Reactivation of Trypanosoma cruzi infection in immunosuppressed patients: a systematic review and meta-analysis.

BACKGROUND: The risk of Trypanosoma cruzi reactivation is poorly understood. Previous studies evaluating the risk of reactivation report imprecise findings, and recommendations for monitoring and management from clinical guidelines rely on consensus opinion. OBJECTIVES: We conducted a systematic review and meta-analysis to estimate the cumulative T. cruzi reactivation incidence in immunosuppressed adults, summarize the available evidence on prognostic factors for reactivation, and examine its prognostic effect on mortality. DATA SOURCES: MEDLINE, Embase, LILACS, Clinical Trials, and CENTRAL from inception to 4 July 2022. STUDY ELIGIBILITY CRITERIA: Studies reporting the incidence of T. cruzi reactivation. PARTICIPANTS: Immunosuppressed adults chronically infected by T. cruzi. METHODS: Two authors independently extracted data (including, but not limited to, incidence data, reactivation definition, follow-up, treatment, monitoring schedule, examined prognostic factors) and evaluated the risk of bias. We pooled cumulative incidence using a random-effects model. RESULTS: Twenty-two studies (806 participants) were included. The overall pooled incidence of T. cruzi reactivation was 27% (95% CI, 19-36), with the highest pooled proportion in the sub-group of transplant recipients (36%; 95% CI, 25-48). The highest risk period was in the first 6 months after transplant (32%; 95% CI, 17-58), decreasing drastically the number of new cases later. People living with HIV and patients with autoimmune diseases experienced significantly lower cumulative reactivation incidences (17%; 95% CI, 8-29 and 18%; 95% CI, 9-29, respectively). A single study explored the independent effect of benznidazole and found benefits for preventing reactivations. No studies evaluated the independent association between reactivation and mortality, while sensitivity analysis results using unadjusted estimates were inconclusive. The heterogeneity of diagnostic algorithms was substantial. CONCLUSIONS: Reactivation occurs in three out of ten T. cruzi-seropositive immunosuppressed adults. These findings can assist clinicians and panel guidelines in tailoring monitoring schedules. There is a great need for an accurate definition of reactivation and targeted monitoring.

Reporting of equity in observational epidemiology: A methodological review.

Background: Observational studies can inform how we understand and address persisting health inequities through the collection, reporting and analysis of health equity factors. However, the extent to which the analysis and reporting of equity-relevant aspects in observational research are generally unknown. Thus, we aimed to systematically evaluate how equity-relevant observational studies reported equity considerations in the study design and analyses. Methods: We searched MEDLINE for health equity-relevant observational studies from January 2020 to March 2022, resulting in 16 828 articles. We randomly selected 320 studies, ensuring a balance in focus on populations experiencing inequities, country income settings, and coronavirus disease 2019 (COVID-19) topic. We extracted information on study design and analysis methods. Results: The bulk of the studies were conducted in North America (n = 95, 30%), followed by Europe and Central Asia (n = 55, 17%). Half of the studies (n = 171, 53%) addressed general health and well-being, while 49 (15%) focused on mental health conditions. Two-thirds of the studies (n = 220, 69%) were cross-sectional. Eight (3%) engaged with populations experiencing inequities, while 22 (29%) adapted recruitment methods to reach these populations. Further, 67 studies (21%) examined interaction effects primarily related to race or ethnicity (48%). Two-thirds of the studies (72%) adjusted for characteristics associated with inequities, and 18 studies (6%) used flow diagrams to depict how populations experiencing inequities progressed throughout the studies. Conclusions: Despite over 80% of the equity-focused observational studies providing a rationale for a focus on health equity, reporting of study design features relevant to health equity ranged from 0-95%, with over half of the items reported by less than one-quarter of studies. This methodological study is a baseline assessment to inform the development of an equity-focussed reporting guideline for observational studies as an extension of the well-known Strengthening Reporting of Observational Studies in Epidemiology (STROBE) guideline.

Protocol for the development of guidance for collaborator and partner engagement in health care evidence syntheses.

