Anticancer Drugs Compared to No Anticancer Drugs in Patients with Advanced Hepatobiliary Cancer: A Mapping Review and Evidence Gap Map.

Introduction: Despite being commonly recommended, the impact of anticancer drugs (ACDs) on patient-important outcomes beyond survival for advanced hepatobiliary cancers (HBCs) may not have been sufficiently assessed. We aim to identify and map the evidence regarding ACDs versus best supportive care (BSC) for advanced HBCs, considering patient-centered outcomes. Methods: In this mapping review, we included systematic reviews, randomized controlled trials, quasi-experimental, and observational studies comparing ACDs (chemotherapy, immunotherapy, biological/targeted therapy) versus BSC for advanced HBCs. We searched MEDLINE (PubMed), EMBASE (Ovid), Cochrane Library, Epistemonikos, PROSPERO and clinicaltrials.gov for eligible studies. Two reviewers performed the screening and data extraction processes. We developed evidence maps for each type of cancer. Results: We included 87 studies (60 for advanced liver cancer and 27 for gallbladder or bile duct cancers). Most of the evidence favored ACDs for survival outcomes, and BSC for toxicity. We identified several evidence gaps for non-survival outcomes, including quality of life or quality of end-of-life care. Discussion: Patient-important outcomes beyond survival in advanced HBCs are insufficiently assessed by the available evidence. Future studies need to address these gaps to better inform decision-making processes.

Assessing the magnitude of changes from protocol to publication-a survey on Cochrane and non-Cochrane Systematic Reviews.

Objective: To explore differences between published reviews and their respective protocols in a sample of 97 non-Cochrane Systematic Reviews (non-CSRs) and 97 Cochrane Systematic Reviews (CSRs) in terms of PICOS (Patients/Population, Intervention, Comparison/Control, Outcome, Study type) elements and the extent to which they were reported. Study Design and Setting: We searched PubMed and Cochrane databases to identify non-CSRs and CSRs that were published in 2018. We then searched for their corresponding Cochrane or PROSPERO protocols. The published reviews were compared to their protocols. The primary outcome was changes from protocol to review in terms of PICOS elements. Results: We identified a total of 227 changes from protocol to review in PICOS elements, 1.11 (Standard Deviation (SD), 1.22) changes per review for CSRs and 1.23 (SD, 1.12) for non-CSRs per review. More than half of each sub-sample (54.6% of CSRs and 67.0% of non-CSRs) (Absolute Risk Reduction (ARR) 12.4% [-1.3%; 26.0%]) had changes in PICOS elements. For both subsamples, approximately a third of all changes corresponded to changes related to primary outcomes. Marked differences were found between the sub-samples for the reporting of changes. 95.8% of the changes in PICOS items were not reported in the non-CSRs compared to 42.6% in the CSRs (ARR 53.2% [43.2%; 63.2%]). Conclusion: CSRs showed better results than non-CSRs in terms of the reporting of changes. Reporting of changes from protocol needs to be promoted and requires general improvement. The limitations of this study lie in its observational design. Registration: https://osf.io/6j8gd/.

Systemic Oncological Treatments versus Supportive Care for Patients with Advanced Hepatobiliary Cancers: An Overview of Systematic Reviews.

BACKGROUND: The trade-off between systemic oncological treatments (SOTs) and UPSC in patients with primary advanced hepatobiliary cancers (HBCs) is not clear in terms of patient-centred outcomes beyond survival. This overview aims to assess the effectiveness of SOTs (chemotherapy, immunotherapy and targeted/biological therapies) versus UPSC in advanced HBCs. METHODS: We searched for systematic reviews (SRs) in PubMed, EMBASE, the Cochrane Library, Epistemonikos and PROSPERO. Two authors assessed eligibility independently and performed data extraction. We estimated the quality of SRs and the overlap of primary studies, performed de novo meta-analyses and assessed the certainty of evidence for each outcome. RESULTS: We included 18 SRs, most of which were of low quality and highly overlapped. For advanced hepatocellular carcinoma, SOTs showed better overall survival (HR = 0.62, 95% CI 0.55-0.77, high certainty for first-line therapy; HR = 0.85, 95% CI 0.79-0.92, moderate certainty for second-line therapy) with higher toxicity (RR = 1.18, 95% CI 0.87-1.60, very low certainty for first-line therapy; RR = 1.58, 95% CI 1.28-1.96, low certainty for second-line therapy). Survival was also better for SOTs in advanced gallbladder cancer. No outcomes beyond survival and toxicity could be meta-analysed. CONCLUSION: SOTs in advanced HBCs tend to improve survival at the expense of greater toxicity. Future research should inform other patient-important outcomes to guide clinical decision making.

Systemic oncological treatments in patients with advanced pancreatic cancer: a scoping review and evidence map.

