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Youth peer support workers (YPSWs) are young adults with lived experience of mental illness during childhood or adolescence who support young people receiving treatment in mental health services. The contributions made by YPSWs are a promising development to facilitate consumer-centered and recovery-oriented care. Although the youth peer support workforce is expanding rapidly, structurally embedding YPSWs in practice is challenging. To overcome these challenges and thereby improve care for young people, insight into YPSW roles, barriers and facilitators for implementing and pursuing youth peer support (YPS) is a necessity. This systematic review examined the published literature to identify existing knowledge on YPSW roles in treatment settings, and the barriers and facilitators for implementing and pursuing YPS in practice. A total of 24 studies from a variety of youth serving contexts were included in this review. Thematic synthesis resulted in six YPSW roles and five themes with barriers and facilitators. The roles included the: engagement role, emotional support role, navigating and planning role, advocacy role, research role and the educational role. The themes explored the needs of YPSWs, experiences of YPSWs, relationships between service users and YPSWs, the collaboration process between YPSWs and non-peer staff, and organizational readiness. This review underlines that YPSWs likely are a valuable addition to numerous youth treatment contexts. Overall, the implementation of YPSWs is a multifaceted operation that requires careful planning. We recommend services to set clear and realistic expectations for YPSWs, to consider potential power imbalances between YPSWs and non-peer staff, to provide adequate resources to pursue YPS, and to approach the implementation of YPSWs with a growth mindset.

Objective Initiation of DMARD-therapy in the ‘window of opportunity’ is thought to result in a more effective modification of the processes underlying rheumatoid arthritis (RA). We questioned whether this effect is true or hyped and performed a systematic literature review. Methods Medical literature databases up to June 2012 were systematically reviewed for cohort studies and randomised controlled trials reporting outcome data of early RA in relation with symptom duration at treatment initiation. The quality of these studies was assessed by two independent reviewers using a criteria scoring system of 15 items. Studies were dichotomised with the median score (79%) as cut-off. Best-evidence synthesis was applied to determine the level of evidence per outcome category. A meta-analysis was performed on the studies reporting on achieving DMARD-free sustained remission (the reverse of disease persistency). Results Out of 836 screened articles, 18 fulfilled the selection criteria and were not duplicates. Ten were scored as high quality. Remission (various definitions) and radiographic progression were frequently studied outcomes. There was strong evidence for an association between symptom duration and radiographic progression. A meta-analysis on datasets evaluating DMARD-free sustained remission showed that symptom duration was independently associated with such remission; HR 0.989 (95% CI 0.983 to 0.995) per week increase in symptom duration. A moderate level of evidence was observed for other remission outcomes. Conclusions Even when heterogeneity of patients is taken into account, prolonged symptom duration is associated with radiographic progression and a lower chance on DMARD-free sustained remission. These data may support the presence of a ‘window of opportunity’.

There are concerns about increased mortality in patients with metal-on-metal bearings in total hip arthroplasty (THA). To determine the mortality and the morbidity in patients with metal-on-metal articulations (MOM THA) compared to patients with non-metal-on-metal articulations (non-MOM THA) after primary total hip arthroplasty. Search of PubMed, MEDLINE, EMBASE, Web of Science, Cochrane, CINAHL, AcademicSearchPremier, ScienceDirect, Wiley and clinical trial registers through March 2015, augmented by a hand search of references from the included articles. No language restrictions were applied. Two reviewers screened and identified randomised controlled trials and observational studies of primary total hip arthroplasty comparing MOM THA with non-MOM THA. Two reviewers independently extracted study data and assessed risk of bias. Risk differences (RD) were calculated with random effect models. Meta-regression was used to explore modifying factors. Difference in mortality and difference in morbidity expressed as revisions and medical complications between patients with MOM THA and non-MOM THA. Forty-seven studies were included, comprising 4,000 THA in randomised trials and over 500,000 THA in observational studies. For mortality, random effects analysis revealed a higher pooled RD of 0.7%, 95%, confidence interval (CI) [0.0%, 2.3%], I-square 42%; the heterogeneity was explained by differences in follow-up. When restricted to studies with long term follow-up (i.e. 10 years or more), the RD for mortality was 8.5%, 95%, CI [5.8%, 11.2%]; number needed to treat was 12. Further subgroup analyses and meta-regression random effects models revealed no evidence for other moderator variables (study level covariates, e.g. resurfacing vs. non-resurfacing MOM) than follow-up duration. The quality of the evidence presented in this meta-analysis was characterized as moderate according to the CLEAR-NPT (for non-pharmacological trials) and Cochrane risk of bias Table. Meta-analysis suggests there may be an increased long-term risk of mortality and revision surgery for patients with MOM THA compared to patients with non-MOM THA. PROSPERO 2014:CRD42014007417.

