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.

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.

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 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.

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.

Consideration of sex and gender in Cochrane reviews of interventions for preventing healthcare-associated infections: a methodology study.

BACKGROUND: Healthcare-associated infections (HAIs) are common and increase morbidity, mortality, and healthcare costs. Their control continues to be an unresolved issue worldwide. HAIs epidemiology shows sex/gender differences. Thus the lack of consideration of sex/gender in Cochrane reviews will limit their applicability and capacity to support informed decisions. This study aims to describe the extent to which Cochrane reviews of interventions for preventing HAIs consider sex and gender. METHODS: Methodology study appraising Cochrane reviews of interventions to prevent HAIs. SEARCH METHODS: Cochrane Database of Systematic Reviews from 1995 (launch of the journal) to 31 December 2016. Two authors independently extracted data with EPPI-Reviewer 4 software, and independently appraised the sex/gender content of the reviews with the Sex and Gender Appraisal Tool for Systematic Reviews (SGAT-SR). RESULTS: This study included 113 reviews assessing the effects of interventions for preventing HAIs. 100 reviews (88%) used at least one sex or gender-related term. The terminology used was heterogeneous, being "sex" the term used in more reviews (51%). No review defined neither sex nor gender. Thus we could not assess the definitions provided. Consideration of sex and gender was practically absent in the included reviews; in fact, no review met all the applicable items of the SGAT-SR, and 51 reviews (50%) fulfilled no item. No review provided a complete description of the sex and the gender of the samples of the included studies. Only ten reviews (10%) planned to perform sex- and gender-based analysis and only three (3%) could complete the analysis. The method chosen was always the subgroup analysis based on sex (one review) or gender (two reviews). Three reviews (3%) considered sex or gender-related findings in the conclusions. CONCLUSION: Consideration of sex and gender in Cochrane reviews of interventions for preventing HAIs was practically absent. This lack of attention to sex and gender reduces the quality of Cochrane reviews, and their applicability for all people: women and men, boys and girls, and people of diverse gender identities. Cochrane should attempt to address the shortfalls detected.

Nutritional supplements for patients being treated for active visceral leishmaniasis.

BACKGROUND: Visceral leishmaniasis (VL) is a disease caused by a parasite, which can lead to death if untreated. Poor nutritional status hastens the progression of VL infection, and VL worsens malnutrition status. Malnutrition is one of the poor prognostic factors identified for leishmaniasis. However, the effects of nutritional supplementation in people treated for VL are not known. OBJECTIVES: To assess the effects of oral nutritional supplements in people being treated with anti-leishmanial drug therapy for VL. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group (CIDG) Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and two trial registers up to 12 September 2017. We checked conference proceedings and WHO consultative meeting reports, the reference lists of key documents and existing reviews, and contacted experts and nutritional supplement companies. SELECTION CRITERIA: Randomized controlled trials (RCTs), quasi-randomized controlled trials (quasi-RCTs), and non-randomized controlled trials (NRCTs) of any oral nutritional supplement, compared to no nutritional intervention, placebo, or dietary advice alone, in people being treated for VL. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature search results for studies that met the inclusion criteria. We had planned for two review authors to independently extract data and assess the risk of bias of the included studies. We planned to follow the Cochrane standard methodological procedures for assessing risk of bias and analysing the data. 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 oral nutritional supplements in people with VL who were being treated with anti-leishmanial drug therapy. Thus, we could not draw any conclusions on the impact of these interventions on primary cure of VL, definitive cure of VL, treatment completion, self-reported recovery from illness or resolution of symptoms, weight gain, increased skinfold thickness, other measures of lean or total mass, or growth in children.This absence of evidence should not be interpreted as evidence of no effect for nutritional supplements in people under VL treatment. It means that we did not identify research that fulfilled our review inclusion criteria.The effects of oral nutritional supplements in people with VL who are being treated with anti-leishmanial drug therapy have yet to be determined by rigorous experimental studies, such as cluster-randomized trials, that focus on outcomes relevant for patients.

