Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts - bone cells that break down bone tissue. This is an update of a Cochrane review first published in 2008. For clinical relevance, we investigated etidronate's effects on postmenopausal women stratified by fracture risk (low versus high). OBJECTIVES: To assess the benefits and harms of intermittent/cyclic etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women at lower and higher risk of fracture, respectively. SEARCH METHODS: We searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE, Embase, two clinical trial registers, the websites of drug approval agencies, and the bibliographies of relevant systematic reviews. We identified eligible trials published between 1966 and February 2023. SELECTION CRITERIA: We included randomized controlled trials that assessed the benefits and harms of etidronate in the prevention of fractures for postmenopausal women. Women in the experimental arms must have received at least one year of etidronate, with or without other anti-osteoporotic drugs and concurrent calcium/vitamin D. Eligible comparators were placebo (i.e. no treatment; or calcium, vitamin D, or both) or another anti-osteoporotic drug. Major outcomes were clinical vertebral, non-vertebral, hip, and wrist fractures, withdrawals due to adverse events, and serious adverse events. We classified a study as secondary prevention if its population fulfilled one or more of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, a low bone mineral density T-score (≤ -2.5), or aged 75 years or older. If none of these criteria were met, we considered the study to be primary prevention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The review has three main comparisons: (1) etidronate 400 mg/day versus placebo; (2) etidronate 200 mg/day versus placebo; (3) etidronate at any dosage versus another anti-osteoporotic agent. We stratified the analyses for each comparison into primary and secondary prevention studies. For major outcomes in the placebo-controlled studies of etidronate 400 mg/day, we followed our original review by defining a greater than 15% relative change as clinically important. For all outcomes of interest, we extracted outcome measurements at the longest time point in the study. MAIN RESULTS: Thirty studies met the review's eligibility criteria. Of these, 26 studies, with a total of 2770 women, reported data that we could extract and quantitatively synthesize. There were nine primary and 17 secondary prevention studies. We had concerns about at least one risk of bias domain in each study. None of the studies described appropriate methods for allocation concealment, although 27% described adequate methods of random sequence generation. We judged that only 8% of the studies avoided performance bias, and provided adequate descriptions of appropriate blinding methods. One-quarter of studies that reported efficacy outcomes were at high risk of attrition bias, whilst 23% of studies reporting safety outcomes were at high risk in this domain. The 30 included studies compared (1) etidronate 400 mg/day to placebo (13 studies: nine primary and four secondary prevention); (2) etidronate 200 mg/day to placebo (three studies, all secondary prevention); or (3) etidronate (both dosing regimens) to another anti-osteoporotic agent (14 studies: one primary and 13 secondary prevention). We discuss only the etidronate 400 mg/day versus placebo comparison here. For primary prevention, we collected moderate- to very low-certainty evidence from nine studies (one to four years in length) including 740 postmenopausal women at lower risk of fractures. Compared to placebo, etidronate 400 mg/day probably results in little to no difference in non-vertebral fractures (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.20 to 1.61); absolute risk reduction (ARR) 4.8% fewer, 95% CI 8.9% fewer to 6.1% more) and serious adverse events (RR 0.90, 95% CI 0.52 to 1.54; ARR 1.1% fewer, 95% CI 4.9% fewer to 5.3% more), based on moderate-certainty evidence. Etidronate 400 mg/day may result in little to no difference in clinical vertebral fractures (RR 3.03, 95% CI 0.32 to 28.44; ARR 0.02% more, 95% CI 0% fewer to 0% more) and withdrawals due to adverse events (RR 1.41, 95% CI 0.81 to 2.47; ARR 2.3% more, 95% CI 1.1% fewer to 8.4% more), based on low-certainty evidence. We do not know the effect of etidronate on hip fractures because the evidence is very uncertain (RR not estimable based on very low-certainty evidence). Wrist fractures were not reported in the included studies. For secondary prevention, four studies (two to four years in length) including 667 postmenopausal women at higher risk of fractures provided the evidence. Compared to placebo, etidronate 400 mg/day may make little or no difference to non-vertebral fractures (RR 1.07, 95% CI 0.72 to 1.58; ARR 0.9% more, 95% CI 3.8% fewer to 8.1% more), based on low-certainty evidence. The evidence is very uncertain about etidronate's effects on hip fractures (RR 0.93, 95% CI 0.17 to 5.19; ARR 0.0% fewer, 95% CI 1.2% fewer to 6.3% more), wrist fractures (RR 0.90, 95% CI 0.13 to 6.04; ARR 0.0% fewer, 95% CI 2.5% fewer to 15.9% more), withdrawals due to adverse events (RR 1.09, 95% CI 0.54 to 2.18; ARR 0.4% more, 95% CI 1.9% fewer to 4.9% more), and serious adverse events (RR not estimable), compared to placebo. Clinical vertebral fractures were not reported in the included studies. AUTHORS' CONCLUSIONS: This update echoes the key findings of our previous review that etidronate probably makes or may make little to no difference to vertebral and non-vertebral fractures for both primary and secondary prevention.

Patient- and family-centred care transition interventions for adults: a systematic review and meta-analysis of RCTs.

