Osteoarthritis subpopulations and implications for clinical trial design

Treatment guidelines for osteoarthritis have stressed the need for research on clinical predictors of response to different treatments. However, identifying such clinical predictors of response is less easy than it seems, and there is not a given classification of osteoarthritis subpopulations. This review article highlights the key methodical issues when analyzing and designing clinical studies to detect important subgroups with respect to treatment effect. In addition, we discuss the main osteoarthritis subpopulations and give examples of how specific treatment effects in these subpopulations have been assessed

E-health intervention for preventing recurrent ankle sprains:a randomised controlled trial in general practice

BACKGROUND: Ankle sprains are frequent injuries in general practice. However, no effective treatment is available yet. AIM: resultTo examine the effectiveness of an unsupervised e-health-supported neuromuscular training programme in combination with usual care compared with usual care alone in patients with acute lateral ankle sprains in general practice. DESIGN AND SETTING: Randomised controlled trial with 1-year follow-up among patients (14-65 years) who visited the GP with an acute lateral ankle sprain within 3 weeks of injury. METHOD: The intervention group received, in addition to usual care, an unsupervised e-health-supported neuromuscular training programme and the control group received usual care alone. The primary outcome was self-reported re-sprains during 52 weeks of follow-up. Secondary outcomes were ankle function, pain in rest and during activity, subjective recovery, and return to the same type and level of sport. RESULTS: In total, 165 participants (mean age 38.3 years and 69 [41.8%] male) were included. No statistically significant difference in the occurrence of a re-sprain were found between the intervention 20.7% (17/82) and control group 24.1% (20/83) (hazard ratio 1.14, 95% confidence interval = 0.59 to 2.21). Also, no statistically significant differences in secondary outcomes were found between groups. The adherence rate to the programme was low (6.1%, 5/82). CONCLUSION: The rate of re-sprains was relatively high and an unsupervised e-health-supported neuromuscular training programme does not yield meaningful effects and does not encourage adherence in preventing re-sprains in patients in general practice. More research is necessary to indicate the best treatment modality and way of delivery for these patients.</p

Incidence and management of Osgood-Schlatter disease in general practice:retrospective cohort study

BACKGROUND: Osgood–Schlatter disease (OSD) is a non-traumatic knee problem that is primarily observed in sports-active children and adolescents aged 8–15 years. AIM: To determine the incidence of OSD and to gain an insight into the management of children and adolescents with OSD in general practice. DESIGN AND SETTING: A retrospective cohort study was conducted using a healthcare database containing full electronic health records of over 200 000 patients in general practice in and around the Dutch city of Rotterdam. METHOD: Patients with a new diagnosis of OSD from 1 January 2012 to 31 December 2017 were extracted using a search algorithm based on International Classification of Primary Health Care coding and search terms in free text. Data on the management of OSD were manually interpreted. RESULTS: The mean incidence over the study period was 3.8 (95% confidence interval [CI] = 3.5 to 4.2) per 1000 person–years in those aged 8–18 years. Boys had a higher incidence rate of 4.9 (95% CI = 4.3 to 5.5) compared with girls (2.7, 95% CI = 2.3 to 3.2). Peak incidence was at 12 years of age for boys and 11 years for girls. Advice was the most commonly applied strategy (55.1%), followed by rest (21.0%), referral for imaging (19.5%), and physiotherapy (13.4%). CONCLUSION: To the authors’ knowledge, for the first time the incidence of OSD has been calculated using GP electronic medical files. There is a discrepancy, especially for imaging and referral to a medical specialist, between the current Dutch general practice guidelines and how GPs actually manage the condition in clinical practice

Effect of corticosteroid injection for trochanter pain syndrome: design of a randomised clinical trial in general practice