Short-course versus long-course therapy of the same antibiotic for community-acquired pneumonia in adolescent and adult outpatients.

BACKGROUND: Community-acquired pneumonia (CAP) is a lung infection that can be acquired during day-to-day activities in the community (not while receiving care in a hospital). Community-acquired pneumonia poses a significant public health burden in terms of mortality, morbidity, and costs. Shorter antibiotic courses for CAP may limit treatment costs and adverse effects, but the optimal duration of antibiotic treatment is uncertain. OBJECTIVES: To evaluate the efficacy and safety of short-course versus longer-course treatment with the same antibiotic at the same daily dosage for CAP in non-hospitalised adolescents and adults (outpatients). We planned to investigate non-inferiority of short-course versus longer-term course treatment for efficacy outcomes, and superiority of short-course treatment for safety outcomes. SEARCH METHODS: We searched CENTRAL, which contains the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE, Embase, five other databases, and three trials registers on 28 September 2017 together with conference proceedings, reference checking, and contact with experts and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing short- and long-courses of the same antibiotic for CAP in adolescent and adult outpatients. DATA COLLECTION AND ANALYSIS: We planned to use standard Cochrane methods. MAIN RESULTS: Our searches identified 5260 records. We did not identify any RCTs that compared short- and longer-courses of the same antibiotic for the treatment of adolescents and adult outpatients with CAP.We excluded two RCTs that compared short courses (five compared to seven days) of the same antibiotic at the same daily dose because they evaluated antibiotics (gemifloxacin and telithromycin) not commonly used in practice for the treatment of CAP. In particular, gemifloxacin is no longer approved for the treatment of mild-to-moderate CAP due to its questionable risk-benefit balance, and reported adverse effects. Moreover, the safety profile of telithromycin is also cause for concern.We found one ongoing study that we will assess for inclusion in future updates of the review. AUTHORS' CONCLUSIONS: We found no eligible RCTs that studied a short-course of antibiotic compared to a longer-course (with the same antibiotic at the same daily dosage) for CAP in adolescent and adult outpatients. The effects of antibiotic therapy duration for CAP in adolescent and adult outpatients remains unclear.

Isolation as a strategy for controlling the transmission of hepatitis C virus (HCV) infection in haemodialysis units.

