A Retrospective Database Analysis to Investigate Treatment Patterns and Health Care Resource Utilisation in Patients who CYCLe AntiMuscarinics in ENgland (CYCLAMEN).

BACKGROUND: Patients with overactive bladder may cycle through different antimuscarinic medications even though there is limited evidence to support this approach. OBJECTIVE: To describe treatment patterns and the associated health care resource utilisation (HCRU) according to antimuscarinic cycling groups. DESIGN, SETTING, AND PARTICIPANTS: The CYCLe AntiMuscarinics in ENgland (CYCLAMEN) study was a retrospective observational investigation that used primary care records from the Clinical Practice Research Datalink GOLD database linked to Hospital Episode Statistics secondary care data. Eligible patients (≥18 yr) were prescribed their first antimuscarinic between January 2014 and December 2017. Patients were categorised into groups prescribed one, two, or three or more (groups 1-3) consecutive unique antimuscarinics over 18 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The HCRU rate and costs were calculated for the period of continuous antimuscarinic therapy (first antimuscarinic treatment episode) and the 18-mo follow-up period. Treatment sequence patterns were displayed using sunburst plots and Kaplan-Meier analysis was used to assess time on treatment. RESULTS AND LIMITATIONS: Overall, 35 369 patients were included, of whom 31 760 (89.8%) received one antimuscarinic (group 1), 3182 (9.0%) received two (group 2), and 427 (1.2%) received three or more (group 3). The most common initial antimuscarinics were solifenacin (13 628 patients, 42.9%) in group 1, and oxybutynin in group 2 (1267 patients, 39.8%) and group 3 (200 patients, 46.8%). The median duration of the first antimuscarinic treatment episode was 57 d and <20% of patients were receiving any antimuscarinic after 18 mo. The number of primary care visits and mean costs increased across groups. The reasons for cycling could not be identified in this study. CONCLUSIONS: Approximately 10% of patients underwent sequential cycling with two or more antimuscarinics. Furthermore, as the majority discontinued treatment within 18 mo, there is a need to improve the management of these patients in the clinical care setting. PATIENT SUMMARY: We investigated treatment patterns and health care use for patients with overactive bladder who were prescribed at least one antimuscarinic drug (AMD), which are drugs that reduce some of the impulses passing from the bladder to the brain. Around 10% of patients accessing primary health care in England received more than one sequential AMD. Most patients discontinued treatment, which may indicate inadequate management of their condition. Prescription of a higher number of AMDs was associated with higher health care costs.

Clinical and molecular associations with outcomes at 2 years after acute knee injury: a longitudinal study in the Knee Injury Cohort at the Kennedy (KICK).