Background. Regional pain in the hip in adults is a common cause of a general practitioner visit. A considerable part of patients suffer from (greater) trochanteric pain syndrome or trochanteric bursitis. Local corticosteroid injections is one of the treatment options. Although clear evidence is lacking, small observational studies suggest that this treatment is effective in the short-term follow-up. So far, there are no randomised controlled trials available evaluating the efficacy of injection therapy. This study will investigate the efficacy of local corticosteroid injections in the trochanter syndrome in the general practice, using a randomised controlled trial design. The cost effectiveness of the corticosteroid injectio

The PEX study – Exercise therapy for patellofemoral pain syndrome: design of a randomized clinical trial in general practice and sports medicine [ISRCTN83938749]

BACKGROUND: Patellofemoral complaints are frequently seen in younger and active patients. Clinical strategy is usually based on decreasing provoking activities as sports and demanding knee activities during work and leisure and reassuring the patient on the presumed good outcome. Exercise therapy is also often prescribed although evidence on effectiveness is lacking. The objective of this article is to present the design of a randomized clinical trial that examines the outcome of exercise therapy supervised by a physical therapist versus a clinically accepted "wait and see" approach (information and advice about the complaints only). The research will address to both effectiveness and cost effectiveness of supervised exercise therapy in patients with patellofemoral pain syndrome (PFPS). METHODS/DESIGN: 136 patients (adolescents and young adults) with patellofemoral pain syndrome are recruited in general practices and sport medicine centers. They will be randomly allocated receiving either 3 months of exercise therapy (or usual care. The primary outcome measures are pain, knee function and perception of recovery after 3 months and 12 months of follow up and will be measured by self reporting. Measurements will take place at baseline, 6 weeks, and 3 monthly until 1 year after inclusion in the study. Secondary outcome measurements include an economic evaluation. A cost-utility analysis will be performed that expresses health improvements in Quality Adjusted Life Years (QALYs) and incorporates direct medical costs and productivity costs DISCUSSION: This study has been designed after reviewing the literature on exercise therapy for patellofemoral pain syndrome. It was concluded that to merit the effect of exercise therapy a trial based on correct methodological concept needed to be executed. The PEX study is a randomized clinical trial where exercise therapy is compared to usual care. This trial started in April 2005 and will finish in June 2007. The first results will be available around December 2007

Design of the Verbiest trial: cost-effectiveness of surgery versus prolonged conservative treatment in patients with lumbar stenosis

Background: Degenerative changes of lumbar spine anatomy resulting in the encroachment of neural structures are often regarded progressive, ultimately necessitating decompressive surgery. However the natural course is not necessarily progressive and the efficacy of a variety of nonsurgical interventions has also been described. At present there is insufficient data to compare surgical and nonsurgical interventions in terms of their relative benefit and safety. Previous attempts failed to provide clear clinical recommendations or to distinguish subgroups that substantially benefit from a certain treatment strategy. We present the design of a randomized controlled trial on (cost-) effectiveness of surgical decompression versus prolonged conservative treatment in patients with neurogenic intermittent claudication caused by lumbar stenosis. Methods/Design. The aim of the Verbiest trial is to evaluate the effectiveness of prolonged conservative treatment compared to decompressive surgery. The study is a multi-center randomized controlled trial with two parallel groups design. Patients (age over 50) presenting

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To assess associations between uCTX-II or uCIIM and severity of hip pain in patients with mild-moderate hip osteoarthritis (OA) over a 2-year period, and establish whether the level of these biomarkers at baseline could estimate a specific trajectory of hip pain. Design: A cohort study with a 2-year follow-up and 6-monthly measurements of urinary biomarkers (uCTX-II and uCIIM) and symptom severity. Patients were recruited from general practices. The primary outcome was hip pain, measured with the Western Ontario and McMasters University Osteoarthritis Index (WOMAC) subscale and the Visual Analog Scale (VAS). Associations between hip pain and biomarkers were assessed using linear mixed-model analysis for repeated measurements. Five previously identified pain trajectories were used as outcome to investigate whether the level of biomarkers at baseline could estimate membership in one of the trajectories using multinomial regression analysis. Results: LoguCTX-II and loguCIIM were not associated with WOMAC pain or VAS pain during the 2-year follow-up. Patients in the highly progressive pain trajectory and the moderate pain trajectory were more likely to have a higher loguCTX-II at baseline (OR 6.7; 95% CI 1.6-28.2 and OR 4.8; 95% CI 1.0-22.8, respectively) than patients in the mild pain trajectory. Conclusion: This study shows that in patients with mild-moderate hip OA the urinary biochemical markers uCTX-II and uCIIM are not cross-sectionally associated with hip pain during the 2-year follow-up. Because the uCTX-II level estimated a progressive or moderate hip pain trajectory, this correlation needs to be confirmed in additional patients with hip OA