BACKGROUND: The hepatitis C virus (HCV) infection affects about 2% of the world's population and can cause chronic liver infection and persistent long-term sequelae such as cirrhosis and liver cancer.The prevalence of HCV infection among people on haemodialysis is often higher than the general population. The virus is easily transmitted parenterally, and blood transfusions have previously played a significant role in transmission; however, erythropoietin therapy has reduced the need for transfusions, and coupled with improved screening of donated blood, has significantly decreased transmission by transfusion. Although control of hospital-acquired infection has improved with the advent of biosafety measures, stopping HCV transmission in haemodialysis units remains challenging.Isolating people infected with HCV involves physical separation from others to limit direct or indirect transmission and includes a number of strategies during dialysis. The evidence for isolating people infected with HCV during haemodialysis is sparse with some inconsistencies. OBJECTIVES: To evaluate the benefits and harms of isolation of HCV-infected patients during haemodialysis on the transmission of HCV to other patients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 26 November 2015 through contact with the Information Specialist using search terms relevant to this review. We also searched the Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to 2015), Web of Science Conference Proceedings Citation Index-Science (CPCI-S, 1990 to 2015), ProQuest Dissertations & Theses Database (1990 to 2015), and Open Grey (1990 to 2015). SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs and cluster RCTs evaluating the clinical benefits and harms of isolating HCV-infected patients during haemodialysis on the transmission of HCV to other patients. We considered incidence of dialysis-acquired HCV infection, all-cause mortality, and adverse effects associated with isolation as the primary outcomes. DATA COLLECTION AND ANALYSIS: Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. MAIN RESULTS: Only one study, which included 12 centres was identified: four centres used dedicated haemodialysis machines for HCV-infected patients and eight centres used non-dedicated machines. The total number of patients enrolled was 593. One centre was excluded after randomisation. Random sequence generation was not described and allocation concealment was not performed. Participants and personnel were not blinded and blinding of outcome assessors was not reported. Only 74.5% of the patients were followed for 9 months; and 47.3% were followed for an additional 9 months. The authors only reported one outcome, measuring the difference in the incidence of HCV in both groups. The authors did not consider the exposure time, to determine the adjusted rate of seroconversion risk/patient-year. The study reported that the incidence of HCV infection during the first follow-up period (9 months) was 1.6% in the dedicated group, and 4.7% in the non-dedicated one (446 patients analysed out of 593 randomised; RR 0.34, 95% CI 0.11 to 1.07). During the second follow-up period (18 months) the incidence was 1.3% in the dedicated group and 5.8% in the control (281 patients analysed out of 593 randomised; RR 0.22, 95% CI 0.05 to 1.02). Therefore, we found no differences in terms of the number of participants developing HCV infection when comparing the dedicated group with the usual care. Moreover, the evidence was of very low quality, which means that we have very little confidence in the effect estimate. AUTHORS' CONCLUSIONS: The benefits and harms of isolation of HCV-infected patients during haemodialysis on the transmission of HCV to other patients are uncertain. Evidence from one short-duration cluster-randomised study with a high risk of bias did not find differences in terms of the number of participants developing HCV infection when comparing the use of dedicated haemodialysis machines for HCV infected patients with the use of non-dedicated machines.

Gloves, gowns and masks for reducing the transmission of meticillin-resistant Staphylococcus aureus (MRSA) in the hospital setting.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA; also known as methicillin-resistant S aureus) is a common hospital-acquired pathogen that increases morbidity, mortality, and healthcare costs. Its control continues to be an unresolved issue in many hospitals worldwide. The evidence base for the effects of the use of gloves, gowns or masks as control measures for MRSA is unclear. OBJECTIVES: To assess the effectiveness of wearing gloves, a gown or a mask when contact is anticipated with a hospitalised patient colonised or infected with MRSA, or with the patient's immediate environment. SEARCH METHODS: We searched the Specialised Registers of three Cochrane Groups (Wounds Group on 5 June 2015; Effective Practice and Organisation of Care (EPOC) Group on 9 July 2013; and Infectious Diseases Group on 5 January 2009); CENTRAL (The Cochrane Library 2015, Issue 6); DARE, HTA, NHS EED, and the Methodology Register (The Cochrane Library 2015, Issue 6); MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations (1946 to June week 1 2015); EMBASE (1974 to 4 June 2015); Web of Science (WOS) Core Collection (from inception to 7 June 2015); CINAHL (1982 to 5 June 2015); British Nursing Index (1985 to 6 July 2010); and ProQuest Dissertations & Theses Database (1639 to 11 June 2015). We also searched three trials registers (on 6 June 2015), references list of articles, and conference proceedings. We finally contacted relevant individuals for additional studies. SELECTION CRITERIA: Studies assessing the effects on MRSA transmission of the use of gloves, gowns or masks by any person in the hospital setting when contact is anticipated with a hospitalised patient colonised or infected with MRSA, or with the patient's immediate environment. We did not assess adverse effects or economic issues associated with these interventions.We considered any comparator to be eligible. With regard to study design, only randomised controlled trials (clustered or not) and the following non-randomised experimental studies were eligible: quasi-randomised controlled trials (clustered or not), non-randomised controlled trials (clustered or not), controlled before-and-after studies, controlled cohort before-after studies, interrupted time series studies (controlled or not), and repeated measures studies. We did not exclude any study on the basis of language or date of publication. DATA COLLECTION AND ANALYSIS: Two review authors independently decided on eligibility of the studies. Had any study having been included, two review authors would have extracted data (at least for outcome data) and assessed the risk of bias independently. We would have followed the standard methodological procedures suggested by Cochrane and the Cochrane EPOC Group for assessing risk of bias and analysing the data. MAIN RESULTS: We identified no eligible studies for this review, either completed or ongoing. AUTHORS' CONCLUSIONS: We found no studies assessing the effects of wearing gloves, gowns or masks for contact with MRSA hospitalised patients, or with their immediate environment, on the transmission of MRSA to patients, hospital staff, patients' caregivers or visitors. This absence of evidence should not be interpreted as evidence of no effect for these interventions. The effects of gloves, gowns and masks in these circumstances have yet to be determined by rigorous experimental studies, such as cluster-randomised trials involving multiple wards or hospitals, or interrupted time series studies.