PURPOSE: To identify, describe, and organise currently available evidence regarding systemic oncological treatments (SOTs) (chemotherapy, targeted/biological therapies, and immunotherapy) compared to best supportive care (BSC) for patients with advanced pancreatic cancer (PC). METHODS: We conducted a scoping review and evidence mapping, adhering to PRISMA-ScR checklist. We searched MEDLINE, EMBASE, Cochrane Library, Epistemonikos, PROSPERO, and clinicaltrials.gov for eligible studies. We included systematic reviews (SRs), randomised controlled trials (RCTs), quasi-experimental, and observational studies evaluating SOTs compared to BSC or no treatment in patients with advanced PC. Two independent reviewers performed the screening process and data extraction. We developed evidence maps as an interactive visualization display, including the assessed interventions and outcomes. RESULTS: Of the 50,601 records obtained from our search, we included 43 studies: 2 SRs, 16 RCTs, 4 quasi-experimental studies, 20 observational studies, and 1 protocol for a quasi-experimental study. Forty-two studies reported survival-related outcomes and most favoured SOTs, while five reported toxicity and most favoured BSC. Other patient-centred outcomes, such as quality of life, were scarcely reported. CONCLUSIONS: This study highlights the current evidence gaps in studies assessing treatments for patients with advanced PC, mainly the lack of reports of non-survival-related outcomes, pointing out research areas that need further attention to make better recommendations for these patients.

European clinical practice guidelines on the use of chemotherapy for advanced oesophageal and gastric cancers: a critical review using the AGREE II and the AGREE-REX instruments.

PURPOSE: To assess the methodological quality of all relevant and recent European clinical practice guidelines (CPGs) for advanced oesophageal and gastric cancers, and to synthesise their recommendations on the use of chemotherapy. METHODS: We searched PubMed, EMBASE, guidelines repositories, and other sources from 2010 onwards. We appraised quality using AGREE-II and AGREE-REX. RESULTS: 11 CPGs were included (five high, five low, and one moderate quality). Most guidelines showed deficiencies in the domain "applicability", with only three scoring above 60%. Nine did not report having sought the views and preferences of the target population. The lowest scores for AGREE-REX were item Values and Preferences of Target Users (1.6; SD 1.3), and item Values and Preferences of Policy/Decision-Makers (1.8; SD 1.7). The domain Clinical Applicability got the highest score and the domain Implementability got the lowest. CONCLUSIONS: An urgent area of research is how to develop credible and implementable recommendations on the clinical use of CT for advanced oesophageal and gastric cancer. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42021236753).

Stem cell therapy for dilated cardiomyopathy.

