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Background: Clinically feasible and reliable methods to measure motor control in people with low back pain (LBP) are lacking. This reliability and measurement error study design (i.e. repeated measurements in stable patients) aimed to determine the intra- and interrater reliability, and measurement errors of several parameters for two clinical lumbar motor control tests. Method: Participants 18–65 years of age, with current or a history of LBP performed a spiral tracking task (n = 33; i.e., tracing a spiral on a computer monitor by making spinal movements) or a repositioning task (n = 34; i.e., returning the trunk to a predefined position). Accelerometers were used to measure trunk positions. To explore the potential of these tests, we evaluated a broad range of parameters. To assess intra- and interrater reliability, we calculated the intraclass correlation coefficient (ICC (2,1) for absolute agreement), standard error of measurement and smallest detectable change for each parameter. Findings: Overall, the interrater reliability of the spiral tracking test was good (ICC>0.75). The reliability of the second and third trial revealed higher ICC values compared to the reliability of the first two trials. The intra- and interrater reliability of the repositioning test was overall poor (ICC

Introduction: Appropriate treatment for people with an increased risk for developing chronic Persistent Somatic Symptoms (PSS) is of great importance at an early stage to improve quality of life and prevent high costs for society. Objective: To evaluate the cost-effectiveness of an integrated blended care intervention compared to usual care for QALYs, subjective symptom impact and physical and mental health status in patients with moderate PSS. Methods: This economic evaluation was conducted alongside a 12-month prospective, multicenter cluster randomized controlled trial in Dutch primary care. 80 participants received the intervention and 80 participants received usual care. Seemingly unrelated regression analyzes were performed to estimate cost and effect differences. Missing data were imputed using multiple imputation. Bootstrapping techniques were used to estimate uncertainty. Results: We found no significant difference in total societal costs. Intervention, primary and secondary healthcare and absenteeism costs were higher for the intervention group. The ICER for QALYs demonstrated the intervention was on average less costly and less effective compared to usual care. For the subjective symptom impact and physical health, the ICER indicated that the intervention group was on average less costly and more effective. For mental health, the intervention was on average more costly and less effective. Conclusion: We didn't find an integrated blended primary care intervention to be cost-effective compared to usual care. However, when looking on relevant, but specific outcome measures (subjective symptom impact and physical health) for this population, average costs are found to be lower and the effectiveness found to be higher.

The objective of the study was to gain an insight into the perceptions and experiences of patients with rheumatoid arthritis and a high cardiovascular disease risk (CVD-RA) when undergoing an exercise intervention aimed at improving their cardiorespiratory fitness. This qualitative study was part of a pilot study, which investigated the effects of an exercise intervention on cardiorespiratory fitness in patients with CVD-RA. Six patients were invited to participate in face-to-face semi-structured interviews. We invited patients who completed the exercise intervention as well as patients who withdrew from the exercise intervention. The interviews were analyzed according to the method of thematic analysis. Six patients were interviewed, of whom four patients completed and two patients discontinued the exercise intervention. The mean (SD) age was 58 (9.7) years, the median disease duration was 10 years, and five patients were female. The analyses revealed seven themes that provided insight into perceptions and experiences: (1) ability to understand reasons for actions; (2) the need to be seen; (3) reaching their maximum effort; (4) experiencing their limits; (5) wanting personalized exercise therapy; (6) happy to be physically active; (7) benefits of exercise. Patients perceived that they were able to perform a cardiopulmonary exercise test with maximum effort and achieved the prescribed intensity of the exercise intervention. They also experienced an improvement in their physical activity by incorporating physical activity in their daily live. Overarching principles that re-occurred in the themes were: the need to be viewed as a person and the importance of feeling safe.

Introduction: Conflicting evidence exists concerning whether having sarcopenic obesity has additive mortality risk over having only sarcopenia or obesity. We examined the independent and combined associations of obesity and probable sarcopenia with all-cause mortality. Methods: The pooled analysis included three large, harmonized datasets (Health 2000 Survey; Health, Aging and Body Composition Study; Longitudinal Aging Study Amsterdam) with mortality follow-up data on individuals aged 70 years and over at baseline (n = 4,612). Obesity indicators included body mass index and waist circumference, and probable sarcopenia was defined based on grip strength. The mixed effects Cox model was used for statistical analyses, adjusting for age, sex, marital status, education, race, physical activity, alcohol consumption, smoking, and baseline diseases. Results: Risk of death increased for those having probable sarcopenia only (hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.39–1.85) or probable sarcopenia with obesity (HR: 1.36, 95% CI: 1.13–1.64) but not for the obese-only group (HR: 0.92, 95% CI: 0.85–1.01), when compared to non-obese non-sarcopenic individuals. The results were similar regardless of adjustments for covariates or different obesity criteria applied. Conclusion: Probable sarcopenia, whether combined with obesity or not, is associated with increased mortality. Obesity did not increase mortality among older adults. Maintaining muscle strength and identifying older adults at risk of sarcopenia is important for the prevention of premature mortality.

Background: In this study, we aimed to provide insight into the 90-day complication rates following the Latarjet procedure. Data from 2015 were collected from multiple hospitals in the Netherlands, with different volumes of Latarjet procedures. Our second aim was to examine which patient and surgical factors were associated with complications.Methods: We conducted a retrospective chart review of 13 hospitals between 2015 and 2022. Data regarding complications within 90 days of Latarjet procedures were extracted. The effect of sex, age, body mass index (BMI), smoking, previous shoulder operations, fixation material, hospital volume, screw size, and operation time on the complication rate was assessed by multivariable logistic regression analysis.Results: Of the 532 included patients, 58 (10.9%) had complications. The most common complications were material failure (n = 19, 3.6%) and nerve injury (n = 13, 2.4%). The risk of complications was lower for male patients than for female patients (odds ratio, 0.40; 95% confidence interval, 0.21-0.77; P = .006). Age, BMI, smoking, previous shoulder operations, type of fixation material, hospital volume, screw size, and operation time were not associated with complications.Conclusion: The 90-day complication rate after the Latarjet procedure was 10.9% and was higher in female patients than in male patients. Age, BMI, smoking, previous shoulder operations, type of fixation material, hospital volume, screw size, and operation time did not affect complication rates. We advise setting up a national registry to prevent under-reporting of complications.

Stretching is applied to lengthen shortened muscles in pathological conditions such as joint contractures. We investigated (i) the acute effects of different types of stretching, i.e. constant length (CL) and constant force (CF) stretching, on acute deformations and changes in passive mechanical properties of medial gastrocnemius muscle (MG) and (ii) the association of acute muscle–tendon deformations or changes in mechanical properties with the impulse or maximal strain of stretching. Forty-eight hindlimbs from 13 male and 12 female Wistar rats (13 weeks old, respectively 424.6 ± 35.5 and 261.8 ± 15.6 g) were divided into six groups (n = 8 each). The MG was initially stretched to a length at which the force was 75%, 95%, or 115% of the force corresponding to estimated maximal dorsiflexion and held at either CF or CL for 30 min. Before and after the stretching protocol, the MG peak force and peak stiffness were assessed by lengthening the passive muscle to the length corresponding to maximal ankle dorsiflexion. Also, the muscle belly length and tendon length were measured. CF stretching affected peak force, peak stiffness, muscle belly length, and tendon length more than CL stretching (p < 0.01). Impulse was associated only with the decrease in peak force, while maximal strain was associated with the decrease in peak force, peak stiffness, and the increase in muscle belly length. We conclude that CF stretching results in greater acute deformations and changes in mechanical properties than CL stretching, which appears to be dependent predominantly on the differences in imposed maximal strain.