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.

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.

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.

Antibiotic prophylaxis for preventing burn wound infection.

BACKGROUND: Infection of burn wounds is a serious problem because it can delay healing, increase scarring and invasive infection may result in the death of the patient. Antibiotic prophylaxis is one of several interventions that may prevent burn wound infection and protect the burned patient from invasive infections. OBJECTIVES: To assess the effects of antibiotic prophylaxis on rates of burn wound infection. SEARCH METHODS: In January 2013 we searched the Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE - In-Process & Other Non-Indexed Citations (2013); Ovid EMBASE; EBSCO CINAHL and reference lists of relevant articles. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: All randomised controlled trials (RCTs) that evaluated the efficacy and safety of antibiotic prophylaxis for the prevention of BWI. Quasi-randomised studies were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed the risk of bias, and extracted relevant data. Risk ratio (RR) and mean difference (MD) were estimated for dichotomous data and continuous data, respectively. When sufficient numbers of comparable RCTs were available, trials were pooled in a meta-analysis to estimate the combined effect. MAIN RESULTS: This review includes 36 RCTs (2117 participants); twenty six (72%) evaluated topical antibiotics, seven evaluated systemic antibiotics (four of these administered the antibiotic perioperatively and three administered upon hospital admission or during routine treatment), two evaluated prophylaxis with non absorbable antibiotics, and one evaluated local antibiotics administered via the airway.The 11 trials (645 participants) that evaluated topical prophylaxis with silver sulfadiazine were pooled in a meta analysis. There was a statistically significant increase in burn wound infection associated with silver sulfadiazine compared with dressings/skin substitute (OR = 1.87; 95% CI: 1.09 to 3.19, I(2) = 0%). These trials were at high, or unclear, risk of bias. Silver sulfadiazine was also associated with significantly longer length of hospital stay compared with dressings/skin substitute (MD = 2.11 days; 95% CI: 1.93 to 2.28).Systemic antibiotic prophylaxis in non-surgical patients was evaluated in three trials (119 participants) and there was no evidence of an effect on rates of burn wound infection. Systemic antibiotics (trimethoprim-sulfamethoxazole) were associated with a significant reduction in pneumonia (only one trial, 40 participants) (RR = 0.18; 95% CI: 0.05 to 0.72) but not sepsis (two trials 59 participants) (RR = 0.43; 95% CI: 0.12 to 1.61).Perioperative systemic antibiotic prophylaxis had no effect on any of the outcomes of this review.Selective decontamination of the digestive tract with non-absorbable antibiotics had no significant effect on rates of all types of infection (2 trials, 140 participants). Moreover, there was a statistically significant increase in rates of MRSA associated with use of non-absorbable antibiotics plus cefotaxime compared with placebo (RR = 2.22; 95% CI: 1.21 to 4.07).There was no evidence of a difference in mortality or rates of sepsis with local airway antibiotic prophylaxis compared with placebo (only one trial, 30 participants). AUTHORS' CONCLUSIONS: The conclusions we are able to draw regarding the effects of prophylactic antibiotics in people with burns are limited by the volume and quality of the existing research (largely small numbers of small studies at unclear or high risk of bias for each comparison). The largest volume of evidence suggests that topical silver sulfadiazine is associated with a significant increase in rates of burn wound infection and increased length of hospital stay compared with dressings or skin substitutes; this evidence is at unclear or high risk of bias. Currently the effects of other forms of antibiotic prophylaxis on burn wound infection are unclear. One small study reported a reduction in incidence of pneumonia associated with a specific systematic antibiotic regimen.