Although patient centredness is part of providing high-quality health care, little is known about the effectiveness of care transition interventions that involve patients and their families on readmissions to the hospital or emergency visits post-discharge. This systematic review (SR) aimed to examine the evidence on patient- and family-centred (PFC) care transition interventions and evaluate their effectiveness on adults' hospital readmissions and emergency department (ED) visits after discharge. Searches of Medline, CINAHL, and Embase databases were conducted from the earliest available online year of indexing up to and including 14 March 2021. The studies included: (i) were about care transitions (hospital to home) of ≥18-year-old patients; (ii) had components of patient-centred care and care transition frameworks; (iii) reported on one or more outcomes were among hospital readmissions and ED visits after discharge; and (iv) were cluster-, pilot- or randomized-controlled trials published in English or French. Study selection, data extraction, and risk of bias assessment were completed by two independent reviewers. A narrative synthesis was performed, and pooled odd ratios, standardized mean differences, and mean differences were calculated using a random-effects meta-analysis. Of the 10,021 citations screened, 50 trials were included in the SR and 44 were included in the meta-analyses. Care transition intervention types included health assessment, symptom and disease management, medication reconciliation, discharge planning, risk management, complication detection, and emotional support. Results showed that PFC care transition interventions significantly reduced the risk of hospital readmission rates compared to usual care [incident rate ratio (IRR), 0.86; 95% confidence interval (CI), 0.75-0.98; I2 = 73%] regardless of time elapsed since discharge. However, these same interventions had minimal impact on the risk of ED visit rates compared to usual care group regardless of time passed after discharge (IRR, 1.00; 95% CI, 0.85-1.18; I2 = 29%). PFC care transition interventions containing a greater number of patient-centred care (IRR, 0.73; 95% CI, 0.57-0.94; I2 = 59%) and care transition components (IRR, 0.76; 95% CI, 0.64-0.91; I2 = 4%) significantly decreased the risk of patients being readmitted. However, these interventions did not significantly increase the risk of patients visiting the ED after discharge (IRR, 1.54; CI 95%, 0.91-2.61). Future interventions should focus on patients' and families' values, beliefs, needs, preferences, race, age, gender, and social determinants of health to improve the quality of adults' care transitions.

An international Delphi consensus process to determine a common data element and core outcome set for frailty: FOCUS (The Frailty Outcomes Consensus Project).

BACKGROUND: Despite increased recognition of frailty and its importance, high quality evidence to guide decision-making is lacking. There has been variation in reported data elements and outcomes which makes it challenging to interpret results across studies as well as to generalize research findings. The creation of a frailty core set, consisting of a minimum set of data elements and outcomes to be measured in all frailty studies, would allow for findings from research and translational studies to be collectively analyzed to better inform care and decision-making. To achieve this, the Frailty Outcomes Consensus Project was developed to reach consensus from the international frailty community on a set of common data elements and core outcomes for frailty. METHODS: An international steering committee developed the methodology and the consensus process to be followed. The committee formulated the initial list of data elements and outcomes. Participants from across the world were invited to take part in the Delphi consensus process. The Delphi consisted of three rounds. Following review of data after three rounds, a final ranking round of data elements and outcomes was conducted. A required retention rate of 80% between rounds was set a priori. RESULTS: One hundred and eighty-four panelists from 25 different countries participated in the first round of the Delphi consensus process. This included researchers, clinicians, administrators, older adults, and caregivers. The retention rate between rounds was achieved. Data elements and outcomes forming primary and secondary core sets were identified, within the domains of participant characteristics, physical performance, physical function, physical health, cognition and mental health, socioenvironmental circumstances, frailty measures, and other. CONCLUSION: It is anticipated that implementation and uptake of the frailty core set will enable studies to be collectively analyzed to better inform care for persons living with frailty and ultimately improve their outcomes. Future work will focus on identification of measurement tools to be used in the application of the frailty core set.

Towards consensus in defining and handling contextual factors within rheumatology trials: an initial qualitative study from an OMERACT working group.

OBJECTIVES: The Outcome Measures in Rheumatology Initiative established the Contextual Factors Working Group to guide the understanding, identification and handling of contextual factors for clinical trials. In clinical research, different uses of the term 'contextual factors' exist. This study explores the perspectives of researchers (including clinicians) and patients in defining 'contextual factor' and its related terminology, identifying such factors and accounting for them in trials across rheumatology. METHODS: We conducted individual semistructured interviews with researchers (including clinicians) who have experience within the field of contextual factors in clinical trials or other potentially relevant areas, and small focus group interviews with patients with rheumatic conditions. We transcribed the interviews and applied qualitative content analysis. RESULTS: We interviewed 12 researchers and 7 patients. Researcher's and patient's descriptions of contextual factors were categorised into two broad themes, each comprising two contextual factors types. The 'treatment effect' theme focused on factors explaining variations in treatment effects (A) among patients and (B) among studies. The 'outcome measurement' theme focused on factors that explain (C) variations in the measurement result itself (apart from actual changes/differences in the outcome) and (D) variations in the outcome itself (beside treatment of interest). Methods for identifying and handling contextual factors differed among these themes and types. CONCLUSIONS: Two main themes for contextual factors with four types of contextual factors were identified based on input from researchers and patients. This will guide operationalisation of contextual factors. Further research should refine our findings and establish consensus among relevant stakeholders.

Population characteristics as important contextual factors in rheumatological trials: an exploratory meta-epidemiological study from an OMERACT Working Group.

OBJECTIVES: To explore whether trial population characteristics modify treatment responses across various interventions, comparators and rheumatic conditions. METHODS: In this meta-epidemiological study, we included trials from systematic reviews available from the Cochrane Musculoskeletal Group published up to 23 April 2019 in Cochrane Library with meta-analyses of five or more randomised controlled trials (RCTs) published from year 2000. From trial reports, we extracted data on 20 population characteristics. For characteristics with sufficient data (ie, available for ≥2/3 of the trials), we performed multilevel meta-epidemiological analyses. RESULTS: We identified 19 eligible systematic reviews contributing 187 RCTs (212 comparisons). Only age and sex were explicitly reported in ≥2/3 of the trials. Using information about the country of the trials led to sufficient data for five further characteristics, that is, 7 out of 20 (35%) protocolised characteristics were analysed. The meta-regressions showed effect modification by economic status, place of residence, and, nearly, from healthcare system (explaining 4.8%, 0.9% and 1.5% of the between-trial variation, respectively). No effect modification was demonstrated from age, sex, patient education/health literacy or predominant religion. CONCLUSIONS: This study demonstrates the scarce reporting of most population characteristics, hampering investigation of their impact with meta-research. Our sparse results suggest that place of residence (ie, continent of the trial), economic status (based on World Bank classifications) and healthcare system (based on WHO index for health system performance) may be important in explaining the variation in treatment response across trials. There is an urgent need for consistent reporting of important population characteristics in trials. PROSPERO REGISTRATION NUMBER: CRD42019127642.