Purpose Adolescent idiopoathic scoliosis (AIS) is a progressive spinal deformity, most often observed in female patients of pubescent age. The deformity’s severity, its progression through time, its treatment and subsequent follow-up are assessed with routine radiological evaluation of the patient’s full spine. This study aimed to determine the cumulative radiation exposure in average patients with AIS treated by brace or surgery throughout their treatment. Methods The average number of imaging procedures and corresponding radiation doses were retrospectively obtained from the medical charts of AIS patients treated conservatively and/or surgically at our institution. The median radiation exposure of all imaging modalities was stated in effective dose (mSv). The estimated cumulative effective radiation dose of the each treatment group was determined by multiplication of the average number of imaging conducted, and the median effective radiation dose per imaging modality. Results In total, 73 AIS patients were included (28 brace, 45 surgically). Patients treated with a brace were subjected to an average of 9.03 full spine radiographs, resulting in an estimated effective cumulative dose of 0.505 mSv over a median treatment period of 3.23 years. Patients treated surgically received an average of 14.29 full spine radiographs over a median treatment period of 2.76 years. The estimated effective cumulative dose amounted from 0.951 to 1.841 mSv, depending on the surgical technique. Conclusion The cumulative effective radiation doses rendered to AIS patients as part of their treatment and follow-up were relatively low. However, every exposure to ionising radiation for medical imaging purposes should be minimised.

Objective: To evaluate differences regarding the number of treatment sessions, costs, and outcomes (including relapses) between a regular payment-per-session system and the recently introduced product payment system in The Netherlands. Design: Prospective cohort study. Setting: Dutch physical therapy practices in primary care over a 2-year period. Participants: 16,103 patients with low back pain (LBP). Intervention: The new product payment system is compared with the regular payment-per-session system. Main Outcome Measures: Pain, disability, recovery, number of physical therapy sessions, therapy duration, costs (per episode), and LBP relapse. Results: At baseline, we found greater pain and disability scores associated with an increased risk profile in both payment systems. With regard to the payment systems, we found greater costs (€283.8 vs €210.8) and a greater percentage of relapse (4.5% vs 2.8%) for the product payment system compared with the payment-per-session system. Comparing the 2 payment systems within each risk strata, we found no significant differences, except for a decrease in pain in the medium-risk stratum. Concerning the therapy characteristics, we found that in the payment-per-session group, the therapy took 6 days longer for low-risk patients (median 27 vs 21 days) and 7 days shorter for high-risk patients (median 42 vs 49 days) compared with the product payment group. Moreover, the mean number of sessions in the payment-per-session group was greater for low-risk patients (5.4 vs 4.8 sessions) and lower for high-risk patients (7.7 vs 8.1 sessions) compared with the payment-per-session group. Finally, the costs were significantly greater in all strata of the product payment group compared with the payment-per-session group. Conclusions: The 2 payment systems are largely comparable regarding patient outcomes, therapy duration, and treatment sessions. Both the average cost per patient per LBP episode and the number of relapses in the product payment system are statistically significantly greater than in the payment-per-session system.

Background: The consequences of radial nerve palsy associated with a humeral shaft fracture are unclear. The aim of this study was to examine the functional recovery of radial nerve palsy, at presentation or postoperatively, in patients with a humeral shaft fracture. Methods: Data from patients who participated in the HUMeral shaft fractures: measuring recovery after operative versus non-operative treatment (HUMMER) study, a multicenter prospective cohort study including adults with a closed humeral shaft fracture Arbeitsgemeinschaft für Osteosynthesefragen (AO) type 12A or 12B, and had radial nerve palsy at presentation or postoperatively, were extracted from the HUMMER database. The primary outcome measure was clinically assessed recovery of motor function of the radial nerve. Secondary outcomes consisted of treatment, functional outcome (Disabilities of the Arm, Shoulder, and Hand and Constant–Murley Score), pain level, quality of life (Short Form-36 and EuroQoL-5D-3L), activity resumption, and range of motion of the shoulder and elbow joint at 12 months after trauma. Results: Three of the 145 nonoperatively treated patients had radial nerve palsy at presentation. One recovered spontaneously and 1 after osteosynthesis. Despite multiple surgical interventions, the third patient had no recovery after entrapment between fracture fragments. Thirteen of the 245 operatively treated patients had radial nerve palsy at presentation; all recovered. Nine other patients had postoperative radial nerve palsy; 8 recovered. One had ongoing recovery at the last follow-up, after nerve release and suture repair due to entrapment under the plate. At 12 months, the functional outcome scores of all patients suggested full recovery regarding functional outcome, pain, quality of life, activity resumption, and range of motion. Conclusion: Radial nerve palsy in patients with a humeral shaft fracture at presentation or postoperatively functionally recovers in 94% and 89%, respectively.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis, of which the pathogenesis and best treatment options are unclear. In this report, we describe the case of a 34-year old woman diagnosed with severe osteoporosis and multiple vertebral fractures after her first pregnancy, who was subsequently treated with teriparatide (TPTD) and zoledronic acid (ZA). We describe the clinical features, imaging examination, and genetic analysis. Substantial improvements were observed in areal and volumetric bone mineral density (BMD), microarchitecture, and strength between 7 and 40 months postpartum as assessed by dual-energy X-ray absorptiometry at the total hip and spine and by high-resolution peripheral quantitative CT at the distal radius and tibiae. At the hip, spine, and distal radius, these improvements were mainly enabled by treatment with TPTD and ZA, while at the distal tibiae, physiological recovery and postpartum physiotherapy due to leg pain after stumbling may have played a major role. Additionally, the findings show that, despite the improvements, BMD, microarchitecture, and strength remained severely impaired in comparison with healthy age- and gender-matched controls at 40 months postpartum. Genetic analysis showed no monogenic cause for osteoporosis, and it is suggested that PLO in this woman could have a polygenic origin with possible susceptibility based on familiar occurrence of osteoporosis.

Purpose To describe the long-term clinical results of arthroscopic fragment fixation for chronic primary osteochondral lesions of the talus (OLT), using the Lift-Drill-Fill-Fix (LDFF) technique. Methods Eighteen patients (20 ankles) underwent fixation for a primary OLT with an osteochondral fragment using arthroscopic LDFF and were evaluated at a minimum of 5-year follow-up. Pre- and postoperative clinical assessment was prospectively performed by measuring the Numeric Rating Scale (NRS) of pain at rest, during walking and when running. Additionally, the change in Foot and Ankle Outcome Score (FAOS) and the procedure survival (i.e., no reoperation for the OLT) at final follow-up was assessed. Results At a mean follow-up of 7 years, the median NRS during walking significantly improved from 7 (IQR 5–8) pre-operatively to 0 (IQR 0–1.5) at final follow-up (p = p p = Conclusion Arthroscopic LDFF for fixable chronic primary OLTs results in excellent pain reduction and improved patient-reported outcomes, with sustained results at long-term follow-up. These results indicate that surgeons may consider arthroscopic LDFF as treatment of choice for fragmentous OLT. Level of evidence Level IV, prospective case series.

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

Background Providing individualized care based on the context and preferences of the patient is important. Knowledge on both prognostic risk stratification and blended eHealth care in musculoskeletal conditions is increasing and seems promising. Stratification can be used to match patients to the most optimal content and intensity of treatment as well as mode of treatment delivery (i.e. face-to-face or blended with eHealth). However, research on the integration of stratified and blended eHealth care with corresponding matched treatment options for patients with neck and/or shoulder complaints is lacking. Methods This study was a mixed methods study comprising the development of matched treatment options, followed by an evaluation of the feasibility of the developed Stratified Blended Physiotherapy approach. In the first phase, three focus groups with physiotherapists and physiotherapy experts were conducted. The second phase investigated the feasibility (i.e. satisfaction, usability and experiences) of the Stratified Blended Physiotherapy approach for both physiotherapists and patients in a multicenter single-arm convergent parallel mixed methods feasibility study. Results In the first phase, matched treatment options were developed for six patient subgroups. Recommendations for content and intensity of physiotherapy were matched to the patient’s risk of persistent disabling pain (using the Keele STarT MSK Tool: low/medium/high risk). In addition, selection of mode of treatment delivery was matched to the patient’s suitability for blended care (using the Dutch Blended Physiotherapy Checklist: yes/no). A paper-based workbook and e-Exercise app modules were developed as two different mode of treatment delivery options, to support physiotherapists. Feasibility was evaluated in the second phase. Physiotherapists and patients were mildly satisfied with the new approach. Usability of the physiotherapist dashboard to set up the e-Exercise app was considered ‘OK’ by physiotherapists. Patients considered the e-Exercise app to be of ‘best imaginable’ usability. The paper-based workbook was not used. Conclusion Results of the focus groups led to the development of matched treatment options. Results of the feasibility study showed experiences with integrating stratified and blended eHealth care and have informed amendments to the Stratified Blended Physiotherapy approach for patients with neck and/or shoulder complaints ready to use within a future cluster randomized trial.

