A Multivariable Prediction Model for the Chronification of Non-traumatic Shoulder Pain: A Systematic Review.

BACKGROUND: Shoulder pain is the third most common musculoskeletal complaint and many patients have an unfavorable outcome with long-term disability. Only 50% of all new episodes of shoulder pain show complete recovery within 6 months. Little is known about factors that contribute to chronicity of shoulder pain, although such information is needed for the management of patients with acute and sub-acute shoulder pain. OBJECTIVE: To systematically review the literature for prognostic factors which are potential predictors for either recovery or chronification in patients with acute and sub-acute non-traumatic shoulder pain. STUDY DESIGN: Systematic review. SETTING: This systematic review examined all studies involving the prognosis of shoulder pain patients. METHODS: This systematic review was reported following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently scored the methodological quality of the selected studies. Due to heterogeneity of studies, a best-evidence synthesis of the available prognostic factors was provided. RESULTS: Nine studies met our inclusion criteria and were included in this systematic review. There is strong evidence that high scores on the Shoulder Pain and Disability Index (SPADI), high scores on shoulder pain severity, and a long duration of complaints are factors that contribute to the chronification of shoulder pain. Moderate evidence was found supportive for other prognostic factors that enhance chronification, like being male, being over 55 years of age, having poor general health, having a gradual onset of complaints, a large amount of sick leave, the perception of high job demand, the perception of low social support, and the amount of visits to a health care professional. Also moderate evidence exists regarding factors that contributed to a reduced possibility of chronification: an active treatment policy and not taking medication on regular basis. LIMITATIONS: The large variability in definitions of shoulder pain, and patient selection bias. In addition, there is a paucity of strong longitudinal prospective studies. CONCLUSION: This systematic review found evidence that high scores on the SPADI questionnaire, more shoulder pain, and a longer duration of complaints are associated with chronification of shoulder pain. In order to reduce chronification, clinicians can use the International Classification of Functioning based model presented here that could aid their decision-making.

Design, synthesis and biological characterization of selective LIMK inhibitors.

Inhibitors of LIM kinases are considered of interest for several indications, including elevated intraocular pressure (IOP), cancer, or infection by HIV-1. LX-7101 (Lexicon Pharmaceuticals) was advanced to Phase-I clinical trials as an IOP-lowering agent for treatment of glaucoma. We here discuss the design, synthesis and evaluation of LIMK inhibitors based on a pyrrolopyrimidine scaffold, which represent close analogs of LX-7101. Exploration of structure-activity relationships revealed that many of such compounds, including LX-7101, cause potent inhibition of LIMK1 and LIMK2, and also ROCK2 and PKA. Molecular variations around the various structural elements of LX-7101 were attempted. Substitution on position 6 of the pyrrolopyrimidine scaffold led to the identification of LX-7101 analogs displaying good selectivity versus ROCK, PKA and Akt.

Design, synthesis, and biological evaluation of novel, highly active soft ROCK inhibitors.

ROCK1 and ROCK2 play important roles in numerous cellular functions, including smooth muscle cell contraction, cell proliferation, adhesion, and migration. Consequently, ROCK inhibitors are of interest for treating multiple indications including cardiovascular diseases, inflammatory and autoimmune diseases, lung diseases, and eye diseases. However, systemic inhibition of ROCK is expected to result in significant side effects. Strategies allowing reduced systemic exposure are therefore of interest. In a continuing effort toward identification of ROCK inhibitors, we here report the design, synthesis, and evaluation of novel soft ROCK inhibitors displaying an ester function allowing their rapid inactivation in the systemic circulation. Those compounds display subnanomolar activity against ROCK and strong differences of functional activity between parent compounds and expected metabolites. The binding mode of a representative compound was determined experimentally in a single-crystal X-ray diffraction study. Enzymes responsible for inactivation of these compounds once they enter systemic circulation are also discussed.

[Dutch College of General Practitioners' practice guideline on symptoms of the hand and wrist: a summary]. / De NHG-standaard 'Hand- en polsklachten': samenvatting.

