Which interventions for alcohol use should be included in a universal healthcare benefit package? An umbrella review of targeted interventions to address harmful drinking and dependence.

BACKGROUND: This study aimed to identify targeted interventions for the prevention and treatment of harmful alcohol use. Umbrella review methodology was used to summarise the effectiveness across a broad range of interventions, in order to identify which interventions should be considered for inclusion within universal health coverage schemes in low- and middle-income countries. METHODS AND FINDINGS: We included systematic reviews with meta-analysis of randomised controlled trials (RCTs) on targeted interventions addressing alcohol use in harmful drinkers or individuals with alcohol use disorder. We only included outcomes related to alcohol consumption, heavy drinking, binge drinking, abstinence, or alcohol-attributable accident, injury, morbidity or mortality. PubMed, Embase, PsycINFO, Cochrane Database of Systematic Reviews, and the International HTA Database were searched from inception to 3 September 2021. Risk of bias of reviews was assessed using the AMSTAR2 tool. After reviewing the abstracts of 9,167 articles, results were summarised narratively and certainty in the body of evidence for each intervention was assessed using GRADE. In total, 86 studies met the inclusion criteria, of which the majority reported outcomes for brief intervention (30 studies) or pharmacological interventions (29 studies). Overall, methodological quality of included studies was low. CONCLUSIONS: For harmful drinking, brief interventions, cognitive behavioural therapy, and motivational interviewing showed a small effect, whereas mentoring in adolescents and children may have a significant long-term effect. For alcohol use disorder, social network approaches and acamprosate showed evidence of a significant and durable effect. More evidence is required on the effectiveness of gamma-hydroxybutyric acid (GHB), nalmefene, and quetiapine, as well as optimal combinations of pharmacological and psychosocial interventions. As an umbrella review, we were unable to identify the extent to which variation between studies stemmed from differences in intervention delivery or variation between country contexts. Further research is required on applicability of findings across settings and best practice for implementation. Funded by the Thai Health Promotion Foundation, grant number 61-00-1812.

Comparative efficacy and safety of pharmacologic interventions to prevent mother-to-child transmission of hepatitis B virus: a systematic review and network meta-analysis.

OBJECTIVE: This study investigated the efficacy and safety of pharmacologic interventions to prevent vertical transmission of the hepatitis B virus. DATA SOURCES: Medline, Cochrane, and Scopus databases were searched up to October 28, 2020. STUDY ELIGIBILITY CRITERIA: All randomized controlled trials reporting vertical hepatitis B virus transmission with pharmacologic intervention were included. METHODS: Risk of bias was assessed using the Cochrane Risk-of-Bias tool, version 2. Treatment efficacy was estimated using stratified network meta-analysis on the basis of maternal hepatitis B envelope antigen status. RESULTS: Nineteen studies were included for mothers positive for hepatitis B surface and envelope antigens. Pooling indicated that a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants significantly reduced transmission risk compared with vaccination alone, with a risk ratio of 0.52 (95% confidence interval; 0.30-0.91). Only the addition of maternal tenofovir disoproxil fumarate, but not telbivudine, lamivudine, or maternal hepatitis B immunoglobulin further reduced transmission risk compared with a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants, with a pooled risk ratio of 0.10 (0.03-0.35). Twelve studies conducted in mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelope antigen status provided limited evidence to suggest that maternal hepatitis B immunoglobulin combined with hepatitis B vaccination and immunoglobulin in infants was the likely best treatment, but this failed to reach statistical significance compared with a combination of hepatitis B vaccination and immunoglobulin in infants. Similarly, infant hepatitis B immunoglobulin, added to vaccination, likely provides additional benefit but failed to reach statistical significance. CONCLUSION: A combination of hepatitis B vaccination and immunoglobulin in infants is the cornerstone for prevention of vertical transmission for mothers positive for both hepatitis B surface and envelope antigens. The addition of maternal tenofovir to this infant combination regimen was considered the likely most effective treatment. For infants of mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelop antigen status, no additional agents provided further benefit beyond hepatitis B vaccination alone.

