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The risk of young-onset colorectal adenomas and cancer (yCRAC) in adults less than 50 years of age is increasing. We conducted a systematic review and meta-analysis of epidemiologic studies to identify lifestyle and clinical risk factors associated with yCRAC risk. We searched Medline, EMBASE, and Cochrane Database of Systematic Reviews for studies which: used an epidemiologic study design, involved individuals with yCRAC, evaluated at least 1 lifestyle or clinical factor, and applied multivariable regression approaches. We critically appraised the quality of included studies and calculated pooled measures of association (e.g. odds ratio [OR]) and 95% confidence intervals (CI) using random-effects models. We identified 499 articles in our search with 9 included in a narrative synthesis and 6 included in a meta-analysis. We found in the pooled analysis that smoking and alcohol consumption were lifestyle factors associated with yCRAC, as were clinical factors including obesity elevated blood glucose, elevated blood pressure, and elevated triglycerides. We identified lifestyle and clinical risk factors associated with risk of yCRAC, which have potential implications for informing preventive efforts and modifying screening to target at-risk populations.

Current heart failure (HF) guidelines recommend titrating angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) and beta-blockers (BBs) to target doses used in pivotal placebo-controlled randomized controlled trials (RCTs). Despite a number of RCTs comparing different doses (i.e. higher versus lower doses) of ACEIs, ARBs and BBs, the effects of higher versus lower doses on efficacy and safety remains unclear. For this reason, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of higher versus lower doses of ACEIs, ARBs and BBs in patients with HFrEF. We searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) via Ovid from inception to April 25th, 2018 and opentrials.net and clinicaltrials.gov for relevant trials that compared different doses of medications in heart failure. We analyzed trials by drug class (ACEIs, ARBs, and BBs) for efficacy outcomes (all-cause mortality, cardiovascular mortality, all-cause hospitalizations, HF hospitalizations, HF worsening). For safety outcomes, we pooled trials within and across drug classes. Our meta-analysis consisted of 14 RCTs. Using GRADE criteria, the quality of evidence for ACEIs and ARBs was assessed as generally moderate for efficacy and high for adverse effects, whereas overall quality for BBs was very low to low. Over ~2-4 years higher versus lower doses of ACEIs, ARBs or BBs did not significantly reduce all-cause mortality [ACEIs relative risk (RR) 0.94 (95% confidence interval 0.87-1.02)], ARBs RR 0.96 (0.87-1.04), BBs RR 0.25 (0.06-1.01)] or all cause hospitalizations [ACEIs relative risk (RR) 0.94 (95% confidence interval 0.86-1.02)], ARBs RR 0.98 (0.93-1.04), BBs RR 0.93 (0.39-2.24)]. However, all point estimates favoured higher doses. Higher doses of ARBs significantly reduced hospitalization for HF [RR 0.89 (0.80-0.99)- 2.8% ARR], and higher doses of ACEIs and ARBs significantly reduced HF worsening [RR 0.85 (0.79-0.92)- 5.1% ARR and 0.91 (0.84-0.99)- 3.2% ARR, respectively] compared to lower doses. None of the differences between higher versus lower doses of BBs were significant; however, precision was low. Higher doses of these medications compared to lower doses increased the risk of discontinuation due to adverse events, hypotension, dizziness, and for ACEIs and ARBs, increased hyperkalemia and elevations in serum creatinine. Absolute increase in harms for adverse effects ranged from ~ 3 to 14%. Higher doses of ACEIs and ARBs reduce the risk of HF worsening compared to lower doses, and higher doses of ARBs also reduce the risk of HF hospitalization but the evidence is sparse and imprecise. Higher doses increase the chance of adverse effects compared to lower doses. Evidence for BBs is inconclusive. These results support initially always starting at low doses of ACEIs/ARBs and only titrating the dose up if the patient tolerates dose increases.