The first edition of the practice guideline for general practitioners (GPs) on hand and wrist symptoms was published in January 2010 by the Dutch College of General Practitioners. This practice guideline provides GPs with pointers for the diagnosis and treatment of hand and wrist symptoms. Carpal tunnel syndrome (CTS) can be diagnosed on its typical clinical presentation alone. The treatment of mild symptoms of CTS, trigger finger and De Quervain's tenosynovitis is conservative, or sometimes a corticosteroid injection: more severe or persistent symptoms require referral to hospital. Mallet finger is treated with a splint for 6 weeks, surgical intervention is necessary for large avulsion fractures or persisting symptoms after treatment with a splint.

Example-based learning: effects of model expertise in relation to student expertise.

BACKGROUND: Worked examples are very effective for novice learners. They typically present a written-out ideal (didactical) solution for learners to study. AIMS: This study used worked examples of patient history taking in physiotherapy that presented a non-didactical solution (i.e., based on actual performance). The effects of model expertise (i.e., worked example based on advanced, third-year student model or expert physiotherapist model) in relation to students' expertise (i.e., first- or second-year) were investigated. SAMPLE: One hundred and thirty-four physiotherapy students (61 first-year and 73 second-year). METHODS: Design was 2 × 2 factorial with factors 'Student Expertise' (first-year vs. second-year) and 'Model Expertise' (expert vs. advanced student). Within expertise levels, students were randomly assigned to the Expert Example or the Advanced Student Example condition. All students studied two examples (content depending on their assigned condition) and then completed a retention and test task. They rated their invested mental effort after each example and test task. RESULTS: Second-year students invested less mental effort in studying the examples, and in performing the retention and transfer tasks than first-year students. They also performed better on the retention test, but not on the transfer test. In contrast to our hypothesis, there was no interaction between student expertise and model expertise: all students who had studied the Expert examples performed better on the transfer test than students who had studied Advanced Student Examples. CONCLUSIONS: This study suggests that when worked examples are based on actual performance, rather than an ideal procedure, expert models are to be preferred over advanced student models.

[Dutch College of General Practitioners' practice guideline on symptoms of the hand and wrist: a summary]. / De NHG-standaard 'Hand- en polsklachten': samenvatting.

The first edition of the practice guideline for general practitioners (GPs) on hand and wrist symptoms was published in January 2010 by the Dutch College of General Practitioners. This practice guideline provides GPs with pointers for the diagnosis and treatment of hand and wrist symptoms. Carpal tunnel syndrome (CTS) can be diagnosed on its typical clinical presentation alone. The treatment of mild symptoms of CTS, trigger finger and De Quervain's tenosynovitis is conservative, or sometimes a corticosteroid injection: more severe or persistent symptoms require referral to hospital. Mallet finger is treated with a splint for 6 weeks, surgical intervention is necessary for large avulsion fractures or persisting symptoms after treatment with a splint.

[Summary of the practice guideline for shoulder complaints from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Schouderklachten' van het Nederlands Huisartsen Genootschap.

The second revision of the practice guideline for shoulder complaints was presented in 2008 by the Dutch College of General Practitioners. This guideline provides a standard for the diagnosis and treatment of shoulder complaints by general practitioners. The most important items in this new guideline are reviewed.

Effect of an education and activation programme on functional limitations and patient-perceived recovery in acute and sub-acute shoulder complaints - a randomised clinical trial.