BACKGROUND: Joint injury is a major risk factor for osteoarthritis and provides an opportunity to prospectively examine early processes associated with osteoarthritis. We investigated whether predefined baseline demographic and clinical factors, and protein analytes in knee synovial fluid and in plasma or serum, were associated with clinically relevant outcomes at 2 years after knee injury. METHODS: This longitudinal cohort study recruited individuals aged 16-50 years between Nov 1, 2010, and Nov 28, 2014, across six hospitals and clinics in London, UK. Participants were recruited within 8 weeks of having a clinically significant acute knee injury (effusion and structural injury on MRI), which was typically treated surgically. We measured several predefined clinical variables at baseline (eg, time from injury to sampling, extent and type of joint injury, synovial fluid blood staining, presence of effusion, self-reported sex, age, and BMI), and measured 12 synovial fluid and four plasma or serum biomarkers by immunoassay at baseline and 3 months. The primary outcome was Knee Injury and Osteoarthritis Outcome Score (KOOS4) at 2 years, adjusted for baseline score, assessed in all patients. Linear and logistic regression models adjusting for predefined covariates were used to assess associations between baseline variables and 2-year KOOS4. This study is registered with ClinicalTrials.gov, number NCT02667756. FINDINGS: We enrolled 150 patients at a median of 17 days (range 1-59, IQR 9-26) after knee injury. 123 (82%) were male, with a median age of 25 years (range 16-50, IQR 21-30). 98 (65%) of 150 participants completed a KOOS4 at 2 (or 3) years after enrolment (50 participants were lost to follow-up and two were withdrawn due to adverse events unrelated to study participation); 77 (51%) participants had all necessary variables available and were included in the core variable adjusted analysis. In the 2-year dataset mean KOOS4 improved from 38 (SD 18) at baseline to 79 (18) at 2 years. Baseline KOOS4, medium-to-large knee effusion, and moderate-to-severe synovial blood staining and their interaction significantly predicted 2-year KOOS4 (n=77; coefficient -20·5, 95% CI -34·8 to -6·18; p=0·0060). The only predefined biomarkers that showed independent associations with 2-year KOOS4 were synovial fluid MCP-1 (n=77; -0·015, 0·027 to -0·004 per change in 1 pg/mL units; p=0·011) and IL-6 (n=77; -0·0005, -0·0009 to -0·0001 per change in 1 pg/mL units; p=0·017). These biomarkers, combined with the interaction of effusion and blood staining, accounted for 39% of outcome variability. Two adverse events occurred that were linked to study participation, both at the time of blood sampling (one presyncopal episode, one tenderness and pain at the site of venepuncture). INTERPRETATION: The combination of effusion and haemarthrosis was significantly associated with symptomatic outcomes after acute knee injury. The synovial fluid molecular protein response to acute knee injury (best represented by MCP-1 and IL-6) was independently associated with symptomatic outcomes but not with structural outcomes, with the biomarkers overall playing a minor role relative to clinical predictors. The relationship between symptoms and structure after acute knee injury and their apparent dissociation early in this process need to be better understood to make clinical progress. FUNDING: Versus Arthritis, Kennedy Trust for Rheumatology Research, and NIHR Oxford Biomedical Research Centre.

Knee osteoarthritis and time-to all-cause mortality in six community-based cohorts: an international meta-analysis of individual participant-level data.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population. METHODS: Seven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung-Knapp modification for random-effects meta-analysis. FINDINGS: 10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA. DISCUSSION: Participants with POA or PROA had a 35-37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality. FUNDING: Versus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International.

The prevalence of hand and wrist osteoarthritis in elite former cricket and rugby union players.

OBJECTIVES: This study aimed to determine the prevalence of hand and wrist osteoarthritis in former elite cricket and rugby union players, by sport and playing position, and to define the prevalence of severe hand injury, and its association with hand osteoarthritis. DESIGN: Cross-sectional. METHODS: Data from cross-sectional studies of former elite male cricket and rugby players were used to determine the prevalence of hand pain, physician-diagnosed osteoarthritis, and previous severe injury. Multivariable logistic regression was used to determine the association of previous injury with pain and osteoarthritis. RESULTS: Data from 200 cricketers and 229 rugby players were available. Complete case analysis resulted in 127 cricketers and 140 rugby players. Hand pain was more prevalent amongst cricketers (19.7%) than rugby players (10.0%). The prevalence did not differ between cricket and rugby players for hand osteoarthritis (2.4% and 3.6%), wrist osteoarthritis (1.6% and 2.1%), or previous severe hand injury (36.2% and 31.4%). No significant association between previous hand injury and pain or osteoarthritis was identified in either sport. CONCLUSIONS: Former elite cricketers reported more hand pain than rugby players. No significant association was found between self-reported severe injury and hand osteoarthritis in either cohort, potentially indicating that risk factors aside from injury may be more prominent in the development of hand osteoarthritis.

Novel Approach to Estimate Osteoarthritis Progression: Use of the Reliable Change Index in the Evaluation of Joint Space Loss.