Introduction Patient and public involvement (PPI) in research emphasizes the importance of doing research with, rather than for people with lived health/illness experience(s). The purpose of this scoping review is to investigate the breadth and depth of scientific literature on PPI in cancer research and to identify how is PPI applied and reported in cancer research. Methods We searched MEDLINE, Embase, CINAHL, and PsycInfo up to March 2022. All titles/s and full‐text results were screened by two reviewers. Data were analyzed and are presented in both narrative and tabular format. Results We screened 22,009 titles/, reviewed 375 full‐text articles, of which 101 studies were included in this review. 66 papers applied PPI; 35 used co‐design methodologies. PPI in cancer research in published research has increased steadily since 2015 and often includes those with a past diagnosis of cancer or relatives/informal caregivers. The most common applied methods were workshops or interviews. PPI was generally used at the level of consultation/advisor and occurred mainly in early stages of research. Costs related to PPI were mentioned in 25 papers and four papers described training provided for PPI. Conclusions Results of our review demonstrate the nature and extent of PPI expansion in cancer research. Researchers and research organizations entering the fray of PPI should consider planning and reporting elements such as the stage, level, and role type of PPI, as well as methods and strategies put in place to assure diversity. Furthermore, a thorough evaluation of whether all these elements meet the stated PPI purpose will help to grasp its impact on research outcomes. Patient or Public Contribution Two patients participated in the stakeholder consultation as part of the scoping review methodology, contributed to the discussion on refining the results, and critically reviewed the manuscript. Both are co‐authors of this manuscript.

Aims The optimal antithrombotic therapy to balance the risk of thrombosis and bleeding in patients who undergo transcatheter aortic valve implantation (TAVI) is unknown. This systematic review/network meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of different oral anticoagulant (OAC) and antiplatelet regimens in patients post-TAVI. Methods and results MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched from inception to April 2023. Co-primary outcomes were all-cause death and major bleeding. We conducted Bayesian network meta-analyses to compare all interventions simultaneously. For each outcome, we generated odds ratios (ORs) with 95% credible intervals using a random-effects model with informative priors, and ranked interventions based on mean surface under the cumulative ranking curve. We included 11 RCTs (n = 6415), including 1 unpublished RCT. Three trials enrolled patients with an indication for an OAC. Overall risk of bias was low or with some concerns. Median age was 81 years. Median follow-up was 6 months. The combination of OAC plus single antiplatelet therapy (SAPT) increased the risk of all-cause death compared with dual antiplatelet therapy (DAPT) (OR 1.78, 95% credible interval 1.15–2.77). No other comparisons for all-cause death were significantly different. For major bleeding, SAPT reduced the risk compared with DAPT, direct-acting OAC, and OAC + SAPT (OR 0.20–0.40), and DAPT reduced the risk compared with OAC + SAPT. SAPT and DAPT ranked best for all-cause death, while SAPT ranked best for major bleeding. Conclusion In post-TAVI patients, SAPT may provide the optimal balance of reducing thrombotic events while minimizing the risk of bleeding.

IntroductionHealth workers (HWs) and their representative health worker organisations (RHWOs) contribute to the design of pharmaceutical policy in low- and middle-income countries (LMICs), but their roles remain underappreciated. HWs and RHWOs can influence drug development, distribution, financing and access; however, which specific aspects HWs and RHWOs contribute to, and how they create change, remains insufficiently mapped within the global health literature. This protocol describes our process for conducting a scoping review to derive, describe, and classify existing literature on how HWs and RHWOs engage in pharmaceutical policy processes in LMICs.Methods and analysisThis review will follow the updated Arksey and O’Malley five-stage scoping review framework supported by iterations of methodological guidance and will be reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. We will search Ovid Medline, Ovid Embase and CAB Global Health for English-language peer-reviewed literature published between 2005 and 2025. Studies must discuss HW and RHWO involvement or influence in pharmaceutical policy or describe the roles, governance contexts or strategies of HWs or RHWOs in the context of pharmaceutical policy. Two reviewers will independently screen titles, abstracts and full texts using Covidence software to determine eligibility. We will chart data using Excel and summarise the findings thematically. We will consult stakeholders in the final stage of this review to provide feedback on the results of our review and guide our findings further in terms of actionable policy implications.Ethics and disseminationEthics approval is not required for this scoping review of published literature. Findings will be disseminated through peer-reviewed publications, academic presentations and policy engagement with global health actors. This review will inform future research and support evidence-informed pharmaceutical policymaking in LMICs.

