A focus on cross-purpose tools, automated recognition of study design in multiple disciplines, and evaluation of automation tools: a summary of significant discussions at the fourth meeting of the International Collaboration for Automation of Systematic Reviews (ICASR)

The fourth meeting of the International Collaboration for Automation of Systematic Reviews (ICASR) was held 5–6 November 2019 in The Hague, the Netherlands. ICASR is an interdisciplinary group whose goal is to maximize the use of technology for conducting rapid, accurate, and efficient systematic reviews of scientific evidence. The group seeks to facilitate the development and acceptance of automated techniques for systematic reviews. In 2018, the major themes discussed were the transferability of automation tools (i.e., tools developed for other purposes that might be used by systematic reviewers), the automated recognition of study design in multiple disciplines and applications, and approaches for the evaluation of automation tools

The Noxa/Mcl-1 Axis Regulates Susceptibility to Apoptosis under Glucose Limitation in Dividing T Cells

SummaryThroughout lymphocyte development, cellular persistence and expansion are tightly regulated by survival and apoptosis. Within the Bcl-2 family, distinct apoptogenic BH3-only members like Bid, Bim, and Puma appear to function in specific cell death pathways. We found that naive human T cells after mitogenic activation, apart from expected protective Bcl-2 members, also rapidly upregulate the BH3-only protein Noxa in a p53-independent fashion. The specific role of Noxa became apparent during glucose limitation and involves interaction with the labile Bcl-2 homolog Mcl-1. Knockdown of Noxa or Mcl-1 results in protection or susceptibility, respectively, to apoptosis induced by glucose deprivation. Declining Mcl-1 levels and apoptosis induction are inversely correlated to Noxa levels and prevented by readdition of glucose. We propose that the Noxa/Mcl-1 axis is an apoptosis rheostat in dividing cells, in a selective pathway that functions to restrain lymphocyte expansion and can be triggered by glucose deprivation

Decision aids to help older people make health decisions: a systematic review and meta-analysis

Background Decision aids have been overall successful in improving the quality of health decision making. However, it is unclear whether the impact of the results of using decision aids also apply to older people (aged 65+). We sought to systematically review randomized controlled trials (RCTs) and clinical controlled trials (CCTs) evaluating the efficacy of decision aids as compared to usual care or alternative intervention(s) for older adults facing treatment, screening or care decisions. Methods A systematic search of (1) a Cochrane review of decision aids and (2) MEDLINE, Embase, PsycINFO, Cochrane library central registry of studies and Cinahl. We included published RCTs/CCTs of interventions designed to improve shared decision making (SDM) by older adults (aged 65+) and RCTs/CCTs that analysed the effect of the intervention in a subgroup with a mean age of 65+. Based on the International Patient Decision aid Standards (IPDAS), the primary outcomes were attributes of the decision and the decision process. Other behavioral, health, and health system effects were considered as secondary outcomes. If data could be pooled, a meta-analysis was conducted. Data for which meta-analysis was not possible were synthesized qualitatively. Results The search strategy yielded 11,034 references. After abstract and full text screening, 22 papers were included. Decision aids performed better than control resp. usual care interventions by increasing knowledge and accurate risk perception in older people (decision attributes). With regard to decision process attributes, decision aids resulted in lower decisional conflict and more patient participation. Conclusions This review shows promising results on the effectiveness of decision aids for older adults. Decision aids improve older adults’ knowledge, increase their risk perception, decrease decisional conflict and seem to enhance participation in SDM. It must however be noted that the body of literature on the effectiveness of decision aids for older adults is still in its infancy. Only one decision aid was specifically developed for older adults, and the mean age in most studies was between 65 and 70, indicating that the oldest-old were not included. Future research should expand on the design, application and evaluation of decision aids for older, more vulnerable adults

Esophageal Endosonography for the Diagnosis of Intrapulmonary Tumors:A Systematic Review and Meta-Analysis

