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.

Factors associated with change in health-related quality of life in people with gout: a 3-year prospective cohort study in primary care.

OBJECTIVE: To describe factors associated with change in health-related quality of life (HRQOL) in people living with gout in primary care. METHODS: In a UK prospective cohort study, adults with a diagnosis of gout registered with 20 general practices completed the Gout Impact Scale (GIS; scale 0-100), 36-item Short Form Physical Function subscale (PF-10; 0-100) and HAQ Disability Index (HAQ-DI; 0-3) via postal questionnaires at baseline and 6, 12, 24 and 36 months. Linear mixed modelling was used to investigate factors associated with changes in HRQOL over 3 years. RESULTS: A total of 1184 participants responded at baseline (adjusted response 65.6%); 990 (83.6%) were male, with a mean age of 65.6 years (s.d. 12.5). A total of 818, 721, 696 and 605 responded at 6, 12, 24 and 36 months, respectively. Factors associated with worse disease-specific and generic HRQOL over 3 years were flare frequency (five or more flares; GIS subscales, PF-10), oligo/polyarticular flares (GIS subscales, PF-10, HAQ-DI), worse pain (GIS subscales, PF-10, HAQ-DI), body pain (GIS subscales, PF-10, HAQ-DI) and more severe depression (GIS subscales, PF-10, HAQ-DI) (P ≤ 0.05). More severe anxiety was associated with worse disease-specific HRQOL only (GIS subscales). Older age (PF-10), being female (PF-10, HAQ-DI) and BMI (HAQ-DI) were associated with worse generic HRQOL (P ≤ 0.05). CONCLUSION: Gout-specific, comorbid and sociodemographic factors were associated with change in HRQOL over a 3-year period, highlighting people at risk of worse outcomes who could be targeted for interventions.

Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care.

OBJECTIVES: To compare the effectiveness and safety of naproxen and low-dose colchicine for treating gout flares in primary care. METHODS: This was a multicentre open-label randomised trial. Adults with a gout flare recruited from 100 general practices were randomised equally to naproxen 750 mg immediately then 250 mg every 8 hours for 7 days or low-dose colchicine 500 mcg three times per day for 4 days. The primary outcome was change in worst pain intensity in the last 24 hours (0-10 Numeric Rating Scale) from baseline measured daily over the first 7 days: mean change from baseline was compared between groups over days 1-7 by intention to treat. RESULTS: Between 29 January 2014 and 31 December 2015, we recruited 399 participants (naproxen n=200, colchicine n=199), of whom 349 (87.5%) completed primary outcome data at day 7. There was no significant between-group difference in average pain-change scores over days 1-7 (colchicine vs naproxen: mean difference -0.18; 95% CI -0.53 to 0.17; p=0.32). During days 1-7, diarrhoea (45.9% vs 20.0%; OR 3.31; 2.01 to 5.44) and headache (20.5% vs 10.7%; 1.92; 1.03 to 3.55) were more common in the colchicine group than the naproxen group but constipation was less common (4.8% vs 19.3%; 0.24; 0.11 to 0.54). CONCLUSION: We found no difference in pain intensity over 7 days between people with a gout flare randomised to either naproxen or low-dose colchicine. Naproxen caused fewer side effects supporting naproxen as first-line treatment for gout flares in primary care in the absence of contraindications. TRIAL REGISTRATION NUMBER: ISRCTN (69836939), clinicaltrials.gov (NCT01994226), EudraCT (2013-001354-95).

The clinical and cost-effectiveness of corticosteroid injection versus night splints for carpal tunnel syndrome (INSTINCTS trial): an open-label, parallel group, randomised controlled trial.

