in which a new marker was recorded in the first year after diagnosis was associated with hospital admission (hazard ratio for ≥4 domains vs. no domains = 1.24; 95% confidence interval = 1.15-1.33), palliative care (1.87; 1.62-2.15), and mortality (1.57; 1.47-1.67). Individual domains were associated with outcomes with varying strengths of association. CONCLUSIONS: Feasibility and validity of potential indicators of progression of dementia derived from primary care records are supported by their frequency of recording and associations with recognised outcomes. Further research should assess whether these markers can help identify patients with poorer prognosis to improve outcomes through stratified care and targeted support.

The association between comorbidity and physical activity levels in people with osteoarthritis: Secondary analysis from two randomised controlled trials.

OBJECTIVE: To determine whether comorbidity presence, frequency or type is associated with Physical Activity (PA) levels in people with Osteoarthritis (OA). DESIGN: Secondary data analysis of adults aged ≥45, with OA related pain recruited to the BEEP trial (knee pain, n = 514) (ISRCTN93634563) and the MOSAICS trial (peripheral joint pain, n = 525) (ISRCTN06984617). Comorbidities considered were respiratory, cardiovascular diseases (CVD), depression, type 2 diabetes and obesity. Self-report PA was measured using the Physical Activity Scale for the Elderly (PASE). Linear regression models were used to estimate the mean change (ß) in PA with comorbidity presence, frequency and type adjusting for potential confounding covariates. RESULTS: In the BEEP trial comorbidity presence was associated with a decrease in PASE score (ß = -32.25 [95% confidence interval (95% CI) -48.57, -15.93]). Each additional comorbidity was associated with an incrementally lower PASE score, one comorbidity (ß = -24.42 [-42.45, -6.38]), two comorbidities ß = -34.76 [-56.05, -13.48]), and three or more comorbidities ß = -73.71 [-106.84, -40.58]) compared to those with no comorbidity. This pattern was similar in MOSAICS, but with a plateau in association from two comorbidities onward. In BEEP and MOSAICS, respiratory (ß = -40.60 [-60.50, -20.35]; ß = -11.82 [-34.95, 11.31]) and CVD (ß = -27.15 [-53.25, -1.05]; ß = -30.84 [-51.89, -9.80]) comorbidities were associated with the largest reduction in PASE scores respectively. CONCLUSION: Comorbidity presence and frequency is associated with lower PA levels and respiratory and CVD comorbidities have the greatest impact. Future exploratory work needs to be done to understand how and why comorbidity is associated with PA levels in people with OA.

Hallux valgus severity, great toe pain, and plantar pressures during gait: A cross-sectional study of community-dwelling adults.

BACKGROUND: Hallux valgus (HV) is a common disabling condition affecting 36% of adults aged 65 years and over. Identifying whether the severity of the deformity alters weight-bearing patterns during walking may assist clinicians optimize offloading interventions. Therefore, we examined how plantar pressure distributions during walking are affected by HV severity. METHODS: Plantar pressures and maximum forces in ten regions of the foot were obtained from 120 participants (40 men, 80 women) aged ≥50 years using a pressure platform (RSscan® International, Olen, Belgium). HV severity was documented using a validated line-drawing instrument with participants separated into four groups: none (n = 30), mild (n = 30), moderate (n = 30) and severe (n = 30). Pressure and force values were compared across HV severity, stratified by the presence or absence of great toe pain. RESULTS: Participants with severe HV were more likely to have great toe pain. More severe HV was associated with significant reductions in peak pressure and maximum force under the hallux but not at other sites of the foot. This association appeared strongest in those reporting great toe pain. CONCLUSIONS: Greater HV severity is associated with great toe pain and reduced loading under the hallux when walking. These observed changes in plantar pressure and maximum force may reflect a pain avoidance mechanism.

Relative prevalence and distribution of knee, hand and foot symptomatic osteoarthritis subtypes in an English population.

In this brief report, we used data from a series of three related cohorts on pain and osteoarthritis (OA) of the knee, hand and foot, which were conducted in North Staffordshire, England. We used a common approach for sampling, data collection and coding, to estimate the relative prevalence of 10 different symptomatic radiographic OA subtypes in the knee, hand and foot and to compare their association with age, sex, socioeconomic position and body mass index. Overall, symptomatic hand OA was more common than knee or foot OA (22.4% vs 17.4% vs 16.5%), due mainly to the high prevalence of nodal interphalangeal joint OA among women. The first carpometacarpal joint OA was the most frequent subtype, with patellofemoral, tibiofemoral, (nodal) interphalangeal and midfoot OA also common. Of the risk factors examined, the greatest differences between subtypes appeared to be their associations with sex and obesity: sex differences were noticeably greater for all forms of hand OA except non-nodal interphalangeal joint OA, while obesity appeared most strongly associated with forms of knee OA. The prevalence of all subtypes was higher among older ages, and among those with lower educational attainment.

Associations Between Calcaneal Enthesophytes and Osteoarthritis of the Hands and Feet.

OBJECTIVE: To examine associations between calcaneal enthesophytes and osteoarthritis (OA) in the hands and feet, and to provide insights into the role of biomechanical and systemic processes in the development of OA. METHODS: Adults ages ≥50 years who were registered with 4 general practices were mailed a Health Survey. Responders reporting foot pain within the last 12 months underwent a detailed assessment, including hand and foot radiographs. Calcaneal enthesophytes (plantar and posterior) and OA features (osteophytes and joint space narrowing) were documented. Associations between enthesophytes and hand and foot OA (including OA phenotypes and OA features at individual joints) were explored using generalized estimating equations, adjusting for age, sex, and body mass index. RESULTS: Data were available from 532 participants (298 women, mean ± SD age 64.9 ± 8.4 years). Calcaneal enthesophytes were not associated with hand OA phenotypes or OA at individual hand joints. In contrast, plantar calcaneal enthesophytes were positively associated with polyarticular foot OA (odds ratio [OR] 1.80 [95% confidence interval (95% CI) 1.02-3.17]). When individual foot joints were examined, posterior enthesophytes were associated with talonavicular joint OA (OR 1.58 [95% CI 1.02-2.44]) and plantar enthesophytes were associated with first metatarsophalangeal joint OA (OR 0.67 [95% CI 0.49-0.98]) and navicular-cuneiform joint OA (OR 2.30 [95% CI 1.40-3.79]). Patterns of association were similar for osteophytes and joint space narrowing. CONCLUSION: Calcaneal enthesophytes are associated with foot OA but not hand OA. The pattern of association is indicative of a local, biomechanical rather than systemic bone-forming process.