BACKGROUND: Biopsy-based diagnosis in patients with paraesophageal intrapulmonary tumors suspected of lung cancer is crucial for adequate treatment planning. OBJECTIVE: To evaluate the performance of transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the diagnosis of intrapulmonary tumors located near or adjacent to the esophagus. METHODS: We performed a systematic review (PROSPERO, CRD42016033737) and searched MEDLINE, Embase, BIOSIS Previews, and Web of Science on September 22, 2016, without date or language restrictions. We included studies that evaluated the yield and/or sensitivity of EUS-FNA for diagnosing intrapulmonary tumors. Yield was defined as the number of patients in whom EUS-FNA made a biopsy-proven diagnosis (malignant or nonmalignant) relative to the total number of patients on whom EUS-FNA was performed. Sensitivity was defined as the number of patients in whom EUS-FNA made a biopsy-proven diagnosis of malignancy relative to the total number of patients in whom the tumor was found to be malignant. We performed a random-effects meta-analysis. RESULTS: Of 3,320 search results, 11 studies were included. Ten had a high risk of bias. The total number of patients was 313; the proportion of patients with malignancy ranged from 87 to 100% across these studies. The average yield was 0.90 (95% CI 0.82-0.95) and the average sensitivity was 0.92 (0.83-0.96). In the subgroup of prospective studies (n = 3), the average yield was 0.80 (0.56-0.93) and the average sensitivity was 0.83 (0.58-0.95). EUS-FNA-induced complications were reported for 5/256 patients (2.0%) for whom this information was available. CONCLUSIONS: Although the number of high-quality studies is limited, these findings suggest that EUS-FNA is safe and has a high yield for diagnosing intrapulmonary tumors

Search filters to identify geriatric medicine in Medline

Objectives To create user-friendly search filters with high sensitivity, specificity, and precision to identify articles on geriatric medicine in Medline. Design A diagnostic test assessment framework was used. A reference set of 2255 articles was created by hand-searching 22 biomedical journals in Medline, and each article was labeled as 'relevant', 'not relevant', or 'possibly relevant' for geriatric medicine. From the relevant articles, search terms were identified to compile different search strategies. The articles retrieved by the various search strategies were compared with articles from the reference set as the index test to create the search filters. Measures Sensitivity, specificity, precision, accuracy, and number-needed-to-read (NNR) were calculated by comparing the results retrieved by the different search strategies with the reference set. Results The most sensitive search filter had a sensitivity of 94.8%, a specificity of 88.7%, a precision of 73.0%, and an accuracy of 90.2%. It had an NNR of 1.37. The most specific search filter had a specificity of 96.6%, a sensitivity of 69.1%, a precision of 86.6%, and an accuracy of 89.9%. It had an NNR of 1.15. Conclusion These geriatric search filters simplify searching for relevant literature and therefore contribute to better evidence-based practice. The filters are useful to both the clinician who wants to find a quick answer to a clinical question and the researcher who wants to find as many relevant articles as possible without retrieving too many irrelevant article

Prognostic models for radiation-induced complications after radiotherapy in head and neck cancer patients

Objectives: This is a protocol for a Cochrane Review (prognosis). The objectives are as follows:. Primary objective The review question is “Which prognostic models are available to predict the risk of radiation-induced side effects after radiation exposure to patients with head and neck cancer, what is their quality, and what is their predictive performance?”. Investigation of sources of heterogeneity between studies We will assess sources of heterogeneity among the prognostic models developed in the eligible studies. The potential sources are study population (e.g. site/stage of cancer, the use of other treatment [surgery and chemotherapy]), predictors, definition and incidence of the predicted outcomes, and prediction horizons. If there are multiple validation studies for the same model, the same sources of between-study heterogeneity will be investigated

Barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review of qualitative literature

Summary Tuberculosis disproportionately affects hard-to-reach populations, such as homeless people, migrants, refugees, prisoners, or drug users. These people often face challenges in accessing quality health care. We did a systematic review of the qualitative literature to identify barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by people from hard-to-reach populations in all European Union (EU), European Economic Area, EU candidate, and Organisation for Economic Co-operation and Development countries. The 12 studies included in this review mainly focused on migrants. Views on perceived susceptibility to and severity of tuberculosis varied widely and included many misconceptions. Stigma and challenges regarding access to health care were identified as barriers to tuberculosis diagnosis and treatment uptake, whereas support from nurses, family, and friends was a facilitator for treatment adherence. Further studies are required to identify barriers and facilitators to the improved identification and management of tuberculosis in hard-to-reach populations to inform recommendations for more effective tuberculosis control programmes