Patients' experience of shoulder disorders: a systematic review of qualitative studies for the OMERACT Shoulder Core Domain Set.

OBJECTIVES: To describe the experiences (including symptoms and perceived impacts on daily living) of people with a shoulder disorder. METHODS: Systematic review of qualitative studies. We searched for eligible qualitative studies indexed in Ovid MEDLINE, Ovid Embase, CINAHL (EBSCO), SportDiscus (EBSCO) and Ovid PsycINFO up until November 2017. Two authors independently screened studies for inclusion, appraised their methodological quality using the Critical Appraisal Skills Programme checklist, used thematic synthesis methods to generate themes describing the experiences reported by participants and assessed the confidence in the findings using the Grading of Recommendations Assessment, Development and Evaluation Confidence in Evidence from Reviews of Qualitative research (GRADE-CERQual) approach. RESULTS: The inclusion criteria were met by eight studies, which included 133 participants (49 females and 84 males) with either rotator cuff disease, adhesive capsulitis, proximal humeral fracture, shoulder instability or unspecified shoulder pain. We generated seven themes to describe what people in the included studies reported experiencing: pain; physical function/activity limitations; participation restriction; sleep disruption; cognitive dysfunction; emotional distress; and other pathophysiological manifestations (other than pain). There were interactions between the themes, with particular experiences impacting on others (e.g. pain leading to reduced activities and sleep disruption). Following grading of the evidence, we considered it likely that most of the review findings were a reasonable representation of the experiences of people with shoulder disorders. CONCLUSION: Patients with shoulder disorders contend with considerable disruption to their life. The experiences described should be considered by researchers seeking to select the most appropriate outcomes to measure in clinical trials and other research studies in people with shoulder disorders.

Effectiveness of immunoglobulin prophylaxis in reducing clinical complications of hematopoietic stem cell transplantation: a systematic review and meta-analysis.

BACKGROUND: Prophylactic immunoglobulin has been used with varying efficacy to reduce complications in hematopoietic stem cell transplant recipients. STUDY DESIGN AND METHODS: A systematic review and meta-analysis was conducted of randomized controlled trials that assessed clinical outcomes (overall survival, transplant-related mortality, graft-versus-host disease [GVHD], veno-occlusive disease [VOD], interstitial pneumonitis, disease relapse, cytomegalovirus [CMV] infection and disease, non-CMV infection) of immunoglobulin prophylaxis versus placebo in hematopoietic stem cell transplant recipients. MEDLINE, EMBASE, EBM Reviews, and the Cochrane Central Register of Controlled Trials were searched up to June 2017. Quality of included studies and outcomes were evaluated via Risk of Bias assessment and Grading of Recommendations, Assessment, Development and Evaluation criteria, respectively. RESULTS: Of 899 citations screened, 27 studies (n = 3934) were included. Immunoglobulin prophylaxis had no impact on survival (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.88-1.01; 11 studies, n = 1962) but decreased risk of acute GVHD (RR, 0.78; 95% CI, 0.65-0.94; eight studies, n = 1097) and CMV disease (RR, 0.52; 95% CI, 0.28-0.97; two studies, n = 167). Meta-analysis revealed increased risk of VOD (RR, 3.04; 95% CI, 1.10-8.41; three studies, n = 384) and disease relapse (RR, 1.26; 95% CI, 1.07-1.49; seven studies, n = 1647). Other outcomes were small in sample size or nonsignificant. Results should be interpreted cautiously given the low quality of studies and evidence of outcomes. CONCLUSION: Immunoglobulin prophylaxis did not have a significant effect on survival. Positive clinical effects were shown for acute GVHD and CMV disease and negative effects against VOD and disease relapse. No studies examined the effect of immunoglobulin treatment in hypogammaglobulinemic patients despite current guidelines, warranting further studies in this population.

Potential predatory and legitimate biomedical journals: can you tell the difference? A cross-sectional comparison.

BACKGROUND: The Internet has transformed scholarly publishing, most notably, by the introduction of open access publishing. Recently, there has been a rise of online journals characterized as 'predatory', which actively solicit manuscripts and charge publications fees without providing robust peer review and editorial services. We carried out a cross-sectional comparison of characteristics of potential predatory, legitimate open access, and legitimate subscription-based biomedical journals. METHODS: On July 10, 2014, scholarly journals from each of the following groups were identified - potential predatory journals (source: Beall's List), presumed legitimate, fully open access journals (source: PubMed Central), and presumed legitimate subscription-based (including hybrid) journals (source: Abridged Index Medicus). MEDLINE journal inclusion criteria were used to screen and identify biomedical journals from within the potential predatory journals group. One hundred journals from each group were randomly selected. Journal characteristics (e.g., website integrity, look and feel, editors and staff, editorial/peer review process, instructions to authors, publication model, copyright and licensing, journal location, and contact) were collected by one assessor and verified by a second. Summary statistics were calculated. RESULTS: Ninety-three predatory journals, 99 open access, and 100 subscription-based journals were analyzed; exclusions were due to website unavailability. Many more predatory journals' homepages contained spelling errors (61/93, 66%) and distorted or potentially unauthorized images (59/93, 63%) compared to open access journals (6/99, 6% and 5/99, 5%, respectively) and subscription-based journals (3/100, 3% and 1/100, 1%, respectively). Thirty-one (33%) predatory journals promoted a bogus impact metric - the Index Copernicus Value - versus three (3%) open access journals and no subscription-based journals. Nearly three quarters (n = 66, 73%) of predatory journals had editors or editorial board members whose affiliation with the journal was unverified versus two (2%) open access journals and one (1%) subscription-based journal in which this was the case. Predatory journals charge a considerably smaller publication fee (median $100 USD, IQR $63-$150) than open access journals ($1865 USD, IQR $800-$2205) and subscription-based hybrid journals ($3000 USD, IQR $2500-$3000). CONCLUSIONS: We identified 13 evidence-based characteristics by which predatory journals may potentially be distinguished from presumed legitimate journals. These may be useful for authors who are assessing journals for possible submission or for others, such as universities evaluating candidates' publications as part of the hiring process.