A study of the factors associated with emergency department visits in advanced cancer patients receiving palliative care.

PURPOSE: Several studies demonstrated that cancer patients visited the emergency department (ED) frequently. This indicates unmet needs and poor-quality palliative care. We aimed to investigate the factors that contribute to ED visits among patients with advanced cancer in order to identify strategies for reducing unnecessary ED visits among these patients. METHODS: A retrospective study was conducted between January and December, 2019. Eligible patients were previously enrolled in the comprehensive palliative care program prior to their ED visit. All patients older than 18 were included. Patients were excluded if they had died at the initial consultation, were referred to other programs at the initial consultation, or had an incomplete record. The trial ended when the patients died, were referred to other palliative programs, or the study ended. The time between the initial palliative consultation and study endpoints was categorized into three groups: 16 days, 16-100 days, and > 100 days, based on the literature review. To investigate the factors associated with ED visits, a logistic regression analysis was conducted. The variables with a P value < 0.15 from the univariate logistic regression analysis were included in the multiple logistic regression analysis. RESULTS: Among a total of 227 patients, 93 visited the ED and 134 did not. Mean age was 65.5 years. Most prevalent cancers were colorectal (18.5%), lung (16.3%), and hepatobiliary (11.9%). At the end, 146 patients died, 45 were alive, nine were referred to other programs, and 27 were lost to follow-up. In univariate logistic regression analysis, patients with > 100 days from palliative consultation (OR 0.23; 95%CI 0.08, 0.66; p-value 0.01) were less likely to attend the ED. In contrast, PPS 50-90% (OR 2.02; 95%CI 1.18, 3.47; p-value 0.01) increased the ED visits. In the multiple logistic regression analysis, these two factors remained associated with ED visits:> 100 days from the palliative consultation (OR 0.18; 95%CI 0.06, 0.55; p-value 0.01) and PPS 50-90% (OR 2.62; 95%CI 1.44, 4.79; p-value 0.01). CONCLUSIONS: There was reduced ED utilization among cancer patients with > 100 days of palliative care. Patients having a lower PPS were associated with a lower risk of ED visits.

Diagnostic performance of clinic and home blood pressure measurements compared with ambulatory blood pressure: a systematic review and meta-analysis.

BACKGROUND: Clinic blood pressure measurement (CBPM) is currently the most commonly used form of screening for hypertension, however it might have a problem detecting white coat hypertension (WCHT) and masked hypertension (MHT). Home blood pressure measurement (HBPM) may be an alternative, but its diagnostic performance is inconclusive relative to CBPM. Therefore, this systematic review aimed to estimate the performance of CBPM and HBPM compared with ambulatory blood pressure measurement(ABPM) and to pool prevalence of WCHT and MHT. METHODS: Medline, Scopus, Cochrane Central Register of Controlled Trials and WHO's International Clinical Trials Registry Platform databases were searched up to 23rd January 2020. Studies having diagnostic tests as CBPM or HBPM with reference standard as ABPM, reporting sensitivity and specificity of both tests and/or proportion of WCHT or MHT were eligible. Diagnostic performance of CBPM and HBPM were pooled using bivariate mixed-effect regression model. Random effect model was applied to pool prevalence of WCHT and MHT. RESULTS: Fifty-eight studies were eligible. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of CBPM, when using 24-h ABPM as the reference standard, were 74% (95% CI: 65-82%), 79% (95% CI: 69%, 87%), and 11.11 (95% CI: 6.82, 14.20), respectively. Pooled prevalence of WCHT and MHT were 0.24 (95% CI 0.19, 0.29) and 0.29 (95% CI 0.20, 0.38). Pooled sensitivity, specificity, and DOR of HBPM were 71% (95% CI 61%, 80%), 82% (95% CI 77%, 87%), and 11.60 (95% CI 8.98, 15.13), respectively. CONCLUSIONS: Diagnostic performances of HBPM were slightly higher than CBPM. However, the prevalence of MHT was high in negative CBPM and some persons with normal HBPM had elevated BP from 24-h ABPM. Therefore, ABPM is still necessary for confirming the diagnosis of HT.