BACKGROUND: Stem cell therapy (SCT) has been proposed as an alternative treatment for dilated cardiomyopathy (DCM), nonetheless its effectiveness remains debatable. OBJECTIVES: To assess the effectiveness and safety of SCT in adults with non-ischaemic DCM. SEARCH METHODS: We searched CENTRAL in the Cochrane Library, MEDLINE, and Embase for relevant trials in November 2020. We also searched two clinical trials registers in May 2020. SELECTION CRITERIA: Eligible studies were randomized controlled trials (RCT) comparing stem/progenitor cells with no cells in adults with non-ischaemic DCM. We included co-interventions such as the administration of stem cell mobilizing agents. Studies were classified and analysed into three categories according to the comparison intervention, which consisted of no intervention/placebo, cell mobilization with cytokines, or a different mode of SCT. The first two comparisons (no cells in the control group) served to assess the efficacy of SCT while the third (different mode of SCT) served to complement the review with information about safety and other information of potential utility for a better understanding of the effects of SCT. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all references for eligibility, assessed trial quality, and extracted data. We undertook a quantitative evaluation of data using random-effects meta-analyses. We evaluated heterogeneity using the I² statistic. We could not explore potential effect modifiers through subgroup analyses as they were deemed uninformative due to the scarce number of trials available. We assessed the certainty of the evidence using the GRADE approach. We created summary of findings tables using GRADEpro GDT. We focused our summary of findings on all-cause mortality, safety, health-related quality of life (HRQoL), performance status, and major adverse cardiovascular events. MAIN RESULTS: We included 13 RCTs involving 762 participants (452 cell therapy and 310 controls). Only one study was at low risk of bias in all domains. There were many shortcomings in the publications that did not allow a precise assessment of the risk of bias in many domains. Due to the nature of the intervention, the main source of potential bias was lack of blinding of participants (performance bias). Frequently, the format of the continuous data available was not ideal for use in the meta-analysis and forced us to seek strategies for transforming data in a usable format. We are uncertain whether SCT reduces all-cause mortality in people with DCM compared to no intervention/placebo (mean follow-up 12 months) (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.54 to 1.31; I² = 0%; studies = 7, participants = 361; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection in people with DCM (data could not be pooled; studies = 7; participants = 361; very low-certainty evidence). We are uncertain whether SCT improves HRQoL (standardized mean difference (SMD) 0.62, 95% CI 0.01 to 1.23; I² = 72%; studies = 5, participants = 272; very low-certainty evidence) and functional capacity (6-minute walk test) (mean difference (MD) 70.12 m, 95% CI -5.28 to 145.51; I² = 87%; studies = 5, participants = 230; very low-certainty evidence). SCT may result in a slight functional class (New York Heart Association) improvement (data could not be pooled; studies = 6, participants = 398; low-certainty evidence). None of the included studies reported major adverse cardiovascular events as defined in our protocol. SCT may not increase the risk of ventricular arrhythmia (data could not be pooled; studies = 8, participants = 504; low-certainty evidence). When comparing SCT to cell mobilization with granulocyte-colony stimulating factor (G-CSF), we are uncertain whether SCT reduces all-cause mortality (RR 0.46, 95% CI 0.16 to 1.31; I² = 39%; studies = 3, participants = 195; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection (studies = 1, participants = 60; very low-certainty evidence). SCT may not improve HRQoL (MD 4.61 points, 95% CI -5.62 to 14.83; studies = 1, participants = 22; low-certainty evidence). SCT may improve functional capacity (6-minute walk test) (MD 140.14 m, 95% CI 119.51 to 160.77; I² = 0%; studies = 2, participants = 155; low-certainty evidence). None of the included studies reported MACE as defined in our protocol or ventricular arrhythmia. The most commonly reported outcomes across studies were based on physiological measures of cardiac function where there were some beneficial effects suggesting potential benefits of SCT in people with non-ischaemic DCM. However, it is unclear if this intermediate effects translates into clinical benefits for these patients. With regard to specific aspects related to the modality of cell therapy and its delivery, uncertainties remain as subgroup analyses could not be performed as planned, making it necessary to wait for the publication of several studies that are currently in progress before any firm conclusion can be reached. AUTHORS' CONCLUSIONS: We are uncertain whether SCT in people with DCM reduces the risk of all-cause mortality and procedural complications, improves HRQoL, and performance status (exercise capacity). SCT may improve functional class (NYHA), compared to usual care (no cells). Similarly, when compared to G-CSF, we are also uncertain whether SCT in people with DCM reduces the risk of all-cause mortality although some studies within this comparison observed a favourable effect that should be interpreted with caution. SCT may not improve HRQoL but may improve to some extent performance status (exercise capacity). Very low-quality evidence reflects uncertainty regarding procedural complications. These suggested beneficial effects of SCT, although uncertain due to the very low certainty of the evidence, are accompanied by favourable effects on some physiological measures of cardiac function. Presently, the most effective mode of administration of SCT and the population that could benefit the most is unclear. Therefore, it seems reasonable that use of SCT in people with DCM is limited to clinical research settings. Results of ongoing studies are likely to modify these conclusions.

Efficacy of systemic oncological treatments in patients with advanced pancreatic cancer at high risk of dying in the short or medium-term: overview of systematic reviews.

BACKGROUND: Patients with advanced pancreatic cancer (PC) have a high risk of dying in the short or medium-term. This overview aimed to assess the evidence regarding systemic oncological treatments (SOT) versus supportive care for advanced PC. METHODS: We searched for systematic reviews (SRs) in MEDLINE, Embase, The Cochrane Library, Epistemonikos, and PROSPERO. Two authors assessed eligibility independently. Data extraction and methodological quality assessment were conducted by one author and cross-checked by another one. We evaluated the overlap of primary studies, performed a de novo meta-analysis, and assessed the certainty of evidence. Primary outcomes were overall survival (OS), quality of life (QoL), functional status (FS), and toxicity. RESULTS: We identified three SRs that assessed SOT versus supportive care in patients with advanced PC. All SRs had critically low methodological quality. At 12 months, OS improved with chemotherapy, radiotherapy followed by chemotherapy, and immunotherapy, but the certainty of the evidence supporting these findings is very low. The evidence on chemotherapy is very uncertain about its effects on QoL; it suggests a slight increase in toxicity and little to no difference in FS. The evidence on immunotherapy is very uncertain about its effects in toxicity. CONCLUSIONS: The identified evidence is very uncertain about the benefits of oncological treatments on OS and QoL in patients with advanced PC with a high risk of dying in the short or medium-term, so its use should be proposed only to selected patients. Further studies that include a thorough assessment of patient-centred outcomes are needed.

Levels of physical activity in children and adolescents with asthma: A systematic review and meta-analysis.