Effectiveness of interventions for diagnosis and treatment of tuberculosis in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review

Tuberculosis is over-represented in hard-to-reach (underserved) populations in high-income countries of low tuberculosis incidence. The mainstay of tuberculosis care is early detection of active tuberculosis (case finding), contact tracing, and treatment completion. We did a systematic review with a scoping component of relevant studies published between 1990 and 2015 to update and extend previous National Institute for Health and Care Excellence (NICE) reviews on the effectiveness of interventions for identifying and managing tuberculosis in hard-to-reach populations. The analyses showed that tuberculosis screening by (mobile) chest radiography improved screening coverage and tuberculosis identification, reduced diagnostic delay, and was cost-effective among several hard-to-reach populations. Sputum culture for pre-migration screening and active referral to a tuberculosis clinic improved identification. Furthermore, monetary incentives improved tuberculosis identification and management among drug users and homeless people. Enhanced case management, good cooperation between services, and directly observed therapy improved treatment outcome and compliance. Strong conclusions cannot be drawn because of the heterogeneity of evidence with regard to study population, methodology, and quality

Accuracy of routine laboratory tests to predict mortality and deterioration to severe or critical COVID-19 in people with SARS-CoV-2

Objectives This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows:  To assess the accuracy of routine blood-based laboratory tests to predict mortality and deterioration to severe or critical (from mild or moderate) COVID-19 in people with SARS-CoV-2 infection. Secondary objectives Where data are available, we will investigate whether prognostic accuracy varies according to a specific measurement or test, reference standard, timing of outcome verification, sample type, study design, and setting, including prevalence of the target condition (either by stratified analysis or meta-regression)

Rapid, point‐of‐care antigen and molecular‐based tests for diagnosis of SARS‐CoV‐2 infection