Cost Utility of Sodium-Glucose Cotransporter 2 Inhibitors in the Treatment of Metformin Monotherapy Failed Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) and associated ailments are leading economic burdens to society. Sodium glucose cotransporter-2 (SGLT2) inhibitors are recent antidiabetic medications with beneficial clinical efficacy. This meta-analysis was conducted to quantitatively pool the incremental net benefit of SGLT2 inhibitors in T2DM patients who failed metformin monotherapy. METHODS: Relevant economic evaluation studies of T2DM patients were identified from PubMed, Scopus, ProQuest, the Cochrane Library, and the Tufts Cost-Effective Analysis Registry until June 2018. Studies were eligible if they studied T2DM patients who failed metformin monotherapy and assessed the cost-effectiveness/utility between SGLT2 inhibitors and other treatments. Details of the study characteristics, economic model inputs, costs, and outcomes were extracted. Risk of bias was assessed using the biases in economic studies (ECOBIAS) checklist. The incremental net benefit was calculated with monetary units adjusting for purchasing power parity for 2017 US dollars. This was then pooled across studies stratified by the country's level of income using a random-effect model if heterogeneity was present and with a fixed-effect model otherwise. Heterogeneity was assessed using the Q test and I2 statistic. RESULTS: A total of 13 studies with 22 comparisons, mainly from high-income countries, were eligible. Six and 4 studies compared SGLT2 with dipeptidyl peptidase-4 inhibitors (DPP4i) and sulfonylureas, respectively. The pooled incremental net benefits (95% confidence interval) for these corresponding comparisons were $164.95 (-$534.71 to $864.61; I2 = 0%) and $3675.09 ($1656.46-$5693.71; I2 = 85.4%), respectively. These results indicate that SGLT2s were cost-effective in comparison with sulfonylureas but not DPP4i. CONCLUSION: SGLT2s were cost-effective as compared with sulfonylureas but not DPP4i. Most of the evidence was from high-income countries with few comparative drug groups, and the results might not be representative of the actual global scenario. Further studies from middle and lower economies and other comparators are still required.

Efficacy and safety of antiscabietic agents: A systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Many drugs have been used to treat scabies, but it is unclear which of them is the most efficacious. OBJECTIVE: To evaluate the comparative efficacy and safety of antiscabietic agents. METHODS: A systematic review of randomized controlled trials was conducted. Direct and network meta-analyses were applied to 13 antiscabietic agents on 3 outcomes (cure, persistent itching, and adverse events). Their probability of having highest efficacy and safety was estimated and ranked. RESULTS: A network meta-analysis of 52 trials including 9917 patients indicated that permethrin (the reference treatment) had a significantly higher cure rate than sulfur, malathion, lindane, crotamiton, and benzyl benzoate. Combination permethrin plus oral ivermectin had a nonsignificantly higher cure rate than permethrin. Combination permethrin plus oral ivermectin was ranked highest in terms of cure, topical ivermectin in terms of persistent itching, and synergized pyrethrins in terms of adverse events. On the basis of clustered ranking, permethrin, oral ivermectin, and synergized pyrethrins seemed to retain balance between cure and adverse events. LIMITATIONS: There are small numbers of trials and patients in some comparisons and a high risk of bias in some trials. CONCLUSION: There is no 1 treatment that ranked highest in all aspects. Physicians should consider the drug's efficacy and safety profiles, along with ease of administration.

Lack of associations between thyroid function and obstructive sleep apnea severity in adults with prediabetes and diabetes mellitus.