During the COVID-19 pandemic, public health measures such as isolation, quarantine, and social distancing are needed. Some of these measures can adversely affect mental health. Activities that can be performed at home may mitigate these consequences and improve overall mental well-being. In this study, home-based activities that have potential beneficial effects on mental health were examined. A rapid review was conducted based on a search of the following databases: MEDLINE, EMBASE, CINAHL, PyscINFO, Global Health, epistemonikos.org, covid19reviews.org, and eppi.ioe.ac.uk/covid19_map_v13.html. Eligible studies include randomized controlled trials and non-randomized studies published between 1/1/2000 and 28/05/2020 and that examined the impact of various activities on mental health outcomes in low-resource settings and contexts that lead to social isolation. Studies of activities that require mental health professionals or that could not be done at home were excluded. Two review authors performed title/abstract screening. At the full-text review stage, 25% of the potentially eligible studies were reviewed in full by two review authors; the rest were reviewed by one review author. Risk of bias assessment and data extraction were performed by one review author and checked by a second review author. The main outcome assessed was change or differences in mental health as expressed in Cohen's d; analysis was conducted following the synthesis without meta-analysis guidelines (SWiM). PROSPERO registration: CRD42020186082. Of 1,236 unique records identified, 160 were reviewed in full, resulting in 16 included studies. The included studies reported on the beneficial effects of exercise, yoga, progressive muscle relaxation, and listening to relaxing music. One study reported on the association between solitary religious activities and post traumatic stress disorder symptoms. While most of the included studies examined activities in group settings, particularly among individuals in prisons, the activities were described as something that can be performed at home and alone. All included studies were assessed to be at risk of bias in one or more of the bias domains examined. There is some evidence that certain home-based activities can promote mental wellness during the COVID-19 pandemic. Guidelines are needed to help optimize benefits while minimizing potential risks when performing these activities.

The search methods used in systematic reviews provide the foundation for establishing the body of literature from which conclusions are drawn and recommendations made. Searches should aim to be comprehensive and reporting of search methods should be transparent and reproducible. Campbell Collaboration systematic reviews strive to adhere to the best methodological guidance available for this type of searching. The current work aims to provide an assessment of the conduct and reporting of searches in Campbell Collaboration systematic reviews. Our objectives were to examine how searches are currently conducted in Campbell systematic reviews, how search strategies, search methods and search reporting adhere to the Methodological Expectations of Campbell Collaboration Intervention Reviews (MECCIR) and PRISMA standards, and identify emerging or novel methods used in searching in Campbell systematic reviews. We also investigated the role of information specialists in Campbell systematic reviews. We handsearched the Campbell Systematic Reviews journal tables of contents from January 2017 to March 2024. We included all systematic reviews published since 2017. We excluded other types of evidence synthesis (e.g., evidence and gap maps), updates to systematic reviews when search methods were not changed from the original pre‐2017 review, and systematic reviews that did not conduct their own original searches. We developed a data extraction form in part based on the conduct and reporting items in MECCIR and PRISMA. In addition, we extracted information about the general quality of searches based on the use of Boolean operators, keywords, database syntax and subject headings. Data extraction included information about reporting of sources searched, some aspects of search quality, the use and reporting of supplementary search methods, reporting of the search strategy, the involvement of information specialists, date of the most recent search, and citation of the Campbell search methods guidance. Items were rated as fully, partially or not conducted or reported. We cross‐walked our data extraction items to the 2019 MECCIR standards and 2020 PRISMA guidelines and provide descriptive analyses of the conduct and reporting of searches in Campbell systematic reviews, indicating level of adherence to standards where applicable. We included 111 Campbell systematic reviews across all coordinating groups published since 2017 up to the search date. Almost all (98%) included reviews searched at least two relevant databases and all reported the databases searched. All reviews searched grey literature and most (82%) provided a full list of grey literature sources. Detailed information about databases such as platform and date range coverage was lacking in 16% and 77% of the reviews, respectively. In terms of search strategies, most used Boolean operators, search syntax and phrase searching correctly, but subject headings in databases with controlled vocabulary were used in only about half of the reviews. Most reviews reported at least one full database search strategy (90%), with 63% providing full search strategies for all databases. Most reviews conducted some supplementary searching, most commonly searching the references of included studies, whereas handsearching of journals and forward citation searching were less commonly reported (51% and 62%, respectively). Twenty‐nine percent of reviews involved an information specialist co‐author and about 45% did not mention the involvement of any information specialist. When information specialists were co‐authors, there was a concomitant increase in adherence to many reporting and conduct standards and guidelines, including reporting website URLs, reporting methods for forward citation searching, using database syntax correctly and using subject headings. No longitudinal trends in adherence to conducting and reporting standards were found and the Campbell search methods guidance published in 2017 was cited in only twelve reviews. We also found a median time lag of 20 months between the most recent search and the publication date. In general, the included Campbell systematic reviews searched a wide range of bibliographic databases and grey literature, and conducted at least some supplementary searching such as searching references of included studies or contacting experts. Reporting of mandatory standards was variable with some frequently unreported (e.g., website URLs and database date ranges) and others well reported in most reviews. For example, database search strategies were reported in detail in most reviews. For grey literature, source names were well reported but search strategies were less so. The findings will be used to identify opportunities for advancing current practices in Campbell reviews through updated guidance, peer review processes and author training and support.

