Objective:To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. Design:Systematic review and network meta-analysis. Data sources:Ovid Medline, Embase, and Cochrane Central up to 14 October 2022. Eligibility criteria for selecting studies:Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach. Results:The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes). Conclusions:This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes.

BACKGROUND AND AIMS: Parkinson's disease patients (PwPD) rely heavily on their family caregivers. However, there remains uncertainty regarding the subjective experience of the family caregivers of PwPD. This study aims to provide an in-depth summary of the current knowledge about the subjective experiences of family caregivers caring for PwPD, to understand the factors that influence this experience and to provide the evidence for healthcare services. METHODS: We conducted a systematic review and meta-ethnography using Noblit and Hare's approach. The search strategy used MeSH terms in combination with free-text searching of 10 databases (from their inception until July 2021). Titles and abstracts were reviewed by two reviewers and, for the studies that met the eligibility criteria, full-text articles were obtained. The Critical Appraisal Skills Program (CASP) checklist was employed to assess the quality of studies. RESULTS: A total of 3318 studies were screened and 29 qualitative studies were included in this review. These studies recorded the experience of 399 participants across 12 countries, most were females. Five themes emerged: (a) feelings related to PD; (b) challenges to family life; (c) external challenges; (d) adjustment and adaptation; (e) external support. We propose a new conceptual model that highlights that the experiences of caregivers for PwPD are dynamic and influenced by a variety of internal and external factors. CONCLUSION: Our findings illustrate the complex and dynamic experiences of family caregivers for PwPD. It is necessary to explore how the influencing factors can be modified to improve the lived experience of family caregivers.

OBJECTIVES: Machine learning (ML) has been increasingly used in clinical medicine including studies focused on Clostridioides difficile infection (CDI) to inform to clinical decision making. We aimed to summarize ML choices in studies that used ML to predict CDI or CDI outcomes. METHODS: We searched Ovid MEDLINE, Ovid EMBASE, Web of Science, medRxiv, bioRxiv and arXiv from inception to March 18, 2021. We included fully published studies that used ML where CDI constituted the study population, exposure or outcome. Two reviewers independently identified studies and abstracted outcomes. We summarized study characteristics and approaches to CDI definition and ML-specific modelling. RESULTS: Forty-three studies of prediction (n = 21), classification (n = 17) or inference (n = 5) were included. Approaches to defining CDI were labelling during a clinical study or chart review (n = 21), electronic phenotyping (n = 13) or not specified (n = 9). None of the studies using an electronic phenotype described phenotype validation. Almost all studies (n = 41, 95%) conducted supervised ML and the most common ML algorithms were penalized logistic regression (n = 20, 47%) and classification tree (n = 17, 40%). Approaches to feature selection and dimension reduction were heterogeneous. Metrics were evaluated in a held-out test set in 16 (37%) studies; only seven used a time-based split. In terms of reporting quality assessment, the most poorly reported items were data leakage prevention (n = 0, 0%), code availability (n = 8, 19%) and class imbalance management (n = 12, 43%). CONCLUSIONS: While many studies have used ML to investigate CDI or CDI outcomes, electronic phenotyping of CDI was uncommon and phenotype validation was not reported in any study. Methodological approaches were heterogeneous. Validating CDI electronic phenotypes, evaluating performances of CDI models during a silent trial and deploying a CDI classifier to guide clinical practice are important future goals.

OBJECTIVE: The studies showed the benefits of virtual reality training (VRT) for functional mobility and balance in older adults. However, a large variance in the study design and results is presented. We, thus, completed a systematic review and meta-analysis to quantitatively examine the effects of VRT on functional mobility and balance in healthy older adults. METHODS: We systematically reviewed the publications in five databases. Studies that examine the effects of VRT on the measures of functional mobility and balance in healthy older adults were screened and included if eligible. Subgroup analyses were completed to explore the effects of different metrics of the intervention design (e.g., session time) on those outcomes related to functional mobility and balance. RESULTS: Fifteen studies of 704 participants were included. The quality of these studies was good. Compared to traditional physical therapy (TPT), VRT induced greater improvement in TUG (MD = -0.31 s, 95% CI = -0.57 to -0.05, p = 0.02, I (2) = 6.34%) and one-leg stance with open eyes (OLS-O) (MD = 7.28 s, 95% CI = 4.36 to 10.20, p = 0.00, I (2) = 36.22%). Subgroup analyses revealed that immersive VRT with more than 800 min of total intervention time over 8 weeks and at least 120 min per week and/or designed by the two motor-learning principles was optimal for functional mobility and balance. CONCLUSION: Virtual reality training can significantly improve functional mobility and balance in healthy older adults compared to TPT, and the findings provided critical knowledge of the optimized design of VRT that can inform future studies with more rigorous designs.