PURPOSE: Hypothyroidism is associated with a high frequency of obstructive sleep apnea (OSA). However, the prevalence of OSA in hypothyroid patients is not different from the general population in many reports. The importance of thyroid function screening in sleep-disordered breathing is still controversial. This study aimed to explore the association between thyroid dysfunction and OSA in the adults with prediabetes or diabetes mellitus type 2, who have very high prevalence of OSA. METHODS: OSA was assessed using an in-home monitoring device, WatchPAT200. OSA severity was measured using apnea-hypopnea index (AHI), oxygen desaturation index (ODI), minimum oxygen saturation (minO2), and time spent under oxygen saturation < 90% (T90). Patients with pre-existing thyroid dysfunction were excluded. RESULTS: Participants included 70 men and 118 women with mean age 52.8 ± 10.9 years and body mass index 28.2 ± 4.9 kg/m2. One hundred forty participants (75%) had OSA, with a median AHI of 10.1 (interquartile range 4.8, 18.3). The percentage of positive thyroid autoantibody (thyroperoxidase and thyroglobulin antibody) was similar among the subjects with and without OSA. There was no correlation between the levels of thyroid function (TSH, FT3, FT4, TSH/FT3, and TSH/FT4 ratio) and the severity indices of OSA (AHI, ODI, minO2, and T90). CONCLUSIONS: These data do not support universal screening for thyroid dysfunction in OSA patients with diabetes or prediabetes.

The relationship between sleep and glucagon-like peptide 1 in patients with abnormal glucose tolerance.

Glucagon-like peptide 1 plays a role in glucose regulation. Sleep disturbances (obstructive sleep apnea, insufficient or poor sleep quality) have been shown to adversely affect glucose metabolism. This study aimed to explore the relationship between sleep and glucagon-like peptide 1 regulation in patients with abnormal glucose tolerance. Seventy-one adults with haemoglobin A1c levels between 5.7% and < 6.5% and no history of diabetes participated. Habitual sleep duration and efficiency were obtained from 7-day actigraphy recordings. Obstructive sleep apnea was assessed using an overnight home monitor. Glucagon-like peptide 1 levels were measured during a 75-g glucose tolerance. The area under the curve of glucagon-like peptide 1 was calculated. The mean age (SD) was 55.1 (8.3) years and median (interquartile range) haemoglobin A1c was 5.97% (5.86, 6.23). There was no relationship between sleep duration or efficiency and fasting or area under the curve glucagon-like peptide 1. Glucagon-like peptide 1 levels did not differ among those sleeping ≤ 5.75, > 5.75-< 6.5 or ≥ 6.5 h per night. Increasing apnea-hypopnea index, an indicator of obstructive sleep apnea severity, correlated with lower area under the curve glucagon-like peptide 1 (B -0.242, P = 0.045), but not with fasting glucagon-like peptide 1 (B -0.213, P = 0.079). After adjusting for sex, haemoglobin A1c and body mass index, increasing apnea-hypopnea index was negatively associated with having area under the curve glucagon-like peptide 1 in the highest quartile (odds ratio 0.581, P = 0.028, 95% CI 0.359, 0.942). This study demonstrated that increasing obstructive sleep apnea severity was associated with lower glucagon-like peptide 1 response to glucose challenge. This could possibly be an additional mechanism by which obstructive sleep apnea affects glucose metabolism. Whether raising glucagon-like peptide 1 levels in patients with abnormal glucose tolerance with more severe obstructive sleep apnea will be beneficial should be explored.

Cartoon versus traditional self-study handouts for medical students: CARTOON randomized controlled trial.