ObjectiveCurrent research in rheumatoid arthritis focuses on preclinical disease phases as it is hypothesised that early preclinical treatment might prevent progression to full-blown disease. Since performance of studies in prearthritis phases in humans is challenging, animal models offer an opportunity to evaluate preventive treatments. We performed a systematic literature review and summarised treatment effects during different stages of arthritis development in animal models.MethodsEight medical literature databases were systematically searched. Studies were selected if they reported effects of synthetic or biological disease-modifying antirheumatic drugs in animal models of arthritis (collagen-induced arthritis and adjuvant-induced arthritis) on arthritis severity, as measured with arthritis severity scores, paw swelling or paw volume. Quality was assessed using an 11-item checklist. Study characteristics were extracted and effect sizes obtained in high-quality studies were summarised in meta-analyses. Studies were categorised into three groups: prophylactic (prior to generation of autoantibody response), prearthritis (after induction of autoantibody response) and therapeutic intervention (after arthritis development).ResultsOut of 1415 screened articles, 22 studies (including n=712 animals) were eligible of good quality and included in meta-analyses. Prophylactic (16 experiments, n=312 animals) and prearthritis treatment (9 experiments, n=156 animals) both were associated with a reduction of arthritis severity (p<0.001 and p=0.005, respectively). Stratified analyses for different antirheumatic drugs initiated in the prearthritis phase suggested higher efficacy of methotrexate than of anti-tumour necrosis factor.ConclusionsData of experimental studies in animal models of arthritis suggest that prophylactic and prearthritis treatment strategies are effective and hint at differences in efficacy between antirheumatic drugs.

Purpose Although the use of Patient-Reported Outcomes Measurement Information System (PROMIS) measures is widely advocated, little is known on their use in patients with inflammatory arthritis. We systematically describe the use and outcomes of PROMIS measures in clinical studies involving people with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA). Methods A systematic review was conducted according to the PRISMA guidelines. Through a systematic search of nine electronic databases, clinical studies including patients with RA or axSpA and reporting the use of PROMIS measure were selected. Study characteristics, details of PROMIS measures and their outcomes, if available, were extracted. Results In total, 29 studies described in 40 articles met the inclusion criteria, of which 25 studies included RA patients, three studies included axSpA patients and one study included both RA and axSpA patients. The use of two general PROMIS measures (PROMIS Global Health, PROMIS-29) and 13 different domain-specific PROMIS measures was reported, of which the PROMIS Pain Interference ( n = 17), Physical Function ( n = 14), Fatigue ( n = 13), and Depression ( n = 12) measures were most frequently used. Twenty-one studies reported their results in terms of T -scores. Most T -scores were worse than the general population mean, indicating impairments of health status. Eight studies did not report actual data but rather measurement properties of the PROMIS measures. Conclusion There was considerable variety regarding the different PROMIS measures used, with the PROMIS Pain interference, Physical function, Fatigue, and Depression measures being the most frequently used. In order to facilitate the comparisons across studies, more standardization of the selection of PROMIS measures is needed.

Background Proton Pump Inhibitors (PPI) are frequently prescribed. Long-term use is associated with side-effects and patients often lack a valid indication. Inappropriate PPI prescribing thus needs to be addressed. This review aims to scope 1) what determinants are studied as reasons for PPI prescribing, 2) what strategies are used for changing PPI (de)prescribing, and 3) whether important determinants are addressed in these interventions. Methods We searched eight databases for papers on determinants of physician PPI prescribing. Studies were included if they were conducted in a Western country and focused on oral PPIs for an adult population. By following the Behaviour Change Wheel, we extracted information regarding PPI prescribing behavior, behavioral determinants and intervention strategies. Findings We included 74 papers. Most focused on the determinants knowledge and beliefs about consequences. The latter was consistently related to PPI prescribing. Results for knowledge were mixed. Most interventions used education or enablement (e.g., algorithms, quality check improvements, involvement of pharmacists) as strategies. Enablement consistently improved PPI prescribing, while results for education were mixed. Interpretation There is an overemphasis on reflective processes in studies on PPI prescribing. Future research should comprehensively identify behavioral determinants, focusing on reflective and impulsive processes, such that interventions can address the most important determinants.

