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Objective: Our objective is to develop a step-by-step approach for our institutes to evaluate the influence of the funding body 1. on risk of bias of an individual study and 2. on publication bias in reviews and meta-analyses for guidelines., Study Design and Setting: Methodologists from guideline organizations in the Netherlands discussed the influence of the funding body in clinical trials researching interventions. Results were discussed in our organizations and presented at the Dutch GRADE Network., Results: Two step-by-step approaches were developed to guide methodologists from our institutes in assessing the influence of the funding body 1. on risk of bias of an individual study and 2. on publication bias in reviews and meta-analyses for guidelines. For risk of bias, the involvement of the funding body in the study is checked as well as the direction of the effect. For publication bias, the exploration by the authors is evaluated, and any difference between industry-funded and non-funded studies in effect is checked. Guiding questions were proposed., Conclusion: The step-by-step approaches make the evaluation of the influence of the funding body more objective and transparent in our institutes. The developed approaches will also be brought forward to the Grading of Recommendations Assessment, Development and Evaluation working group., Competing Interests: Declaration of competing interest B.S., A.S., T.K., and S.H. are members of the Dutch GRADE Network and the GRADE Working Group., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In patients with osteoarthritis of the hip or knee, radiological examinations are only indicated in general practice if there is discrepancy between the history and the findings in the physical examination. The treatment of first choice is a combination of physiotherapy and oral analgesics. If paracetamol fails to reduce the pain sufficiently, NSAIDs can be prescribed. Glucosamine sulfate can be advised for a trial period of three months to reduce knee pain. Intra-articular high molecular hyaluronic acid, intra-articular glucocorticoids, and systemic NSAID's have a similar effect on reducing pain and improving function in the case of osteoarthritis of the knee. The choice of a hip prosthesis should be based on well-documented long term efficiency and the direct and indirect costs. For total knee replacement a cemented non-mobile bearing, posterior stabilised total condylar prosthesis is the first choice. Thromboembolic complications after total hip and knee replacement can be reduced by low molecular weight heparin, fondaparinux, coumarin derivatives, or, after knee replacement, intermittent pneumatic compression. A combination of systemic antibiotics and antibiotic loaded cement is recommended for the prevention of infection during joint replacement. During dental surgery in patients with joint prostheses one oral dose of amoxicillin-clavulinic acid is sufficient as antibiotic prophylaxis. This is only indicated in case of infection.

The multidisciplinary guideline 'Diagnosis and treatment of obesity in adults and children' developed by the Dutch Institute for Healthcare Improvement (CBO) is based on published scientific evidence whenever possible. Diagnosis ofobesity requires a body-mass index (BMI) of 30 kg/m2 or more with additional assessment of waist circumference and comorbidity. For children and adolescents, use ofage-specific BMI thresholds is recommended. Treatment of obesity consists of multiple lifestyle interventions for at least 1 year, followed by long-term management aimed at weight maintenance or any further weight loss. In adults, the goal is to achieve weight loss of at least 5% and a reduction in waist circumference of at least 10% after 1 year. If weight loss after 1 year is less than 5%, the addition of pharmacological interventions to lifestyle interventions can be considered. Bariatric surgery can be considered for patients with a BMI of 40 kg/m2 or more and for those with BMI 35-40 kg/m2 with one or more comorbidities. Pharmacological and surgical interventions are not recommended for children and adolescents.

Objectives: To investigate the course and prognosis of shoulder pain in the first 6 months after presentation to the general practitioner. We separately studied patients with acute, subacute and chronic shoulder pain, as duration of symptoms at presentation has been shown to be the strongest predictor of outcome., Methods: A prospective cohort study with 6 months follow-up was carried out in The Netherlands, including 587 patients with a new episode of shoulder pain. Patients were categorized as having acute (symptoms <6 weeks), subacute (6-12 weeks) or chronic (>3 months) shoulder pain. The course of shoulder pain, functional disability and quality of life was analysed over 6 months. Patient and disease characteristics, including physical and psychosocial factors, were investigated as possible predictors of outcome using multivariable regression analyses., Results: Acute shoulder symptoms showed the most favourable course over 6 months follow-up, with larger pain reduction and improvement of functional disability. Patients with chronic shoulder symptoms showed the poorest results. The multivariable regression analysis showed that predictors of a better outcome at 6 months for acute shoulder pain were lower baseline disability scores and higher baseline pain intensity (explained variance 46%). Predictors of a better outcome for chronic shoulder pain were lower scores on pain catastrophizing and higher baseline pain intensity (explained variance 21%)., Conclusions: The results indicate that, besides a different course of symptoms in patients presenting with acute or chronic shoulder pain, predictors of outcome may also differ with psychosocial factors being more important in chronic shoulder pain.