OBJECTIVE: The objective of this study is to compare the effectiveness of a "cartoon-style" handout with a "traditional-style" handout in a self-study assignment for preclinical medical students. METHODS: Third-year medical students (n = 93) at the Faculty of Medicine Ramathibodi Hospital, Mahidol University, took a pre-learning assessment of their knowledge of intercostal chest drainage. They were then randomly allocated to receive either a "cartoon-style" or a "traditional-style" handout on the same topic. After studying these over a 2-week period, students completed a post-learning assessment and estimated their levels of reading completion. RESULTS: Of the 79 participants completing the post-learning test, those in the cartoon-style group achieved a score 13.8% higher than the traditional-style group (p = 0.018). A higher proportion of students in the cartoon-style group reported reading ≥75% of the handout content (70.7% versus 42.1%). In post-hoc analyses, students whose cumulative grade point averages (GPA) from previous academic assessments were in the middle and lower range achieved higher scores with the cartoon-style handout than with the traditional one. In the lower-GPA group, the use of a cartoon-style handout was independently associated with a higher score. CONCLUSIONS: Students given a cartoon-style handout reported reading more of the material and achieved higher post-learning test scores than students given a traditional handout.

The association between different opioid doses and the survival of advanced cancer patients receiving palliative care.

BACKGROUND: Concerns that opioids may hasten death can be a cause of the physicians' reluctance to prescribe opioids, leading to inadequate symptom palliation. Our aim was to find if there was an association between different opioid doses and the survival of the cancer patients that participated in our palliative care program. METHODS: A retrospective study was conducted at Ramathibodi Hospital, Bangkok between January 2013 and December 2015. All of the cancer patients that were referred to palliative care teams by their primary physicians were included in the study. The study data included the patients' demographics, disease status, comorbidities, functional status, type of services, cancer treatments, date of consultation, and the date of the patient's death or last follow-up. The information concerning opioid use was collected by reviewing the medical records and this was converted to an oral morphine equivalent (OME), following a standard ratio. The time-varying covariate in the Cox regression analysis was applied in order to determine the association between different doses of opioids and patient survival. RESULTS: A total of 317 cancer patients were included in the study. The median (IQR) of the OME among our patients was 6.43 mg/day (0.53, 27.36). The univariate Cox regression analysis did not show any association between different opioid doses (OME ≤ 30 mg/day and > 30 mg/day) and the patients' survival (p = 0.52). The PPS levels (p < 0.01), palliative care clinic visits (HR 0.32, 95%CI 0.24-0.43), home visits (HR 0.75, 95%CI 0.57-0.99), chemotherapy (HR 0.32, 95%CI 0.22-0.46), and radiotherapy (HR 0.53, 95%CI 0.36-0.78) were identified as factors that increased the probability of survival. CONCLUSIONS: Our study has demonstrated that different opioid doses in advanced cancer patients are not associated with shortened survival period.

The efficacy of local infiltration analgesia in the early postoperative period after total knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Local infiltration analgesia (LIA) has emerged as an alternative treatment for postoperative pain after total knee arthroplasty (TKA). Its efficacy remains inconclusive with inconsistent results from previous studies and meta-analyses. There is no agreement on which local anaesthetic agent and infiltration technique is most effective and well tolerated. OBJECTIVE: The objective was to compare LIA after primary TKA with placebo or no infiltration in terms of early postoperative pain relief, mobilisation, length of hospital stay (LOS) and complications when used as a primary treatment or as an adjunct to regional anaesthesia. The role of injection sites, postoperative injection or infusion and multimodal drug injection with ketorolac were also explored. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: A literature search was performed using PubMed and SCOPUS up to September 2015. ELIGIBILITY CRITERIA: RCTs comparing LIA with placebo or no infiltration after primary TKA in terms of pain score and opioid consumption at 24 and 48 h, mobilisation, LOS and complications were included. RESULTS: In total 38 RCTs were included. LIA groups had lower pain scores, opioid consumption and postoperative nausea and vomiting, higher range of motion at 24 h and shorter LOS than no injection or placebo. After subgroup analysis, intraoperative peri-articular but not intra-articular injection had lower pain score at 24 h than no injection or placebo with the pooled mean difference of pain score at rest of -0.89 [95% CI (-1.40 to -0.38); I = 92.0%]. Continuing with postoperative injection or infusion reduced 24-h pain score with the pooled mean difference at rest of -1.50 [95% CI (-1.92 to -1.08); I = 60.5%]. There was no additional benefit in terms of pain relief during activity, opioid consumption, range of movement or LOS when LIA was used as an adjunct to regional anaesthesia. Four out of 735 patients receiving LIA reported deep knee infection, three of whom had had postoperative catheter placement. CONCLUSION: LIA is effective for acute pain management after TKA. Intraoperative peri-articular but not intra-articular injection may be helpful in pain control up to 24 h. The use of postoperative intra-articular catheter placement is still inconclusive. The benefit of LIA as an adjunctive treatment to regional anaesthesia was not demonstrated.