BACKGROUND: To our knowledge, the comparative effectiveness of commonly used conservative treatments for carpal tunnel syndrome has not been evaluated previously in primary care. We aimed to compare the clinical and cost-effectiveness of night splints with a corticosteroid injection with regards to reducing symptoms and improving hand function in patients with mild or moderate carpal tunnel syndrome. METHODS: We did this randomised, open-label, pragmatic trial in adults (≥18 years) with mild or moderate carpal tunnel syndrome recruited from 25 primary and community musculoskeletal clinics and services. Patients with a new episode of idiopathic mild or moderate carpal tunnel syndrome of at least 6 weeks' duration were eligible. We randomly assigned (1:1) patients (permutated blocks of two and four by site) with an online web or third party telephone service to receive either a single injection of 20 mg methylprednisolone acetate (from 40 mg/mL) or a night-resting splint to be worn for 6 weeks. Patients and clinicians could not be masked to the intervention. The primary outcome was the overall score of the Boston Carpal Tunnel Questionnaire (BCTQ) at 6 weeks. We used intention-to-treat analysis, with multiple imputation for missing data, which was concealed to treatment group allocation. The trial is registered with the European Clinical Trials Database, number 2013-001435-48, and ClinicalTrial.gov, number NCT02038452. FINDINGS: Between April 17, 2014, and Dec 31, 2016, 234 participants were randomly assigned (118 to the night splint group and 116 to the corticosteroid injection group), of whom 212 (91%) completed the BCTQ at 6 weeks. The BCTQ score was significantly better at 6 weeks in the corticosteroid injection group (mean 2·02 [SD 0·81]) than the night splint group (2·29 [0·75]; adjusted mean difference -0·32; 95% CI -0·48 to -0·16; p=0·0001). No adverse events were reported. INTERPRETATION: A single corticosteroid injection shows superior clinical effectiveness at 6 weeks compared with night-resting splints, making it the treatment of choice for rapid symptom response in mild or moderate carpal tunnel syndrome presenting in primary care. FUNDING: Arthritis Research UK.

Risk of fracture among patients with polymyalgia rheumatica and giant cell arteritis: a population-based study.

BACKGROUND: Glucocorticoids are associated with increased fracture risk and are the mainstay of treatment in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). However, fracture risk in these conditions has not been previously quantified. The aim of this study was to quantify the risk of fracture among patients with PMR and GCA. METHODS: A retrospective cohort study was conducted using primary care records from the UK-based Clinical Practice Research Datalink. Individuals aged 40 years and over, with incident diagnoses of PMR or GCA were separately identified from 1990-2004 and followed up until 2015. For each exposed individual, four age-, sex- and practice-matched controls were randomly selected. Incidence rates of fracture per 10,000 person-years were calculated for each disease group and hazard rates were compared to the unexposed using Cox regression models. RESULTS: Overall, 12,136 and 2673 cases of PMR and GCA, respectively, were identified. The incidence rate of fracture was 148.05 (95% CI 141.16-155.28) in PMR and 147.15 (132.91-162.91) in GCA per 10,000 person-years. Risk of fracture was increased by 63% in PMR (adjusted hazard ratio 1.63, 95% CI 1.54-1.73) and 67% in GCA (1.67, 1.49-1.88) compared to the control populations. Fewer than 13% of glucocorticoid-treated cases were prescribed bisphosphonates. CONCLUSIONS: This study reports, for the first time, a similar increase in fracture risk for patients with PMR and GCA. More needs to be done to improve adherence to guidelines to co-prescribe bisphosphonates. Further research needs to identify whether lower glucocorticoid starting doses and/or aggressive dose reduction reduces fracture risk.

Impairment-targeted exercises for older adults with knee pain: a proof-of-principle study (TargET-Knee-Pain).

BACKGROUND: Therapeutic exercise is an effective intervention for knee pain and osteoarthritis (OA) and should be individualised. In a preliminary, proof-of-principle study we sought to develop a home exercise programme targeted at specific physical impairments of weak quadriceps, reduced knee flexion range of motion (ROM) and poor balance, and evaluate whether receipt of this was associated with improvements in those impairments and in patient-reported outcomes among older adults with knee pain. METHODS: This community-based study used a single group, before-after study design with 12-week follow-up. Participants were 58 adults aged over 56 years with knee pain and evidence of quadriceps weakness, loss of flexion ROM, or poor balance, recruited from an existing population-based, observational cohort. Participants received a 12-week home exercise programme, tailored to their physical impairments. The programme was led, monitored and progressed by a physiotherapist over six home visits, alternating with six telephone calls. Primary outcome measures were maximal isometric quadriceps strength, knee flexion ROM and timed single-leg standing balance, measured at baseline, 6 and 12 weeks by a research nurse blinded to the nature and content of participants' exercise programmes. Secondary outcome measures included the WOMAC. RESULTS: At 12 weeks, participants receiving strengthening exercises demonstrated a statistically significant change in quadriceps isometric strength compared to participants not receiving strengthening exercises: 3.9 KgF (95 % CI 0.1, 7.8). Changes in knee flexion ROM (2.1° (-2.3, 6.5)) and single-leg balance time (-2.4 s (-4.5, 6.7)) after stretching and balance retraining exercises respectively, were not found to be statistically significant. There were significant improvements in mean WOMAC Pain and Physical Function scores: -2.2 (-3.1, -1.2) and -5.1 (-7.8, -2.5). CONCLUSIONS: A 12-week impairment-targeted, home-based exercise programme for symptomatic knee OA appeared to be associated with modest improvements in self-reported pain and function but no strong evidence of greater improvement in the specific impairments targeted by each exercise package, with the possible exception of quadriceps strengthening. TRIAL REGISTRATION: Clinical Trial Registration Number: ISRCTN 61638364 Date of registration: 24 June 2010.