OBJECTIVE: Osteoarthritis-related changes in joint space measurements over time are small and sensitive to measurement error. The Reliable Change Index (RCI) determines whether the magnitude of change observed in an individual can be attributed to true change. This study aimed to examine the RCI as a novel approach to estimating osteoarthritis progression. METHODS: Data were from 167 men and 392 women with knee osteoarthritis (diagnosed using the American College of Rheumatology criteria) randomized to the placebo arm of the 3-year Strontium Ranelate Efficacy in Knee Osteoarthritis trial (SEKOIA) and assessed annually. The RCI was used to determine whether the magnitude of change in joint space width (JSW) on radiographs between study years was likely to be true or due to measurement error. RESULTS: Between consecutive years, 57-69% of participants had an apparent decrease (change <0) in JSW, while 31-43% of participants had annual changes indicating improvement in JSW. The RCI identified JSW decreases in only 6.0% of patients between baseline and year 1, and in 4.5% of patients between the remaining study years. The apparent increases in JSW were almost eliminated between baseline and year 1, and between years 1 and 2 only 1.3% of patients had a significant increase, dropping to 0.9% between years 2 and 3. CONCLUSION: The RCI provides a method to identify change in JSW, removing many apparent changes that are likely to be due to measurement error. This method appears to be useful for assessing change in JSW from radiographs in clinical and research settings.

Osteoarthritis and other long-term health conditions in former elite cricketers.

OBJECTIVES: This study aimed to describe the prevalence and risk of chronic conditions in former elite cricketers compared to a normal population, and describe wellbeing in former elite cricketers. DESIGN: Cross-sectional study. METHODS: Former elite cricketers, recruited from the Professional Cricketers' Association, completed a self-report cross-sectional questionnaire. The English Longitudinal Study of Ageing (ELSA) served as the normal population. The prevalence of self-reported, GP-diagnosed conditions (heart problems, hypertension, stroke, diabetes, asthma, dementia, osteoarthritis (OA), total hip replacement (THR), total knee replacement (TKR), anxiety, depression) were reported for both population samples. Standardised morbidity ratios (SMRs) compared chronic conditions in sex-, age- and BMI-matched former cricketers (n=113) and normal population (n=4496). RESULTS: Heart problems were reported by 13.3% of former cricketers, significantly lower than the normal population, SMR 0.55 (0.33-0.91). Former cricketers reported 31.9% hypertension, 1.8% stroke, 6.2% diabetes, 15.0% asthma, and no dementia, none significantly different to the normal population. OA, THR, and TKR were reported by 51.3%, 14.7% and 10.7% of former cricketers, respectively, significantly higher than the normal population, SMRs 3.64 (2.81-4.71), 3.99 (2.21-7.20) and 3.84 (1.92-7.68). Anxiety and depression were reported by 12.4% and 8.8% of former cricketers, respectively, SMRs 3.95 (2.34-6.67) and 2.22 (1.20-4.14). 97% of former cricketers reflected they would undertake their cricket career again, 98% agreed that cricket enriched their lives. CONCLUSIONS: Heart problems were significantly lower, while OA, THR, TKR, anxiety, and depression were significantly higher in the former cricketers compared to the normal population (ELSA). Most former cricketers reflected positively on their career.

Development of a Prediction Model for Stress Fracture During an Intensive Physical Training Program: The Royal Marines Commandos.

BACKGROUND: Stress fractures (SFs) are one of the more severe overuse injuries in military training, and therefore, knowledge of potential risk factors is needed to assist in developing mitigating strategies. PURPOSE: To develop a prediction model for risk of SF in Royal Marines (RM) recruits during an arduous military training program. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: RM recruits (N = 1082; age range, 16-33 years) who enrolled between September 2009 and July 2010 were prospectively followed through the 32-week RM training program. SF diagnosis was confirmed from a positive radiograph or magnetic resonance imaging scan. Potential risk factors assessed at week 1 included recruit characteristics, anthropometric assessment, dietary supplement use, lifestyle habits, fitness assessment, blood samples, 25(OH)D, bone strength as measured by heel broadband ultrasound attention, history of physical activity, and previous and current food intake. A logistic least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation was used to select potential predictors among 47 candidate variables. Model performance was assessed using measures of discrimination (c-index) and calibration. Bootstrapping was used for internal validation of the developed model and to quantify optimism. RESULTS: A total of 86 (8%) volunteer recruits presented at least 1 SF during training. Twelve variables were identified as the most important risk factors of SF. Variables strongly associated with SF were age, body weight, pretraining weightbearing exercise, pretraining cycling, and childhood intake of milk and milk products. The c-index for the prediction model, which represents the model performance in future volunteers, was 0.73 (optimism-corrected c-index, 0.68). Although 25(OH)D and VO2max had only a borderline statistically significant association with SF, the inclusion of these factors improved the performance of the model. CONCLUSION: These findings will assist in identifying recruits at greater risk of SF during training and will support interventions to mitigate this injury risk. However, external validation of the model is still required.