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.

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).

Topical cyclosporine for atopic keratoconjunctivitis.

BACKGROUND: Atopic keratoconjunctivitis (AKC) is a chronic ocular surface non-infectious inflammatory condition that atopic dermatitis patients may suffer at any time point in the course of their dermatologic disease and is independent of its degree of severity. AKC is usually not self resolving and it poses a higher risk of corneal injuries and severe sequelae. Management of AKC should prevent or treat corneal damage. Although topical corticosteroids remain the standard treatment for patients with AKC, prolonged use may lead to complications. Topical cyclosporine A (CsA) may improve AKC signs and symptoms, and be used as a corticosteroid sparing agent. OBJECTIVES: To determine the efficacy and gather evidence on safety from randomised controlled trials (RCTs) of topical CsA in patients with AKC. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to July 2012), EMBASE (January 1980 to July 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2012), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to July 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en), the IFPMA Clinical Trials Portal (http://clinicaltrials.ifpma.org/no_cache/en/myportal/index.htm) and Web of Science Conference Proceedings Citation Index- Science (CPCI-S). We did not use any date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 9 July 2012. We also handsearched the following conference proceedings: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, International Council of Opthalmology and Societas Ophthalmologica Europaea from 2005 to July 2011. SELECTION CRITERIA: We included randomised controlled trials only. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. Due to the small number of studies and the diversity of outcome measures, interventions and participants, we presented results narratively. MAIN RESULTS: We found three RCTs with a total of 58 participants that were eligible for inclusion. There was significant variability between the trials in interventions, methodology and outcome measures and therefore we did not perform meta-analysis.One study reported on the use of 2% CsA in maize oil and two on the use of a commercial emulsion of 0.05% CsA. Of these three studies, one showed a beneficial effect of topical CsA in controlling signs and symptoms of AKC, one in controlling signs of AKC and one did not show evidence of an improvement. Only two studies analysed the effect of topical CsA in reducing topical steroid use; one showed a significant reduction in topical steroid use with CsA, but the other did not show evidence of this improvement. No serious adverse events were reported in the trials. AUTHORS' CONCLUSIONS: This systematic review highlights the relative scarcity of controlled clinical trials assessing the efficacy of topical CsA therapy in AKC and suggests that evidence on the efficacy and safety of topical CsA treatment in patients with CsA remains limited. However, the data suggest that topical CsA may provide clinical and symptomatic relief in AKC and may help to reduce topical steroid use in patients with steroid-dependent or steroid-resistant AKC. No serious adverse events were reported. Reported adverse events in patients treated with topical CsA include intense stinging and eyelid skin maceration. One patient in the placebo group developed a severe allergic response to maize antigens. However, the total number of patients in the trials was too small to assess the safety of this treatment.Additional well-designed and powered RCTs of topical CsA in AKC are needed. Ideal study designs should include adequate randomisation and concealment of allocation; masking of participants, personnel and outcome assessors; adequate follow-up periods and minimisation of attrition bias; and comparison groups with similar clinical and epidemiologic characteristics. Samples should be large enough to provide sufficient statistical power to assess the safety of CsA and to detect clinically relevant treatment effect sizes of the primary outcomes. Analyses should be appropriate to the study's design and outcome measures. Moreover, standardisation of outcome measures and follow-up periods across studies would be beneficial to maximise study comparability.

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.