Limited Evidence for the Benefits of Exercise in Older Adults with Hematological Malignancies: A Systematic Review and Meta-Analysis.

Older patients receiving antineoplastic treatment face challenges such as frailty and reduced physical capacity and function. This systematic review and meta-analysis aimed to evaluate the effects of exercise interventions on physical function outcomes, health-related quality of life (QoL), and symptom burden in older patients above 65 years with hematological malignancies undergoing antineoplastic treatment. This review adheres to Cochrane guidelines, with the literature searches last updated on 27 March 2024, including studies with patients above 18 years. Screening of identified studies, data extraction, risk of bias, and GRADE assessments were performed independently by two authors. Meta-analyses evaluated the impact of exercise, considering advancing age. Forty-nine studies contributed data to the meta-analyses. Five studies included patients with a mean age above 60 years, and none included only patients above 60. Exercise interventions had moderate to small positive effects on QoL global (SMD 0.34, 95% CI [0.04-0.64]) and physical function (SMD 0.29, 95% CI [0.12-0.45]). Age did not explain the variability in exercise effects, except for physical function (slope 0.0401, 95% CI [0.0118-0.0683]) and pain (slope 0.0472, 95% CI [0.01-0.09]), which favored younger patients. Exercise interventions improve physical function and QoL and reduce symptoms in adults with hematological malignancies undergoing antineoplastic treatment; however, the influence of age remains inconclusive.

Immune Checkpoint Inhibitor-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis.

Importance: Immune checkpoint inhibitors (ICIs) improve outcomes in a wide range of cancers; however, serious adverse effects, including cardiovascular adverse effects (CVAEs), can occur. Objective: To determine the incidence of CVAEs and analyze data on the management of myocarditis in patients exposed to ICIs. Data Sources: PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception were searched on April 4, 2023. Study Selection: Two separate studies were performed. Key inclusion criteria for study 1 were phases 1 to 4 trials involving adults with malignant neoplasms treated with an ICI and toxicity data; for study 2, publications (case reports and retrospective analyses) on clinical manifestations and treatment of patients with ICI-induced CVAEs. Studies with dose escalation or fewer than 11 patients in each group and all case reports, retrospective analyses, letters, reviews, and editorials were excluded from study 1. Studies not published in English were excluded from study 2. Data Extraction and Synthesis: The PRISMA guidelines and Cochrane Handbook for Systematic Reviews were followed. Data were extracted independently by 2 researchers. A meta-analysis of the incidence of CVAEs in clinical trials and a systematic review of the evidence for the management of myocarditis were performed. Data were pooled using a random-effects model. Main Outcomes and Measures: In study 1, the primary outcome was incidence CVAEs in clinical trials with ICIs and ICI combination therapies. Study 2 examined evidence supporting specific management strategies that may decrease the mortality rate of myocarditis. The primary outcomes were planned before data collection began. Results: In study 1, a total of 83 315 unique participants in 589 unique trials were included in the meta-analysis. Incidence of CVAEs induced by anti-programmed cell death 1 and/or programmed cell death ligand 1 was 0.80% (95% CI, 0%-1.66%) in clinical trials, with no differences between the compounds, except for cemiplimab, which was associated with a higher risk of CVAEs. Incidence of CVAEs following ipilimumab treatment was 1.07% (95% CI, 0%-2.58%). The incidence of myocarditis was significantly higher following treatment with dual ICIs. However, CVAE incidence was not higher with dual ICIs, ICI combination with chemotherapy, or tyrosine kinase inhibitors. Evidence from randomized clinical trials on recommended monitoring and treatment strategies for ICI-induced myocarditis was lacking. Study 2 showed that myocarditis-associated mortality occurred in 83 of 220 patients (37.7%). Prospective data from 40 patients with myocarditis indicated that systematic screening for respiratory muscle involvement, coupled with active ventilation, prompt use of abatacept, and the addition of ruxolitinib, may decrease the mortality rate. Conclusions and Relevance: Immune checkpoint inhibitor-induced CVAEs and/or myocarditis were recorded in 1.07% of patients in clinical trials. The CVAE mortality risk remains high, justifying the need for monitoring and management strategies for which evidence from randomized clinical trials is absent. Early recognition, ICI therapy cessation, prompt initiation of corticosteroid therapy, and escalation of therapy are all crucial elements for achieving optimal outcomes. Prospective clinical trials or at least prospective registration of treatments and outcomes are highly warranted.

Prevention of weight loss in patients with head and neck cancer in ongoing radiation or chemoradiation therapy-A systematic review and meta-analysis.