Considerations and guidance in designing equity-relevant clinical trials.

Health research has documented disparities in health and health outcomes within and between populations. When these disparities are unfair and avoidable they may be referred to as health inequities. Few trials attend to factors related to health inequities, and there is limited understanding about how to build consideration of health inequities into trials. Due consideration of health inequities is important to inform the design, conduct and reporting of trials so that research can build evidence to more effectively address health inequities and importantly, ensure that inequities are not aggravated. In this paper, we discuss approaches to integrating health equity-considerations in randomized trials by using the PROGRESS Plus framework (Place of residence, Race/ethnicity/culture/language, Occupation, Gender, Religion, Education, Socio-economic status, Social capital and "Plus" that includes other context specific factors) and cover: (i) formulation of research questions, (ii) two specific scenarios relevant to trials about health equity and (iii) describe how the PROGRESS Plus characteristics may influence trial design, conduct and analyses. This guidance is intended to support trialists designing equity-relevant trials and lead to better design, conduct, analyses and reporting, by addressing two main issues: how to avoid aggravating inequity among research participants and how to produce information that is useful to decision-makers who are concerned with health inequities.

WITHDRAWN: Celecoxib for rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic auto-immune disorder, involving persistent joint inflammation. NSAIDs are used to control the symptoms of RA, but are associated with significant gastro-intestinal toxicity, including a risk of potentially life threatening gastroduodenal perforations, ulcers and bleeds. The NSAIDs known as the selective Cox II inhibitors, of which celecoxib is a member, were developed in order to reduce the GI toxicity, but are more expensive. OBJECTIVES: To establish the efficacy and safety of celecoxib in the management of RA by systematic review of available evidence. SEARCH METHODS: We searched the following databases up to August 2002: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment Database. The bibliographies of retrieved papers and content experts were consulted for additional references. SELECTION CRITERIA: All eligible randomised controlled trials (RCTs) were included. No unpublished RCTs were included in this edition of the review. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers. Data was analysed using a fixed effects model. A validated checklist was used to score the quality of the RCTs. The planned analysis was to pool, where appropriate continuous outcomes using mean differences and dichotomous outcomes using relative risk ratios. This was not however possible due to the lack of data. MAIN RESULTS: Five RCTs were included (4465 participants); three of the studies also enrolled individuals with OA. The comparators were placebo, naproxen, diclofenac and ibuprofen. The evidence reviewed suggests that celecoxib controls the symptoms of RA to a similar degree to that of the active comparators examined (naproxen, diclofenac and ibuprofen). When compared to placebo, the percentage of patients showing improvement according to ACR 20 criteria at week 4 were 42/82 (51%) in the twice daily celecoxib 200mg group and 43/82 (52%) in the twice daily celecoxib 400mg group; these were significantly different from the placebo group in which 25/85 (29%) improved. The six month data reviewed support a reduced rate of UGI complications with celecoxib but there is also evidence to suggest that these benefits may not be evident in the long-term and that celecoxib offers no additional benefit in patients who are also receiving cardio-prophylactic low dose aspirin. AUTHORS' CONCLUSIONS: For an individual with RA the potential benefits of celecoxib need to be balanced against the uncertainty that the short-term reduced incidence of upper GI complications are maintained in the long-term and its increased cost in comparison to traditional NSAIDs.

Food supplementation for improving the physical and psychosocial health of socio-economically disadvantaged children aged three months to five years.