BACKGROUND: The education and activation programme (EAP) aims at coping with psychosocial determinants to prevent the development of chronic shoulder complaints (SCs). The effect of the EAP on functional limitations and patient-perceived recovery after 6 and 26 weeks is evaluated in a randomised clinical trial. METHODS: Patients with SCs present at rest or elicited by movement and lasting no longer than 3 months were allocated at random to either EAP as an addition to usual care (UC), or to UC only. Measurements were taken at baseline and after 6 and 26 weeks and were analysed by means of multilevel analysis for the group effect. EAP was administered by GPs or by an ambulant therapist (CDB). Patients in the UC group were given UC by their own GP. RESULTS: Multilevel analysis failed to show a significant effect of the EAP on either functional limitations or patient-perceived recovery. Analysis showed coincidentally a relation between catastrophising at baseline and functional limitations. CONCLUSION: The EAP has no significant effect on the outcome of SCs after 6 and 26 weeks. The relation between catastrophising at baseline and functional limitations suggests that an intervention focusing specifically on catastrophising may be more successful in reducing functional limitations in the long term. Further research is however needed to evaluate the effect of catastrophising at baseline on the course of SCs. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71777817.

General practitioners apply the usual care for shoulder complaints better than expected--analysis of videotaped consultations.

BACKGROUND: The education and activation program (EAP) is a newly developed intervention to prevent the development of chronic shoulder complaints (SCs). Trained general practitioners (GPs) administer the EAP. The EAP addresses inadequate cognitions and maladaptive behavior related to the SCs. The effect of the EAP is evaluated in a randomized clinical trial. The aim of the present study is to use videotaped consultations to study (1) the performance of trained GPs administering the EAP and (2) the presence of key features of the EAP already embedded in usual care (UC). METHODS: Five trained GPs were videotaped while treating a standardized patient with EAP. Additionally, five GPs administering UC were videotaped. Two blinded observers evaluated the videotapes in relation to key features of the EAP which were scored on the EAP checklist. RESULTS: The mean total score on the EAP checklist was 4.7 (SD = 2.9) for the UC group and 7.1 (SD = 2.1) for the EAP group. Neither group reached a score higher than 8, which was considered to reflect an acceptable number of key EAP features. CONCLUSION: Our comparison of the presence of key features of EAP shows that the UC and EAP groups differed less than was expected. GPs in the UC group performed above expectation, with a mean total score of 4.7. Moreover, the low number of key features present in the EAP group may very well have led to a reduced effectiveness of the EAP. The results of this study can be used to optimize the training of GPs using the EAP.

Cost-effectiveness of an education and activation program for patients with acute and subacute shoulder complaints compared to usual care.

OBJECTIVES: Shoulder complaints (SCs) constitute the second largest group of musculoskeletal disorders after low back pain. The economic burden in terms of costs of healthcare use and costs due to work absenteeism underlines the need for a cost-effectiveness analysis of the interventions involved. The education and activation program (EAP) is a newly developed early intervention to prevent the development of chronic SCs. A cost-effectiveness analysis should provide more information on the effect of an EAP on total costs related to SCs. METHODS: We conducted a cost-effectiveness analysis alongside a randomized clinical trial comparing the effectiveness of the EAP in addition to usual care (EAP group) with that of usual care alone (UC group) in terms of preventing chronicity in patients with acute SCs. The aim of the cost-effectiveness analysis was to compare the observed difference in costs with the clinical effectiveness (i.e., patient-perceived recovery after 26 weeks), using bootstraps. RESULTS: The comparison of total costs between treatment groups showed no significant (p = .077) difference after 26 weeks. The majority (82 percent) of the cost-effect pairs after bootstrap analysis were located in the northeast quadrant, suggesting more effect but at higher costs. CONCLUSIONS: In view of the clinical relevance of the clinical outcomes and the considerable costs needed to achieve this, it can be concluded that the EAP is currently not cost-effective.

Cost-effectiveness of a graded exercise therapy program for patients with chronic shoulder complaints.