BACKGROUND: Involving collaborators and partners in research may increase relevance and uptake, while reducing health and social inequities. Collaborators and partners include people and groups interested in health research: health care providers, patients and caregivers, payers of health research, payers of health services, publishers, policymakers, researchers, product makers, program managers, and the public. Evidence syntheses inform decisions about health care services, treatments, and practice, which ultimately affect health outcomes. Our objectives are to: A. Identify, map, and synthesize qualitative and quantitative findings related to engagement in evidence syntheses B. Explore how engagement in evidence synthesis promotes health equity C. Develop equity-oriented guidance on methods for conducting, evaluating, and reporting engagement in evidence syntheses METHODS: Our diverse, international team will develop guidance for engagement with collaborators and partners throughout multiple sequential steps using an integrated knowledge translation approach: 1. Reviews. We will co-produce 1 scoping review, 3 systematic reviews and 1 evidence map focusing on (a) methods, (b) barriers and facilitators, (c) conflict of interest considerations, (d) impacts, and (e) equity considerations of engagement in evidence synthesis. 2. Methods study, interviews, and survey. We will contextualise the findings of step 1 by assessing a sample of evidence syntheses reporting on engagement with collaborators and partners and through conducting interviews with collaborators and partners who have been involved in producing evidence syntheses. We will use these findings to develop draft guidance checklists and will assess agreement with each item through an international survey. 3. CONSENSUS: The guidance checklists will be co-produced and finalised at a consensus meeting with collaborators and partners. 4. DISSEMINATION: We will develop a dissemination plan with our collaborators and partners and work collaboratively to improve adoption of our guidance by key organizations. CONCLUSION: Our international team will develop guidance for collaborator and partner engagement in health care evidence syntheses. Incorporating partnership values and expectations may result in better uptake, potentially reducing health inequities.

Treatment with anticancer drugs for advanced pancreatic cancer: a systematic review.

BACKGROUND: Patients with advanced pancreatic cancer have a poor prognosis and high burden of cancer-related symptoms. It is necessary to assess the trade-off of clinical benefits and possible harms of treatments with anticancer drugs (TAD). This systematic review aims to compare the effectiveness of TAD versus supportive care or no treatment, considering all patient-important outcomes. METHODS: We searched PubMed, Embase, Cochrane Library, and Epistemonikos. Two reviewers performed selection, data extraction and risk of bias assessment. We assessed certainty of the evidence using the GRADE approach. RESULTS: We included 14 randomised controlled trials. Chemotherapy may result in a slight increase in overall survival (MD: 2.97 months (95%CI 1.23, 4.70)) and fewer hospital days (MD: -6.7 (-8.3, -5.1)), however, the evidence is very uncertain about its effect on symptoms, quality of life, functional status, and adverse events. Targeted/biological therapy may result in little to no difference in overall survival and a slight increment in progression-free survival (HR: 0.83 (95%CI 0.63, 1.10)), but probably results in more adverse events (RR: 5.54 (95%CI 1.24, 23.97)). The evidence is very uncertain about the effect of immunotherapy in overall survival and functional status. CONCLUSIONS: The evidence is very uncertain about whether the benefits of using treatment with anticancer drugs outweigh their risks for patients with advanced pancreatic cancer. This uncertainty is further highlighted when considering immunotherapy or a second line of chemotherapy and thus, best supportive care would be an appropriate alternative. Future studies should assess their impact on all patient-important outcomes to inform patients in setting their goals of care.

A scoping review establishes need for consensus guidance on reporting health equity in observational studies.

OBJECTIVES: To evaluate the support from the available guidance on reporting of health equity in research for our candidate items and to identify additional items for the Strengthening Reporting of Observational studies in Epidemiology-Equity extension. STUDY DESIGN AND SETTING: We conducted a scoping review by searching Embase, MEDLINE, CINAHL, Cochrane Methodology Register, LILACS, and Caribbean Center on Health Sciences Information up to January 2022. We also searched reference lists and gray literature for additional resources. We included guidance and assessments (hereafter termed "resources") related to conduct and/or reporting for any type of health research with or about people experiencing health inequity. RESULTS: We included 34 resources, which supported one or more candidate items or contributed to new items about health equity reporting in observational research. Each candidate item was supported by a median of six (range: 1-15) resources. In addition, 12 resources suggested 13 new items, such as "report the background of investigators". CONCLUSION: Existing resources for reporting health equity in observational studies aligned with our interim checklist of candidate items. We also identified additional items that will be considered in the development of a consensus-based and evidence-based guideline for reporting health equity in observational studies.

Improving social justice in observational studies: protocol for the development of a global and Indigenous STROBE-equity reporting guideline.