BACKGROUND: Undernutrition contributes to five million deaths of children under five each year. Furthermore, throughout the life cycle, undernutrition contributes to increased risk of infection, poor cognitive functioning, chronic disease, and mortality. It is thus important for decision-makers to have evidence about the effectiveness of nutrition interventions for young children. OBJECTIVES: Primary objective1. To assess the effectiveness of supplementary feeding interventions, alone or with co-intervention, for improving the physical and psychosocial health of disadvantaged children aged three months to five years.Secondary objectives1. To assess the potential of such programmes to reduce socio-economic inequalities in undernutrition.2. To evaluate implementation and to understand how this may impact on outcomes.3. To determine whether there are any adverse effects of supplementary feeding. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE, PsycINFO, and seven other databases for all available years up to January 2014. We also searched ClinicalTrials.gov and several sources of grey literature. In addition, we searched the reference lists of relevant articles and reviews, and asked experts in the area about ongoing and unpublished trials. SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster-RCTs, controlled clinical trials (CCTs), controlled before-and-after studies (CBAs), and interrupted time series (ITS) that provided supplementary food (with or without co-intervention) to children aged three months to five years, from all countries. Adjunctive treatments, such as nutrition education, were allowed. Controls had to be untreated. DATA COLLECTION AND ANALYSIS: Two or more review authors independently reviewed searches, selected studies for inclusion or exclusion, extracted data, and assessed risk of bias. We conducted meta-analyses for continuous data using the mean difference (MD) or the standardised mean difference (SMD) with a 95% confidence interval (CI), correcting for clustering if necessary. We analysed studies from low- and middle-income countries and from high-income countries separately, and RCTs separately from CBAs. We conducted a process evaluation to understand which factors impact on effectiveness. MAIN RESULTS: We included 32 studies (21 RCTs and 11 CBAs); 26 of these (16 RCTs and 10 CBAs) were in meta-analyses. More than 50% of the RCTs were judged to have low risk of bias for random selection and incomplete outcome assessment. We judged most RCTS to be unclear for allocation concealment, blinding of outcome assessment, and selective outcome reporting. Because children and parents knew that they were given food, we judged blinding of participants and personnel to be at high risk for all studies.Growth. Supplementary feeding had positive effects on growth in low- and middle-income countries. Meta-analysis of the RCTs showed that supplemented children gained an average of 0.12 kg more than controls over six months (95% confidence interval (CI) 0.05 to 0.18, 9 trials, 1057 participants, moderate quality evidence). In the CBAs, the effect was similar; 0.24 kg over a year (95% CI 0.09 to 0.39, 1784 participants, very low quality evidence). In high-income countries, one RCT found no difference in weight, but in a CBA with 116 Aboriginal children in Australia, the effect on weight was 0.95 kg (95% CI 0.58 to 1.33). For height, meta-analysis of nine RCTs revealed that supplemented children grew an average of 0.27 cm more over six months than those who were not supplemented (95% CI 0.07 to 0.48, 1463 participants, moderate quality evidence). Meta-analysis of seven CBAs showed no evidence of an effect (mean difference (MD) 0.52 cm, 95% CI -0.07 to 1.10, 7 trials, 1782 participants, very low quality evidence). Meta-analyses of the RCTs demonstrated benefits for weight-for-age z-scores (WAZ) (MD 0.15, 95% CI 0.05 to 0.24, 8 trials, 1565 participants, moderate quality evidence), and height-for-age z-scores (HAZ) (MD 0.15, 95% CI 0.06 to 0.24, 9 trials, 4638 participants, moderate quality evidence), but not for weight-for-height z-scores MD 0.10 (95% CI -0.02 to 0.22, 7 trials, 4176 participants, moderate quality evidence). Meta-analyses of the CBAs showed no effects on WAZ, HAZ, or WHZ (very low quality evidence). We found moderate positive effects for haemoglobin (SMD 0.49, 95% CI 0.07 to 0.91, 5 trials, 300 participants) in a meta-analysis of the RCTs.Psychosocial outcomes. Eight RCTs in low- and middle-income countries assessed psychosocial outcomes. Our meta-analysis of two studies showed moderate positive effects of feeding on psychomotor development (SMD 0.41, 95% CI 0.10 to 0.72, 178 participants). The evidence of effects on cognitive development was sparse and mixed.We found evidence of substantial leakage. When feeding was given at home, children benefited from only 36% of the energy in the supplement. However, when the supplementary food was given in day cares or feeding centres, there was less leakage; children took in 85% of the energy provided in the supplement. Supplementary food was generally more effective for younger children (less than two years of age) and for those who were poorer/ less well-nourished. Results for sex were equivocal. Our results also suggested that feeding programmes which were given in day-care/feeding centres and those which provided a moderate-to-high proportion of the recommended daily intake (% RDI) for energy were more effective. AUTHORS' CONCLUSIONS: Feeding programmes for young children in low- and middle-income countries can work, but good implementation is key.

Deep transverse friction massage for treating lateral elbow or lateral knee tendinitis.