OBJECTIVES: The present study evaluated the cost-effectiveness of a behavioral graded exercise therapy (GET) program compared with usual care (UC) in terms of the performance of daily activities by patients with chronic shoulder complaints in primary care. METHODS: A total of 176 patients were randomly assigned either to GET (n=87) or to UC (n=89). Clinical outcomes (main complaints, shoulder disability [SDQ] and generic health-related quality of life [EQ-5D], and costs [intervention costs, direct health care costs, direct non-health-related costs, and indirect costs]) were assessed during the 12-week treatment period and at 52 weeks of follow-up. RESULTS: Results showed that GET was more effective than UC in restoring daily activities as assessed by the main complaints instrument after the 12-week treatment period (p = .049; mean difference, 7.5; confidence interval [CI], 0.0-15.0). These effects lasted for at least 52 weeks (p = .025; mean difference 9.2; CI, 1.2-17.3). No statistically significant differences were found on the SDQ or EQ5D. GET significantly reduced direct health care costs (p = .000) and direct non-health care costs (p = .029). Nevertheless, total costs during the 1-year follow-up period were significantly higher (p = .001; GET = Euro 530 versus UC = Euro 377) due to the higher costs of the intervention. Incremental cost-effectiveness ratios for the main complaints (0-100), SDQ (0-100), and EQ-5D (-1.0-1.0) were Euro 7, Euro 74, and Euro 5278 per unit of improvement, respectively. CONCLUSIONS: GET proved to be more effective in the short- and long-term and reduces direct health care costs and direct non-health care costs but is associated with higher costs of the intervention itself.

Comparison of two recruitment strategies for patients with chronic shoulder complaints.

BACKGROUND: Recruiting adequate numbers of participants represents a major problem to the completion of randomised clinical trials in primary care. Information on different recruitment strategies applied in one trial is scarce. AIM: To evaluate the application of two recruitment strategies in one trial. DESIGN OF STUDY: The study was performed within the framework of a randomised clinical trial on the effectiveness of a behavioural treatment for patients with chronic shoulder complaints. SETTING: Thirty-two general practices in the Netherlands. METHOD: Patients recruited during a consultation with their GP for chronic shoulder complaints were compared with patients recruited by advertisement in a local newspaper as regards baseline characteristics, withdrawals (drop-outs and losses to follow-up) and post-treatment clinical outcomes. RESULTS: Patients recruited by the GPs (n = 83) were similar to those recruited by advertisement (n = 83) in terms of demographic characteristics and clinical outcome measures at baseline, but differed slightly in disease characteristics and treatment preferences. Recruitment strategy was not related to reasons for or numbers of withdrawals. Improvements on outcome measures were greater in patients recruited by the GPs, irrespective of allocated treatment. Results on the clinical effectiveness of treatments at the end of the treatment period or during follow-up were neither modified by recruitment strategy, nor by differences between the two strategy groups in patient characteristics found at baseline. CONCLUSION: Using two recruitment strategies did not influence the outcomes on clinical effectiveness in this trial.However, recruitment strategy should be considered as a putative modifying factor in the design of a study.

Implications of process evaluation for clinical effectiveness and clinical practice in a trial on chronic shoulder complaints.

OBJECTIVE: The intervention process was evaluated in a randomised clinical trial on the effectiveness of a behavioural Graded Exercise Therapy (GET) programme for patients with chronic shoulder complaints in primary care settings. This process evaluation was done for three reasons: first, to know whether the programme was performed as planned; second, to know whether or not this treatment is feasible in normal practice; third, to identify needs for improvement of the protocol to facilitate implication. METHODS: We evaluated the extent to which the programme is being applied according to protocol, patient adherence to the programme and the suitability of the programme according to patients and physiotherapists. Twenty participating physiotherapists and 87 patients allocated to GET were asked to evaluate the intervention process. Furthermore, a sample of 10 patients, taken from the total number of 87 patients allocated to GET, was invited to take part in a focus group interview at the end of the study. We evaluated the intervention process using a treatment registration form filled in by the physiotherapists during treatment, evaluation forms filled in independently by physiotherapists and patients 26 weeks after the start of the treatment period, and information gathered during the focus group interview at the end of the study. RESULTS: GET was applied according to protocol to an acceptable extent, and participating patients showed satisfactory adherence to the programme. CONCLUSIONS: Clinical effectiveness of GET in this trial is not influenced by flaws in the application of the programme or by lack of patient adherence. PRACTICE IMPLICATIONS: The programme could be improved in terms of the process of goal-setting, and the implementation of GET could be facilitated if the programme is embedded in a multidisciplinary approach in primary care.

