Patient motivation as a predictor of digital health intervention effects: A meta-epidemiological study of cancer trials.

The objective of this meta-epidemiological study was to develop a rating that captures participants' motivation at the study level in digital health intervention (DHI) randomised controlled trials (RCTs). The rating was used to investigate whether participants' motivation is associated with the effect estimates in DHI RCTs for cancer patients. The development of the rating was based on a bottom-up approach involving the collection of information that captures participants' baseline motivation in empirical studies from the Smartphone-RCCT Database. We specified three indicators for rating: indicator 1 captures whether the study team actively selects or enhances the motivation of the potential study participants; indicator 2 captures the study participants' active engagement before the treatment allocation; and indicator 3 captures the potential bond and trust between the study participants and the person/institution referring to the study. The rating of each indicator and the overall rating varies between high motivation, moderate motivation, and low motivation. We applied the rating across 27 DHI RCTs with cancer patients. We performed meta-regression analysis to examine the effect of patient motivation on quality of life (QoL), psychological outcomes, and attrition. The intraclass correlation coefficient (ICC) indicated moderate to poor inter-rater reliability. The meta-regression showed that cancer patients' overall motivation before engaging in the intervention was associated with the treatment effect of QoL. Patient motivation was not found to be associated with psychological outcomes or attrition. Subgroup analyses revealed that the clinical effects of DHIs were more prevalent in the high-motivation subgroups, whereas the low-motivation subgroups were unlikely to show intervention benefits. The likelihood of dropouts from DHIs seems to be especially high among the low-bond (indicator 3) subgroup. We suggest using single indicators since they reflect specific content. Better reporting about baseline motivation is required to enable meaningful interpretations in not only primary studies but also in evidence syntheses.

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.

Corrigendum: CD4/CD8 ratio and CD8+ T-cell count as prognostic markers for non-AIDS mortality in people living with HIV. A systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fimmu.2024.1343124.].

Methodological challenges in systematic reviews of mHealth interventions: Survey and consensus-based recommendations.

OBJECTIVE: Mobile Health (mHealth) refers to using mobile devices to support health. This study aimed to identify specific methodological challenges in systematic reviews (SRs) of mHealth interventions and to develop guidance for addressing selected challenges. STUDY DESIGN AND SETTING: Two-phase participatory research project. First, we sent an online survey to corresponding authors of SRs of mHealth interventions. On a five-category scale, survey respondents rated how challenging they found 24 methodological aspects in SRs of mHealth interventions compared to non-mHealth intervention SRs. Second, a subset of survey respondents participated in an online workshop to discuss recommendations to address the most challenging methodological aspects identified in the survey. Finally, consensus-based recommendations were developed based on the workshop discussion and subsequent interaction via email with the workshop participants and two external mHealth SR authors. RESULTS: We contacted 953 corresponding authors of mHealth intervention SRs, of whom 50 (5 %) completed the survey. All the respondents identified at least one methodological aspect as more or much more challenging in mHealth intervention SRs than in non-mHealth SRs. A median of 11 (IQR 7.25-15) out of 24 aspects (46 %) were rated as more or much more challenging. Those most frequently reported were: defining intervention intensity and components (85 %), extracting mHealth intervention details (71 %), dealing with dynamic research with evolving interventions (70 %), assessing intervention integrity (69 %), defining the intervention (66 %) and maintaining an updated review (65 %). Eleven survey respondents participated in the workshop (five had authored more than three mHealth SRs). Eighteen consensus-based recommendations were developed to address issues related to mHealth intervention integrity and to keep mHealth SRs up to date. CONCLUSION: mHealth SRs present specific methodological challenges compared to non-mHealth interventions, particularly related to intervention integrity and keeping SRs current. Our recommendations for addressing these challenges can improve mHealth SRs.

CD4/CD8 ratio and CD8+ T-cell count as prognostic markers for non-AIDS mortality in people living with HIV. A systematic review and meta-analysis.