Background Deep transverse friction massage, one of several physical therapy interventions suggested for the management of tendinitis pain, was first demonstrated in the 1930s by Dr James Cyriax, a renowned orthopedic surgeon in England. Its goal is to prevent abnormal fibrous adhesions and abnormal scarring. This is an update of a Cochrane review first published in 2001.Objectives To assess the benefits and harms of deep transverse friction massage for treating lateral elbow or lateral knee tendinitis.Search methods We searched the following electronic databases: the specialized central registry of the Cochrane Field of Physical and Related Therapies,the Cochrane Central Register of Controlled Trials (CENTRAL),MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Clinicaltrials.gov, and the Physiotherapy Evidence Database (PEDro), up until July 2014. The reference lists of these trials were consulted for additional studies.Selection criteria All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing deep transverse friction massage with control or other active interventions for study participants with two eligible types of tendinitis (ie, extensor carpi radialis tendinitis (lateral elbow tendinitis, tennis elbow or lateral epicondylitis or lateralis epicondylitis humeri) and iliotibial band friction syndrome (lateral knee tendinitis)) were selected. Only studies published in English and French languages were included.Data collection and analysis Two review authors independently assessed the studies on the basis of inclusion and exclusion criteria. Results of individual trials were extracted from the included study using extraction forms prepared by two independent review authors before the review was begun.Data were cross-checked by a third review author. Risk of bias of the included studies was assessed using the "Risk of bias"tool of The Cochrane Collaboration. A pooled analysis was performed using mean difference (MD) for continuous outcomes and risk ratio (RR)for dichotomous outcomes with 95% confidence intervals (CIs).Main results Two RCTs (no new additional studies in this update) with 57 participants met the inclusion criteria. These studies demonstrated high risk of performance and detection bias, and the risk of selection, attrition, and reporting bias was unclear.The first study included 40 participants with lateral elbow tendinitis and compared (1) deep transverse friction massage combined with therapeutic ultrasound and placebo ointment (n = 11) versus therapeutic ultrasound and placebo ointment only (n = 9) and (2)deep transverse friction massage combined with phonophoresis (n = 10) versus phonophoresis only (n = 10). No statistically significant differences were reported within five weeks for mean change in pain on a 0 to 100 visual analog scale (VAS) (MD -6.60, 95%CI -28.60 to 15.40; 7% absolute improvement), grip strength measured in kilograms of force (MD 0.10, 95% CI -0.16 to 0.36) and function ona 0 to 100 VAS (MD -1.80, 95% CI -0.18.64 to 15.04; 2% improvement), pain-free function index measured as the number of painfree items (MD 1.10, 95% CI -1.00 to 3.20) and functional status (RR 3.3, 95% CI 0.4 to 24.3) for deep transverse friction massage,and therapeutic ultrasound and placebo ointment compared with therapeutic ultrasound and placebo ointment only. Likewise for deep transverse friction massage and phonophoresis compared with phonophoresis alone, no statistically significant differences were found for pain (MD -1.2, 95% CI -20.24 to 17.84; 1% improvement), grip strength (MD -0.20, 95% CI -0.46 to 0.06) and function (MD3.70, 95% CI -14.13 to 21.53; 4% improvement). In addition, the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach was used to evaluate the quality of evidence for the pain outcome, which received a score of "very low".Pain relief of 30% or greater, quality of life, patient global assessment, adverse events, and withdrawals due to adverse events were not assessed or reported.The second study included 17 participants with iliotibial band friction syndrome (knee tendinitis) and compared deep transverse friction massage with physical therapy intervention versus physical therapy intervention alone, at two weeks. Deep transverse friction massage with physical therapy intervention showed no statistically significant differences in the three measures of pain relief on a 0 to 10 VAS when compared with physical therapy alone: daily pain (MD -0.40, 95% CI -0.80 to -0.00; absolute improvement 4%), pain while running (scale from 0 to 150) (MD -3.00, 95% CI -11.08 to 5.08), and percentage of maximum pain while running (MD -0.10, 95% CI -3.97 to 3.77). For the pain outcome, absolute improvement showed a 4% reduction in pain. However, the quality of the body of evidence received a grade of "very low."Pain relief of 30% or greater, function, quality of life, patient global assessment of success, adverse events, and withdrawals due to adverse events were not assessed or reported.Authors' conclusions We do not have sufficient evidence to determine the effects of deep transverse friction on pain, improvement in grip strength, and functional status for patients with lateral elbow tendinitis or knee tendinitis, as no evidence of clinically important benefits was found.The confidence intervals of the estimate of effects overlapped the null value for deep transverse friction massage in combination with physical therapy compared with physical therapy alone in the treatment of lateral elbow tendinitis and knee tendinitis. These conclusions are limited by the small sample size of the included randomized controlled trials. Future trials, utilizing specific methods and adequate sample sizes, are needed before conclusions can be drawn regarding the specific effects of deep transverse friction massage on lateral elbow tendinitis.

Methotrexate for treating rheumatoid arthritis.