Background Given the rising incidence of young-onset colorectal cancer (yCRC) among individuals younger than 50 years old, understanding the economic burden of yCRC is required to inform the delivery of healthcare services. Therefore, we conducted a systematic review of studies assessing the direct medical costs of yCRC, and where relevant average-age onset CRC (aCRC). Methods We searched MEDLINE, EMBASE, and Web of Science from inception to May 2022 for original, peer-reviewed studies, that reported direct medical costs (e.g., chemotherapy, radiotherapy, outpatient visits, inpatient care, prescription medications) for yCRC and aCRC. We used a modified version of the Consolidated Health Economic Evaluation Reporting Standards checklist to appraise the studies. Costs were inflation-adjusted to 2020 US dollars. Results We included 14 studies from 10 countries, including the USA, England, France, Korea, Vietnam, China, Italy, Australia, Canada and Japan. Five studies focused on prevalent disease and reported annualized per-capita cost of prevalent yCRC, ranging from $2,263 to $16,801 and $1,412 to $14,997 among yCRC and aCRC cases, respectively. Nine studies estimated the cost of incident disease. Synthesis of per-capita costs incurred 12 months following colorectal cancer diagnosis ranged from $23,368 to $89,945 for yCRC and $19,929 to $67,195 for aCRC. Five studies used multivariable approaches to compare costs associated with yCRC and aCRC, four showed no differences and one suggested greater costs with yCRC. Conclusion Our synthesis of direct medical costs of yCRC across multiple jurisdictions provide relevant information for healthcare decisions, including on-going considerations for expanding CRC screening strategies to younger adults.

Background To conduct a systematic review and thematic synthesis of qualitative studies on the pregnancy and early parenting experiences of patients with inflammatory arthritis (IA). Methods We searched online databases for English-language, qualitative studies capturing the experiences of females with IA or their healthcare providers with pregnancy and/or early parenthood. We extracted findings from included studies and used thematic synthesis to develop descriptive and higher-order analytical themes. Results Of 20 included studies, our analysis identified 5 analytical themes among patients and 3 among providers. Patients’ reproductive desires, the impact of IA on their ability to experience pregnancy, and the availability of information to guide preparedness informed their pregnancy decisions. Patients’ IA management, pregnancy expectations, and access to support influenced their reproductive experiences. Patients’ experiences seeking information and care revealed substantial gaps in reproductive care provision to patients with IA. Reproductive uncertainty related to IA placed a heavy burden on patients’ emotional and psychological wellbeing. Reproductive care provision was influenced by providers’ perceived professional responsibility to address patients’ reproductive goals, fears of negative outcomes, and capacity to harness patient trust, incorporate reproductive care into rheumatology practice and facilitate multi-disciplinary care coordination. Conclusions Our review illuminated several barriers to experiencing pregnancy among patients with IA, particularly related to pregnancy planning support, availability of information, and care coordination among the patient’s healthcare team. To improve care, these barriers may be mitigated through the provision of relevant, practical, and consistent information as well as patient-centred multi-disciplinary approaches for managing pregnancy among patients with IA.