Background: In people living with HIV (PLHIV), the CD4/CD8 ratio has been proposed as a useful marker for non-AIDS events. However, its predictive ability on mortality over CD4 counts, and the role of CD8+ T-cell counts remain controversial. Methods: We conducted a systematic review and meta-analysis of published studies from 1996 to 2023, including PLHIV on antiretroviral treatment, and reporting CD4/CD8 ratio or CD8+ counts. The primary outcome was non-AIDS mortality or all-cause mortality. We performed a standard random-effects pairwise meta-analysis comparing low versus high CD4/CD8 ratio with a predefined cut-off point of 0.5. (CRD42020170931). Findings: We identified 2,479 studies for screening. 20 studies were included in the systematic review. Seven studies found an association between low CD4/CD8 ratio categories and increased mortality risk, with variable cut-off points between 0.4-1. Four studies were selected for meta-analysis, including 12,893 participants and 618 reported deaths. Patients with values of CD4/CD8 ratio below 0.5 showed a higher mortality risk (OR 3.65; 95% CI 3.04 - 4.35; I2 = 0.00%) compared to those with higher values. While the meta-analysis of CD8+ T-cell counts was not feasible due to methodological differences between studies, the systematic review suggests a negative prognostic impact of higher values (>1,138 to 1,500 cells/uL) in the long term. Conclusions: Our results support the use of the CD4/CD8 ratio as a prognostic marker in clinical practice, especially in patients with values below 0.5, but consensus criteria on ratio timing measurement, cut-off values, and time to event are needed in future studies to get more robust conclusions. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020170931, identifier CRD42020170931.

Basal procalcitonin, C-reactive protein, interleukin-6, and presepsin for prediction of mortality in critically ill septic patients: a systematic review and meta-analysis.

BACKGROUND: Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due to this life-threatening condition fail to address the complexity of this condition and the risk of bias associated with prognostic studies. We evaluate the predictive performance of four of these biomarkers in the prognosis of mortality through a methodologically sound evaluation. METHODS: We conducted a systematic review a systematic review and meta-analysis to determine, in critically ill adults with sepsis, whether procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin (sCD14) are independent prognostic factors for mortality. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to March 2023. Only Phase-2 confirmatory prognostic factor studies among critically ill septic adults were included. Random effects meta-analyses pooled the prognostic association estimates. RESULTS: We included 60 studies (15,681 patients) with 99 biomarker assessments. Quality of the statistical analysis and reporting domains using the QUIPS tool showed high risk of bias in > 60% assessments. The biomarker measurement as a continuous variable in models adjusted by key covariates (age and severity score) for predicting mortality at 28-30 days showed a null or near to null association for basal PCT (pooled OR = 0.99, 95% CI = 0.99-1.003), CRP (OR = 1.01, 95% CI = 0.87 to 1.17), and IL-6 (OR = 1.02, 95% CI = 1.01-1.03) and sCD14 (pooled HR = 1.003, 95% CI = 1.000 to 1.006). Additional meta-analyses accounting for other prognostic covariates had similarly null findings. CONCLUSION: Baseline, isolated measurement of PCT, CRP, IL-6, and sCD14 has not been shown to help predict mortality in critically ill patients with sepsis. The role of these biomarkers should be evaluated in new studies where the patient selection would be standardized and the measurement of biomarker results. TRIAL REGISTRATION: PROSPERO (CRD42019128790).

Acupuncture for the prevention of chemotherapy-induced nausea and vomiting in cancer patients: A systematic review and meta-analysis.