Background:This study aims to develop an evidence-based clinical practice guideline of acupuncture in the treatment of patients with moderate and severe cancer pain. Methods:The development of this guideline was triggered by a systematic review published in JAMA Oncology in 2020. We searched databases and websites for evidence on patient preferences and values, and other resources of using acupuncture for treatment of cancer pain. Recommendations were developed through a Delphi consensus of an international multidisciplinary panel including 13 western medicine oncologists, Chinese medicine/acupuncture clinical practitioners, and two patient representatives. The certainty of evidence, patient preferences and values, resources, and other factors were fully considered in formulating the recommendations. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to rate the certainty of evidence and the strength of recommendations. Results:The guideline proposed three recommendations: (1) a strong recommendation for the treatment of acupuncture rather than no treatment to relieve pain in patients with moderate to severe cancer pain; (2) a weak recommendation for the combination treatments with acupuncture/acupressure to reduce pain intensity, decrease the opioid dose, and alleviate opioid-related side effects in moderate to severe cancer pain patients who are using analgesics; and (3) a strong recommendation for acupuncture in breast cancer patients to relieve their aromatase inhibitor-induced arthralgia. Conclusion:This proposed guideline provides recommendations for the management of patients with cancer pain. The small sample sizes of evidence limit the strength of the recommendations and highlights the need for additional research.

OBJECTIVE: To systematically evaluate the effects of health literacy intervention on health literacy level and glycolipid metabolism of people with diabetes in mainland China. METHODS: A systematic review of journal articles discussing diabetes and health literacy was performed by searching PubMed, Embase, the Science Citation Index Expanded (SCIE) database of Web of Science, the China National Knowledge Infrastructure (CNKI) database, the Chinese Scientific and Technical Journals database (CQVIP), and the Wanfang database. Cochrane Effective Practice and Organization of Care Review Group (EPOC) standards were applied for quality assessment. A meta-analysis was performed using Stata 12.0 software. RESULTS: A total of 44 articles, including seven controlled before-and-after trials (CBAs), 27 randomized controlled trials (RCTs), and 10 nonrandomized controlled trials (non-RCTs), were included. The results showed that (1) health literacy level in the intervention group was improved compared with the preintervention and the control group; (2) fasting plasma glucose (FPG) (standardized mean difference (SMD) = -1.85, 95% CI: -2.28, -1.42), 2-hour plasma glucose (2hPG) (SMD = -2.18, 95% CI: -2.68, -1.68), and HbA1c (weighted mean difference (WMD) = -1.21, 95% CI: -1.48, -0.94) were significantly reduced in the intervention group; (3) total cholesterol (TC) (WMD = -0.43, 95% CI: -0.64, -0.23) was significantly reduced in the intervention group, although there were no statistically significant differences for triglycerides (TG) (WMD = -0.34, 95% CI: -0.73, 0.05), low-density lipoprotein cholesterol (LDL-C) (WMD = -0.20, 95% CI: -0.46, 0.07), or high-density lipoprotein cholesterol (HDL-C) (WMD = -0.06, 95% CI: -0.29, 0.17). CONCLUSION: Intervention based on health literacy can effectively improve health literacy levels and reduce glucose metabolism and TC level among people with diabetes mellitus, although it has no significant effect on TG, LDL-C, or HDL-C.

OBJECTIVE: The aim of this study was to determine the effect of empowerment-based interventions on glucose metabolism control and psychosocial self-efficacy in people with type 2 diabetes mellitus (T2DM). METHODS: The Cochrane Library, Embase, PubMed, and Web of Science electronic databases were searched up to 22 February 2021 for randomized controlled trials (RCTs) that evaluated the effectiveness of empowerment-based intervention versus conventional treatment in type 2 diabetes cases. At least two investigators independently screened the literature, extracted data and evaluated the methodological quality. We calculated the pooled effect size using the mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CIs) through RevMan V 5.4.1. RESULTS: Fifteen randomized controlled trials (RCTs) were eligible for inclusion in the present study. A total of 2344 adults (1128 in the intervention groups and 1216 in the control) were covered. Five of these studies involved 671 cases of psychosocial self-efficacy, and 4 studies included 622 cases of diabetes knowledge. The meta-analysis showed that compared to routine care, empowerment-based intervention was associated with reduced glycated hemoglobin levels (SMD -0.20; 95% CI -0.31 to -0.08; Z = 3.40, P < .001, I2 = 42%), increased diabetes empowerment scores (SMD 0.24; 95% CI 0.10-0.37; Z = 3.42, P < .001, I2 = 0%), and increased diabetes knowledge scores (SMD 0.96; 95% CI 0.55-1.36; Z = 4.61, P < .001, I2 = 80%). CONCLUSIONS: Empowerment-based intervention in adults with T2DM results in improvements in glycated hemoglobin, psychosocial self-efficacy and diabetes knowledge.

