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.

Methods for developing and reporting living evidence synthesis.

BACKGROUND AND OBJECTIVES: Identify currently methodological aspects proposed for planning, conducting, and reporting living evidence (LE) synthesis. Develop a preliminary checklist of key LE synthesis elements. METHODS: A survey of methodological articles describing or analyzing methods for the design, conduction, or reporting of LE synthesis. RESULTS: Twelve methodological articles were identified and analyzed. Key elements were related to: i) definition of LE and characteristics of LE synthesis, ii) methods and tools for the living process, iii) new evidence integration (methods and considerations), iv) updates dissemination and publication, v) revisiting living parameters, and vi) protocol considerations for LE synthesis. CONCLUSION: This survey displays basic methodological concepts that can drive the development of LE synthesis and identifies specific aspects with opportunities for development. The potential impact of the LE approach calls for a change in the current evidence synthesis updating processes to more open, collaborative, transparent, and efficient systems. LE approaches also challenge journal editors to shift toward more efficient processes for synthesis update dissemination, which minimizes the risks of reliability of published information.

Evidence Mapping of the Treatments for Breast Cancer-related Lymphedema.

Women treated for breast cancer are facing a lifetime risk of developing lymphedema, which occurs in up to 40% of this population. There is a lack of evidence and limited knowledge regarding the treatment of breast cancer-related lymphedema (BCRL). The aim of this study was to identify, describe, and organize the currently available evidence in the treatment of BCRL. METHODS: We conducted an evidence mapping review study according to the methodology proposed by Global Evidence Mapping. We performed a systematic search in Medline, Embase, Central (Cochrane), and Epistemonikos, from 2000-2020. We included studies about all treatment types for BCRL, including surgical and nonsurgical treatment. Results were summarized in narrative and tabular forms. RESULTS: A total of 240 studies were included in this mapping review, distributed as follows: 147 experimental studies [102 randomized clinical trials (RCTs) and 45 quasi-experimental clinical trials], 48 observational studies (34 prospective and 14 retrospective studies), and 45 systematic reviews (17 of them with metanalysis). Most of the RCTs were on nonsurgical interventions. Only two RCTs addressed surgical intervention. CONCLUSIONS: In the last 20 years, there were an average of 12 publications per year on the treatment of BCRL. Recently this lack of attention has been partially corrected, as the majority were published in the past 5 years. However, most of them were on nonsurgical interventions. Well-designed RCTs on surgery are needed to measure the effectiveness of the applied interventions.

Effectiveness and Safety of Dabigatran Compared to Vitamin K Antagonists in Non-Asian Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Real-life data about the use of dabigatran in patients with non-valvular atrial fibrillation are warranted. The objective of this systematic review and meta-analysis was to assess the effectiveness and safety of dabigatran, globally and stratified by dose (110/150 mg twice daily), vs vitamin K antagonists in non-Asian patients with non-valvular atrial fibrillation from "real-world" studies. METHODS: A systematic review was performed according to Cochrane methodological standards. The results were reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement) statement. The ROBINS-I tool was used to assess bias risk. MEDLINE and EMBASE, from inception up to May 2021, using appropriate controlled vocabulary and free search terms, were searched.  RESULTS: A total of 34 studies, corresponding to 37 articles involving 1,600,722 participants (1,154,283 exposed to vitamin K antagonists and 446,439 to dabigatran) were eligible for this review. Dabigatran 150 mg reduced the risk of ischemic stroke compared with vitamin K antagonists, with a 14% risk reduction (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.74-0.98). Globally, dabigatran reduced the risk of all-cause mortality compared with vitamin K antagonists (HR 0.76, 95% CI 0.69-0.84), with a greater effect observed with dabigatran 150 mg (HR 0.65, 95% CI 0.58-0.73). There was a trend towards a lower risk of myocardial infarction with dabigatran 150 mg (HR 0.86, 95% CI 0.71-1.04). Regarding the primary safety outcomes, dabigatran (either at a dose of 150 mg or 110 mg) reduced the risk of major bleeding compared with vitamin K antagonists (HR 0.77, 95% CI 0.70-0.83), as well as the risk of intracranial bleeding (HR 0.44, 95% CI 0.39-0.50) and fatal bleeding (HR 0.76, 95% CI 0.60-0.95), but with a slight increase in gastrointestinal bleeding risk (HR 1.16, 95% CI 1.08-1.26). CONCLUSIONS: Dabigatran has a favorable impact on effectiveness and safety outcomes compared with vitamin K antagonists in real-world populations.

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.

Systematic review on long-term adverse effects of inhaled corticosteroids in the treatment of COPD.