PURPOSE: This systematic review (PROSPERO: CRD4202345740) identified and synthesised existing evidence on nutrition interventions performed by healthcare professionals, and the contents of the interventions that prevented weight loss in patients with HNC undergoing RT/CRT. METHODS: We included quantitative studies. PubMed, CINAHL, Cochrane Library, and Scopus were searched, and the outcomes of interest were weight change and nutritional status. A narrative synthesis was undertaken to elaborate on the findings across the included studies. Furthermore, a meta-analysis was conducted. RESULTS: A total of 27 studies were identified. Most focused on the effect of oral nutritional supplements (ONS) and individualised nutrition counselling (INC). A beneficial effect of ONS combined with weekly INC were identified, and compliance, management of adverse effects, involvement of family as well as the knowledge and approach of the healthcare professionals were identified as key elements when supporting the management of nutrition intake in HNC patients during RT/CRT. The meta-analysis showed a non-significant effect of ONS, yet significant when combined with INC, and no overall effect of INC, but significant effect in the RCTs. CONCLUSION: Our results suggest an optimal effect of ONS combined with weekly INC, requiring a focus on enhancing compliance as well as support from a multidisciplinary team to manage adverse treatment effects. Compliance must be emphasised to provide maximum support to the patient, as well as focus on the knowledge of the health care professionals performing the intervention. Further research on strategies to enhance patient compliance and involvement is needed.

Prognostic factors of chronic postsurgical pain following gastrointestinal surgery: A systematic review protocol.

BACKGROUND: Chronic postsurgical pain (CPSP) presents a considerable healthcare challenge, impacting patients, and healthcare providers, particularly in the context of gastrointestinal surgery. The notable incidence of CPSP in this specific surgical domain emphasizes the need to identify patients with a high risk of developing this condition. Despite various studies exploring this topic, a comprehensive systematic review focusing on prognostic factors of CPSP following gastrointestinal surgery is currently lacking. Therefore, the aim of this systematic review is, through systematically examination of existing literature, to assess both established and potentially novel prognostic factors, associated with CPSP following gastrointestinal surgery. METHODS: Adhering to the Cochrane Handbook and the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) checklist, we will use pre-established criteria based on Population, Intervention, Comparator, Outcome, Timing, and Setting (PICOT-S), to determine eligibility for inclusion. Essentially, this entails studies reporting on prognostic factors of CPSP following gastrointestinal surgery. Relevant studies will be identified through systematic searches in medical databases, examination of reference lists from included studies, and screening of Clinicaltrials.gov. No restrictions will be imposed regarding language, publication time or source, and both randomized trials and observational studies will be included. Data extraction will follow the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) and for quality assessment, we will use the Quality in Prognosis Studies (QUIPS) tool. RESULTS: The aim for the systematic review is to identify and assess the prognostic value of potential factors for the development of CPSP following gastrointestinal surgery. CONCLUSION: By creating a comprehensive overview of important prognostic factors for the development of CPSP following gastrointestinal surgery, the findings of this systematic review have the potential to guide future research and to enhance patient information resources.

The IBD-FITT study - moderate-intensity exercise for patients with inflammatory bowel disease with moderate disease activity: an open-label randomized controlled trial.

BACKGROUND: Inflammatory bowel disease (IBD), Crohn's disease, and ulcerative colitis are chronic autoimmune lifelong diseases with fluctuating activity over time. The treatment includes medical therapy and surgery, however, there is no definite cure. Therefore, the quest for new and supplementary treatment options is imperative to improve patients' general health and quality of life. Physical activity and exercise have been suggested to be elements in both the prevention and supplementary treatment of IBD; however, this is based on limited underpowered trials. Thus, the role of exercise as a treatment option still has to be settled. We aim to investigate the effect of a 12-week exercise intervention in adult patients with moderately active IBD on three categories of outcomes (1) disease-specific health-related quality of life (IBDQ); (2) general health status of the patients, i.e., waist circumference, disease activity by clinical scorings systems (Harvey Bradshaw Index, Simple Clinical Colitis Activity Index), blood pressure, blood lipids, and non-disease specific quality of life (EQ5D) scores; and (3) explorative outcomes on biomarkers (C-reactive protein and fecal calprotectin) plus different biomarkers of immunology (cytokine panel). METHODS: We will apply a superiority design in this open-label randomized clinical trial including 150 patients equally allocated to intervention and usual care. The intervention will be based on a 12-week aerobic exercise program and will include two supervised exercise sessions of 60 min per week, combined with one weekly home training session. We have defined a moderate exercise level as 60-80% of patients' maximum heart rate. The patients in the intervention group will also be offered an online video lesson of 15-25 min on lifestyle guidance, and the same online video lesson will be offered in the comparator group. Questionnaires on quality of life will be forwarded electronically both at inclusion and at the end of the study, and the patients will have blood samples, and fecal samples for calprotectin at baseline, weeks 4 and 8, as well as after 12 weeks (study end). DISCUSSION: This will be a clinical trial investigating the effect of exercise on patients with Crohn's disease and ulcerative colitis. This trial will add to the evidence on the possible effect of exercise and might clarify whether exercise can benefit as a supplementary treatment addendum. Thus, the trial may provide a new patient-active disease management approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT04816812. Date of first registration: March 23, 2021.