Objectives To investigate cartilage tissue turnover in response to a supervised 12-week exercise-related joint loading training program followed by a 6-month period of unsupervised training in patients with knee osteoarthritis (OA). To study the difference in cartilage tissue turnover between high- and low-resistance training. Method Patients with knee OA were randomized into either high-intensity or low-intensity resistance supervised training (two sessions per week) for 3 months and unsupervised training for 6 months. Blood samples were collected before and after the supervised training period and after the follow-up period. Biomarkers huARGS, C2M, and PRO-C2, quantifying cartilage tissue turnover, were measured by ELISA. Changes in biomarker levels over time within and between groups were analyzed using linear mixed models with baseline values as covariates. Results huARGS and C2M levels increased after training and at follow-up in both low- and high-intensity exercise groups. No changes were found in PRO-C2. The huARGS level in the high-intensity resistance training group increased significantly compared to the low-intensity resistance training group after resistance training (p = 0.029) and at follow-up (p = 0.003). Conclusion Cartilage tissue turnover and cartilage degradation appear to increase in response to a 3-month exercise-related joint loading training program and at 6-month follow-up, with no evident difference in type II collagen formation. Aggrecan remodeling increased more with high-intensity resistance training than with low-intensity exercise. These exploratory biomarker results, indicating more cartilage degeneration in the high-intensity group, in combination with no clinical outcome differences of the VIDEX study, may argue against high-intensity training.

Background: This study aimed to assess the feasibility of postmortem ultra-high-field magnetic resonance imaging (UHF-MRI) to study fetal musculoskeletal anatomy and explore the contribution of variation in iodine and formaldehyde (paraformaldehyde, PFA) treatment of tissue. Methods: Seven upper extremities from human fetuses with gestational ages of 19 to 24 weeks were included in this experimental study, approved by the Medical Research Ethics Committee. The specimens were treated with various storage (0.2–4% PFA) and staining (Lugol’s solution) protocols and the wrist joint was subsequently imaged with 7.0 T UHF-MRI. Soft-tissue contrast was quantified by determining regions of interest within a chondrified carpal bone (CCB) from the proximal row, the triangular fibrocartilage (TFC), and the pronator quadratus muscle (PQM) and calculating the contrast ratios (CRs) between mean signal intensities of CCB to TFC and CCB to PQM. Results: UHF-MRI showed excellent soft-tissue contrast in different musculoskeletal tissues. Increasing storage time in 4% PFA, CRs decreased, resulting in a shift from relatively hyperintense to hypointense identification of the CCB. Storage in 0.2% PFA barely influenced the CRs over time. Lugol’s solution caused an increase in CRs and might have even contributed to the inversion of the CRs. Conclusions: UHF-MRI is a feasible technique to image musculoskeletal structures in fetal upper extremities and most successful after short storage in 4% PFA or prolonged storage in 0.2% PFA. The use of Lugol’s solution is not detrimental on soft-tissue MRI contrast and therefore enables effectively combining UHF-MRI with contrast-enhanced micro-computed tomography using a single preparation of the specimen. Relevance statement: UHF-MRI can be performed after CE-micro-CT to take advantage of both techniques. Key points: • UHF-MRI is feasible to study human fetal cartilaginous and ligamentous anatomy. • Storage in low PFA concentrations (i.e., 0.2%) improves soft-tissue contrast in UHF-MRI. • Limited preservation time in high concentrations of PFA improves soft-tissue contrast in UHF-MRI. • Prior staining with Lugol’s solution does not reduce soft-tissue contrast in UHF-MRI. Graphical Abstract: [Figure not available: see fulltext.].

Background: Baricitinib is an oral selective inhibitor of Janus kinase 1 and 2 approved for the treatment of rheumatoid arthritis, atopic dermatitis, and alopecia areata. In a 24-week phase 2 study in patients with systemic lupus erythematosus (SLE), baricitinib 4 mg significantly improved SLE disease activity compared with placebo. The objective of this trial was to evaluate the efficacy and safety of baricitinib in patients with active SLE in a 52-week phase 3 study. Methods: In a multicentre, double-blind, randomised, placebo-controlled, parallel-group, phase 3 study, SLE-BRAVE-I, patients (aged ≥18 years) with active SLE receiving stable background therapy were randomly assigned 1:1:1 to baricitinib 4 mg, 2 mg, or placebo once daily for 52 weeks with standard of care. Glucocorticoid tapering was encouraged but not required per protocol. The primary endpoint was the proportion of patients reaching an SLE Responder Index (SRI)-4 response at week 52 in the baricitinib 4 mg treatment group compared with placebo. The primary endpoint was assessed by logistic regression analysis with baseline disease activity, baseline corticosteroid dose, region, and treatment group in the model. Efficacy analyses were done on a modified intention-to-treat population, comprising all participants who were randomly assigned and received at least one dose of investigational product. Safety analyses were done on all randomly assigned participants who received at least one dose of investigational product and who did not discontinue from the study for the reason of lost to follow-up at the first post-baseline visit. This study is registered with ClinicalTrials.gov, NCT03616912. Findings: 760 participants were randomly assigned and received at least one dose of baricitinib 4 mg (n=252), baricitinib 2 mg (n=255), or placebo (n=253). A significantly greater proportion of participants who received baricitinib 4 mg (142 [57%]; odds ratio 1·57 [95% CI 1·09 to 2·27]; difference with placebo 10·8 [2·0 to 19·6]; p=0·016), but not baricitinib 2 mg (126 [50%]; 1·14 [0·79 to 1·65]; 3·9 [–4·9 to 12·6]; p=0·47), reached SRI-4 response compared with placebo (116 [46%]). There were no significant differences between the proportions of participants in either baricitinib group reaching any of the major secondary endpoints compared with placebo, including glucocorticoid tapering and time to first severe flare. 26 (10%) participants receiving baricitinib 4 mg had serious adverse events, 24 (9%) participants receiving baricitinib 2 mg, and 18 (7%) participants receiving placebo. The safety profile of baricitinib in participants with SLE was consistent with the known baricitinib safety profile. Interpretation: The primary endpoint in this study was met for the 4 mg baricitinib group. However, key secondary endpoints were not. No new safety signals were observed. Funding: Eli Lilly and Company.

Objective The primary aim was to determine and compare the complication rate of different surgical treatment options for osteochondral lesions of the talus (OLTs). The secondary aim was to analyze and compare the severity and types of complications. Design A literature search was performed in MEDLINE (PubMed), EMBASE (Ovid), and the Cochrane Library. Methodological quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS). Primary outcome was the complication rate per surgical treatment option. Secondary outcomes included the severity (using the Modified Clavien-Dindo-Sink Complication Classification System for Orthopedic Surgery) and types of complications. The primary outcome, the severity, and the sub-analyses were analyzed using a random effects model. A moderator test for subgroup-analysis was used to determine differences. The types of complications were presented as rates. Results In all, 178 articles from the literature search were included for analysis, comprising 6,962 OLTs with a pooled mean age of 35.5 years and follow-up of 46.3 months. Methodological quality was fair. The overall complication rate was 5% (4%-6%; treatment group effect, P = 0.0015). Analysis resulted in rates from 3% (2%-4%) for matrix-assisted bone marrow stimulation to 15% (5%-35%) for metal implants. Nerve injury was the most observed complication. Conclusions In 1 out of 20 patients treated surgically for an OLT, a complication occurs. Metal implants have a significantly higher complication rate compared with other treatment modalities. No life-threatening complications were reported.