Inhaled corticosteroids (ICSs) are indicated for the prevention of exacerbations in COPD; however, a significant proportion of patients at low risk of exacerbations are treated with ICSs. We conducted a systematic review including a diversity of types of study designs and safety outcomes with the objective of describing the risk of adverse effects associated with the long-term use of ICSs in patients with COPD.A total of 90 references corresponding to 83 studies were included, including 26 randomised clinical trials (RCTs), 33 cohort studies, and 24 nested case-control (NCC) studies. Analysis of 19 RCTs showed that exposure to ICSs for ≥1 year increased the risk of pneumonia by 41% (risk ratio 1.41, 95% CI 1.23-1.61). Additionally, cohort and NCC studies showed an association between ICSs and risk of tuberculosis and mycobacterial disease. There was a strong association between ICS use and local disorders such as oral candidiasis and dysphonia. The association between ICSs and the risk of diabetes and fractures was less clear and appeared significant only at high doses of ICSs.Since most patients with COPD are elderly and with frequent comorbidities, an adequate risk-benefit balance is crucial for the indication of ICSs.

Implementing living evidence to inform health decisions: A strategy for building capacity in health sector (Protocol).

Every day important healthcare decisions are made with incomplete or outdated information about the effects of the healthcare interventions available, what delivers the best value for the health system and where more research is needed. It is necessary to invest in strategies that allow access to reliable and updated evidence on which to base health decisions. The objective is to develop and evaluate a strategy for building the capacity among different actors of a country's health system to implement the model known as "Living Evidence" [LE] in the evidence synthesis and dissemination of knowledge transfer [KT] products to inform health decisions. The study will involve professional members of health system organizations in charge of developing KT products to inform health decisions. The project will be developed in three complementary phases: 1) LE-implementation framework development through review of the literature, brainstorming meetings, user testing, and expert consultation; 2) training in LE tools and strategies; 3) developing LE synthesis for KT products by applying the framework to real-life diverse situations. To achieve the capacity-building strategy assessment goal, several surveys and interviews will take place during the process to assess: 1) the LE-implementation framework for the incorporation of LE synthesis in the development of KT products; 2) the training workshops; 3) the whole capacity-building strategy used for health system organizations be able of implementing the LE as part of the KT products they regularly produce. The expected results are an effective capacity-building strategy for health system organizations to implement the living evidence model in different KT products; a LE-implementation framework to be applicable to any country or region to incorporate LE in the KT products; LE synthesis for KT products directly applicable to the real-setting situations; integration of Epistemonikos-L.OVE platform for keeping the LE process in the development and updating of KT products.

Methodological approaches for developing and reporting living evidence synthesis: a study protocol.

Background: Living evidence (LE) refers to the methodological processes that permit new research findings to be continually incorporated into evidence synthesis. This approach is of great value in the resolution of relevant and rapidly changing clinical questions. To date, the methods to carry out this type of synthesis are not completely defined, and great variability is observed in the approaches used by different groups of authors. Objective: To identify, evaluate and summarise the current methods used for living evidence synthesis Methods: We will conduct a methodological study based on a systematic literature search to identify any type of evidence synthesis such as systematic reviews, network metanalyses and overviews that used "living evidence synthesis" as part of their methods. The search will be conducted in Medline (via PubMed) and Epistemonikos databases. Additionally, we will search websites of the organisations publishing any living evidence synthesis retrieved in the two databases, in order to identify unpublished subsequent reports. Two reviewers will independently assess each article against the selection criteria, extract data on methods and procedures, and assess the methodological quality of each publication. Data will be analysed descriptively.

Prevalence study of intermittent hormonal therapy of Prostate Cancer patients in Spain.

Background: Although intermittent androgen deprivation therapy was introduced many years ago to improve patients' quality of life with the same carcinologic efficiency as continuous hormonal therapy, recent data suggest that those patients could be overtreated. This study aims to estimate the prevalence of prostate cancer patients receiving intermittent androgen deprivation therapy in Spain. Methods: A retrospective, longitudinal study was conducted using electronic drug dispensation data from four Spanish autonomous communities, which encompass 17.23 million inhabitants (36.22% of the total population in Spain). We estimated intermittent androgen therapy use (%IAD) and the prevalence of patients under intermittent androgen therapy (P IAD) overall and stratified by region. Other outcome variables included the pharmaceutical forms dispensed and the total direct annual expenditure on androgen deprivation therapy-associated medications. Results: A total of 863,005 dispensations corresponding to a total of 65,752 men were identified, treated with either luteinizing hormone-releasing hormone (LHRH) analogues (353,162) administered alone or in combination with anti-androgens (509,843). Overall, the mean (±SD) age of the patients was 76.9 (±10.4) years. Results revealed that the mean annual P IAD along the study was 6.6% in the total population studied, and the overall %IAD during the five-year study period was 5.6%. The mean cost of hormonal therapy per year was 25 million euros for LHRH analogues and 6.3 million euros for anti-androgens. Conclusions:  An important proportion of prostate cancer patients in Spain could benefit from intermittent androgen therapy during the study period while avoiding overtreatment harms associated with continuous hormonal therapy.