PURPOSE: To assess the effectiveness and safety of acupuncture for the prevention of chemotherapy-induced nausea and vomiting (CINV), with a specific intention on exploring sources of between-study variation in treatment effects. METHODS: MEDLINE, EMBASE, Cochrane CENTRAL, CINAHL, Chinese Biomedical Literature Database, VIP Chinese Science and Technology Periodicals Database, China National Knowledge Infrastructure, and Wanfang were searched to identify randomized controlled trials (RCTs) that compared acupuncture to sham acupuncture or usual care (UC). The main outcome is complete control (no vomiting episodes and/or no more than mild nausea) of CINV. GRADE approach was used to rate the certainty of evidence. RESULTS: Thirty-eight RCTs with a total of 2503 patients were evaluated. Acupuncture in addition to UC may increase the complete control of acute vomiting (RR, 1.13; 95% CI, 1.02 to 1.25; 10 studies) and delayed vomiting (RR, 1.47; 95% CI, 1.07 to 2.00; 10 studies) when compared with UC only. No effects were found for all other review outcomes. The certainty of evidence was generally low or very low. None of the predefined moderators changed the overall findings, but in an exploratory moderator analysis we found that an adequate reporting of planned rescue antiemetics might decrease the effect size of complete control of acute vomiting (p = 0.035). CONCLUSION: Acupuncture in addition to usual care may increase the complete control of chemotherapy-induced acute vomiting and delayed vomiting but the certainty of evidence was very low. Well-designed RCTs with larger sample sizes, standardized treatment regimens, and core outcome measures are needed.

CHARMS and PROBAST at your fingertips: a template for data extraction and risk of bias assessment in systematic reviews of predictive models.

BACKGROUND: Systematic reviews of studies of clinical prediction models are becoming increasingly abundant in the literature. Data extraction and risk of bias assessment are critical steps in any systematic review. CHARMS and PROBAST are the standard tools used for these steps in these reviews of clinical prediction models. RESULTS: We developed an Excel template for data extraction and risk of bias assessment of clinical prediction models including both recommended tools. The template makes it easier for reviewers to extract data, to assess the risk of bias and applicability, and to produce results tables and figures ready for publication. CONCLUSION: We hope this template will simplify and standardize the process of conducting a systematic review of prediction models, and promote a better and more comprehensive reporting of these systematic reviews.

Smartphone-RCCT: an online repository of randomized controlled clinical trials of smartphone applications for chronic conditions.

BACKGROUND: Chronic health conditions have a big impact on disability, morbidity, and mortality worldwide. Smartphone health applications (apps) can improve the health of patients with chronic conditions and enhance the quality and efficiency of healthcare. The number of randomized controlled trials (RCTs) of smartphone health apps is increasing, but a collection of the available evidence into a single database is still missing. The purpose of this study is to describe Smartphone-RCCT, which is an in-progress database of RCTs of smartphone apps for chronic conditions. METHODS: For a study to be included in the database, the following criteria had to be met: (a) RCT published in a peer-reviewed journal; (b) population: adult study participants with one or several chronic conditions that represent the main health problem addressed by the study intervention; (c) intervention: smartphone health app used by the patient; (d) comparator: any control condition; (e) outcomes: any patient-reported health outcome (studies exclusively measuring the patients' knowledge about the chronic conditions or their satisfaction with the smartphone app were excluded); (f) sample size: at least 15 participants per study arm. We searched in electronic databases and other resources to identify relevant studies. Two reviewers selected the studies and extracted data independently. Annual updates are planned. RESULTS: The proposed database is called Smartphone-RCCT, an open-access repository collecting bibliographic references and important characteristics of RCTs of smartphone apps for chronic conditions. The database is available for free in Open Science Framework (OSF): https://osf.io/nxerf/ . To date, it includes 70 trials. Their references can be exported to standard reference management software and the extracted data is available in a Microsoft Excel file. CONCLUSIONS: Smartphone-RCCT is the first systematic open-access database collecting peer-reviewed publications of RCTs of smartphone apps for patients with chronic conditions. The database accelerates the delivery of evidence-based information in a dynamic research field. It represents an essential resource for different stakeholders, such as professionals working in evidence synthesis, meta-epidemiological studies, or planning an RCT.

Comparability of Patients in Trials of eHealth and Face-to-Face Psychotherapeutic Interventions for Depression: Meta-synthesis.