Introduction Negative pain-related cognitions are associated with persistence of low-back pain (LBP), but the mechanism underlying this association is not well understood. We propose that negative pain-related cognitions determine how threatening a motor task will be perceived, which in turn will affect how lumbar movements are performed, possibly with negative long-term effects on pain. Objective To assess the effect of postural threat on lumbar movement patterns in people with and without LBP, and to investigate whether this effect is associated with task-specific pain-related cognitions. Methods 30 back-healthy participants and 30 participants with LBP performed consecutive two trials of a seated repetitive reaching movement (45 times). During the first trial participants were threatened with mechanical perturbations, during the second trial participants were informed that the trial would be unperturbed. Movement patterns were characterized by temporal variability (CyclSD), local dynamic stability (LDE) and spatial variability (meanSD) of the relative lumbar Euler angles. Pain-related cognition was assessed with the task-specific ‘Expected Back Strain’-scale (EBS). A three-way mixed Manova was used to assess the effect of Threat, Group (LBP vs control) and EBS (above vs below median) on lumbar movement patterns. Results We found a main effect of threat on lumbar movement patterns. In the threat-condition, participants showed increased variability (MeanSDflexion-extension, p2 = 0.26; CyclSD, p = 0.003, η2 = 0.14) and decreased stability (LDE, p = 0.004, η2 = 0.14), indicating large effects of postural threat. Conclusion Postural threat increased variability and decreased stability of lumbar movements, regardless of group or EBS. These results suggest that perceived postural threat may underlie changes in motor behavior in patients with LBP. Since LBP is likely to impose such a threat, this could be a driver of changes in motor behavior in patients with LBP, as also supported by the higher spatial variability in the group with LBP and higher EBS in the reference condition.

ObjectiveTo examine the prevalence of hip involvement between sexes in patients with ankylosing spondylitis (AS) treated with tumor necrosis factor inhibitors (TNFi) and to estimate the effect of TNFi on radiographic progression of hip involvement compared to the spine.MethodsTwo hundred ninety-nine patients with AS treated with TNFi (215 men; median age: 43 yrs [IQR 36-52], median disease duration: 7.6 yrs [IQR 2-15]) were evaluated for hip involvement, defined radiographically as Bath AS Radiological Hip Index (BASRI-hip) score ≥ 2. Those who received TNFi for ≥ 2 years (263/299) were assessed for radiographic progression. Radiographs of the pelvis and spine, obtained at baseline (ie, before TNFi initiation), were compared retrospectively to those obtained after 2.5 (SD 0.7) years and 7.0 (SD 2.3) years of TNFi treatment. Both hips were scored by BASRI-hip score and mean joint space width (MJSW). Spinal radiographs were scored by modified Stoke AS Spinal Score (mSASSS).ResultsThe prevalence of hip involvement at baseline was 113/299 (38%) patients, of whom 87/215 (41%) were male and 26/84 (31%) were female (P= 0.10). In both sexes with hip involvement at baseline, BASRI-hip score and MJSW did not change significantly during follow-up. In males and females without baseline hip involvement, the BASRI-hip score remained unchanged after 2.5 (SD 0.7) years but increased significantly after 7.0 (SD 2.3) years, without reaching the cut-off of 2. In contrast, the MJSW slightly decreased at the 2 follow-up timepoints (ie, after 2.5 and 7.0 yrs). The mSASSS increased significantly during the follow-up in both sexes, regardless of hip involvement.ConclusionIn our study, approximately one-third of patients with AS had hip involvement, which seemed to stabilize with TNFi treatment. No sex differences in the prevalence or progression of this manifestation were found.

IntroductionThe effectiveness of rotator cuff tear repair surgery is influenced by multiple patient-related, pathology-centred and technical factors, which is thought to contribute to the reported retear rates between 17% and 94%. Adequate patient selection is thought to be essential in reaching satisfactory results. However, no clear consensus has been reached on which factors are most predictive of successful surgery. A clinical decision tool that encompassed all aspects is still to be made. Artificial intelligence (AI) and machine learning algorithms use complex self-learning models that can be used to make patient-specific decision-making tools. The aim of this study is to develop and train an algorithm that can be used as an online available clinical prediction tool, to predict the risk of retear in patients undergoing rotator cuff repair.Methods and analysisThis is a retrospective, multicentre, cohort study using pooled individual patient data from multiple studies of patients who have undergone rotator cuff repair and were evaluated by advanced imaging for healing at a minimum of 6 months after surgery. This study consists of two parts. Part one: collecting all potential factors that might influence retear risks from retrospective multicentre data, aiming to include more than 1000 patients worldwide. Part two: combining all influencing factors into a model that can clinically be used as a prediction tool using machine learning.Ethics and disseminationFor safe multicentre data exchange and analysis, our Machine Learning Consortium adheres to the WHO regulation ‘Policy on Use and Sharing of Data Collected by WHO in Member States Outside the Context of Public Health Emergencies’. The study results will be disseminated through publication in a peer-reviewed journal. Institutional Review Board approval does not apply to the current study protocol.

Background: Low back pain (LBP) is the leading cause of disability worldwide and has an excessive societal burden. Accumulating evidence has shown that some medical approaches such as imaging in absence of clear indications, medication and some invasive treatments may contribute to the problem rather than alleviating it. Objectives: To determine the extent of de-implementation of non-evidence-based hospital treatments for LBP care in the Netherlands in the last three decades. Methods: Using a register-based population-level observational study with Dutch hospital data, providing a nearly complete coverage of hospital admissions in the Netherlands in 1991–2018, we assessed five frequently applied non-evidence-based hospital treatments for LBP. Time trends in treatment use (absolute and per 100,000 inhabitants) were plotted and analysed using Poisson regression. Results: The use of bed rest for non-specific LBP and hernia nuclei pulposi, and discectomy for spinal stenosis decreased 91%, 81% and 86% since the availability of evidence/guidelines, respectively. De-implementation, beyond 84%, was reached after 18 and 17 years for bed rest for non-specific LBP and discectomy respectively, while it was not reached after 28 years for bed rest for hernia nuclei pulposi. For spinal fusion and invasive pain treatment, there was an initial increase followed by a reduction. Overall, these treatments reduced by 85% and 75%, respectively. Conclusions: In the Netherlands, de-implementation of five non-recommended hospital LBP treatments, if at all, took several decades. Although de-implementation was substantial, slow de-implementation has likely resulted in considerable waste of resources and avoidable harm to many patients in Dutch hospitals. Significance: Medically intensive approaches to low-back pain care contribute to the high societal burden of this disease. There have been calls to avoid such care. Using Dutch hospital data, we showed that de-implementation of five non-recommended hospital low-back pain treatments, if at all, took several decades (i.e. ≥17 years) after availability of evidence and guidelines. Slow de-implementation has likely resulted in considerable waste of resources and avoidable harm to hospital patients; better ways for de-implementation of non-evidence-based care are needed.

The Doha agreement classification is used to classify groin pain in athletes. We evaluated the inter-examiner reliability of this classification system. We prospectively recruited 48 male athletes (66 symptomatic sides) with groin pain between 10–2017 and 03–2020 at a sports medicine hospital in Qatar. Two examiners (23 and 10 years of clinical experience) performed history taking, and a standardized clinical examination blinded to each other's findings. Examiners classified groin pain using the Doha agreement terminology (adductor-, inguinal-, iliopsoas-, pubic-, hip-related groin pain, or other causes of groin pain). Multiple entities were ranked in order of perceived clinical importance. Each side was classified separately for bilateral groin pain. Inter-examiner reliability was calculated using Cohen's Kappa statistic (κ). Inter-examiner reliability was slight to moderate for adductor- (κ = 0.40), inguinal- (κ = 0.44), iliopsoas- (κ = 0.57), and pubic-related groin pain (κ = 0.12), substantial for hip-related groin pain (κ = 0.62), and slight for “other causes of groin pain” (κ = 0.13). Ranking entities in order of perceived clinical importance improved inter-examiner reliability for adductor-, inguinal-, and iliopsoas-related groin pain (κ = 0.52–0.65), but not for pubic (κ = 0.12), hip (κ = 0.51), and “other causes of groin pain” (κ = 0.03). For participants with unilateral groin pain classified with a single entity (n = 7), there was 100% agreement between the two examiners. Inter-examiner reliability of the Doha agreement meeting classification system varied from slight to substantial, depending on the clinical entity. Agreement between examiners was perfect when athletes were classified with a single clinical entity of groin pain, but lower when athletes were classified with multiple clinical entities.