Telephone consultation for cancer survivors with unclarified need for rehabilitation in a primary healthcare setting: a mixed methods process evaluation.

PURPOSE: To evaluate the implementation of telephone consultations to assess cancer patients' needs for rehabilitation, with focus on patients' acceptance, health professionals' experience and contextual factors. METHODS: A mixed methods process evaluation was conducted at a primary healthcare rehabilitation clinic. Cancer survivors above 18 years of age with an unclarified rehabilitation need at discharge from hospital, was offered a telephone consultation provided by health professionals. Data on implementation and acceptability were collected using medical records systems, data collection forms and semi-structured interviews with six patients and two health professionals. RESULTS: Eighty-one cancer survivors were referred to the intervention, and 54% continued to further rehabilitation. The telephone consultations were executed approximately eight days after referral and took on average 44 min to deliver. Overall, the patients found that the telephone consultation addressed what they considered the most important topics, and the health professionals found the intervention to be acceptable. Both patients and health professionals reported challenges regarding the referral process. CONCLUSION: Patient acceptance of the intervention was high, and the telephone consultation was implemented to a high degree, resulting in more than half of the patients continuing to further rehabilitation. Patients' and health professionals' perspectives provided valuable insights about contextual factors.

Spinal Manipulative Therapy for Nonspecific Low Back Pain: Does Targeting a Specific Vertebral Level Make a Difference?: A Systematic Review With Meta-analysis.

OBJECTIVE: We aimed to examine whether targeting spinal manipulative therapy (SMT), by applying the intervention to a specific vertebral level, produces superior clinical outcomes than a nontargeted approach in patients with nonspecific low back pain. DESIGN: Systematic review with meta-analysis. LITERATURE SEARCH: MEDLINE, Embase, CENTRAL, CINAHL, Scopus, PEDro, and Index to Chiropractic Literature were searched up to May 31, 2023. STUDY SELECTION CRITERIA: Randomized controlled trials comparing targeted SMT (mobilization or manipulation) to a nontargeted approach in patients with nonspecific low back pain, and measuring the effects on pain intensity and patient-reported disability. DATA SYNTHESIS: Data extraction, risk of bias, and evaluation of the overall certainty of evidence using the GRADE approach were performed by 2 authors independently. Meta-analyses were performed using the restricted maximum likelihood method. RESULTS: Ten randomized controlled trials (n = 931 patients) were included. There was moderate-certainty evidence of no difference between targeted SMT and a nontargeted approach for pain intensity at postintervention (weighted mean difference = -0.20 [95% CI: -0.51, 0.10]) and at follow-up (weighted mean difference = 0.05 [95% CI: -0.26, 0.36]). For patient-reported disability, there was moderate-certainty evidence of no difference at postintervention (standardized mean difference = -0.04 [95% CI: -0.36, 0.29]) and at follow-up (standardized mean difference = -0.05 [95% CI: -0.24, 0.13]). Adverse events were reported in 4 trials, and were minor and evenly distributed between groups. CONCLUSION: Targeting a specific vertebral level when administering SMT for patients with nonspecific low back pain did not result in improved outcomes on pain intensity and patient-reported disability compared to a nontargeted approach. J Orthop Sports Phys Ther 2023;53(9):1-11. Epub: 28 July 2023. doi:10.2519/jospt.2023.11962.

Effectiveness of Non-Budesonide Therapies in Management of Microscopic Colitis: A Systematic Review and Meta-analysis.