EFFECTIVENESS OF DIAPERS AMONG PEOPLE WITH CHRONIC INCONTINENCE IN THAILAND.

OBJECTIVES: The aim of this study was to assess effect of adult diapers on health-related quality of life (HRQOL) and the independent level of performing activities of daily living (ADLs) in people with urinary or fecal incontinence. Psychological consequences of patients' caregivers were also measured. METHODS: This quasi-experimental study was conducted at two rehabilitation centers in Thailand. People aged 15 years or greater with chronic urinary or fecal incontinence were eligible. Study participants received adult diapers for 10 weeks after recruitment. Thai EuroQol Five Dimensions (EQ-5D) and the Barthel Index were measured at baseline and weeks 2, 6, and 10 to evaluate HRQOL and the independent level of performing ADLs, respectively. The Braden Scale was used to assess the risk of having pressure ulcers. Mean differences in the Thai EQ-5D, the Barthel Index, and the Braden Scale, before and after receiving adult diapers, were estimated using a multilevel linear regression model. RESULTS: There were ninety patients and forty-eight caregivers who took part in this study. HRQOL and independent level of performing ADLs had improved significantly by week 10 after receiving adult diapers with mean differences of 0.102 (95% confidence interval [CI], 0.046-0.158) and 4.40 (95% CI, 1.74-7.07), respectively. The risk of having pressure ulcers had significantly decreased by 67 percent (95% CI, 16 percent-78 percent) by week 10 after receiving adult diapers. CONCLUSIONS: The results indicate a significant improvement of HRQOL and the independent level of performing ADLs among incontinent patients after receiving adult diapers. These results were used to inform the development of the health benefits package under the Universal Health Coverage Scheme in Thailand.

Efficacy of additional psychosocial intervention in reducing low birth weight and preterm birth in teenage pregnancy: A systematic review and meta-analysis.

This systematic review aimed to assess the efficacy of psychosocial interventions in reducing risk of low birth weight (LBW) and preterm birth (PTB) in teenage pregnancy. Relevant studies were identified from Medline, Scopus, CINAHL, and CENTRAL databases. Randomized controlled trials investigating effect of psychosocial interventions on risk of LBW and PTB, compared to routine antenatal care (ANC) were eligible. Relative risks (RR) of LBW and PTB were pooled using inverse variance method. Mean differences of birth weight (BW) between intervention and control groups were pooled using unstandardized mean difference (USMD). Five studies were included in the review. Compared with routine ANC, psychosocial interventions significantly reduced risk of LBW by 40% (95%CI: 8%,62%) but not for PTB (pooled RR = 0.67, 95%CI: 0.42,1.05). Mean BW of the intervention group was significantly higher than that of the control group with USMD of 200.63 g (95% CI: 21.02, 380.25). Results of our study suggest that psychosocial interventions significantly reduced risk of LBW in teenage pregnancy.

Evidence-informed frameworks for cost-effective cancer care and prevention in low, middle, and high-income countries.

Evidence-informed frameworks for cost-effective cancer prevention and management are essential for delivering equitable outcomes and tackling the growing burden of cancer in all resource settings. Evidence can help address the demand side pressures (ie, pressures exerted by people who need care) faced by economies with high, middle, and low incomes, particularly in the context of transitioning towards (or sustaining) universal health-care coverage. Strong systems, as opposed to technology-based solutions, can drive the development and implementation of evidence-informed frameworks for prevention and management of cancer in an equitable and affordable way. For this to succeed, different stakeholders-including national governments, global donors, the commercial sector, and service delivery institutions-must work together to address the growing burden of cancer across economies of low, middle, and high income.