The clinical and cost effectiveness of steroid injection compared with night splints for carpal tunnel syndrome: the INSTINCTS randomised clinical trial study protocol.

BACKGROUND: Patients diagnosed with idiopathic mild to moderate carpal tunnel syndrome (CTS) are usually managed in primary care and commonly treated with night splints and/or corticosteroid injection. The comparative effectiveness of these interventions has not been reliably established nor investigated in the medium and long term. The primary objective of this trial is to investigate whether corticosteroid injection is effective in reducing symptoms and improving hand function in mild to moderate CTS over 6 weeks when compared with night splints. Secondary objectives are to determine specified comparative clinical outcomes and cost effectiveness of corticosteroid injection over 6 and 24 months. METHOD/DESIGN: A multicentre, randomised, parallel group, clinical pragmatic trial will recruit 240 adults aged ≥18 years with mild to moderate CTS from GP Practices and Primary-Secondary Care Musculoskeletal Interface Clinics. Diagnosis will be by standardised clinical assessment. Participants will be randomised on an equal basis to receive either one injection of 20 mg Depo-Medrone or a night splint to be worn for 6 weeks. The primary outcome is the overall score of the Boston Carpal Tunnel Questionnaire (BCTQ) at 6 weeks. Secondary outcomes are the BCTQ symptom severity and function status subscales, symptom intensity, interrupted sleep, adherence to splinting, perceived benefit and satisfaction with treatment, work absence and reduction in work performance, EQ-5D-5L, referral to surgery and health utilisation costs. Participants will be assessed at baseline and followed up at 6 weeks, 6, 12 and 24 months. The primary analysis will use an intention to treat (ITT) approach and multiple imputation for missing data. The sample size was calculated to detect a 15 % greater improvement in the BTCQ overall score in the injection group compared to night-splinting at approximately 90 % power, 5 % two-tailed significance and allows for 15 % loss to follow-up. DISCUSSION: The trial makes an important contribution to the evidence base available to support effective conservative management of CTS in primary care. No previous trials have directly compared these treatments for CTS in primary care populations, reported on clinical effectiveness at more than 6 months nor compared cost effectiveness of the interventions. TRIAL REGISTRATION: Trial registration: EudraCT 2013-001435-48 (registered 05/06/2013), ClinicalTrials.gov NCT02038452 (registered 16/1/2014), and Current Controlled Trials ISRCTN09392969 (retrospectively registered 01/05/2014).

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.

Symptom patterns and life with post-acute COVID-19 in children aged 8-17 years: a mixed-methods study protocol.

BACKGROUND: While there is a substantial body of knowledge about acute COVID-19, less is known about long-COVID, where symptoms continue beyond 4 weeks. AIM: To describe longer-term effects of COVID-19 infection in children and young people (CYP) and identify their needs in relation to long-COVID. DESIGN & SETTING: This study comprises an observational prospective cohort study and a linked qualitative study, identifying participants aged 8-17 years in the West Midlands of England. METHOD: CYP will be invited to complete online questionnaires to monitor incidences and symptoms of COVID-19 over a 12-month period. CYP who have experienced long-term effects of COVID will be invited to interview, and those currently experiencing symptoms will be asked to document their experiences in a diary. Professionals who work with CYP will be invited to explore the impact of long-COVID on the wider experiences of CYP, in a focus group. Descriptive statistics will be used to describe the incidence and rates of resolution of symptoms, and comparisons will be made between exposed and non-exposed groups. Logistic regression models will be used to estimate associations between candidate predictors and the development of long-COVID, and linear regression will be used to estimate associations between candidate predictors. Qualitative data will be analysed thematically using the constant comparison method. CONCLUSION: This study will describe features and symptoms of long-COVID and explore the impact of long-COVID within the lives of CYP and their families, to provide better understanding of long-COVID and inform clinical practice.