Fibrodysplasia ossificans progressiva (FOP) is a catastrophic, ultra-rare disease of heterotopic ossification caused by genetic defects in the ACVR1 gene. The mutant ACVR1 receptor, when triggered by an inflammatory process, leads to heterotopic ossification of the muscles and ligaments. Activin A has been discovered as the main osteogenic ligand of the FOP ACVR1 receptor. However, the source of Activin A itself and the trigger of its production in FOP individuals have remained elusive. We used primary dermal fibroblasts from five FOP patients to investigate Activin A production and how this is influenced by inflammatory cytokines in FOP. FOP fibroblasts showed elevated Activin A production compared to healthy controls, both in standard culture and osteogenic transdifferentiation conditions. We discovered TGFβ1 to be an FOP-specific stimulant of Activin A, shown by the upregulation of the INHBA gene and protein expression. Activin A and TGFβ1 were both induced by BMP4 in FOP and control fibroblasts. Treatment with TNFα and IL6 produced negligible levels of Activin A and TGFβ1 in both cell groups. We present for the first time TGFβ1 as a triggering factor of Activin A production in FOP. As TGFβ1 can promote the induction of the main driver of FOP, TGFβ1 could also be considered a possible therapeutic target in FOP treatment.

The analysis of single motor unit (SMU) activity provides the foundation from which information about the neural strategies underlying the control of muscle force can be identified, due to the one-to-one association between the action potentials generated by an alpha motor neuron and those received by the innervated muscle fibers. Such a powerful assessment has been conventionally performed with invasive electrodes (i.e., intramuscular electromyography (EMG)), however, recent advances in signal processing techniques have enabled the identification of single motor unit (SMU) activity in high-density surface electromyography (HDsEMG) recordings. This matrix, developed by the Consensus for Experimental Design in Electromyography (CEDE) project, provides recommendations for the recording and analysis of SMU activity with both invasive (needle and fine-wire EMG) and non-invasive (HDsEMG) SMU identification methods, summarizing their advantages and disadvantages when used during different testing conditions. Recommendations for the analysis and reporting of discharge rate and peripheral (i.e., muscle fiber conduction velocity) SMU properties are also provided. The results of the Delphi process to reach consensus are contained in an appendix. This matrix is intended to help researchers to collect, report, and interpret SMU data in the context of both research and clinical applications.

Background Overloading is hypothesized to be one of the failure mechanisms following total elbow arthroplasty (TEA). It is unclear whether the current post-operative loading instruction is compliant with reported failure mechanisms. Aim is therefore to evaluate the elbow joint load during activities of daily living (ADL) and compare these loads with reported failure limits from retrieval and finite element studies. Methods A scoping review of studies until 23 November 2021 investigating elbow joint load during ADL were identified by searching PubMed/Medline and Web of Science. Studies were eligible when: (1) reporting on the elbow joint load in native elbows or elbows with an elbow arthroplasty in adults; (2) full-text article was available. Results Twenty-eight studies with a total of 256 participants were included. Methodological quality was low in 3, moderate in 22 and high in 3 studies. Studies were categorized as 1) close to the body and 2) further away from the body. Tasks were then subdivided into: 1) cyclic flexion/extension, 2) push-up, 3) reaching, 4) self-care, 5) work. Mean flexion–extension joint load was 17 Nm, mean varus-valgus joint load 9 Nm, mean pronation-supination joint load 8 Nm and mean bone-on-bone contact force 337 N. Conclusion The results of our scoping review give a first overview of the current knowledge on elbow joint loads during ADL. Surprisingly, the current literature is not sufficient to formulate a postoperative instruction for elbow joint loading, which is compliant with failure limits of the prosthesis. In addition, our current instruction does not appear to be evidence-based. Our recommendations offer a starting point to assist clinicians in providing informed decisions about post-operative instructions for their patients.

Background Experienced assessors show good intra-rater reproducibility (within-session and between-session agreement and reliability) when using an algometer to determine pressure pain thresholds (PPT). However, it is unknown whether novice assessors perform equally well. This study aimed to determine within and between-session agreement and reliability of PPT measurements performed by novice assessors and explored whether these parameters differed per assessor and algometer type. Methods Ten novice assessors measured PPTs over four test locations (tibialis anterior muscle, rectus femoris muscle, extensor carpi radialis brevis muscle and paraspinal muscles C5-C6) in 178 healthy participants, using either a Somedic Type II digital algometer (10 raters; 88 participants) or a Wagner Force Ten FDX 25 digital algometer (nine raters; 90 participants). Prior to the experiment, the novice assessors practiced PPTs for 3 h per algometer. Each assessor measured a different subsample of ~9 participants. For both the individual assessor and for all assessors combined (i.e., the group representing novice assessors), the standard error of measurement (SEM) and coefficient of variation (CV) were calculated to reflect within and between-session agreement. Reliability was assessed using intraclass correlation coefficients (ICC1,1). Results Within-session agreement expressed as SEM ranged from 42 to 74 kPa, depending on the test location and device. Between-session agreement, expressed as SEM, ranged from 36 to 76 kPa and the CV ranged from 9–16% per body location. Individual assessors differed from the mean group results, ranging from −55 to +32 kPa or from −9.5 to +6.6 percentage points. Reliability was good to excellent (ICC1,1: 0.87 to 0.95). Results were similar for both types of algometers. Conclusions Following 3 h of algometer practice, there were slight differences between assessors, but reproducibility in determining PPTs was overall good.

Purpose To relate [18F]fluoride uptake on PET with abnormalities on magnetic resonance imaging (MRI) and conventional radiography (CR) in ankylosing spondylitis (AS) patients. Methods Ten clinically active AS patients (female 6/10, age 38 ± 11 years) were included, and both spine and SI-joints were examined. PET scans were dichotomously scored for enhanced [18F]fluoride uptake, MRI scans were scored for fatty lesions, erosions, ankylosis, and bone marrow edema (BME), and CR was scored for erosions, syndesmophytes, and ankylosis. The overlap of lesions across all modalities was evaluated through univariate and multivariate analyses using a generalized mixed model. Results In the spine, 69 lesions with enhanced [18F]fluoride uptake, 257 MRI lesions, and 88 CR lesions were observed. PET lesions were mostly located in costovertebral and facet joints, outside the field of view (FOV) of the MRI and CR. However, PET lesions inside the FOV of MRI and CR partially showed no abnormality on MRI and CR. In lesions with abnormalities on multiple modalities, both univariate and multivariate analysis showed that PET activity had the strongest association with BME on MRI and ankylosis on CR. In the SI joints, 15 lesions (75%) with PET uptake were found, with 87% showing abnormalities on MRI and CR. Conclusion [18F]fluoride PET lesions are often found outside the scope of MRI and CR, and even in the same location show only partial overlap with abnormalities on MRI (especially BME) and CR (especially ankylosis). This suggests that [18F]fluoride PET partially visualizes aspects of AS separate from MRI and CR, providing novel information. Clinical trial registration NL43223.029.13 registered at 02-05-2013. https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=C1257BA2002CC066C1257B4E0049A65A

After multiple waves of the COVID-19 pandemic, it has become clear that the impact of SARS-CoV-2 will carry on for years to come. Acutely infected patients show a broad range of disease severity, depending on virus variant, vaccination status, age and the presence of underlying medical and physical conditions, including obesity. Additionally, a large number of patients who have been infected with the virus present with post-COVID syndrome. In September 2020, the International Society for the Advancement of Respiratory Psychophysiology organized a virtual interest meeting on ‘Respiratory research in the age of COVID-19’, which aimed to discuss how research in respiratory psychophysiology could contribute to a better understanding of psychophysiological interactions in COVID-19. In the resulting current paper, we propose an interdisciplinary research agenda discussing selected research questions on acute and long-term neurobiological, physiological and psychological outcomes and mechanisms related to respiration and the airways in COVID-19, as well as research questions on comorbidity and potential treatment options, such as physical rehabilitation.

INTRODUCTION: Measurement instruments are important in clinical practice and research for assessing physical function in critically ill patients in the intensive care unit (ICU).OBJECTIVE: To investigate inter-rater reliability and responsiveness of the Danish version of the CPAx (CPAx-D).METHOD: Critically ill patients from three Danish ICUs were included. Patients were assessed with CPAx-D by two blinded testers during a regular physiotherapy session. Follow-up tests were performed in patients who stayed in the ICU for more than 24 hours, were not transferred to another hospital or received palliative care. Floor and ceiling effects were examined in all assessments.Results For the reliability analysis 66 patients were included.Results Showed no significant difference between raters. For the total score, intra class correlation coefficient (ICC) was 0.996 (95% CI: 0.993; 0.997), standard error of measurement was 0.72 point and minimal detectable change 2.0 points. Bland-Altman plot revealed no heteroscedacity. The responsiveness results of 24 patients showed that the effect size was 1.2 and the standardized response mean 1.1, which was in accordance with the hypothesis. No ceiling or floor effect was revealed.CONCLUSION: The CPAx-D showed excellent inter-rater reliability and responsiveness.