Association between biomarkers of tissue inflammation and progression of osteoarthritis: evidence from the Rotterdam study cohort

__Background:__ We aimed to investigate the prognostic value of two biomarkers of tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive protein (CRPM) and connective tissue type I collagen turnover (C1M), on the incidence and progression of radiographic osteoarthritis (OA) in the Rotterdam Study, a prospective cohort. Moreover, the independent effect of these biomarkers with respect to the established biomarkers of OA progression, like urinary type II collagen degradation (uCTX-II) and serum cartilage oligomeric protein (COMP), was evaluated. __Methods:__ Serum levels of C1M, CRPM, COMP and CRP of 1335 participants aged >55 years were measured in fasting serum using ELISA. The commercial ELISA detecting CTX-II was used in urine. Radiographs at baseline and 5-year follow-up were scored for OA stage by Kellgren-Lawrence grade. The associations between progression and incidence of OA and the baseline biomarkers were examined using logistic regression and generalized estimating equations adjusted for age, sex, BMI, and possible other confounders. __Results:__ The uCTX-II, COMP, and CRP concentrations were associated with the incidence and progression of OA. Moreover, OA progression was positively associated with CRPM (OR = 1.3, p = 0.01) and CRP (OR = 1.3, p = 0.01) levels with similar effect size as uCTX-II (OR = 1.3, p = 0.01) and COMP (OR = 1.2, p = 0.02). CRPM had prognostic value for progression of OA independent from the uCTX-II and COMP. __Conclusions:__ Our study confirmed the associations between uCTX-II and COMP concentrations and OA progression. Importantly, we showed for the first time that CRPM predicts the risk of OA progression independent of the established biomarkers uCTX-II and COMP

Knee complaints seen in general practice: active sport participants versus non-sport participants

Background. Since knee complaints are common among athletes and are frequently presented in general practice, it is of interest to investigate the type of knee complaints represented in general practice of athletes in comparison with those of non-athletes. Therefore, the aim of this study is to investigate the differences in type of knee complaints between sport participants, in this study defined as athletes, and non-sport participants, defined as non-athletes, presenting in general practice. Further, differences in the initial policy of the GP, medical consumption, and outcome at one-year follow-up were also investigated. Methods. Patients consulting their GP for a new episode of knee complaints were invited to participate in this prospective cohort study. From the total HONEUR knee cohort population (n = 1068) we extracted patients who were athletes (n = 421) or non-athletes (n = 388). Results. The results showed that acute distortions of the knee were significantly more diagnosed in athletes than in non-athletes (p = 0.04). Further, more athletes were advised by their GP to 'go easy on the knee' than the non-athletes (p < 0.01), but no differences were found in number of referrals and medication prescribed by the GP. The medical consumption was significantly higher among athletes; however, no significant differences were found between the two groups for recovery at one-year follow-up. Conclusion. There are no major differences in the diagnosis and prognosis of knee complaints between athletes and non-athletes presented to the GP. This implies that there are no indications for different treatment strategies applied in both groups. However, athletes are more often advised to 'go easy on the knee' and to rest than non-athletes. Further, there is a trend towards increased medical consumption among athletes while functional disability and pain are lower than among the non-athletes