BACKGROUND: Methotrexate is a folic acid antagonist widely used for the treatment of neoplastic disorders. Methotrexate inhibits the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and proteins by binding to dihydrofolate reductase. Currently, methotrexate is among the most commonly used drugs for the treatment of rheumatoid arthritis (RA). This is an update of the previous Cochrane systematic review published in 1997. OBJECTIVES: To evaluate short term benefits and harms of methotrexate for treating RA compared to placebo. SEARCH METHODS: The Cochrane Musculoskeletal Group Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched from 1966 to 1997 and then updated to November 2013. The search was complemented with a bibliography search of the reference lists of trials retrieved from the electronic search. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials comparing methotrexate (MTX) monotherapy against placebo alone in people with RA. Any trial duration and MTX doses were included. DATA COLLECTION AND ANALYSIS: Two review authors independently determined which studies were eligible for inclusion, extracted data and assessed risk of bias. Outcomes were pooled using mean differences (MDs) for continuous variables or standardized mean differences (SMDs) when different scales were used to measure the same outcome. Pooled risk ratio (RR) was used for dichotomous variables. Fixed-effect models were used throughout, although random-effects models were used for outcomes showing heterogeneity. MAIN RESULTS: Five trials with 300 patients were included in the original version of the review. An additional two trials with 432 patients were added to the 2013 update of the review for a total of 732 participants. The trials were generally of unclear to low risk of bias with a follow-up duration ranging from 12 to 52 weeks. All trials included patients who have failed prior treatment (for example, gold therapy, D-penicillamine, azathioprine or anti-malarials); mean disease duration that ranged between 1 and 14 years with six trials reporting more than 4 years; and weekly doses that ranged between 5 mg and 25 mg. BENEFITS: Statistically significant and clinically important differences were observed for most efficacy outcomes. MTX monotherapy showed a clinically important and statistically significant improvement in the American College of Rheumatology (ACR) 50 response rate when compared with placebo at 52 weeks (RR 3.0, 95% confidence interval (CI) 1.5 to 6.0; number needed to treat (NNT) 7, 95% CI 4 to 22). Fifteen more patients out of 100 had a major improvement in the ACR 50 outcome compared to placebo (absolute treatment benefit (ATB) 15%, 95% CI 8% to 23%).Statistically significant improvement in physical function (scale of 0 to 3) was also observed in patients receiving MTX alone compared with placebo at 12 to 52 weeks (MD -0.27, 95% CI -0.39 to -0.16; odds ratio (OR) 2.8, 95% CI 0.23 to 32.2; NNT 4, 95% CI 3 to 7). Nine more patients out of 100 improved in physical function compared to placebo (ATB -9%, 95% CI -13% to -5.3%). Similarly, the proportion of patients who improved at least 20% on the Short Form-36 (SF-36) physical component was higher in the MTX-treated group compared with placebo at 52 weeks (RR 1.5, 95% CI 1.0 to 2.1; NNT 9, 95% CI 4 to 539). Twelve more patients out of 100 showed an improvement of at least 20% in the physical component of the quality of life measure compared to placebo (ATB 12%, 95% CI 1% to 24%). No clinically important or statistically significant differences were observed in the SF-36 mental component.Although no statistically significant differences were observed in radiographic scores (that is, Total Sharp score, erosion score, joint space narrowing), radiographic progression rates (measured by an increase in erosion scores of more than 3 units on a scale ranging from 0 to 448) were statistically significantly lower for patients in the MTX group compared with placebo-treated patients (RR 0.31, 95% CI 0.11 to 0.86; NNT 13, 95% CI 10 to 60). Eight more patients out of 100 showed less damage to joints measured by an increase in erosion scores compared to placebo (ATB -8%, 95% CI -16% to -1%). In the one study measuring remission, no participants in either group met the remission criteria. These are defined by at least five of (≥ 2 months): morning stiffness of < 15 minutes, no fatigue, no joint pain by history, no joint tenderness, no joint swelling, and Westergren erythrocyte sedimentation rate (ESR) of < 20 mm/hr in men and < 30 mm/hr in women. HARMS: Patients in the MTX monotherapy group were twice as likely to discontinue from the study due to adverse events compared to patients in the placebo group, at 12 to 52 weeks (16% versus 8%; RR 2.1, 95% CI 1.3 to 3.3; NNT 13, 95% CI 6 to 44). Compared to placebo, nine more people out of 100 who took MTX withdrew from the studies because of side effects (ATB 9%, 95% CI 3% to 14%). Total adverse event rates at 12 weeks were higher in the MTX monotherapy group compared to the placebo group (45% versus 15%; RR 3.0, 95% CI 1.4 to 6.4; NNT 4, 95% CI 2 to 17). Thirty more people out of 100 who took MTX compared to those who took placebo experienced any type of side effect (common or rare) (ATB 30, 95% CI 13% to 47%). No statistically significant differences were observed in the total number of serious adverse events between the MTX group and the placebo group at 27 to 52 weeks. Three people out of 100 who took MTX alone experienced rare but serious side effects compared to 2 people out of 100 who took a placebo (3% versus 2%, respectively). AUTHORS' CONCLUSIONS: Based on mainly moderate to high quality evidence, methotrexate (weekly doses ranging between 5 mg and 25 mg) showed a substantial clinical and statistically significant benefit compared to placebo in the short term treatment (12 to 52 weeks) of people with RA, although its use was associated with a 16% discontinuation rate due to adverse events.

Patient research partner engagement in OMERACT: Enhancing engagement through the implementation of patient engagement in research tools.

OBJECTIVES: This paper describes the evolution and impact of Patient Research Partners (PRPs) in shaping research within OMERACT and provides a framework to enhance their engagement. This session explored one component of a validated framework to evaluate meaningful patient engagement. It provides insights, identifies opportunities for improvement, and recommends using the Patient Engagement in Research (PEIR) Framework, PEIR Plan Guide (workbook), and PEIRS-22 (scale) to guide and measure PRPs' engagement. METHODS: Before the conference, the team held planning sessions and selected the Feel-Valued component of the PEIR Workbook for exploration. During OMERACT 2023, we discussed this topic using the PEIR Plan Guide in an interactive plenary session. RESULTS: The plenary session produced 72 items from 14 breakout tables addressing PEIR Framework themes. CONCLUSIONS: This paper highlights the role and evolution of PRPs in shaping research within OMERACT. It emphasizes enhancing and accurately measuring PRP engagement through the PEIR Framework, PEIR Plan Guide, and PEIRS-22. The insights and methodologies presented aim to fortify future PRP engagement, ensuring it aligns with OMERACT's principles of patient-centred research.

The use of virtual nominal groups in healthcare research: An extended scoping review.

INTRODUCTION: The Nominal Group Technique (NGT) is a consensus group method used to synthesize expert opinions. Given the global shift to virtual meetings, the extent to which researchers leveraged virtual platforms is unclear. This scoping review explores the use of the vNGT in healthcare research during the COVID-19 pandemic. METHODS: Following the Arksey and O'Malley's framework, eight cross-disciplinary databases were searched (January 2020-July 2022). Research articles that reported all four vNGT stages (idea generation, round robin sharing, clarification, voting) were included. Media Synchronicity Theory informed analysis. Corresponding authors were surveyed for additional information. RESULTS: Of 2,589 citations, 32 references were included. Articles covered healthcare (27/32) and healthcare education (4/32). Platforms used most were Zoom, MS Teams and GoTo but was not reported in 44% of studies. Only 22% commented on the benefits/challenges of moving the NGT virtually. Among authors who responded to our survey (16/32), 80% felt that the vNGT was comparable or superior. CONCLUSIONS: The vNGT provides several advantages such as the inclusion of geographically dispersed participants, scheduling flexibility and cost savings. It is a promising alternative to the traditional in-person meeting, but researchers should carefully describe modifications, potential limitations, and impact on results.

Rapid review method series: interim guidance for the reporting of rapid reviews.