BACKGROUND: Addressing persistent and pervasive health inequities is a global moral imperative, which has been highlighted and magnified by the societal and health impacts of the COVID-19 pandemic. Observational studies can aid our understanding of the impact of health and structural oppression based on the intersection of gender, race, ethnicity, age and other factors, as they frequently collect this data. However, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline, does not provide guidance related to reporting of health equity. The goal of this project is to develop a STROBE-Equity reporting guideline extension. METHODS: We assembled a diverse team across multiple domains, including gender, age, ethnicity, Indigenous background, disciplines, geographies, lived experience of health inequity and decision-making organizations. Using an inclusive, integrated knowledge translation approach, we will implement a five-phase plan which will include: (1) assessing the reporting of health equity in published observational studies, (2) seeking wide international feedback on items to improve reporting of health equity, (3) establishing consensus amongst knowledge users and researchers, (4) evaluating in partnership with Indigenous contributors the relevance to Indigenous peoples who have globally experienced the oppressive legacy of colonization, and (5) widely disseminating and seeking endorsement from relevant knowledge users. We will seek input from external collaborators using social media, mailing lists and other communication channels. DISCUSSION: Achieving global imperatives such as the Sustainable Development Goals (e.g., SDG 10 Reduced inequalities, SDG 3 Good health and wellbeing) requires advancing health equity in research. The implementation of the STROBE-Equity guidelines will enable a better awareness and understanding of health inequities through better reporting. We will broadly disseminate the reporting guideline with tools to enable adoption and use by journal editors, authors, and funding agencies, using diverse strategies tailored to specific audiences.

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.

Lack of sex-related analysis and reporting in Cochrane Reviews: a cross-sectional study.

BACKGROUND: Sex-specific analysis and reporting may allow a better understanding of intervention effects and can support the decision-making process. Well-conducted systematic reviews (SRs), like those carried out by the Cochrane Collaboration, provide clinical responses transparently and stress gaps of knowledge. This study aimed to describe the extent to which sex is analysed and reported in a cross-section of Cochrane SRs of interventions, and assess the association with the gender of main authorships. METHODS: We searched SRs published during 2018 within the Cochrane Database of Systematic Reviews. An investigator appraised the sex-related analysis and reporting across sections of SRs and collected data on gender and country of affiliation of the review first and last authors, and a second checked for accuracy. We conducted descriptive statistics and bivariate logistic regression to explore the association between the gender of the authors and sex-related analysis and reporting. RESULTS: Six hundred and ten Cochrane SRs were identified. After removing those that met no eligibility criteria, 516 reviews of interventions were included. Fifty-six reviews included sex-related reporting in the abstract, 90 considered sex in their design, 380 provided sex-disaggregated descriptive data, 142 reported main outcomes or performed subgroup analyses by sex, and 76 discussed the potential impact of sex or the lack of such on the interpretations of findings. Women represented 53.1 and 42.2% of first and last authorships, respectively. Women authors (in first and last position) had a higher possibility to report sex in at least one of the review sections (OR 2.05; CI 95% 1.12-3.75, P=0.020) than having none. CONCLUSIONS: Sex consideration amongst Cochrane SRs was frequently missing. Structured guidance to sex-related analysis and reporting is needed to enhance the external validity of findings. Likewise, including gender diversity within the research workforce and relevant authorship positions may foster equity in the evidence generated.

Methodological guidance for incorporating equity when informing rapid-policy and guideline development.

OBJECTIVES: We provide guidance for considering equity in rapid reviews through examples of published COVID-19 rapid reviews. STUDY DESIGN AND SETTING: This guidance was developed based on a series of methodological meetings, review of internationally renowned guidance such as the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for equity-focused systematic reviews (PRISMA-Equity) guideline. We identified Exemplar rapid reviews by searching COVID-19 databases and requesting examples from our team. RESULTS: We proposed the following key steps: 1. involve relevant stakeholders with lived experience in the conduct and design of the review; 2. reflect on equity, inclusion and privilege in team values and composition; 3. develop research question to assess health inequities; 4. conduct searches in relevant disciplinary databases; 5. collect data and critically appraise recruitment, retention and attrition for populations experiencing inequities; 6. analyse evidence on equity; 7. evaluate the applicability of findings to populations experiencing inequities; and 8. adhere to reporting guidelines for communicating review findings. We illustrated these methods through rapid review examples. CONCLUSION: Implementing this guidance could contribute to improving equity considerations in rapid reviews produced in public health emergencies, and help policymakers better understand the distributional impact of diseases on the population.