BACKGROUND: Budesonide is accepted as first-choice therapy for microscopic colitis (MC); however, symptoms often recur and some patients may be dependent, intolerant, or even fail budesonide. We performed a systematic review and meta-analysis to determine the effectiveness of non-budesonide therapies (thiopurines, bismuth subsalicylate [BSS], bile acid sequestrants [BAS], loperamide and biologics) for MC suggested by international guidelines. METHODS: We searched the CENTRAL, MEDLINE, and EMBASE databases from their inception to 18 April 2023 for the above-mentioned therapeutics in MC. We pooled the response and remission rates by medication using a random-effects model. RESULTS: Twenty-five studies comprising 1475 patients were included in the meta-analysis. Treatment with BSS showed the highest response rate of 75% (95% confidence interval [CI] 0.65-0.83; I2 = 70.12%), with 50% achieving remission of symptoms (95% CI 0.35-0.65; I2 = 71.06%). Treatment with tumor necrosis factor (TNF) inhibitors (infliximab and adalimumab) demonstrated a response rate of 73% (95% CI 0.63-0.83; I2 = 0.00%), with a remission rate of 44% (95% CI 0.32-0.56; I2 = 0.00%). The response rate for those treated with vedolizumab was similar; 73% responded to treatment (95% CI 0.57-0.87; I2 = 35.93%), with a remission rate of 56% (95% CI 0.36-0.75; I2 = 46.30%). Loperamide was associated with response and remission rates of 62% (95% CI 0.43-0.80; I2 = 92.99%) and 14% (95% CI 0.07-0.25), respectively, whereas BAS use was associated with response and remission rates of 60% (95% CI 0.51-0.68; I2 = 61.65%) and 29% (95% CI 0.12-0.55), respectively. Finally, the outcomes for thiopurine use were 49% (95% CI 0.27-0.71; I2 = 81.45%) and 38% (95% CI 0.23-0.54; I2 = 50.05%), respectively DISCUSSION: The present systematic review and meta-analysis provides rates of effectiveness of non-budesonide therapies for MC based on available data in the field. Studies in the meta-analysis showed a large amount of heterogeneity due to the variability in assessing the clinical effects of intervention between the studies caused by differences in the definitions of response or remission rates between the studies included. This may likely result in overestimating the benefit of a treatment. Furthermore, the number of participants and drug dosages varied, and only a few studies applied disease-specific activity indices. Only one randomized controlled trial (RCT) was identified. All other 24 included studies were either case series or (retrospective) cohort studies, which complicated efforts to perform further sensitivity analyses to adjust for potential confounders and risk of bias. In addition, the overall evidence on the effect of these treatment options was judged as low, mostly due to comparability bias and the observational nature of the available studies, which limited statistically robust comparisons of rates of effectiveness of the different non-budesonide agents ranked against each other. However, our observational findings may inform clinicians regarding the most rational selection of non-budesonide therapies to patients with MC. CLINICAL TRIALS REGISTRATION: PROSPERO protocol #CRD42020218649.

Factors influencing functioning after volar locking plate fixation of distal radius fractures: a scoping review of 148 studies.

BACKGROUND AND PURPOSE: A better understanding of factors that influence functioning may improve the identification of patients with distal radius fractures (DRFs) who need hand therapy. The purpose of this scoping review was to provide a comprehensive overview of factors that have been evaluated for their influence on hand functioning following volar plate fixation of DRFs. MATERIAL AND METHODS: 6 databases were searched from 2005 to 2021 for publications regarding surgical treatment for a DRF with a volar locking plate. Included studies evaluated demographic, perioperative, and postoperative factors within the 6 weeks post-surgery for their influence on functioning at least 3 months post-surgery. Functioning was assessed with patient-reported outcome measures. The factors were categorized into themes and mapped to the International Classification of Functioning, Disability and Health (ICF). RESULTS: 148 studies were included. 708 factors were categorized into 39 themes (e.g. pain) and mapped to the ICF components. The themes were primarily mapped to "body functions and structures" (n = 26) and rarely to "activities and participation" (n = 5). Fracture type (n = 40), age (n = 38), and sex (n = 22) were the most frequently evaluated factors. CONCLUSION: This scoping review identified an extensive number of factors evaluated within 6 weeks after surgery for their influence on functioning at least 3 months after volar plate fixation of a DRF and the existing research has primarily evaluated factors related to "body functions and structures," with limited focus on factors related to "activities and participation."

The Effects of Different Management Strategies or Rehabilitation Approaches on Knee Joint Structural and Molecular Biomarkers Following Traumatic Knee Injury: A Systematic Review of Randomized Controlled Trials for the OPTIKNEE Consensus.