BACKGROUND: Depressive disorders (DDs) are a public health problem. Face-to-face psychotherapeutic interventions are a first-line option for their treatment in adults. There is a growing interest in eHealth interventions to maximize accessibility for effective treatments. Thus, the number of randomized controlled trials (RCTs) of eHealth psychotherapeutic interventions has increased, and these interventions are being offered to patients. However, it is unknown whether patients with DDs differ in internet-based and face-to-face intervention trials. This information is essential to gain knowledge about eHealth trials' external validity. OBJECTIVE: We aimed to compare the baseline characteristics of patients with DDs included in the RCTs of eHealth and face-to-face psychotherapeutic interventions with a cognitive component. METHODS: In this meta-epidemiological study, we searched 5 databases between 1990 and November 2017 (MEDLINE, Embase, PsycINFO, Google Scholar, and the database of Cuijpers et al). We included RCTs of psychotherapeutic interventions with a cognitive component (eg, cognitive therapy, cognitive behavioral therapy [CBT], or interpersonal therapy) delivered face-to-face or via the internet to adults with DDs. Each included study had a matching study for predefined criteria to allow a valid comparison of characteristics and was classified as a face-to-face (CBT) or eHealth (internet CBT) intervention trial. Two authors selected the studies, extracted data, and resolved disagreements by discussion. We tested whether predefined baseline characteristics differed in face-to-face and internet-based trials using a mixed-effects model and testing for differences with z tests (statistical significance set at .05). For continuous outcomes, we also estimated the difference in means between subgroups with 95% CI. RESULTS: We included 58 RCTs (29 matching pairs) with 3846 participants (female: n=2803, 72.9%) and mean ages ranging from 20-74 years. White participants were the most frequent (from 63.6% to 100%). Other socioeconomic characteristics were poorly described. The participants presented DDs of different severity measured with heterogeneous instruments. Internet CBT trials had a longer depression duration at baseline (7.19 years higher, CI 95% 2.53-11.84; 10.0 vs 2.8 years; P=.002), but the proportion of patients with previous depression treatment was lower (24.8% vs 42%; P=.04). Subgroup analyses found no evidence of differences for the remaining baseline characteristics: age, gender, education, living area, depression severity, history of depression, actual antidepressant medication, actual physical comorbidity, actual mental comorbidity, study dropout, quality of life, having children, family status, and employment. We could not compare proficiency with computers due to the insufficient number of studies. CONCLUSIONS: The baseline characteristics of patients with DDs included in the RCTs of eHealth and face-to-face psychotherapeutic interventions are generally similar. However, patients in eHealth trials had a longer duration of depression, and a lower proportion had received previous depression treatment, which might indicate that eHealth trials attract patients who postpone earlier treatment attempts. TRIAL REGISTRATION: PROSPERO CRD42019085880; https://tinyurl.com/4xufwcyr.

The RIPI-f (Reporting Integrity of Psychological Interventions delivered face-to-face) checklist was developed to guide reporting of treatment integrity in face-to-face psychological interventions.

OBJECTIVES: Intervention integrity is the degree to which the study intervention is delivered as intended. This article presents the RIPI-f checklist (Reporting Integrity of Psychological Interventions delivered face-to-face) and summarizes its development methods. RIPI-f proposes guidance for reporting intervention integrity in evaluative studies of face-to-face psychological interventions. STUDY DESIGN AND SETTING: We followed established procedures for developing reporting guidelines. We examined 56 documents (reporting guidelines, bias tools, and methodological guidance) for relevant aspects of face-to-face psychological intervention integrity. Eighty four items were identified and grouped as per the template for intervention description and replication (TIDieR) domains. Twenty nine experts from psychology and medicine and other scholars rated the relevance of each item in a single-round Delphi survey. A multidisciplinary panel of 11 experts discussed the survey results in three online consensus meetings and drafted the final version of the checklist. RESULTS: We propose RIPI-f, a checklist with 50 items. Our checklist enhances TIDieR with important extensions, such as therapeutic alliance, provider's allegiance, and the adherence of providers and participants. CONCLUSION: RIPI-f can improve the reporting of face-to-face psychological interventions. The tool can help authors, researchers, systematic reviewers, and guideline developers. We suggest using RIPI-f alongside other reporting guidelines.

Development and evaluation of a search filter to identify prognostic factor studies in Ovid MEDLINE.