Integrating sex and gender in studies of cardiac resynchronization therapy: a systematic review.

AIMS: To examine the prevalence, temporal changes, and impact of the National Institute of Health (NIH) Sex as a Biological Variable (SABV) policy on sex and gender reporting and analysis in cardiac resynchronization therapy (CRT) cohort studies. METHODS AND RESULTS: We searched MEDLINE, EMBASE, and Web of Science for cohort studies reporting the effectiveness and safety of CRT in heart failure patients from January 2000 to June 2020, with no language restrictions. Segmented regression analysis was used for policy analysis. We included 253 studies. Fourteen per cent considered sex in the study design. Outcome data disaggregated by sex were only reported in 17% of the studies. Of the studies with statistical models (n = 173), 57% were adjusted for sex. Sixty-eight per cent of those reported an effect size for sex on the outcome. Sex-stratified analyses were conducted in 13% of the studies. Temporal analysis shows an increase in sex reporting in background, statistical models, study design, and discussion. Besides statistical models, NIH SABV policy analysis showed no significant change in the reporting of sex in study sections. Gender was not reported or analysed in any study. CONCLUSIONS: There is a need to improve the study design, analysis, and completeness of reporting of sex in CRT cohort studies. Inadequate sex integration in study design and analysis may potentially hinder progress in understanding sex disparities in CRT. Deficiencies in the integration of sex in studies could be overcome by implementing guidance that already exists.

Improving Social Justice in COVID-19 Health Research: Interim Guidelines for Reporting Health Equity in Observational Studies.

The COVID-19 pandemic has highlighted the global imperative to address health inequities. Observational studies are a valuable source of evidence for real-world effects and impacts of implementing COVID-19 policies on the redistribution of inequities. We assembled a diverse global multi-disciplinary team to develop interim guidance for improving transparency in reporting health equity in COVID-19 observational studies. We identified 14 areas in the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist that need additional detail to encourage transparent reporting of health equity. We searched for examples of COVID-19 observational studies that analysed and reported health equity analysis across one or more social determinants of health. We engaged with Indigenous stakeholders and others groups experiencing health inequities to co-produce this guidance and to bring an intersectional lens. Taking health equity and social determinants of health into account contributes to the clinical and epidemiological understanding of the disease, identifying specific needs and supporting decision-making processes. Stakeholders are encouraged to consider using this guidance on observational research to help provide evidence to close the inequitable gaps in health outcomes.

Sex as a prognostic factor for mortality in critically ill adults with sepsis: a systematic review and meta-analysis.

OBJECTIVE: To assess the role of sex as an independent prognostic factor for mortality in patients with sepsis admitted to intensive care units (ICUs). DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase, Web of Science, ClinicalTrials.gov and the WHO Clinical Trials Registry from inception to 17 July 2020. STUDY SELECTION: Studies evaluating independent associations between sex and mortality in critically ill adults with sepsis controlling for at least one of five core covariate domains prespecified following a literature search and consensus among experts. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted and assessed the risk of bias using Quality In Prognosis Studies tool. Meta-analysis was performed by pooling adjusted estimates. The Grades of Recommendations, Assessment, Development and Evaluation approach was used to rate the certainty of evidence. RESULTS: From 14 304 records, 13 studies (80 520 participants) were included. Meta-analysis did not find sex-based differences in all-cause hospital mortality (OR 1.02, 95% CI 0.79 to 1.32; very low-certainty evidence) and all-cause ICU mortality (OR 1.19, 95% CI 0.79 to 1.78; very low-certainty evidence). However, females presented higher 28-day all-cause mortality (OR 1.18, 95% CI 1.05 to 1.32; very low-certainty evidence) and lower 1-year all-cause mortality (OR 0.83, 95% CI 0.68 to 0.98; low-certainty evidence). There was a moderate risk of bias in the domain adjustment for other prognostic factors in six studies, and the certainty of evidence was further affected by inconsistency and imprecision. CONCLUSION: The prognostic independent effect of sex on all-cause hospital mortality, 28-day all-cause mortality and all-cause ICU mortality for critically ill adults with sepsis was uncertain. Female sex may be associated with decreased 1-year all-cause mortality. PROSPERO REGISTRATION NUMBER: CRD42019145054.