OBJECTIVE: To summarize the effectiveness of management strategies and rehabilitation approaches for knee joint structural and molecular biomarker outcomes following anterior cruciate ligament (ACL) and/or meniscal tear. DESIGN: Intervention systematic review. LITERATURE SEARCH: We searched the MEDLINE, Embase, CINAHL, CENTRAL, and SPORTDiscus databases from their inception up to November 3, 2021. STUDY SELECTION CRITERIA: We included randomized controlled trials (RCTs) investigating the effectiveness of management strategies or rehabilitation approaches for structural/molecular biomarkers of knee joint health following ACL and/or meniscal tear. DATA SYNTHESIS: We included 5 RCTs (9 papers) with primary ACL tear (n = 365). Two RCTs compared initial management strategies (rehabilitation plus early vs optional delayed ACL surgery), reporting on structural biomarkers (radiographic osteoarthritis, cartilage thickness, meniscal damage) in 5 papers and molecular biomarkers (inflammation, cartilage turnover) in 1 paper. Three RCTs compared different post-ACL reconstruction (ACLR) rehabilitation approaches (high vs low intensity plyometric exercises, accelerated vs nonaccelerated rehabilitation, continuous passive vs active motion), reporting on structural biomarkers (joint space narrowing) in 1 paper and molecular biomarkers (inflammation, cartilage turnover) in 2 papers. RESULTS: There were no differences in structural or molecular biomarkers between post-ACLR rehabilitation approaches. One RCT comparing initial management strategies demonstrated that rehabilitation plus early ACLR was associated with greater patellofemoral cartilage thinning, elevated inflammatory cytokine response, and reduced incidence of medial meniscal damage over 5 years compared to rehabilitation with no/delayed ACLR. CONCLUSION: Very low-certainty evidence suggests that different initial management strategies (rehabilitation plus early vs optional delayed ACL surgery) but not postoperative rehabilitation approaches may influence the incidence of meniscal damage, patellofemoral cartilage loss and cytokine concentrations over 5 years post-ACL tear. J Orthop Sports Phys Ther 2023;53(4):1-22. Epub: 20 February 2023. doi:10.2519/jospt.2023.11576.

Adjuvant treatment with trastuzumab of patients with HER2-positive, T1a-bN0M0 breast tumors: A systematic review and meta-analysis.

The benefit of adjuvant trastuzumab treatment in patients with HER2-positive breast tumors ≤ 10 mm without lymph node involvement (T1abN0) is insufficiently investigated. The aim of this systematic review and meta-analysis was to examine if adjuvant trastuzumab improves the prognosis in these patients. Databases were searched to identify interventional and observational studies evaluating the effect of trastuzumab on breast cancer specific survival (BCSS), disease free survival (DFS), distant recurrence free survival (DRFS), overall survival (OS) or recurrence free survival (RFS). Twelve studies examining the effect of trastuzumab and nine control studies without trastuzumab were identified (n = 6927). Median follow-up was 36-123 months. Significantly improved DFS (Hazard Ratio (HR) 0.14, p < 0.0001) and OS (HR 0.17, p = 0.011) were found for patients receiving trastuzumab and chemotherapy compared to no trastuzumab/chemotherapy based on four and two studies. The prognosis was good even for patients without trastuzumab treatment: 5-year DFS 88.3% and 5-year OS 95.9%.

Biopsychosocial Rehabilitation for Inflammatory Arthritis and Osteoarthritis Patients: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: To assess the benefits and harms associated with biopsychosocial rehabilitation in patients with inflammatory arthritis and osteoarthritis (OA). METHODS: We performed a systematic review and meta-analysis. Data were collected through electronic searches of Cochrane CENTRAL, MEDLINE, Embase, PsycInfo, and CINAHL databases up to March 2019. Trials examining the effect of biopsychosocial rehabilitation in adults with inflammatory arthritis and/or OA were considered eligible, excluding rehabilitation adjunct to surgery. The primary outcome for benefit was pain and total withdrawals for harm. RESULTS: Of the 27 trials meeting the eligibility criteria, 22 trials (3,750 participants) reported sufficient data to be included in the quantitative synthesis. For patient-reported outcome measures, biopsychosocial rehabilitation was slightly superior to control for pain relief (standardized mean difference [SMD] -0.19 [95% confidence interval (95% CI) -0.31, -0.07]), had a small effect on patient global assessment score (SMD -0.13 [95% CI -0.26, -0.00]), with no apparent effect on health-related quality of life, fatigue, self-reported disability/physical function, mental well-being, and reduction in pain intensity ≥30%. Clinician-measured outcomes displayed a small effect on observed disability/physical function (SMD -0.34 [95% CI -0.57, -0.10]), a large effect on physician global assessment score (SMD -0.72 [95% CI -1.18, -0.26]), and no effect on inflammation. No difference in harms existed in terms of the number of withdrawals, adverse events, or serious adverse events. CONCLUSION: Biopsychosocial rehabilitation produces a significant but clinically small beneficial effect on patient-reported pain among patients with inflammatory arthritis and OA, with no difference in harm. Methodologic weaknesses were observed in the included trials, suggesting low-to-moderate confidence in the estimates of effect.