Objective: To evaluate the cost-effectiveness of olaparib as a maintenance treatment versus routine surveillance (RS) in patients with BRCA mutated (BRCAm) advanced ovarian cancer (OC) following response to first-line platinum-based chemotherapy in Singapore. Methods: A 4-health state partitioned survival model was developed to simulate the lifetime (50 years) incremental cost-effectiveness ratio (ICER) of olaparib versus RS from a healthcare payer perspective. Progression-free survival, time to second disease progression, and overall survival were estimated using SOLO-1 data and extrapolated beyond the trial period using parametric survival models. Any patient who remained progression-free at year 7 was assumed to be no longer at risk of progression. Mortality rates were based on all-cause mortality, adjusted based on BRCA1/2 mutation. Health state utilities and adverse event frequencies were from SOLO-1. Drug costs were from local public healthcare institutions. Healthcare resource usage and costs were from local clinician input and publications. A 3% discount rate was applied to costs and outcomes. Deterministic and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of results. Results: The base-case analysis of olaparib maintenance therapy versus RS resulted in an ICER of Singapore dollar (SGD) 19,822 per quality-adjusted life-year (QALY) gained. The ICER was most sensitive to variations in the discount rate. PSA demonstrated that olaparib had an 87% probability of being cost-effective versus RS at a willingness-to-pay of SGD 60,000 per QALY gained. Conclusion: Olaparib has a high potential of being a cost-effective maintenance treatment versus RS for patients with BRCA1/2m advanced OC after response to first-line chemotherapy in Singapore.

BACKGROUND: Low and middle income countries (LMICs) face severe resource limitations but the highest burden of disease. There is a growing evidence base on effective and cost-effective interventions for these diseases. However, questions remain about the most cost-effective method of delivery for these interventions. We aimed to review the scope, quality, and findings of economic evaluations of service delivery interventions in LMICs. METHODS: We searched PUBMED, MEDLINE, EconLit, and NHS EED for studies published between 1st January 2000 and 30th October 2016 with no language restrictions. We included all economic evaluations that reported incremental costs and benefits or summary measures of the two such as an incremental cost effectiveness ratio. Studies were grouped by both disease area and outcome measure and permutation plots were completed for similar interventions. Quality was judged by the Drummond checklist. RESULTS: Overall, 3818 potentially relevant abstracts were identified of which 101 studies were selected for full text review. Thirty-seven studies were included in the final review. Twenty-three studies reported on interventions we classed as "changing by whom and where care was provided", specifically interventions that entailed task-shifting from doctors to nurses or community health workers or from facilities into the community. Evidence suggests this type of intervention is likely to be cost-effective or cost-saving. Nine studies reported on quality improvement initiatives, which were generally found to be cost-effective. Quality and methods differed widely limiting comparability of the studies and findings. CONCLUSIONS: There is significant heterogeneity in the literature, both methodologically and in quality. This renders further comparisons difficult and limits the utility of the available evidence to decision makers.

Introduction Telehealth intervention has been proposed as an innovative intervention approach to breast cancer patients, but there are still conflicting results in the literature about its effect. Methods PubMed, EMBASE, CENTRAL and China National Knowledge Infrastructure (CNKI) were searched from inception to 3 October 2016 for randomized controlled trials (RCTs) which assessed the effect of telehealth intervention versus usual care in breast cancer patients. No language restrictions were used. Standardized mean difference (SMD) with corresponding 95% confidence interval (95% CI) was pooled when needed. Subgroup and sensitivity analyses were conducted if necessary and feasible. Results Twenty RCTs with a total of 2190 participants were included into this meta-analysis. Compared with usual care, telehealth intervention was associated with higher quality of life (SMD = 0.60, 95% CI 0.18-1.01, p = 0.005) and self-efficacy (SMD = 0.59, 95% CI 0.19-0.98, p = 0.003), with less depression (SMD = -1.29, 95% CI -2.28 to -0.30, p = 0.01), distress (SMD = -0.25, 95% CI -0.40 to -0.10, p = 0.001) and perceived stress (SMD = -0.30, 95% CI, -0.59 to -0.02, p = 0.04). However, anxiety score did not differ significantly between the two groups (SMD = -0.09, 95% CI -0.22 to 0.04, p = 0.17). Discussion Telehealth intervention is superior to usual care in breast cancer patients for improved quality of life, higher self-efficacy and less depression, distress, and perceived stress. However, these results should be recognized cautiously due to between-study heterogeneity, indicating that further well-designed RCTs are warranted.