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.

Sex as a Prognostic Factor in Systematic Reviews: Challenges and Lessons Learned.

Sex is a common baseline factor collected in studies that has the potential to be a prognostic factor (PF) in several clinical areas. In recent years, research on sex as a PF has increased; however, this influx of new studies frequently shows conflicting results across the same treatment or disease state. Thus, systematic reviews (SRs) addressing sex as a PF may help us to better understand diseases and further personalize healthcare. We wrote this article to offer insights into the challenges we encountered when conducting SRs on sex as a PF and suggestions on how to overcome these obstacles, regardless of the clinical domain. When carrying out a PF SR with sex as the index factor, it is important to keep in mind the modifications that must be made in various SR stages, such as modifying the PF section of CHARMS-PF, adjusting certain sections of QUIPS and extracting data on the sex and gender terms used throughout the studies. In this paper, we provide an overview of the lessons learned from carrying out our reviews on sex as a PF in different disciplines and now call on researchers, funding agencies and journals to realize the importance of studying sex as a PF.

Over half of the WHO guidelines published from 2014 to 2019 explicitly considered health equity issues: a cross-sectional survey.

OBJECTIVE: To evaluate how and to what extent health equity considerations are assessed in World Health Organization (WHO) guidelines. STUDY DESIGN AND SETTING: We evaluated WHO guidelines published between January 2014 and May 2019. Health equity considerations were assessed in relation to differences in baseline risk, importance of outcomes for socially disadvantaged populations, inclusion of health inequity as an outcome, equity-related subgroup analysis, and indirectness in each recommendation. RESULTS: We identified 111 WHO guidelines, and 54% (60 of 111) of these used the Evidence to Decision (EtD) framework. For the 60 guidelines using an EtD framework, the likely impact on health equity was supported by research evidence in 28% of the recommendations (94 of 332). Research evidence was mostly provided as differences in baseline risk (23%, 78/332). Research evidence less frequently addressed the importance of outcomes for socially disadvantaged populations (11%, 36/332), considered indirectness of the evidence for socially disadvantaged populations (2%, 5/332), considered health inequities as an outcome (2%, 5/332) and considered differences in the magnitude of effect in relative terms between disadvantaged and more advantaged populations (1%, 3/332). CONCLUSION: The provision of research evidence to support equity judgements in WHO guidelines is still suboptimal, suggesting the need for better guidance and more training.

Female under-representation in sepsis studies: a bibliometric analysis of systematic reviews and guidelines.

OBJECTIVES: The objective of the study was to assess female representation in primary studies underpinning recommendations from clinical guidelines and systematic reviews for sepsis treatment in adults. STUDY DESIGN AND SETTING: We conducted a bibliometric study. We removed studies pertaining to sex-specific diseases and included quasirandomized, randomized clinical trials (RCTs), and observational studies. We analyzed the female participation-to-prevalence ratio (PPR). RESULTS: We included 277 studies published between 1973 and 2017. For the 246 studies for which sex data were available, the share of female participation was 40%. Females overall were under-represented relative to their share of the sepsis population (PPR 0.78). Disaggregated results were reported by sex in 57 studies. In univariate analyses, non-intensive care unit setting and consideration of other social health determinants were significantly associated with greater female participation (P < 0.001 and P = 0.023, respectively). In regression models, studies published in 1996 or later were likely to report sex, while RCTs were unlikely to do so (P = 0.019 and P < 0.001, respectively). CONCLUSION: Our study points to female underenrollment in sepsis studies. Primary studies underpinning recommendations for sepsis have poorly reported their findings by sex.

Buffered Solutions Versus Isotonic Saline for Resuscitation in Nonsurgical Critically Ill: Protocol for Cochrane Review.

Fluid resuscitation is one of the most prevalent treatment in critical care. There is not definitive evidence about the best fluid for resuscitation. The aim of this review will be to asses the efficacy and safety of buffered solution versus saline. We will perform an electronic search in Medline, Embase, and Central. Studies will be eligible if they are clinical trials who including critical ill patients. Primary outcomes are mortality and renal failure. All findings will be tabulated and synthesized. We will perform a meta-analysis according to Cochrane Review standards. We will design a summary of findings table.