Factors influencing self-perceived functioning after volar locking plate fixation of distal radius fractures: a scoping review protocol.

OBJECTIVE: The objective of this review is to give an overview of the demographic, peri-, and postoperative factors that have been assessed for influence on self-perceived functioning at least 3 months after volar locking plate fixation of a distal radius fracture. INTRODUCTION: Most patients treated with a volar locking plate for a distal radius fracture recover within months after surgery; however, a subgroup of patients experience complications and slow recovery. A variety of demographic, peri-, and postoperative factors may influence self-perceived functioning. To facilitate functioning after surgery, supervised rehabilitation can be offered by a hand therapist. In the decision-making process about which patients to offer supervised rehabilitation, demographic, peri-, and postoperative factors may provide additional information, but no updated overview of explored factors has been found. INCLUSION CRITERIA: This review will consider all studies reporting on peri- and postoperative factors identified within 6 weeks after surgery, or demographic factors assessed for influence on self-perceived functioning experienced by patients at least 3 months after volar locking plate fixation of distal radius fractures. METHODS: MEDLINE, CINAHL, Embase, Cochrane Library, PsycINFO, SPORTSdiscus, and Web of Science will be searched for eligible studies. The review will consider peer-reviewed studies published after 2005 in English and Scandinavian languages. Two reviewers will independently perform study selection and data extraction. Following a content analysis of each identified factor, the factors will be mapped to the International Classification of Functioning, Disability and Health (ICF) components by using the ICF linking rules. An overview will be depicted graphically or in tabular format for different timepoints based on assessment of the self-perceived functioning.

Physicians' vs patients' global assessments of disease activity in rheumatology and musculoskeletal trials: A meta-research project with focus on reasons for discrepancies.

BACKGROUND: In most rheumatic and musculoskeletal diseases (RMDs), global assessments of disease activity by physicians and patients are 'anchor outcomes' in therapeutic trials evaluating whether a treatment is effective. OBJECTIVES: To compare physicians' vs patients' global assessments of disease activity in RMD trials and explore reasons for discrepancies between them. METHODS: Eligible trials were sampled from systematic reviews of treatments for RMDs by using the Cochrane database of systematic reviews (i.e., reviews from the Cochrane Musculoskeletal Group, [CMSG]). Randomized controlled trials (RCTs) of interventions for RMDs were eligible if they reported quantitative analyses of both physicians´ and patients´ global assessments at the same time point for the comparison of the same experimental intervention against the same comparator (i.e., placebo, no treatment, or other treatment). We accepted data from trial comparisons for each type of outcome, regardless of the type of intervention and type of RMD within the CMSG. Using mixed-effects meta-regression models, we assigned the dependent variable as the ratio of odds ratios (ROR) of global change with the experimental intervention, versus the control comparator. An ROR>1 would indicate that physicians rated the experimental intervention more favorable than their patients did. RESULTS: We were able to estimate the ROR (data from both physicians' and patients' global assessments) across 70 trials (116 randomized comparisons) in 7 diseases (ankylosing spondylitis, fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus, and gout). The combined ROR across all effectiveness comparisons were rated significantly in favor of the intervention by physicians: ROR=1.15 CI 95% (1.07 to 1.23). This combined ROR was based on a substantial heterogeneity across comparisons (I2=89.1%). Across all the stratified analyses, the type of the RMD was an informative reason for discrepancies, with a statistically significant ROR in rheumatoid arthritis ROR=1.33, CI 95% (1.13 to 1.56), unlike the ROR in all other conditions (ROR=1.04, CI 95% (0.95-1.14). CONCLUSION: In comparative effectiveness research on rheumatology, physicians' global assessments of disease activity, surprisingly, are more in favor of the experimental interventions than are those of the patients.

Effectiveness of different types, delivery modes and extensiveness of exercise in patients with breast cancer receiving systemic treatment - A systematic review and meta-analysis.