The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI.We conducted a 3-part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group.Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life-course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment.We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development.

Considering the stochastic nature of electromyographic (EMG) signals, nonlinear methods may be a more accurate approach to study intermuscular coordination than the linear approach. The aims of this study were to assess the coordination between two ankle plantar flexors using EMG by applying the causal decomposition approach and assessing whether the intermuscular coordination is affected by the slope of the treadmill. The medial gastrocnemius (MG) and soleus muscles (SOL) were analyzed during the treadmill walking at inclinations of 0°, 5°, and 10°. The coordination was evaluated using ensemble empirical mode decomposition, and the causal interaction was encoded by the instantaneous phase dependence of time series bi-directional causality. To estimate the mutual predictability between MG and SOL, the cross-approximate entropy (XApEn) was assessed. The maximal causal interaction was observed between 40 and 75 Hz independent of inclination. XApEn showed a significant decrease between 0° and 5° (p = 0.028), between 5° and 10° (p = 0.038), and between 0° and 10° (p = 0.014), indicating an increase in coordination. Thus, causal decomposition is an appropriate methodology to study intermuscular coordination. These results indicate that the variation of loading through the change in treadmill inclination increases the interaction of the shared input between MG and SOL, suggesting increased intermuscular coordination. Graphical abstract: [Figure not available: see fulltext.].

Item does not contain fulltext OBJECTIVE: Real-world studies are needed to identify factors associated with response to biologic therapies in patients with axial spondyloarthritis (SpA). The objective was to assess sex differences in response to tumor necrosis factor inhibitors (TNFi) and to explore possible risk factors associated with TNFi efficacy. METHODS: A total of 969 patients with axial SpA (315 females, 654 males) enrolled in the BIOBADASER registry (2000-2019) who initiated a TNFi (first, second, or further lines) were studied. Statistical and artificial intelligence (AI)-based data analyses were used to explore the association of sex differences and other factors to TNFi response, using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), to calculate the BASDAI50, with an improvement of at least 50% of the BASDAI score, and using the Ankylosing Spondylitis Disease Activity Score, calculated using the C-reactive protein level (ASDAS-CRP). RESULTS: Females had a lower probability of reaching a BASDAI50 response with a first line TNFi treatment at the second year of follow-up (P = 0.018) and a lesser reduction of the ASDAS-CRP at this time point. The logistic regression model showed lower BASDAI50 responses to TNFi in females (P = 0.05). Other factors, such as older age (P = 0.004), were associated with unfavorable responses. The AI data analyses reinforced the idea that age at the beginning of the treatment was the main factor associated with an unfavorable response. The combination of age with other clinical characteristics (female sex or cardiovascular risk factors and events) potentially contributed to an unfavorable response to TNFi. CONCLUSION: In this national multicenter registry, female sex was associated with less response to a first-line TNFi by the second year of follow-up. A higher age at the start of the TNFi was the main factor associated with an unfavorable response to TNFi. 01 januari 2023

INTRODUCTION: Romosozumab is a monoclonal antibody that binds to sclerostin (an inhibitor of the Wingless-related integration site (Wnt) signaling pathway). It is a new osteoanabolic drug that simultaneously increases bone formation and decreases bone resorption. It has recently been approved by the US and EU authorities in postmenopausal women with at high risk of fractures.AREAS COVERED: The literature on romosozumab in preclinical and in phase II and III clinical studies has been reviewed about the effect on bone, bone markers, and fracture reduction and its safety.EXPERT OPINION: Compared to antiresorptive agents, its unique mechanism of action results in a quicker and greater increase in bone mineral density, it repairs and restores trabecular and cortical bone microarchitecture, and reduces fracture risk more rapidly and more effectively than alendronate, with persisting effects for at least two years after transition to antiresorptive agents. This finding has introduced the concept that, in patients at very high risk of fractures, the optimal sequence of treatment is to start with an osteoanabolic agent, followed by a potent AR drug. Recent national and international guidelines recommend the use of romosozumab as an initial treatment in patients at very high fracture risk without a history of stroke or myocardial infarction.

Purpose: Optimizing return to work after knee arthroplasty is becoming more important because of the growing incidence of KA among workers and poor return to work outcomes. The purpose of this study is to investigate the feasibility of Back At work After Surgery (BAAS): an integrated clinical pathway for return to work after knee arthroplasty. Method: Working patients who received unicompartmental knee arthroplasty (UKA) or total knee arthroplasty (TKA) between January 2021 and November 2021, younger than 65 years and motivated to return to work were eligible to participate. Feasibility was investigated on five domains: reach, dose delivered, dose received, fidelity and patients’ attitudes. These outcomes were obtained by a patient-reported questionnaire and an interview with the occupational case manager and medical case manager.Results: Of the eligible 29 patients, eleven were willing to participate (response rate 38%; due to travel distance to and from the hospital). The dose delivered was between 91 and 100%, except information given about return to work from the orthopedic surgeon which was 18%. The dose received was 100%. For fidelity, case managers reported nine shortcomings for which five solutions were mentioned. In terms of patients’ attitude, all patients were satisfied and one patient mentioned an improvement. Conclusions: In terms of reach, participation was low: only 29%. The BAAS clinical pathway seems feasible based on dose delivered, dose received, fidelity and patient attitudes. The next step is to assess the effectiveness of the BAAS clinical pathway for return to work.

Systematic reviews are necessary to synthesize available evidence and inform clinical practice and health policy decisions. There has been an explosion of evidence available in many fields; this makes it challenging to keep evidence syntheses up to date and useful. Comparative effectiveness systematic reviews are informative; however, producing these often-large reviews bring intense time and resource demands. This commentary describes the implementation of a systematic review using a collaborative model of evidence synthesis. We are implementing the collaborative review model to update a large Cochrane review investigating the efficacy and comparative effectiveness of the design, delivery, and type of exercise treatment for people with chronic low-back pain. Three key benefits of the collaborative review model for evidence synthesis are (1) team coordination and collaboration, (2) quality control measures, and (3) advanced comparative and other analyses. This new collaborative review model is developed and implemented to produce and share high-quality, comparative evidence more efficiently while building capacity and community within a research field.

Background Biologicals, such as anti-tumor necrosis factor (anti-TNF), reduce cardiovascular disease (CVD) in patients with inflammatory rheumatic diseases. Impaired renal function is a known predictor of CVD and elevated in ankylosing spondylitis (AS). Objective To assess the effect of anti-TNF on renal function in patients with AS and whether anti-TNF use is safe in AS patients with pre-existing risk factors for renal decline. Method Biological-naïve consecutive AS patients treated with etanercept or adalimumab were prospectively followed from 2005 to 2014. Renal function was determined by calculation of the estimated glomerular filtration rate (eGFR), estimated with the abbreviated modification of diet in renal disease (MDRD) formula. The effect of anti-TNF on eGFR was analyzed using mixed model analysis. Results 211 AS patients were followed for a median of 156 (36–286) weeks. Overall mixed model analyses showed a significant decrease of eGFR over time (β = − 0.040, p = 0.000), although this association did not remain significant after adjustment for responding to anti-TNF, alcohol use, disease duration, body mass index (BMI), C-reactive protein (CRP), and disease activity (β = − 0.018, p = 0.094). However, patients with pre-existing risk factors for renal decline did have a significant change in eGFR over time (β = − 0.029, p = 0.006). Conclusions We found a significant change in eGFR over time, although this small decrease was not clinically relevant. This study further demonstrates that anti-TNF does not affect renal function in AS patients with and without existing risk factors for renal decline, which means that use of anti-TNF is safe concerning renal function in patients with AS. Key Points• Previous studies showed that biologicals, such as anti-tumor necrosis factor (anti-TNF), reduce cardiovascular disease (CVD) in patients with inflammatory rheumatic diseases, such as ankylosing spondylitis (AS).• Impaired renal function is a known predictor of CVD, and also a known concern for many AS patients.• Use of anti-TNF is safe with regard to renal function in patients with AS.• The effect of anti-TNF on CVD in AS patients does not seem to be mediated by changes in renal function.