Rapid reviews (RRs) are produced using abbreviated methods compared with standard systematic reviews (SR) to expedite the process for decision-making. This paper provides interim guidance to support the complete reporting of RRs. Recommendations emerged from a survey informed by empirical studies of RR reporting, in addition to collective experience. RR producers should use existing, robustly developed reporting guidelines as the foundation for writing RRs: notably Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020; reporting for SRs), but also preferred reporting items for overviews of reviews (PRIOR) items (reporting for overviews of SRs) where SRs are included in the RR. In addition, a minimum set of six items were identified for RRs: three items pertaining to methods and three addressing publication ethics. Authors should be reporting what a priori-defined iterative methods were used during conduct, what distinguishes their RR from an SR, and knowledge user (eg, policymaker) involvement in the process. Explicitly reporting deviations from standard SR methods, including omitted steps, is important. The inclusion of publication ethics items reflects the predominance of non-journal published RRs: reporting an authorship byline and corresponding author, acknowledging other contributors, and reporting the use of expert peer review. As various formats may be used when packaging and presenting information to decision-makers, it is practical to think of complete reporting as across a set of explicitly linked documents made available in an open-access journal or repository that is barrier-free. We encourage feedback from the RR community of the use of these items as we look to develop a consolidated list in the development of PRISMA-RR.

Exploring the complexities of pain phenotypes: OMERACT 2023 chronic pain working group workshop.

OBJECTIVE: To educate and discuss pain mechanisms (nociceptive, neuropathic, nociplastic) illuminating its possible impact when measuring different outcomes, which may modify, confound and potentially bias the outcome measures applied across various aspects of Rheumatic Musculoskeletal Diseases (RMDs) clinical trials. METHODS: In the plenary presentations, PM lectured on different pain mechanisms and impact on disease activity assessment. Data from two data sets of RMDs patients, which assessed the prevalence and impact of nociplastic pain were presented and reviewed. Audience breakout group sessions and polling were conducted. RESULTS: Mixed pain etiologies may differentially influence disease activity assessment and therapeutic decision-making. Polling demonstrated a consensus on the need to assess different types of pain as a phenotype, as it constitutes an important contextual factor (a variable that is not an outcome of the trial, but needs to be recognized [and measured] to understand the study results), and to standardize across RMDs. CONCLUSION: There is need for a standardized pain measure that can differentiate underlying pain mechanisms.

Protocol for the development of a reporting guideline for umbrella reviews on epidemiological associations using cross-sectional, case-control and cohort studies: the Preferred Reporting Items for Umbrella Reviews of Cross-sectional, Case-control and Cohort studies (PRIUR-CCC).

INTRODUCTION: Observational studies are fraught with several biases including reverse causation and residual confounding. Overview of reviews of observational studies (ie, umbrella reviews) synthesise systematic reviews with or without meta-analyses of cross-sectional, case-control and cohort studies, and may also aid in the grading of the credibility of reported associations. The number of published umbrella reviews has been increasing. Recently, a reporting guideline for overviews of reviews of healthcare interventions (Preferred Reporting Items for Overviews of Reviews (PRIOR)) was published, but the field lacks reporting guidelines for umbrella reviews of observational studies. Our aim is to develop a reporting guideline for umbrella reviews on cross-sectional, case-control and cohort studies assessing epidemiological associations. METHODS AND ANALYSIS: We will adhere to established guidance and prepare a PRIOR extension for systematic reviews of cross-sectional, case-control and cohort studies testing epidemiological associations between an exposure and an outcome, namely Preferred Reporting Items for Umbrella Reviews of Cross-sectional, Case-control and Cohort studies (PRIUR-CCC). Step 1 will be the project launch to identify stakeholders. Step 2 will be a literature review of available guidance to conduct umbrella reviews. Step 3 will be an online Delphi study sampling 100 participants among authors and editors of umbrella reviews. Step 4 will encompass the finalisation of PRIUR-CCC statement, including a checklist, a flow diagram, explanation and elaboration document. Deliverables will be (i) identifying stakeholders to involve according to relevant expertise and end-user groups, with an equity, diversity and inclusion lens; (ii) completing a narrative review of methodological guidance on how to conduct umbrella reviews, a narrative review of methodology and reporting in published umbrella reviews and preparing an initial PRIUR-CCC checklist for Delphi study round 1; (iii) preparing a PRIUR-CCC checklist with guidance after Delphi study; (iv) publishing and disseminating PRIUR-CCC statement. ETHICS AND DISSEMINATION: PRIUR-CCC has been approved by The Ottawa Health Science Network Research Ethics Board and has obtained consent (20220639-01H). Participants to step 3 will give informed consent. PRIUR-CCC steps will be published in a peer-reviewed journal and will guide reporting of umbrella reviews on epidemiological associations.

Embracing unity at OMERACT: Valuing equity, promoting diversity, fostering inclusivity.

OBJECTIVE: To increase awareness and understanding of the principles of Equity, Diversity, and Inclusivity (EDI) within Outcome Measures in Rheumatology's (OMERACT) members. For this, we aimed to obtain ideas on how to promote and foster these principles within the organization and determine the diversity of the current membership in order to focus future efforts. METHODS: We held a plenary workshop session at OMERACT 2023 with roundtable discussions on barriers and solutions to increased diversity within OMERACT. We conducted an anonymous, web-based survey of members to record characteristics including population group, gender identity, education level, age, and ability. RESULTS: The workshop generated ideas to increase diversity of participants across the themes of building relationships [12 topics], materials and methods [5 topics], and conference-specific [6 topics]. Four hundred and seven people responded to the survey (25 % response rate). The majority of respondents were White (75 %), female (61 %), university-educated (94 %), Christian (42 %), spoke English at home (60 %), aged 35 to 55 years (50 %), and did not report a disability (64 %). CONCLUSION: OMERACT is committed to improving its diversity. Next steps include strategic recruitment of members to the EDI working group, drafting an EDI mission statement centering equity and inclusivity in the organization, and developing guidance for the OMERACT Handbook to help all working groups create actionable plans for promoting EDI principles.