BACKGROUND: Effects of exercise in patients with breast cancer have been thoroughly investigated. The aim was to explore differences in effects regarding type, delivery mode and extensiveness (e.g. intensity; volume) of the interventions. METHODS: We searched for randomised controlled trials including patients with breast cancer receiving systemic treatment, exercise-based interventions, and measures on patient reported- and objectively measured outcomes. RESULTS: Exercise showed significant and moderate effects on the primary outcomes quality of life and physical function, Standardised Mean Difference: 0.52 (95 % CI 0.38-0.65) and 0.52 (95 % CI 0.38-0.66), respectively. Type of exercise had little influence on the effects, however combined aerobic- and resistance exercise seemed superior for increasing physical function, compared to aerobic or resistance exercise. Supervised interventions were superior to partly and unsupervised. Extensiveness of the intervention only influenced physical function. CONCLUSIONS: Supervised interventions, more than type or extensiveness of interventions, seem to increase effects.

Immune checkpoint Inhibitor-Induced diarrhea and Colitis: Incidence and Management. A systematic review and Meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved cancer outcomes. However, immune-related adverse effects are common. The aim was to investigate the incidence of diarrhea and colitis of ICIs alone and in combination with chemotherapy or tyrosine kinase inhibitors (TKIs), histopathological findings, and management. METHODS: Two separate studies, including meta-analyses, were performed. Key inclusion criteria were for Study I) phase I-IV trials, and data on diarrhea and/or colitis; for Study II) studies describing histopathologic and endoscopic findings and/or biologic treatment for ICI-induced colitis. RESULTS: The incidence of anti-PD-1/PD-L1 antibody-induced diarrhea and colitis was 10% and 2%, respectively, with no clinically relevant differences between the compounds. The CTLA-4 inhibitor, ipilimumab, induced diarrhea and colitis in 33% and 7% of patients, respectively, whereas the incidence of diarrhea and colitis following ipilimumab combined with nivolumab was 21%-37% and 4%-8%, depending on regimen. The incidence of all-grade diarrhea following ICIs combined with chemotherapy or TKIs was high (17%-56%), whereas only 0.5% of patients developed severe (≥grade 3) colitis. The main patterns of histopathologic presentation after PD-1/CTLA-4 inhibitor mono- or combination therapy were acute and chronic active colitis and microscopic colitis-like. Infliximab and vedolizumab were equally effective against ICI-induced colitis. CONCLUSION: Expanding treatment options include combinations of ICIs and chemotherapy/TKI with a high incidence of diarrhea and a low incidence of colitis; thus, a potential risk of overtreatment with corticosteroids exists. We suggest a more tailored approach, particularly for the management of low-grade diarrhea. Prospective clinical trials are needed to refine management.

Benefits and Harms of Interventions With Surgery Compared to Interventions Without Surgery for Musculoskeletal Conditions: A Systematic Review With Meta-analysis.

OBJECTIVE: To estimate the benefits and harms of interventions with and without surgery for musculoskeletal (MSK) conditions. DESIGN: Intervention systematic review with meta-analysis of randomized controlled trials (RCTs). LITERATURE SEARCH: MEDLINE, EMBASE, CINAHL, Web of Science, and CENTRAL, all up to January 7, 2021. STUDY SELECTION CRITERIA: RCTs (English, German, Danish, Swedish, and Norwegian) of interventions with and without surgery conducted in any setting for any non-fracture MSK condition in adults (mean age: 18+ years) evaluating the outcomes on a continuous (benefits) or count (harms) scale. Outcomes were pain, self-reported physical function, quality of life, serious adverse events (SAEs), and death at 1 year. DATA SYNTHESIS: Random-effects metaanalyses for MSK conditions where there were data from at least 2 trials. RESULTS: One hundred RCTs (n = 12 645 patients) across 28 different conditions at 9 body sites were included. For 9 out of 13 conditions with data on pain (exceptions include some spine conditions), 11 out of 11 for function, and 9 out of 9 for quality of life, there were no clinically relevant differences (standardized mean difference of 0.50 or above) between interventions with and without surgery. For 13 out of 16 conditions with data on SAEs and 16 out of 16 for death, there were no differences in harms. Only 6 trials were at low risk of bias. CONCLUSION: The low certainty of evidence does not support recommending surgery over nonsurgical alternatives for most MSK conditions with available RCTs. Further high-quality RCTs may change this conclusion. J Orthop Sports Phys Ther 2022;52(6):312-344. doi:10.2519/jospt.2022.11075.