Effectiveness of a graded exercise therapy program for patients with chronic shoulder complaints.

An operant behavioural and time-contingent graded exercise therapy program was developed to improve functional ability irrespective of pain experience in patients with chronic shoulder complaints. The clinical effectiveness of graded exercise therapy compared to usual care was evaluated in a randomised clinical trial. Assessments were carried out before and after 12 weeks of treatment. Performance of daily activities was measured by two outcome measures: the main complaints instrument and the Shoulder Disability Questionnaire (SDQ). Patients were eligible for participation if they had suffered from shoulder complaints for at least three months. Patients suffering from systemic diseases, referred pain or severe biomedical or psychiatric disorders were excluded. Patients (n = 176) were randomised and allocated either to graded exercise therapy (n = 87) or usual care (n = 89). Graded exercise therapy led to greater improvement in the performance of daily activities than usual care. However, only mean differences between groups in performance of activities related to the main complaints reached statistical significance (p = 0.049; 95% CI 0.0 to 15.0). The observed beneficial effects were considered to be small to moderate (calculated effect sizes: 0.30 for the main complaints instrument and 0.07 for the SDQ). Subgroup analysis showed larger improvements on the mean complaints instrument in patients not reporting pain reduction over time. Graded exercise therapy seems to be less effective in restoring performance of daily activities as assessed by the SDQ in patients showing a painful arc during physical examination. Results showed that graded exercise therapy is more effective in restoring the ability to daily activities in patients with chronic shoulder complaints than usual care, although beneficial effects are small.

Evaluation of an education and activation programme to prevent chronic shoulder complaints: design of an RCT [ISRCTN71777817].

BACKGROUND: About half of all newly presented episodes of shoulder complaints (SC) in general practice are reported to last for at least six months. Early interventions aimed at the psychological and social determinants of SC are not common in general practice, although such interventions might prevent the development of chronic SC. The Education and Activation Programme (EAP) consists of an educational part and a time-contingent activation part. The aim of the EAP is to provide patients with the proper cognitions by means of education, and to stimulate adequate behaviour through advice on activities of daily living. DESIGN: The article describes the design of a randomised clinical trial (RCT) to evaluate the effectiveness and cost-effectiveness of an EAP in addition to usual care, compared to usual care only, in the prevention of chronic SC after six months. It also describes the analysis of the cost and effect balance. Patients suffering from SC for less than three months are recruited in general practice and through open recruitment. A trained general practitioner or a trained therapist administers the EAP.Primary outcome measures are patient-perceived recovery, measured by self-assessment on a seven-point scale, and functional limitations in activities of daily living. Questionnaires are used to study baseline measures, prognostic measures, process measures and outcome measures. DISCUSSION: The inclusion of patients in the study lasted until December 31st 2003. Data collection is to end in June 2004.

A behavioural treatment for chronic shoulder complaints: concepts, development, and study design.

This paper discusses the rationale for and content of a newly developed treatment for shoulder complaints, and describes a randomised study which is currently being conducted to test effectiveness of the treatment. In current practice, approximately 50% of all patients with shoulder complaints mention limitations in the performance of daily activities and persisting pain after six months. To improve the functional ability of patients with chronic shoulder complaints, despite their pain, we have developed an operant behavioural and time-contingent graded exercise therapy programme for use in a primary care setting. We present the theory and conceptual model underlying this programme, report on its development and content, and describe the design of a randomised clinical trial to evaluate the programme's effectiveness and cost-effectiveness. One hundred and thirty-two patients who suffer from shoulder complaints for at least 3 months are being recruited in general practice. After inclusion in the study, patients are allocated randomly to the graded exercise therapy programme or to usual care. Questionnaires will be used to measure factors like severity of the main complaint, functional limitations of daily activities, perceived recovery, global health status, shoulder pain, generic health-related quality of life, and costs. These factors will be assessed at baseline, during treatment (6 weeks), and after treatment (12, 26, and 52 weeks).