The association between anxiety and disease activity and quality of life in rheumatoid arthritis: a systematic review and meta-analysis.

OBJECTIVES: In people with rheumatoid arthritis (RA), mental health problems are common, but often not recognized or treated, contributing to increased morbidity and mortality. Most studies examining the impact of mental health problems in RA have focused on depression. We aimed to determine the association between anxiety, and disease activity and quality of life (QoL) in people with RA. METHODS: A systematic review and meta-analysis were performed. A protocol was registered with PROSPERO (CRD2-17062580). Databases (Web of Science, PsycINFO, CINAHL, Embase, Medline) were searched for studies examining the association between anxiety and disease activity and QoL, in adults with RA, from inception to February 2019. Primary outcome measures were DAS28 and SF-36. Eligibility screening and data extraction were completed by two reviewers. Disagreements were resolved by discussion or a third reviewer. Quality assessment was carried out using the Newcastle-Ottawa Scale. RESULTS: From 7712 unique citations, 60 articles were assessed for eligibility. The final review included 20 studies involving 7452 people with RA (14 cross-sectional, 6 cohort). Eleven examined disease activity, 6 reported QoL outcome measures and 3 included both. Anxiety was associated with increased disease activity and worse QoL. Meta-analysis showed anxiety to be correlated with increased DAS28 scores (r = 0.23, CI 0.14, 0.31) and reduced physical (r = - 0.39, CI - 0.57, - 0.20) and mental QoL (- 0.50, CI - 0.57, - 0.43). CONCLUSIONS: Anxiety in people with RA is associated with increased disease activity and worse QoL. Improved recognition and management of comorbid anxiety may help to improve outcomes for people with RA.Key Points• This is the first systematic review and meta-analysis to examine the relationship between anxiety and disease activity and QoL in people with RA.• Anxiety was associated with higher disease activity both cross-sectionally and at up to 12-month follow-up.• Anxiety may have a more significant impact on disease activity in early RA, highlighting the importance of early recognition and management of comorbid anxiety.• People with anxiety had poorer self-reported physical and mental QoL, although there was some heterogeneity in study findings, particularly for physical QoL (I2 = 78.5%).

Correction to: The association between anxiety and disease activity and quality of life in rheumatoid arthritis: a systematic review and meta-analysis.

The authors of the published original version of the above article wanted to correct the below text in the Abstract section.

Reasons why osteoarthritis predicts mortality: path analysis within a Cox proportional hazards model.

Objectives: To identify potentially modifiable factors that mediate the association between symptomatic osteoarthritis (OA) and premature mortality. Methods: A population-based prospective cohort study; primary care medical record data were linked to self-report information collected by questionnaire in adults aged 50 years and over (n=10 415). OA was defined by primary care consultation and moderate-to-severe pain interference in daily life. A Cox proportional hazards analysis determined the total effect (TE) of OA on mortality after adjustment for potential confounders. Within the Cox model, path analysis was used to decompose the TE to assess the indirect and direct effects for selected potential mediators (anxiety, depression, unrefreshed sleep and walking frequency). Results are expressed as HRs with 95% CIs derived from bootstrap resampling. Results: OA was significantly associated with mortality (TE-adjusted HR 1.14; 95% CI 1.00 to 1.29). The indirect effects for walking frequency were 1.05 (95% CI 1.04 to 1.06), depression 1.02 (95% CI 1.02 to 1.03), anxiety 1.01 (95% CI 1.00 to 1.02) and unrefreshed sleep 1.01 (95% CI 1.00 to 1.01). Conclusions: The analysis indicates that encouraging people to walk and 'get out and about' in addition to targeting OA could be protective against excessive mortality. The findings also suggest that depression, anxiety and unrefreshed sleep have a role in premature mortality for people with OA; however, this has low clinical significance.