To assess the reporting quality of interventions aiming at promoting physical activity (PA) using a wearable activity tracker (WAT) in patients with inflammatory arthritis (IA) or hip/knee osteoarthritis (OA). A systematic search was performed in eight databases (including PubMed, Embase and Cochrane Library) for studies published between 2000 and 2022. Two reviewers independently selected studies and extracted data on study characteristics and the reporting of the PA intervention using a WAT using the Consensus on Exercise Reporting Template (CERT) (12 items) and Consolidated Standards of Reporting Trials (CONSORT) E-Health checklist (16 items). The reporting quality of each study was expressed as a percentage of reported items of the total CERT and CONSORT E-Health (50% or less = poor; 51–79% = moderate; and 80–100% = good reporting quality). Sixteen studies were included; three involved patients with IA and 13 with OA. Reporting quality was poor in 6/16 studies and moderate in 10/16 studies, according to the CERT and poor in 8/16 and moderate in 8/16 studies following the CONSORT E-Health checklist. Poorly reported checklist items included: the description of decision rule(s) for determining progression and the starting level, the number of adverse events and how adherence or fidelity was assessed. In clinical trials on PA interventions using a WAT in patients with IA or OA, the reporting quality of delivery process is moderate to poor. The poor reporting quality of the progression and tailoring of the PA programs makes replication difficult. Improvements in reporting quality are necessary.

N,N-Dimethyltryptamine (DMT) is currently being studied for its therapeutic potential in various psychiatric disorders. An understanding of its pharmacokinetics (PK) is essential to determine appropriate dose ranges in future clinical studies. We conducted a systematic literature review on the PK of DMT. Clinical studies that administered known amounts of DMT and reported PK data and/or parameters in humans were included. Additionally, raw PK data were requested from authors and/or extracted from publications. In total, 219 references were retrieved, of which 13 publications were included, covering eight distinct datasets. All studies administered DMT intravenously in various infusion schemes, except for one intramuscular administration. High variability in dose-normalized exposure parameters and differences in exposure for bolus versus infusion administration were observed. DMT is extensively redistributed to other tissues, based on its biphasic elimination profile and high volume of distribution in the terminal elimination phase (range 123-1084 L). It is eliminated rapidly, with a half-life of 4.8-19.0 min and clearance of 8.1-46.8 L/min. This is a result of the rapid metabolization of DMT to indole-3-acetic acid (IAA), which is also reflected in the fact that the time of maximum concentration of IAA is similar to that of DMT. This review demonstrates that the PK of DMT in humans have been characterized to a limited extent, and publications lack details with regards to demographics, absolute doses, and PK parameters. Additional studies are necessary to investigate high intersubject variability and differences in exposure following bolus or prolonged infusion. Addressing these issues is essential for the development of DMT as a pharmacotherapeutic in neuropsychiatry.

Objective To determine the evidence of effectiveness and safety for introduction of five recent and ostensibly high value implantable devices in major joint replacement to illustrate the need for change and inform guidance on evidence based introduction of new implants into healthcare.Design Systematic review of clinical trials, comparative observational studies, and registries for comparative effectiveness and safety of five implantable device innovations.Data sources PubMed (Medline), Embase, Web of Science, Cochrane, CINAHL, reference lists of articles, annual reports of major registries, summaries of safety and effectiveness for pre-market application and mandated post-market studies at the US Food and Drug Administration.Study selection The five selected innovations comprised three in total hip replacement (ceramic-on-ceramic bearings, modular femoral necks, and uncemented monoblock cups) and two in total knee replacement (high flexion knee replacement and gender specific knee replacement). All clinical studies of primary total hip or knee replacement for symptomatic osteoarthritis in adults that compared at least one of the clinical outcomes of interest (patient centred outcomes or complications, or both) in the new implant group and control implant group were considered. Data searching, abstraction, and analysis were independently performed and confirmed by at least two authors. Quantitative data syntheses were performed when feasible.Results After assessment of 10 557 search hits, 118 studies (94 unique study cohorts) met the inclusion criteria and reported data related to 15 384 implants in 13 164 patients. Comparative evidence per device innovation varied from four low to moderate quality retrospective studies (modular femoral necks) to 56 studies of varying quality including seven high quality (randomised) studies (high flexion knee replacement). None of the five device innovations was found to improve functional or patient reported outcomes. National registries reported two to 12 year follow-up for revision occurrence related to more than 200 000 of these implants. Reported comparative data with well established alternative devices (over 1 200 000 implants) did not show improved device survival. Moreover, we found higher revision occurrence associated with modular femoral necks (hazard ratio 1.9) and ceramic-on-ceramic bearings (hazard ratio 1.0-1.6) in hip replacement and with high flexion knee implants (hazard ratio 1.0-1.8).Conclusion We did not find convincing high quality evidence supporting the use of five substantial, well known, and already implemented device innovations in orthopaedics. Moreover, existing devices may be safer to use in total hip or knee replacement. Improved regulation and professional society oversight are necessary to prevent patients from being further exposed to these and future innovations introduced without proper evidence of improved clinical efficacy and safety.