Efficacy of migraine prophylaxis treatments for treatment-naïve patients and those with prior treatment failure: a protocol for systematic review and network meta-analysis of randomised controlled trials.

INTRODUCTION: Migraine headache is a significant health problem affecting patients' psychological well-being and quality of life. Several network meta-analyses (NMAs) have compared the efficacy of migraine prophylaxis medications. However, some have focused exclusively on oral medications, while others were limited to injectable medications. Moreover, none of these NMAs conducted a stratified analysis between treatment-naïve patients and those with prior treatment failure. Therefore, this systematic review and NMA will compare the efficacy among all treatments for migraine prophylaxis, stratified by the treatment status of patients (ie, treatment-naïve and previous treatment failure). METHODS AND ANALYSIS: Randomised-controlled trials that included patients with chronic or episodic migraine, assessed the efficacy of oral or injectable treatments for migraine prophylaxis and measured the outcomes as monthly migraine day, monthly headache day, migraine-related disability, health-related quality of life or adverse drug events will be eligible for inclusion in this review. Relevant studies will be searched from Medline, Scopus, the US National Institutes of Health Register, and the World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) databases since inception through 15 August 2023. Risk of bias assessment will be performed using a revised tool for assessing the risk of bias in randomised trials. Two-stage NMA will be applied to compare relative treatment effects among all treatments of migraine prophylaxis. Surface under the cumulative ranking curve will be applied to estimate and rank the probability to be the best treatment. Consistency assumption will be assessed using a design-by-treatment interaction model. Publication bias will be assessed by comparison-adjusted funnel plot. All analyses will be stratified according to patients' status (ie, treatment-naïve and prior treatment failure). ETHICS AND DISSEMINATION: This study is a systematic review protocol collecting data from published literature and does not require approval from an institutional review board. Results from this systematic review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020171843.

Multidimensional sleep health and diabetic retinopathy: Systematic review and meta-analysis.

Diabetic retinopathy (DR) is one of the most prevalent microvascular diabetic complications. Poor sleep health and obstructive sleep apnea (OSA) are risk factors for diabetes and poor glycemic control. Recent studies have suggested associations between poor sleep health/OSA and DR. Furthermore, there have been suggestions of melatonin dysregulation in the context of DR. We conducted a systematic review and meta-analysis exploring the associations between multidimensional sleep health (duration, satisfaction, efficiency, timing/regularity and alertness), OSA and melatonin with DR. Forty-two studies were included. Long, but not short sleep, was significantly associated with DR, OR 1.41 (95%CI 1.21, 1.64). Poor sleep satisfaction was also significantly associated with DR, OR 2.04 (1.41, 2.94). Sleep efficiency and alertness were not associated with DR, while the evidence on timing/regularity was scant. Having OSA was significantly associated with having DR, OR 1.34 (1.07, 1.69). Further, those with DR had significantly lower melatonin/melatonin metabolite levels than those without DR, standardized mean difference -0.94 (-1.44, -0.44). We explored whether treating OSA with continuous positive airway pressure (CPAP) led to improvement in DR (five studies). The results were mixed among studies, but potential benefits were observed in some. This review highlights the association between poor multidimensional sleep health and DR.

The efficacy of gait rehabilitations for the treatment of incomplete spinal cord injury: a systematic review and network meta-analysis.