Athlete development depends on many factors that need to be balanced by the coach. The amount of data collected grows with the development of sensor technology. To make data-informed decisions for training prescription of their athletes, coaches could be supported by feedback through a coach dashboard. The aim of this paper is to describe the design of a coach dashboard based on scientific knowledge, user requirements, and (sensor) data to support decision making of coaches for athlete development in cyclic sports. The design process involved collaboration with coaches, embedded scientists, researchers, and IT professionals. A classic design thinking process was used to structure the research activities in five phases: empathise, define, ideate, prototype, and test phases. To understand the user requirements of coaches, a survey (n = 38), interviews (n = 8) and focus-group sessions (n = 4) were held. Design principles were adopted into mock-ups, prototypes, and the final coach dashboard. Designing a coach dashboard using the co-operative research design helped to gain deep insights into the specific user requirements of coaches in their daily training practice. Integrating these requirements, scientific knowledge, and functionalities in the final coach dashboard allows the coach to make data-informed decisions on training prescription and optimise athlete development.Keywords: dashboard; training load; coach; feedback; athlete development; performance; overreaching; overtraining

Objective: In patients with rheumatoid arthritis (RA) with cardiovascular disease risk, it is unknown whether exercises are safe, improve cardiorespiratory fitness and reduce disease-related symptoms and cardiovascular-disease (CVD) risk factors. We aimed to investigate in RA patients with CVD risk: (1) safety of medium to high-intensity aerobic exercises, (2) potential changes of cardiorespiratory fitness and (3) disease activity and CVD risk factors in response to the exercises. Methods: Single-arm pilot-exercise intervention study including 26 consecutive patients (21 women) with > 4% 10-year risk of CVD mortality according to the Dutch Systematic Coronary Risk Evaluation. Aerobic exercises consisted of two supervised-sessions and five home-sessions per week for 12 weeks. Patients were required to exercise at intensities between 65 and 85% of their maximum heart rate. To assess safety, we recorded exercise related adverse events. Before and after the exercises, cardiorespiratory fitness was assessed with a graded maximal oxygen-uptake exercise test, while disease activity was evaluated via the Disease Activity Score-28 (DAS28) using the erythrocyte segmentation rate (ESR). Resting blood pressure, ESR and total cholesterol were assessed as CVD risk factors. Results: Twenty out of 26 patients performed the 12-week exercises without any adverse events. According to patients, withdrawals were unrelated to the exercises. Exercises increased cardiorespiratory fitness (pre: 15.91 vs. post: 18.15 ml.kg−1 min−1, p = 0.003) and decreased DAS28 (pre: 2.86 vs. post: 2.47, p = 0.04). No changes were detected in CVD risk factors. Conclusion: A 12-week exercise intervention seems to be safe and improves cardiorespiratory fitness and disease activity in patients with RA with a high risk for cardiovascular diseases.Key Points1. Rheumatoid arthritis patients with high cardiovascular disease risk were able to perform a maximum exercise test and a 12-week aerobic-based medium-to-high intensity exercise intervention.2. The exercise intervention improved cardiorespiratory fitness and disease activity in rheumatoid arthritis patients with high cardiovascular disease risk.3. Cardiorespiratory fitness levels were still low post-exercise intervention (i.e. 18.15 ml.kg−1min−1 compared to the 20.9 ml.kg−1min−1 baseline mean of the RA patients without CVD risk).

Purpose: To address the feasibility, reliability and internal validity of natural language processing (NLP) for automated functional assessment of hospitalised COVID-19 patients in key International Classification of Functioning, Disability and Health (ICF) categories and levels from unstructured text in electronic health records (EHR) from a large teaching hospital. Materials and methods: Eight human annotators assigned four ICF categories to relevant sentences: Emotional functions, Exercise tolerance, Walking and Moving, Work and Employment and their ICF levels (Functional Ambulation Categories for Walking and Moving, metabolic equivalents for Exercise tolerance). A linguistic neural network-based model was trained on 80% of the annotated sentences; inter-annotator agreement (IAA, Cohen’s kappa), a weighted score of precision and recall (F1) and RMSE for level detection were assessed for the remaining 20%. Results: In total 4112 sentences of non-COVID-19 and 1061 of COVID-19 patients were annotated. Average IAA was 0.81; F1 scores were 0.7 for Walking and Moving and Emotional functions; RMSE for Walking and Moving (5- level scale) was 1.17 for COVID-19 patients. Conclusion: Using a limited amount of annotated EHR sentences, a proof-of-concept was obtained for automated functional assessment of COVID-19 patients in ICF categories and levels. This allows for instantaneous assessment of the functional consequences of new diseases like COVID-19 for large numbers of patients.Key messages Hospitalised Covid-19 survivors may persistently suffer from low physical and mental functioning and a reduction in overall quality of life requiring appropriate and personalised rehabilitation strategies. For this, assessment of functioning within multiple domains and categories of the International Classification of Function is required, which is cumbersome using structured data. We show a proof-of-concept using Natural Language Processing techniques to automatically derive the aforementioned information from free-text notes within the Electronic Health Record of a large academic teaching hospital.

Background Chiropractors commonly provide care to people with low-back pain (LBP). The aim of this survey was to determine the opinions and beliefs of chiropractors regarding the support and management of LBP. We also investigated whether their management is in accordance with the three most commonly recommended approaches to LBP based upon international guidelines (i.e. advice regarding return-to-work, limit bedrest, and stay active). Methods A web-based survey was sent out in 2013 to collect data from registered Dutch and Belgian chiropractors. In addition to providing a description of their sociodemographic and practice characteristics, chiropractors were asked to complete six patient vignettes representing people with LBP who typically present to a chiropractor. The respondents indicated which intervention(s) they would recommend or undertake. Based upon these vignettes, we were able to determine whether their management approach adhered to clinical guidelines. Generalized mixed models were used to explore guidelines adherence and their relationship to chiropractors’ characteristics. Results In total, 60% (n = 203/340) of the chiropractors who were invited, chose to participate. Chiropractors reported applying a chiropractic adjustment in 90% of all vignettes, while the advice to exercise varied from one-third in the chronic cases to approximately half of those with acute LBP. More than 75% of the chiropractors would initially treat LBP 1–2 times a week. More than 90% of the chiropractors advised against bedrest. Overall, self-reported adherence to clinical guidelines for all six vignettes was [64.5% (CI 58.7–70.0)]. Adherence in the chronic vignettes [73.4% (CI 66.7–79.2)] was better than in the acute vignettes [55.9% (CI 50.5–61.1)]. Importantly, regarding recommended approaches to LBP, chiropractors more consistently followed guidelines regarding advice to limit bedrest [98.5% (CI 97.3–99.1)] than advice to stay active [77.5% (CI 72.3–81.9)] or return-to-work [59.4% (CI 55.2–63.4)]. Finally, Dutch chiropractors were more likely to adhere to the guidelines than Belgian chiropractors. Conclusions Chiropractic adjustments were the most common self-reported treatment modalities supplemented by exercise in the management of LBP patients. Two-thirds of the chiropractors reported adhering to the guidelines regarding management and advice for LBP patients. Practitioners should improve guideline adherence, particularly for acute LBP cases, and when advising on return-to-work.