Background Accurate rapid diagnostic tests for SARS‐CoV‐2 infection could contribute to clinical and public health strategies to manage the COVID‐19 pandemic. Point‐of‐care antigen and molecular tests to detect current infection could increase access to testing and early confirmation of cases, and expediate clinical and public health management decisions that may reduce transmission. Objectives To assess the diagnostic accuracy of point‐of‐care antigen and molecular‐based tests for diagnosis of SARS‐CoV‐2 infection. We consider accuracy separately in symptomatic and asymptomatic population groups. Search methods Electronic searches of the Cochrane COVID‐19 Study Register and the COVID‐19 Living Evidence Database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) were undertaken on 30 Sept 2020. We checked repositories of COVID‐19 publications and included independent evaluations from national reference laboratories, the Foundation for Innovative New Diagnostics and the Diagnostics Global Health website to 16 Nov 2020. We did not apply language restrictions. Selection criteria We included studies of people with either suspected SARS‐CoV‐2 infection, known SARS‐CoV‐2 infection or known absence of infection, or those who were being screened for infection. We included test accuracy studies of any design that evaluated commercially produced, rapid antigen or molecular tests suitable for a point‐of‐care setting (minimal equipment, sample preparation, and biosafety requirements, with results within two hours of sample collection). We included all reference standards that define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction (RT‐PCR) tests and established diagnostic criteria). Data collection and analysis Studies were screened independently in duplicate with disagreements resolved by discussion with a third author. Study characteristics were extracted by one author and checked by a second; extraction of study results and assessments of risk of bias and applicability (made using the QUADAS‐2 tool) were undertaken independently in duplicate. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and pooled data using the bivariate model separately for antigen and molecular‐based tests. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status. Main results Seventy‐eight study cohorts were included (described in 64 study reports, including 20 pre‐prints), reporting results for 24,087 samples (7,415 with confirmed SARS‐CoV‐2). Studies were mainly from Europe (n = 39) or North America (n = 20), and evaluated 16 antigen and five molecular assays. We considered risk of bias to be high in 29 (37%) studies because of participant selection; in 66 (85%) because of weaknesses in the reference standard for absence of infection; and in 29 (37%) for participant flow and timing. Studies of antigen tests were of a higher methodological quality compared to studies of molecular tests, particularly regarding the risk of bias for participant selection and the index test. Characteristics of participants in 35 (45%) studies differed from those in whom the test was intended to be used and the delivery of the index test in 39 (50%) studies differed from the way in which the test was intended to be used. Nearly all studies (97%) defined the presence or absence of SARS‐CoV‐2 based on a single RT‐PCR result, and none included participants meeting case definitions for probable COVID‐19. Antigen tests Forty‐eight studies reported 58 evaluations of antigen tests. Estimates of sensitivity varied considerably between studies. There were differences between symptomatic (72.0%, 95% CI 63.7% to 79.0%; 37 evaluations; 15530 samples, 4410 cases) and asymptomatic participants (58.1%, 95% CI 40.2% to 74.1%; 12 evaluations; 1581 samples, 295 cases). Average sensitivity was higher in the first week after symptom onset (78.3%, 95% CI 71.1% to 84.1%; 26 evaluations; 5769 samples, 2320 cases) than in the second week of symptoms (51.0%, 95% CI 40.8% to 61.0%; 22 evaluations; 935 samples, 692 cases). Sensitivity was high in those with cycle threshold (Ct) values on PCR ≤25 (94.5%, 95% CI 91.0% to 96.7%; 36 evaluations; 2613 cases) compared to those with Ct values >25 (40.7%, 95% CI 31.8% to 50.3%; 36 evaluations; 2632 cases). Sensitivity varied between brands. Using data from instructions for use (IFU) compliant evaluations in symptomatic participants, summary sensitivities ranged from 34.1% (95% CI 29.7% to 38.8%; Coris Bioconcept) to 88.1% (95% CI 84.2% to 91.1%; SD Biosensor STANDARD Q). Average specificities were high in symptomatic and asymptomatic participants, and for most brands (overall summary specificity 99.6%, 95% CI 99.0% to 99.8%). At 5% prevalence using data for the most sensitive assays in symptomatic people (SD Biosensor STANDARD Q and Abbott Panbio), positive predictive values (PPVs) of 84% to 90% mean that between 1 in 10 and 1 in 6 positive results will be a false positive, and between 1 in 4 and 1 in 8 cases will be missed. At 0.5% prevalence applying the same tests in asymptomatic people would result in PPVs of 11% to 28% meaning that between 7 in 10 and 9 in 10 positive results will be false positives, and between 1 in 2 and 1 in 3 cases will be missed. No studies assessed the accuracy of repeated lateral flow testing or self‐testing. Rapid molecular assays Thirty studies reported 33 evaluations of five different rapid molecular tests. Sensitivities varied according to test brand. Most of the data relate to the ID NOW and Xpert Xpress assays. Using data from evaluations following the manufacturer’s instructions for use, the average sensitivity of ID NOW was 73.0% (95% CI 66.8% to 78.4%) and average specificity 99.7% (95% CI 98.7% to 99.9%; 4 evaluations; 812 samples, 222 cases). For Xpert Xpress, the average sensitivity was 100% (95% CI 88.1% to 100%) and average specificity 97.2% (95% CI 89.4% to 99.3%; 2 evaluations; 100 samples, 29 cases). Insufficient data were available to investigate the effect of symptom status or time after symptom onset. Authors' conclusions Antigen tests vary in sensitivity. In people with signs and symptoms of COVID‐19, sensitivities are highest in the first week of illness when viral loads are higher. The assays shown to meet appropriate criteria, such as WHO's priority target product profiles for COVID‐19 diagnostics (‘acceptable’ sensitivity ≥ 80% and specificity ≥ 97%), can be considered as a replacement for laboratory‐based RT‐PCR when immediate decisions about patient care must be made, or where RT‐PCR cannot be delivered in a timely manner. Positive predictive values suggest that confirmatory testing of those with positive results may be considered in low prevalence settings. Due to the variable sensitivity of antigen tests, people who test negative may still be infected. Evidence for testing in asymptomatic cohorts was limited. Test accuracy studies cannot adequately assess the ability of antigen tests to differentiate those who are infectious and require isolation from those who pose no risk, as there is no reference standard for infectiousness. A small number of molecular tests showed high accuracy and may be suitable alternatives to RT‐PCR. However, further evaluations of the tests in settings as they are intended to be used are required to fully establish performance in practice. Several important studies in asymptomatic individuals have been reported since the close of our search and will be incorporated at the next update of this review. Comparative studies of antigen tests in their intended use settings and according to test operator (including self‐testing) are required