BACKGROUND: Systematic reviews (SRs) are valuable resources as they address specific clinical questions by summarizing all existing relevant studies. However, finding all information to include in systematic reviews can be challenging. Methodological search filters have been developed to find articles related to specific clinical questions. To our knowledge, no filter exists for finding studies on the role of prognostic factor (PF). We aimed to develop and evaluate a search filter to identify PF studies in Ovid MEDLINE that has maximum sensitivity. METHODS: We followed current recommendations for the development of a search filter by first identifying a reference set of PF studies included in relevant systematic reviews on the topic, and by selecting search terms using a word frequency analysis complemented with an expert panel discussion. We evaluated filter performance using the relative recall methodology. RESULTS: We constructed a reference set of 73 studies included in six systematic reviews from a larger sample. After completing a word frequency analysis using the reference set studies, we compiled a list of 80 of the frequent methodological terms. This list of terms was evaluated by the Delphi panel for inclusion in the filter, resulting in a final set of 8 appropriate terms. The consecutive connection of these terms with the Boolean operator OR produced the filter. We then evaluated the filter using the relative recall method against the reference set, comparing the references included in the SRs with our new search using the filter. The overall sensitivity of the filter was calculated to be 95%, while the overall specificity was 41%. The precision of the filter varied considerably, ranging from 0.36 to 17%. The NNR (number needed to read) value varied largely from 6 to 278. The time saved by using the filter ranged from 13-70%. CONCLUSIONS: We developed a search filter for OVID-Medline with acceptable performance that could be used in systematic reviews of PF studies. Using this filter could save as much as 40% of the title and abstract screening task. The specificity of the filter could be improved by defining additional terms to be included, although it is important to evaluate any modification to guarantee the filter is still highly sensitive.

Prognostic models for mortality after cardiac surgery in patients with infective endocarditis: a systematic review and aggregation of prediction models.

BACKGROUND: There are several prognostic models to estimate the risk of mortality after surgery for active infective endocarditis (IE). However, these models incorporate different predictors and their performance is uncertain. OBJECTIVE: We systematically reviewed and critically appraised all available prediction models of postoperative mortality in patients undergoing surgery for IE, and aggregated them into a meta-model. DATA SOURCES: We searched Medline and EMBASE databases from inception to June 2020. STUDY ELIGIBILITY CRITERIA: We included studies that developed or updated a prognostic model of postoperative mortality in patient with IE. METHODS: We assessed the risk of bias of the models using PROBAST (Prediction model Risk Of Bias ASsessment Tool) and we aggregated them into an aggregate meta-model based on stacked regressions and optimized it for a nationwide registry of IE patients. The meta-model performance was assessed using bootstrap validation methods and adjusted for optimism. RESULTS: We identified 11 prognostic models for postoperative mortality. Eight models had a high risk of bias. The meta-model included weighted predictors from the remaining three models (EndoSCORE, specific ES-I and specific ES-II), which were not rated as high risk of bias and provided full model equations. Additionally, two variables (age and infectious agent) that had been modelled differently across studies, were estimated based on the nationwide registry. The performance of the meta-model was better than the original three models, with the corresponding performance measures: C-statistics 0.79 (95% CI 0.76-0.82), calibration slope 0.98 (95% CI 0.86-1.13) and calibration-in-the-large -0.05 (95% CI -0.20 to 0.11). CONCLUSIONS: The meta-model outperformed published models and showed a robust predictive capacity for predicting the individualized risk of postoperative mortality in patients with IE. PROTOCOL REGISTRATION: PROSPERO (registration number CRD42020192602).

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.

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.

Challenges in applying the GRADE approach in public health guidelines and systematic reviews: a concept article from the GRADE Public Health Group.