Objective Pituitary tumours that compress the optic chiasm are associated with long-term alterations in sleep–wake rhythm. This may result from damage to intrinsically photosensitive retinal ganglion cells (ipRGCs) projecting from the retina to the hypothalamic suprachiasmatic nucleus via the optic chiasm to ensure photoentrainment (i.e. synchronisation to the 24-h solar cycle through light). To test this hypothesis, we compared the post-illumination pupil response (PIPR), a direct indicator of ipRGC function, between hypopituitarism patients with and without a history of optic chiasm compression. Design Observational study, comparing two predefined groups. Methods We studied 49 patients with adequately substituted hypopituitarism: 25 patients with previous optic chiasm compression causing visual disturbances (CC+ group) and 24 patients without (CC– group). The PIPR was assessed by chromatic pupillometry and expressed as the relative change between baseline and post-blue-light stimulus pupil diameter. Objective and subjective sleep parameters were obtained using polysomnography, actigraphy, and questionnaires. Results Post-blue-light stimulus pupillary constriction was less sustained in CC+ patients compared with CC– patients, resulting in a significantly smaller extended PIPR (mean difference: 8.1%, 95% CI: 2.2–13.9%, P = 0.008, Cohen's d = 0.78). Sleep–wake timing was consistently later in CC+ patients, without differences in sleep duration, efficiency, or other rest–activity rhythm features. Subjective sleep did not differ between groups. Conclusion Previous optic chiasm compression due to a pituitary tumour in patients with hypopituitarism is associated with an attenuated PIPR and delayed sleep timing. Together, these data suggest that ipRGC function and consequently photoentrainment of the central biological clock is impaired in patients with a history of optic chiasm compression.

Low back pain (LBP), associated with spine, pelvis, and hip mobility impairments can be caused by tight muscle contractions, to protect sensitized lumbar fasciae. Fascia tissue manipulations are used to treat lumbar fascia in LBP. The effect of fascia tissue manipulations through lumbodorsal skin displacement (SKD) on mobility is inconclusive likely depending on the location and displacement direction of the manipulation. This study aimed to assess whether lumbodorsal SKD affects the flexion -and extension range of motion (ROM), in healthy subjects. Furthermore, we aimed to test the effect of SKD at different locations and directions. Finally, to assess intertester and intratester reliability of SKD. Effects of SKD were tested in a motion capture, single-blinded, longitudinal, experimental study. Sixty-three subjects were randomly assigned to SKD- or sham group. SKD group was subjected to either mediolateral directed SKD during flexion or extension movement, versus a sham. The thoracic, lumbar, and hip angles and finger floor distance were measured to assess the change in ROM. Statistics indicated that the effect size in instantaneously change of flexion -and extension ROM by SKD was large (Effect size: flexion η2p = 0.12–0.90; extension η2p = 0.29–0.42). No significant effect was present in the sham condition. Flexion ROM decreased whereas the extension ROM increased, depending on SKD location- and displacement direction (p < 0.05). The ICC indicates a good intertester and intratester reliability (resp. ICC3,k = 0.81–0.93; ICC3,1 = 0.70–0.84). Lumbodorsal SKD affects the flexion- and extension spine, pelvis, and hip range of motion. The effects of SKD are direction- and location dependent as well as movement (flexion/extension) specific. Lumbodorsal SKD during flexion and extension may be useful to determine whether or not a patient would benefit from fascia tissue manipulations. Further research is required to obtain insight into the mechanisms via which the SKD affects ROM and muscle activation, in healthy, asymptomatic-LBP, and LBP subjects.

BackgroundEvidence is lacking to what extent patients with Whiplash-Associated Disorders (WAD), those with non-traumatic neck pain (NTNP), and pain-free individuals differ regarding type and severity of impairments, disability, and psychological factors.Objective To compare clinical characteristics between patients with WAD, with NTNP, and pain-free individuals in primary care physiotherapy. Additionally, differences between patient groups for both acute and chronic symptoms were assessed.MethodA cross-sectional study was conducted including 168 patients with WAD, 336 matched patients with NTNP, and 336 pain-free individuals. Differences and prevalence rates were calculated for pain intensity, pain distribution, cervical range of motion, neck flexor muscle endurance, self-reported disability, and psychological factors.Results Patients with WAD had higher pain intensity (median 6/10 vs. 5/10 p83%) scored in the normal range. No significant differences between the patient groups were observed (p>.16). Both patient groups scored significantly worse than pain-free individuals on all characteristics. Patients with WAD and NTNP experienced different types of activity limitations and participation restrictions.ConclusionWAD is a more severe condition than NTNP and should be considered a separate subgroup. A different approach in clinical practice and research is required for WAD and NTNP.

Purpose Perceived discomfort could indicate an early sign of pain, for example, as a result of a biomechanical load on the musculoskeletal system. Assessing discomfort can, therefore, help to identify workers at increased risk of musculoskeletal disorders for targeted intervention development. We aimed: (1) to identify the optimal cut-off value of neck and low back discomfort among office workers and (2) to evaluate its predictive validity with future neck and low back pain, respectively. Methods At baseline healthy participants (n = 100) completed questionnaires, including the Borg CR-10 discomfort scale (on a 0–10 scale), and were followed for six months, during which musculoskeletal pain was assessed monthly. Logistic regression analyses were performed to assess the associations of baseline discomfort with the onset of future neck or low back pain. Sensitivity, specificity, and the area under the receiver operating characteristics curve were estimated to identify the optimal discomfort cut-off value predicting future pain. Results Borg CR-10 scores ≥ 3.5 for perceived neck and low back discomfort had acceptable sensitivity and specificity to predict future neck and low back pain, respectively. Perceived discomfort at baseline as a dichotomous measure (using the ≥ 3.5 cut-off) was a statistically significant predictor of future neck pain (OR = 10.33) and low back pain (OR = 11.81). Conclusion We identified the optimal cut-off value of the Borg CR-10 discomfort scale to identify office workers at increased risk of developing neck and low back pain. These findings might benefit ergonomists, primary health care providers, and occupational health researchers in developing targeted interventions.

Background The prevalence of inflicted femur fractures in young children varies (1.5–35.2%), but these data are based on small retrospective studies with high heterogeneity. Age and mobility of the child seem to be indicators of inflicted trauma. Objective This study describes other factors associated with inflicted and neglectful trauma that can be used to distinguish inflicted and neglectful from accidental femur fractures. Materials and methods This retrospective study included children (0–6 years) who presented with an isolated femur fracture at 1 of the 11 level I trauma centers in the Netherlands between January 2010 and January 2016. Outcomes were classified based on the conclusions of the Child Abuse and Neglect teams or the court. Cases in which conclusions were unavailable and there was no clear accidental cause were reviewed by an expert panel. Results The study included 328 children; 295 (89.9%) cases were classified as accidental trauma. Inflicted trauma was found in 14 (4.3%), while 19 (5.8%) were cases of neglect. Indicators of inflicted trauma were age 0–5 months (29%, positive likelihood ratio [LR +] 8.35), 6–12 months (18%, LR + 5.98) and 18–23 months (14%, LR + 3.74). Indicators of neglect were age 6–11 months (18%, LR + 4.41) and age 18–23 months (8%, LR + 1.65). There was no difference in fracture morphology among groups. Conclusion It is unlikely that an isolated femur fracture in ambulatory children age > 24 months is caused by inflicted trauma/neglect. Caution is advised in children younger than 24 months because that age is the main factor associated with inflicted trauma/neglect and inflicted femur fractures.

Multi-ancestry genome-wide association analyses identify 124 risk loci for rheumatoid arthritis, of which 34 are novel. A polygenic risk score based on multi-ancestry data showed comparable performance between populations of European and East Asian ancestries.Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 x 10(-8)), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.

Objectives: The objective of this study was to estimate the minimal important change (MIC) and responsiveness of core patient reported outcome measures for chronic low back pain (LBP) and Modic changes. Study Design and Setting: In the Antibiotics in Modic changes (AIM) trial we measured disability (RMDQ, ODI), LBP intensity (NRS) and health-related quality of life (EQ5D) electronically at baseline, three- and 12-month follow-up. MICs were estimated using Receiver Operating Curve (ROC) curve and Predictive modeling analyses against the global perceived effect. Credibility of the estimates was assessed by a standardized set of criteria. Responsiveness was assessed by a construct and criterion approach according to COSMIN guidelines. Results: The MIC estimates of RMDQ, ODI and NRS scores varied between a 15–40% reduction, depending on including “slightly improved” in the definition of MIC or not. The MIC estimates for EQ5D were lower. The credibility of the estimates was moderate. For responsiveness, five out of six hypotheses were confirmed and AUC was >0.7 for all PROMs. Conclusion: When evaluated in a clinical trial of patients with chronic LBP and Modic changes, MIC thresholds for all PROMs were on the lower spectrum of previous estimates, varying depending on the definition of MIC. Responsiveness was sufficient. publishedVersion