Association Between Overweight and Obesity and Risk of Clinically Diagnosed Knee, Hip, and Hand Osteoarthritis: A Population-Based Cohort Study.

OBJECTIVE: Studies of previous cohorts have demonstrated an association between a status of overweight/obesity and the presence of knee and hand osteoarthritis (OA). However, no data on the effect of these factors on the OA burden are available. The aim of the present study was to analyze the effect of being overweight or obese on the incidence of routinely diagnosed knee, hip, and hand OA. METHODS: The study was conducted in a population-based cohort using primary care records from the Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària database (>5.5 million subjects, covering >80% of the population of Catalonia, Spain). Participants were subjects ages ≥40 years who were without a diagnosis of OA on January 1, 2006 and had available body mass index (BMI) data. All subjects were followed up from January 1, 2006 to December 31, 2010 or to the time of loss to follow-up or death. Measures included the World Health Organization categories of BMI (exposure), and incident clinical diagnoses of knee, hip, or hand OA according to International Classification of Diseases, Tenth Revision codes. RESULTS: In total, 1,764,061 subjects were observed for a median follow-up period of 4.45 years (interquartile range 4.19-4.98 years). Incidence rates (per 1,000 person-years at risk) of knee, hip, and hand OA were 3.7 (99% confidence interval [99% CI] 3.6-3.8), 1.7 (99% CI 1.7-1.8), and 2.6 (99% CI 2.5-2.7), respectively, among subjects in the normal weight category, and 19.5 (99% CI 19.1-19.9), 3.8 (99% CI 3.7-4.0), and 4.0 (99% CI 3.9-4.2), respectively, in those with a classification of grade II obesity. Compared to subjects with normal weight, being overweight or obese increased the risk of OA at all 3 joint sites, especially at the knee. A status of overweight, grade I obesity, and grade II obesity increased the risk of knee OA by a factor of 2-fold, 3.1-fold, and 4.7-fold, respectively. CONCLUSION: Being overweight or obese increases the risk of hand, hip, and knee OA, with the greatest risk in the knee, and this occurs on a dose-response gradient of increasing BMI.

Obesity and the Relative Risk of Knee Replacement Surgery in Patients With Knee Osteoarthritis: A Prospective Cohort Study.

OBJECTIVE: It is unclear what impact obesity has on the progression of knee osteoarthritis (OA) from diagnosis to knee replacement surgery. This study was undertaken to examine the relative risk of knee replacement surgery in overweight and obese patients who were newly diagnosed as having knee OA in a community setting. METHODS: Subjects were selected from the Information System for Development of Primary Care Research database, which compiles comprehensive clinical information collected by health care professionals for >5.5 million people in Catalonia, Spain (80% of the population). Patients newly diagnosed as having knee OA in primary care between 2006 and 2011 were included. Knee replacement was ascertained using International Classification of Diseases, Ninth Revision, Clinical Modification codes from linked hospital admissions data. Multivariable Cox regression models were fitted for knee replacement according to body mass index (BMI), and were adjusted for relevant confounders. Population proportional attributable risk was calculated. RESULTS: A total of 105,189 participants were followed up for a median of 2.6 years (interquartile range 1.3-4.2). Of these patients, 7,512 (7.1%) underwent knee replacement. Adjusted hazard ratios and 95% confidence intervals (95% CIs) for knee replacement for the World Health Organization BMI categories were 1.41 (95% CI 1.27-1.57) for overweight, 1.97 (95% CI 1.78-2.18) for obese I, 2.39 (95% CI 2.15-2.67) for obese II, and 2.67 (95% CI 2.34-3.04) for obese III compared to normal weight. The effect of BMI on risk of knee replacement was stronger among younger participants. The population attributable risk of obesity for knee OA-related knee replacement was 31.0%. CONCLUSION: Overweight and obese patients are at >40% and 100% increased risk of knee replacement surgery, respectively, compared to patients with normal weight. This association is even stronger in younger patients. Weight reduction strategies could potentially reduce the need for knee replacement surgery by 31% among patients with knee OA.