BACKGROUND AND OBJECTIVE: This article explores the need for conceptual advances and practical guidance in the application of the GRADE approach within public health contexts. METHODS: We convened an expert workshop and conducted a scoping review to identify challenges experienced by GRADE users in public health contexts. We developed this concept article through thematic analysis and an iterative process of consultation and discussion conducted with members electronically and at three GRADE Working Group meetings. RESULTS: Five priority issues can pose challenges for public health guideline developers and systematic reviewers when applying GRADE: (1) incorporating the perspectives of diverse stakeholders; (2) selecting and prioritizing health and "nonhealth" outcomes; (3) interpreting outcomes and identifying a threshold for decision-making; (4) assessing certainty of evidence from diverse sources, including nonrandomized studies; and (5) addressing implications for decision makers, including concerns about conditional recommendations. We illustrate these challenges with examples from public health guidelines and systematic reviews, identifying gaps where conceptual advances may facilitate the consistent application or further development of the methodology and provide solutions. CONCLUSION: The GRADE Public Health Group will respond to these challenges with solutions that are coherent with existing guidance and can be consistently implemented across public health decision-making contexts.

The prevalence of intraarticular associated lesions after acute acromioclavicular joint injuries is 20%. A systematic review and meta-analysis.

PURPOSE: To synthesise the evidence on the prevalence of associated intraarticular lesions in subjects with acute acromioclavicular joint (ACJ) dislocations. METHODS: A search in two electronic databases (PUMBMED and EMBASE) was performed from 1985 to 2019. Two independent reviewers selected studies that complied with the following inclusion criteria: (1) the study included data on surgically treated ACJ dislocation grade III-V in the Rockwood classification, (2) the ACJ injuries were acute (the surgery was performed less than 6 weeks after injury), (3) an arthroscopic evaluation of the glenohumeral joint was performed during surgery. The quality of the studies included was assessed using the tool of the Joanna Briggs Institute. RESULTS: A total of 47 studies with acute ACJ injuries met the initial inclusion criteria. Of these, 21 studies (9 retrospective case series, 9 prospective case series and 3 retrospective cohort studies) presented data on associated intraarticular lesions amenable for use in the meta-analysis. The meta-analysed studies included a total of 860 subjects with acute ACJ dislocations with a male/female ratio of 6.5 and a mean age of 32 years. The meta-analysis showed a prevalence of associated intraarticular lesions in subjects with acute ACJ of 19.9% (95% confidence interval [CI] 14.0-26.4%; 21 studies, 860 analysed participants; P = 0.000; I2: 74.5% random-effects model; low risk of bias). CONCLUSION: One in five subjects with surgically treated acute ACJ dislocations will have an associated intraarticular lesion that requires further intervention. The case for a customary arthroscopic evaluation of the joint, even when an open procedure is performed to deal with the ACJ dislocation, is strong. Level of evidence IV Trial registry Systematic review registration number: PROSPERO CRD42018090609.

Current State of Research About Chinese Herbal Medicines (CHM) for the Treatment of Coronavirus Disease 2019 (COVID-19): A Scoping Review.

Background: There is currently no effective treatment against coronavirus disease 2019 (COVID-19). The optimal selection of interventions targeting the virus is unknown. Therefore, evidence from randomized controlled trials (RCTs) to support specific treatment against COVID-19 is urgently needed. The use of Chinese herbal medicines (CHMs) might have a role in the treatment and symptomatic management of patients with COVID-19. It was aimed at providing an overview of the available evidence and ongoing trials concerning the effects of CHMs for the treatment of COVID-19. Methods: This is a narrative review of relevant studies. Searches were conducted to identify documents published till April 22, 2020. Electronic databases, evidence-based collections, websites of relevant organizations, and trial registries were consulted. Results: A total of 25 guidelines on the treatment of patients with COVID-19 were identified. Four guidelines provided recommendations on the use of CHMs; these guidelines were developed in China and South Korea and were based on the consensus of experts exclusively. The remaining 21 guidelines provided no guidance on CHMs. No finished RCTs of CHMs for the treatment of patients with COVID-19 was found. According to the evidence evaluated in this review, a Cochrane review of CHMs for severe acute respiratory syndrome and five uncontrolled observational studies of the effects of CHMs in patients with COVID-19, the effects of CHMs for COVID-19 are unknown. A total of 52 ongoing clinical trials of CHM interventions for the treatment of COVID-19 were found. These trials will be carried out mostly in China (n = 51). Forty (77%) of the ongoing trials will be randomized, whereas 12 (23%) have an unclear sequence generation procedure. Forty-seven trials (90%) will have a sample size <400 participants. Conclusions: To the authors' knowledge, only the Chinese and the South Korean guidelines recommend CHMs as a treatment option for patients with COVID-19. These guidelines base their recommendations on the consensus of experts. Clinical guidelines or health authorities from other countries do not provide advice on CHMs. Due to the absence of RCT, there is currently no reliable evidence on the effects of any specific CHM intervention for the treatment of patients with COVID-19. A high number of clinical trials of different herbal products are being currently conducted in China.