BACKGROUND: In children and adolescents with asthma, the disease may reduce the perceived capability to participate in physical activity (PA) contributing to an increase in the sedentary lifestyle. The literature is unclear as to whether children and adolescents with asthma differ their PA levels from their healthy peers. OBJECTIVE: Our objective was to describe the different methods and instruments used to measure PA and to compare the PA levels of children and adolescents with asthma with those of their healthy peers. STUDY DESIGN: We conducted a systematic review of five databases. We included studies that compared the PA measured by objective and subjective instruments in children and adolescents with asthma versus controls. Two independent reviewers analyzed the studies, extracted the data, and assessed the quality of evidence. RESULTS: Of the 5966 reports returned by the initial search, 28 articles reporting on 3184 patients were included in the data synthesis. A forest plot showed that both groups had similar values of moderate to vigorous PA (MVPA; mean difference, -0.05 h/day; 95% confidence interval [CI], -0.11-0.01; p = .13), sedentary time (mean difference 0.00 h/day; 95% CI, -0.22-0.23 h/day; p = .99) and steps/day (mean difference 354 steps/day; 95% CI, -563-1270 steps/day; p = .45). CONCLUSION: Children and adolescents with asthma have similar MVPA, steps/day, and sedentary time compared to the controls. The main instruments used were questionnaires and accelerometers.

Physical Activity in Children and Adolescents With Chronic Respiratory Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND: The literature is unclear as to whether children and adolescents with chronic respiratory diseases (CRDs) differ from their healthy peers in physical activity (PA). OBJECTIVE: To determine the PA levels measured through accelerometers in children and adolescents with CRDs. METHODS: The authors conducted a systematic review using five databases. The authors included studies that assessed the PA measured by accelerometers in children and adolescents with CRDs. Two independent reviewers analyzed the studies, extracted the data, and assessed the quality of evidence. RESULTS: From 11,497 reports returned by the initial search, 29 articles reporting on 4381 patients were included. In the sensitivity analysis, the authors found that children and adolescents with CRDs had a moderate-to-vigorous PA (MVPA) of -0.08 hours per day (95% confidence interval [CI], -0.12 to -0.03 h/d; P = .001), which was lower than the healthy controls; the values for sedentary time (mean difference -0.47 h/d; 95% CI, -1.29 to 0.36 h/d; P = .27) and steps/d (mean difference 361 steps/d; 95% CI -385 to 1707 steps/d; P = .45) were similar for both. CONCLUSION: Children and adolescents with CRDs have a slight reduction in MVPA in comparison with healthy controls, but sedentary time and steps/d were similar for both.

Physical activity in children and adolescents with cystic fibrosis: A systematic review and meta-analysis.

BACKGROUND: Exercise and physical activity (PA) are essential components of the care of cystic fibrosis (CF) patients. Lower PA levels have been associated with worse pulmonary function, aerobic fitness, glycemic control, and bone mineral density. Most people with CF do not engage in the recommended amounts of PA. OBJECTIVE: To determine the level of PA in children and adolescents with CF. METHODS: A systematic review with meta-analysis was conducted without language restrictions in five databases. Were included studies that analyzed PA measured by objective and subjective instruments in children and adolescents with CF. Two independent reviewers analyzed the studies, extracted the data, and assessed the quality of evidence. The risk of bias of the included studies was assessed with the National Heart, Lung, and Blood Institute's risk-of-bias tool. RESULTS: Of the 1535 reports returned by the initial search, 20 articles reporting on 785 patients were included in the data synthesis. The forest plot showed that the CF group had a similar moderate-to-vigorous PA (MVPA) (mean difference, -7.79; 95% CI -15.65 to 0.08 min/d; P = .05) and sedentary time (mean difference, -50.81; 95%CI, -109.96 to 8.35 min/d; P = .09) to the control group. CONCLUSION: Children and adolescents with CF have a similar MVPA and sedentary time compared to controls. There are many options, subjective and objective, for assessing PA in this population. Optimal tool selection should guarantee more valid results.

Physical activity assessments in children with congenital heart disease: A systematic review.

AIM: To describe the physical activity (PA) of children with congenital heart disease (CHD) according to different assessment methods and compare their results with the World Health Organization (WHO) recommendations. METHODS: A systematic review was conducted using five databases. We included cross-sectional, longitudinal, observational studies and clinical trials in a paediatric population with CHD. In publications with indirect measurement, the score in each dimension was considered. Similarly, moderate-to-vigorous PA (MVPA) was considered as the main outcome in articles with direct measurement. RESULTS: A total of 1103 articles were found, and 16 primary articles were considered. Eight articles evaluated PA with indirect methods, six with direct methods and two used both methods, representing 1649 subjects evaluated. It was found that 46% of children with CHD do not exceed WHO recommendations for MVPA, with no differences depending on the severity of CHD. CONCLUSION: There are a variety of ways to measure PA in children with CHD. In the articles that objectively evaluated PA, the most measured outcome was the MVPA, which shows that the MVPA time was shorter in about half of the children with CHD than what is recommended by WHO.