Validation of statistical shape modelling to predict hip osteoarthritis in females: data from two prospective cohort studies (Cohort Hip and Cohort Knee and Chingford).

OBJECTIVES: To prospectively investigate whether hip shape variants at baseline are associated with the need for future total hip replacement (THR) in women and to validate the resulting associated shape variants of the Cohort Hip and Cohort Knee (CHECK) cohort and the Chingford cohort. METHODS: Female participants from the CHECK cohort without radiographic OA (Kellgren-Lawrence score <2) at baseline were included (1100 hips); 22 hips had a THR within 5 years of follow-up. For the Chingford cohort, with only female participants, hips without radiographic OA at baseline were selected and a nested case-control design was used, with 19 THR cases within 19 years of follow-up and 95 controls matched 5 to 1 for age and BMI. Hip shape on baseline anteroposterior pelvic radiographs was assessed by statistical shape modelling (SSM) using the same model for both cohorts. RESULTS: In the CHECK and Chingford cohorts, the respective mean age was 55.8 (s.d. 5.1) and 53.6 (s.d. 5.4) and the BMI was 26.14 (s.d. 4.3) and 25.7 (s.d. 3.3), respectively. Multiple shape variants of the hip were significantly (P < 0.05) associated with future THR in both the CHECK (modes 4, 11, 15, 17 and 22) and Chingford (modes 2 and 17) cohorts. Mode 17 [odds ratio (OR) 0.51 (95% CI 0.33, 0.80) in the CHECK cohort], representing a flattened head-neck junction and flat greater trochanter, could be confirmed in the Chingford cohort [OR 0.41 (95% CI 0.23, 0.82)]. Modes 4 and 15 of the CHECK cohort also showed non-significant trends in the Chingford cohort. CONCLUSION: Several baseline shape variants are associated with the future need for THR within a cohort. Despite differences in participant characteristics, radiographic protocol and follow-up time, we could validate at least one shape variant, suggesting that SSM is reasonably transferable between cohorts.

Associations between body mass index and foot joint pain in middle-aged and older women: a longitudinal population-based cohort study.

OBJECTIVE: To investigate the relationship between body mass index (BMI) and foot joint pain (FJP) over a 5-year period in a community-based cohort. METHODS: We examined a subset of women from the Chingford Women's Study, a community cohort followed up for 20 years. From a baseline of 1,003 female participants, we reviewed data from 639 women (64%) for whom complete data sets for FJP and BMI were obtained over a 5-year period between year 10 (Y10) and year 15 (Y15). Descriptive statistics, binary regression modeling, and odds ratios (ORs) were used to examine the longitudinal relationship between BMI and FJP. RESULTS: For Y10 and Y15, the median age was 61 years (interquartile range [IQR] 57-67) and 66 years (IQR 62-72), respectively, and the mean ± SD BMI was 26.7 ± 4.6 kg/m(2) and 27.2 ± 4.8 kg/m(2) , respectively. FJP prevalence was 21.6% at Y10 and 26.6% at Y15. Longitudinal analyses showed that both BMI and FJP increased significantly from Y10 to Y15 (P < 0.001). The odds of having FJP after a 5-year period increased by 4.9% for each BMI unit increase 5 years earlier (OR 1.049 [95% confidence interval (95% CI) 1.011-1.089], P = 0.012). This remained significant when adjusted for age, diabetes mellitus, and rheumatoid arthritis (OR 1.051 [95% CI 1.011-1.091], P = 0.012). CONCLUSION: This is the first large longitudinal cohort study demonstrating that, in middle-aged women, a high BMI precedes and is predictive of FJP independent of age. Evidence from our findings can be used to identify those individuals at risk of developing FJP.