OBJECTIVE: To describe telehealth interventions delivered by allied health professionals and nurses in rural and remote areas, and to compare the effects of telehealth interventions with standard face-to-face interventions. DATA SOURCES: CINAHL, Embase, PsycINFO and PubMed databases were searched. The content of relevant journals and published articles were also searched. STUDY SELECTION: Studies examining the effectiveness of allied health and nursing telehealth interventions for rural and remote populations were included in descriptive analyses. Studies comparing telehealth intervention with standard face-to-face interventions grouped by type of intervention approach were used to examine between-groups effect sizes. DATA EXTRACTION: Methodological quality of studies was rated using the QualSyst critical appraisal tool and the National Health and Medical Research Council (NHMRC) Evidence Hierarchy levels. DATA SYNTHESIS: After quality ratings, 43 studies were included. A majority of studies had strong methodological quality. The disciplines of psychology and nursing were represented most frequently, as were studies using a cognitive intervention approach. Meta-analysis results slightly favoured telehealth interventions compared with face-to-face interventions, but did not show significant differences. Interventions using a combined physical and cognitive approach appeared to be more effective. CONCLUSION: Telehealth services may be as effective as face-to-face interventions, which is encouraging given the potential benefits of telehealth in rural and remote areas with regards to healthcare access and time and cost savings.

BACKGROUND Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been widely used in the diagnosis of mediastinal lymphadenopathies. Here, we performed a systematic review and meta-analysis to explore the diagnostic value of EBUS-TBNA in mediastinal tuberculous lymphadenopathy (TBLA). MATERIAL AND METHODS PubMed, EMBASE, and Sinoced were systematically searched for articles published in English or Chinese that reported the diagnostic yield of EBUS-TBNA in mediastinal TBLA. The quality of studies was assessed using the QualSyst tool. Using 95% confidence intervals (CI), the diagnostic yields of EBUS-TBNA were calculated for the individual studies, and the results were then pooled using a random-effects model. Heterogeneity and publication bias were also assessed. RESULTS A total of 14 studies, consisting of 684 patients with mediastinal TBLA, were finally included. The pooled diagnostic yield of EBUS-TBNA for mediastinal TBLA was 80% (95% CI: 74-86%). Significant heterogeneity (I2=77.9%) and significant publication bias were detected (Begg's test p=0.05 and Egger's test p=0.02). From subgroup analyses, significant differences in the diagnostic yield of EBUS-TBNA were associated with Asian vs. European (UK) studies, retrospective vs. prospective studies, those employing rapid on-site cytological evaluation vs. not, those employing different anesthetic types, and those employing smear vs. culture. However, microbiological examination and the number of lymph node passes did not have a significant effect on the diagnostic yield of EBUS-TBNA. Fifteen minor complications for EBUS-TBNA were reported. CONCLUSIONS EBUS-TBNA appears to be an efficacious and safe procedure and should be used as an initial diagnostic tool for mediastinal TBLA

BACKGROUND: From the viewpoint of human factors and ergonomics (HFE), errors often occur because of the mismatch between the system, technique and characteristics of the human body. HFE is a scientific discipline concerned with understanding interactions between human behavior, system design and safety. OBJECTIVE: To evaluate the effectiveness of HFE interventions in improving health care workers' outcomes and patient safety and to assess the quality of the available evidence. METHODS: We searched databases, including MEDLINE, EMBASE, BIOSIS Previews and the CBM (Chinese BioMedical Literature Database), for articles published from 1996 to Mar.2015. The quality assessment tool was based on the risk of bias criteria developed by the Cochrane Effective Practice and Organization of Care (EPOC) Group. The interventions of the included studies were categorized into four relevant domains, as defined by the International Ergonomics Association. RESULTS: For this descriptive study, we identified 8, 949 studies based on our initial search. Finally, 28 studies with 3,227 participants were included. Among the 28 included studies, 20 studies were controlled studies, two of which were randomized controlled trials. The other eight studies were before/after surveys, without controls. Most of the studies were of moderate or low quality. Five broad categories of outcomes were identified in this study: 1) medical errors or patient safety, 2) health care workers' quality of working life (e.g. reduced fatigue, discomfort, workload, pain and injury), 3) user performance (e.g., efficiency or accuracy), 4) health care workers' attitudes towards the interventions(e.g., satisfaction and preference), and 5) economic evaluations. CONCLUSION: The results showed that the interventions positively affected the outcomes of health care workers. Few studies considered the financial merits of these interventions. Most of the included studies were of moderate quality. This review highlights the need for scientific and standardized guidelines regarding how HFE should be implemented in health care