Systematic review and meta-analysis of C-reactive protein as a biomarker in breast cancer.

Inflammation is an enabling characteristic of the hallmarks of cancer. There has therefore been increasing interest in the clinical value of circulating inflammatory biomarkers in cancer. In this review, we summarize results on C-reactive protein (CRP), alone or as part of the Glasgow Prognostic Score (GPS, composed of CRP and serum albumin), as a biomarker of prognosis or prediction and monitoring of therapeutic response in patients with breast cancer. A systematic literature search was performed in Medline and Embase from 1990 to August 2021. The association of serum CRP and overall survival and disease/progression-free survival was summarized in meta-analyses using a random effects model. The results from a total of 35 included studies (20,936 patients) were divided according to three identified patient settings (metastatic, non-metastatic, and general setting). Most of the studies examined prognostic utility. Several larger studies observed associations between high serum CRP and poor survival, but the meta-analyses suggested a limited value in a non-metastatic and general breast cancer setting (populations with unknown or varied disease stage). In metastatic patients, however, more consistent findings supported an association between serum CRP and prognosis (hazard ratio for overall survival: 1.87 (95% CI 1.31-2.67). Only five studies examined a role in prediction or monitoring of therapeutic response. One study reported a significant association between serum CRP levels and response to chemotherapy. Findings regarding serum CRP as a biomarker in breast cancer appear inconsistent, particularly in non-metastatic and general breast cancer, where the prognostic value could not be confirmed. In patients with metastatic breast cancer we suggest that high serum CRP is an indicator of poor prognosis. Too few studies assessed the role of serum CRP in prediction or monitoring of treatment response to allow conclusions.

The predictive value of disability at 2 weeks after plating of distal radial fractures: a prospective study of 101 patients.

Assuming that some patients may benefit from early supervised rehabilitation after distal radial fractures, we investigated to what extent self-reported measures of disability, pain and performance of daily activities 2 weeks after anterior locking plating of distal radial fractures could predict long-lasting disability. We included 101 patients in a prediction study and recorded the scores of the Disability of the Arm, Shoulder and Hand questionnaire, visual analogue scales for pain and the Canadian Occupational Performance Measure. We found that the Disability of the Arm, Shoulder and Hand scores with a cut-off score of 50 were the best at predicting disability at 6 months in patients who did not receive early supervised therapy. The positive predictive value was 65% and the negative predictive value was 71%. We conclude that these scores could be used as a single measure to predict patient disability, although the predictive value was rather weak.Level of evidence: II.

Exercise Therapy Is Effective at Improving Short- and Long-Term Mobility, Activities of Daily Living, and Balance in Older Patients Following Hip Fracture: A Systematic Review and Meta-Analysis.

BACKGROUND: A systematic review and meta-analysis was performed to evaluate the short- and long-term effects of exercise therapy on physical function, independence, and well-being in older patients following hip fracture and, secondly, whether the effect was modified by trial-level characteristics such as intervention modality, duration, and initiation timepoint. METHOD: Medline, CENTRAL, Embase, CINAHL, and PEDro were searched up to November 2020. Eligibility criteria were randomized controlled trials investigating the effect of exercise therapy on physical function, independence, and well-being in older patients following hip fracture, initiated from time of surgery up to 1 year. RESULTS: Forty-nine studies involving 3 905 participants showed a small-to-moderate effect of exercise therapy at short term (end of intervention) on mobility (standardized mean difference [SMD] 0.49, 95% confidence interval [CI]: 0.22-0.76); activities of daily living (ADL) (SMD 0.31, 95% CI: 0.16-0.46); lower limb muscle strength (SMD 0.36, 95% CI: 0.13-0.60); and balance (SMD 0.34, 95% CI: 0.14-0.54). At long term (closest to 1 year), small-to-moderate effects were found for mobility (SMD 0.74, 95% CI: 0.15-1.34), ADL (SMD 0.42, 95% CI: 0.23-0.61), balance (SMD 0.50, 95% CI: 0.07-0.94), and health-related quality of life (SMD 0.31, 95% CI: 0.03-0.59). Certainty of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation ranging from moderate to very low, due to study limitation and inconsistency. CONCLUSION: We found low certainty of evidence for a moderate effect of exercise therapy on mobility in older patients following hip fracture at end of treatment and follow-up. Further, low evidence was found for small-to-moderate short-term effect on ADL, lower limb muscle strength and balance. CLINICAL TRIALS REGISTRATION NUMBER: CRD42020161131.