Objectives: Recently, a rule was developed to predict sick leave related to shoulder pain during a period of 6 months after patients have consulted a general practitioner for a new episode of shoulder pain. The objective was to evaluate the generalizability of this prediction rule by testing it in two other populations of workers who had gone for a consultation in primary care for a new episode of shoulder pain., Methods: The prediction rule was derived in a prognostic cohort study (N=350). The outcome was sick leave related to shoulder pain during 6 months following the first consultation. The rule was tested on merged control groups from three trials on shoulder pain (N=128). In addition to this population, a recently conducted study on musculoskeletal disorders (N=224) was used to validate the prediction rule. The generalizability of the prediction rule was tested by studying calibration and discrimination in the validation cohorts., Results: The prediction rule showed reasonable calibration in both validation cohorts. The discriminative ability, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.70 in the derivation cohort was stable in the cohort of the musculoskeletal disorder study (AUC 0.71). In the control groups of the three randomized controlled trials of a Dutch shoulder study, the discriminative ability decreased to an AUC of 0.66., Conclusions: The prediction rule for sick leave related to shoulder pain in a 6-month period following the first consultation in primary care showed adequate generalizability to another population of workers with shoulder pain participating in an observational cohort study. In the control groups of the three randomized controlled trials the prediction rule performed less well.

Shoulder pain is common in primary care and has an unfavourable outcome in many patients. Information about predictors of outcome is scarce and inconsistent. The objective of this study was to develop clinical prediction rules for calculating the absolute risk of persistent shoulder symptoms for individual patients, 6 weeks and 6 month after the first consultation in general practice. A prospective cohort study with 6 months follow-up was carried out in three geographic areas in The Netherlands. In this study, 587 patients with a new episode of shoulder pain were included. The main outcome measure was persistent symptoms at 6 weeks and 6 months, perceived by the patient. Potential predictors included the results of a physical examination, sociodemographic variables, disease characteristics (duration of symptoms, pain intensity, disability and comorbidity), physical activity, physical workload and psychosocial factors. Response rates to the follow-up questionnaires were 83% at 6 weeks and 92% at 6 months. A longer duration of symptoms, gradual onset of pain and high pain severity at presentation were consistently associated with persistent symptoms at 6 weeks and 6 months. The discriminative validity of our prediction rules was satisfactory with area under the curves of 0.74 (95% CI 0.70, 0.79) at 6 weeks and 0.67 (95% CI 0.63, 0.71) at 6 months. The performance of our rules needs to be tested in other populations of patients with shoulder pain to enable valid and reliable use of the rules in everyday clinical practice.

Mannose-binding protein (MBL) is a critical component of innate immunity and provides first-line protection against pathogens. Both circulating MBL serum levels and functional activity have been correlated with common genetic variants in the MBL2 gene. Associations between MBL deficiency and severe infections have been reported in immuno-incompetent patients and for autoimmune disorders; however, measured MBL serum levels do not fully correlate with the 'secretor haplotypes'. Previously, the MBL2 locus was resequenced and determined that a recombination hotspot divides MBL2 into two haplotype blocks. It was sought to investigate whether additional variants, in either block structure could associate with MBL serum levels. Therefore, 31 common variants were analysed across the locus in 212 DNA samples of healthy Caucasian individuals with known MBL serum concentrations. The additional 5' variants were in strong linkage to the elements of the 'secretor haplotypes'; functional alleles B, C and D also lie on restricted haplotypes. Four variants in the 3' block (Ex4-1483T>C, Ex4-1067G>A, Ex4-901G>A and Ex4-710G>A) are components of a distinct haplotype block. The results of this study suggest that additional 5' variants as well as markers of distinct 3' haplotype blocks in MBL2 may contribute to circulating protein levels, but further studies are required to confirm these observations. Last, there could be a selective advantage for diversification of the 3' region of the gene.