The Risk of Gout Among Patients With Sleep Apnea: A Matched Cohort Study.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with a range of serious comorbidities. This study was undertaken to investigate whether people with OSA are more likely to develop gout, in the short and long term, compared to those without OSA. METHODS: A matched retrospective cohort study was undertaken using the UK Clinical Practice Research Datalink. Individuals age ≥18 years who received a diagnosis of OSA between 1990 and 2010 were identified and matched on age, sex, and practice with up to 4 individuals without OSA; follow-up was until the end of 2015. Hazard ratios (HRs) were estimated using Cox regression adjusted for general health, lifestyle, and comorbidity characteristics. The risk of developing gout was assessed at different time points, and the body mass index (BMI) category-specific results were presented. RESULTS: The study sample included 15,879 patients with OSA and 63,296 without. The median follow-up was 5.8 years. We found that 4.9% of patients with OSA and 2.6% of patients without the disorder developed gout. The incidence rate per 1,000 person-years was 7.83 (95% confidence interval [95% CI] 7.29-8.40) and 4.03 (95% CI 3.84-4.23) among those with and without OSA, respectively. The adjusted HR was 1.42 (95% CI 1.29-1.56). The risk of developing gout among OSA patients compared to those without was highest 1-2 years after the index date (HR 1.64 [95% CI 1.30-2.06]). This finding persisted among those who were overweight and obese. For those with normal BMI, the highest significant HR (2.02 [95% CI 1.13-3.62]) was observed at 2-5 years after the index date. CONCLUSION: In this study, patients with OSA continued to be at higher risk of developing gout beyond the first year following the diagnosis. Our results further indicate that peak incidences of gout vary according to BMI.

Predictors of pain interference and potential gain from intervention in community dwelling adults with joint pain: A prospective cohort study.

INTRODUCTION: There is little research on identifying modifiable risk factors that predict future interference of pain with daily activity in people with joint pain, and the estimation of the corresponding population attributable risk (PAR). The present study therefore investigated modifiable predictors of pain interference and estimated maximum potential gain from intervention in adults with joint pain. METHODS: A population-based cohort aged ≥50 years was recruited from eight general practices in North Staffordshire, UK. Participants (n = 1878) had joint pain at baseline lasting ≥3 months and indicated no pain interference. Adjusted associations of self-reported, potentially modifiable prognostic factors (body mass index, anxiety/depressive symptoms, widespread pain, inadequate joint pain control, physical inactivity, sleep problems, smoking and alcohol intake) with onset of pain interference 3 years later were estimated via Poisson regression, and corresponding PAR estimates were obtained. RESULTS: Inadequate joint-specific pain control, insomnia and infrequent walking were found to be independently significantly associated with the onset of pain interference after 3 years, with associated PARs of 6.3% (95% confidence interval -0.3, 12.4), 7.6% (-0.4, 15.0) and 8.0% (0.1, 15.2), respectively, with only the PAR for infrequent walking deemed statistically significant. The PAR associated with insomnia, infrequent walking and inadequate control of joint pain simultaneously was 20.3% (8.6, 30.4). CONCLUSIONS: There is potential to reduce moderately the onset of pain interference from joint pain in the over-50s if clinical and public health interventions targeted pain management and insomnia, and promoted an active lifestyle. However, most of the onset of significant pain interference in the over-50s, would not be prevented, even assuming that these factors could be eliminated.

How common is depression in patients with polymyalgia rheumatica?

Depression is common in inflammatory disorders such as rheumatoid arthritis and systemic lupus erythematosus and negatively impacts on outcomes. Given the long-term nature of polymyalgia rheumatica (PMR) and its glucocorticoid treatment, these patients may be at an increased risk of depression, although few studies exist to date. This study aimed to investigate the prevalence of, and factors associated with, depression in PMR patients. Prevalent PMR patients (with a first diagnostic code for PMR in the last 3 years) were mailed a postal questionnaire (n = 704) examining PMR symptoms, glucocorticoid use and patient reported comorbidities. Depressive symptoms were assessed using the Patient Health Questionnaire-8 (PHQ-8), with a score of ≥10 defined as current depressive symptoms. Logistic regression was used to examine association between demographics, comorbidity and current depressive symptoms. Five hundred fifty (78%) patients responded, of which 365 (66%) were female, with a mean (SD) age of 74.1 years (8.4). The prevalence of current depressive symptoms was 15% (n = 81) and was significantly associated with female gender: OR 1.87 (95%CI 1.08-3.22), current PMR symptoms: OR 2.1 (1.11-3.97), self-reported acid reflux: OR 1.75 (1.05-2.93) and diabetes: OR 2.86 (1.6-5.09). Older patients were less likely to report current depressive symptoms (OR 0.35 (0.13-0.9) for those >80 years versus those aged 50-59 years). Depressive symptoms are common in patients with PMR patients, especially younger patients and those with comorbidities. Clinicians should consider screening these patients for depressive symptoms and managing them appropriately, as untreated depression may negatively impact on health-related outcomes and quality of life.