Evaluation of the role of sex as a prognostic factor in critically ill adults with sepsis: systematic review protocol.

INTRODUCTION: Sepsis is a leading cause of mortality in critically ill patients. Recently, it has been recognised that sex may contribute to a differential risk for developing sepsis and it remains uncertain if the prognosis of sepsis varies between the sexes. The aim of this systematic review is to summarise the available evidence to assess the role of sex as a prognostic factor in patients with sepsis managed in the intensive care unit (ICU). METHODS AND ANALYSIS: This is a systematic review protocol of prognostic studies of sex in patients with sepsis managed in the ICU. The primary outcomes include all-cause hospital mortality and all-cause hospital mortality during the first 28 days. The secondary outcomes include all-cause hospital mortality during the first 7 days and all-cause mortality at 1 year. We will conduct a search strategy based on the population (sepsis), the prognostic factor (sex), the outcome of interest (mortality) and prognostic study methods. We will search in the following databases up to December 2019: MEDLINE Ovid (from 1976), Embase Elsevier (from 1974), Web of Science and two trial registries. We will impose no language restrictions. Two authors will independently screen titles, abstracts and full-text articles for eligibility of studies, and subsequently extract data. Two authors will independently assess the risk of bias of each study using the Quality in Prognostic Studies (QUIPS) tool. If possible, we will carry out a meta-analysis to provide a pooled prognostic effect estimate for each outcome. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the quality of evidence. ETHICS AND DISSEMINATION: Ethical approval will not be required. Findings from this review will be reported in a peer-reviewed scientific journal. Additionally, the results will be disseminated at conferences and in the mass media. PROSPERO REGISTRATION NUMBER: CRD42019145054.

Indomethacin for intracranial hypertension secondary to severe traumatic brain injury in adults.

BACKGROUND: Among people who have suffered a traumatic brain injury, increased intracranial pressure continues to be a major cause of early death; it is estimated that about 11 people per 100 with traumatic brain injury die. Indomethacin (also known as indometacin) is a powerful cerebral vasoconstrictor that can reduce intracranial pressure and, ultimately, restore cerebral perfusion and oxygenation. Thus, indomethacin may improve the recovery of a person with traumatic brain injury. OBJECTIVES: To assess the effects of indomethacin for adults with severe traumatic brain injury. SEARCH METHODS: We ran the searches from inception to 23 August 2019. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8) in the Cochrane Library, Ovid MEDLINE, Ovid Embase, CINAHL Plus (EBSCO), four other databases, and clinical trials registries. We also screened reference lists and conference abstracts, and contacted experts in the field. SELECTION CRITERIA: Our search criteria included randomised controlled trials (RCTs) that compared indomethacin with any control in adults presenting with severe traumatic brain injury associated with elevated intracranial pressure, with no previous decompressive surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently decided on the selection of the studies. We followed standard Cochrane methods. MAIN RESULTS: We identified no eligible studies for this review, either completed or ongoing. AUTHORS' CONCLUSIONS: We found no studies, either completed or ongoing, that assessed the effects of indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. Thus, we cannot draw any conclusions about the effects of indomethacin on intracranial pressure, mortality rates, quality of life, disability or adverse effects. This absence of evidence should not be interpreted as evidence of no effect for indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. It means that we have not identified eligible research for this review.