BACKGROUND: Recent pieces of evidence about the efficacy of gait rehabilitation for incomplete spinal cord injury remain unclear. We aimed to estimate the treatment effect and find the best gait rehabilitation to regain velocity, distance, and Walking Index Spinal Cord Injury (WISCI) among incomplete spinal cord injury patients. METHOD: PubMed and Scopus databases were searched from inception to October 2022. Randomized controlled trials (RCTs) were included in comparison with any of the following: conventional physical therapy, treadmill, functional electrical stimulation and robotic-assisted gait training, and reported at least one outcome. Two reviewers independently selected the studies and extracted the data. Meta-analysis was performed using random-effects or fixed-effect model according to the heterogeneity. Network meta-analysis (NMA) was indirectly compared with all interventions and reported as pooled unstandardized mean difference (USMD) and 95% confidence interval (CI). Surface under the cumulative ranking curve (SUCRA) was calculated to identify the best intervention. RESULTS: We included 17 RCTs (709 participants) with the mean age of 43.9 years. Acute-phase robotic-assisted gait training significantly improved the velocity (USMD 0.1 m/s, 95% CI 0.05, 0.14), distance (USMD 64.75 m, 95% CI 27.24, 102.27), and WISCI (USMD 3.28, 95% CI 0.12, 6.45) compared to conventional physical therapy. In NMA, functional electrical stimulation had the highest probability of being the best intervention for velocity (66.6%, SUCRA 82.1) and distance (39.7%, SUCRA 67.4), followed by treadmill, functional electrical stimulation plus treadmill, robotic-assisted gait training, and conventional physical therapy, respectively. CONCLUSION: Functional electrical stimulation seems to be the best treatment to improve walking velocity and distance for incomplete spinal cord injury patients. However, a large-scale RCT is required to study the adverse events of these interventions. TRIAL REGISTRATION: PROSPERO number CRD42019145797.

Comparison of diagnostic accuracy for diabetes diagnosis: A systematic review and network meta-analysis.

Aim: Fasting Plasma Glucose (FPG) and Hemoglobin A1c (HbA1c) are used as diagnostic tests for diagnosing diabetes mellitus, but it is unclear which test has the best diagnostic accuracy. This systematic review and network meta-analysis aimed to estimate the diagnostic accuracy of HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and the combination of HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl (HbA1c| FPG), compared with Oral Glucose Tolerance Test (OGTT) ≥ 200 mg/dl for diagnosis diabetes. Materials and methods: We performed a comprehensive search in PubMed, Embase, Cochrane Library, and Scopus from inception to September 24th, 2021. Inclusion criteria were any study design comparing HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl with OGTT ≥ 200 mg/dl as the reference test. Data were independently extracted, risk of bias was assessed using QUADAS-2 by two reviewers. Network meta-analysis was done using a bivariate regression model using the Bayesian framework. The relative ranking of all tests was also assessed. Results: Out of 5,026 studies, 73 were included. The sensitivities of HbA1c, FPG, and HbA1c| FPG were 0.51 [95% Credible Interval (CrI): 0.43, 0.58], 0.49 (95% CrI: 0.43, 0.55), and 0.64 (95% CrI: 0.51, 0.75), while the specificities were 0.96 (95% CrI: 0.94, 0.97), 0.98 (95% CrI: 0.97, 0.98), and 0.95 (95% CrI: 0.88, 0.98), respectively. The corresponding positive likelihood ratios (LR) were 13.36 (95% CrI: 8.91, 20.72), 21.94 (95% CrI: 15.04, 31.88), and 11.78 (95% CrI: 5.48, 26.56). HbA1c| FPG is superior based on sensitivity, whereas FPG is ranked best based on specificity and positive LR. Conclusion: Our findings suggest that FPG ≥ 126 mg/dl should be recommended as the best diagnostic test for diabetes. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021282856.

The association between rest-activity parameters and hemoglobin A1c in patients with prediabetes.

Circadian abnormalities can adversely affect glucose metabolism. This study determined whether behavioral circadian parameters, as assessed by rest-activity rhythm, were predictors of glycemic control in patients with prediabetes. Seventy-nine patients with prediabetes participated. Nonparametric rest-activity rhythm parameters, sleep duration and efficiency were obtained from 7-d actigraphy recordings. Sleep-disordered breathing severity was assessed using a home sleep apnea test. Hemoglobin A1c (HbA1c) was obtained to evaluate glycemic control. The results revealed that shorter sleep duration, lower relative amplitude and higher L5 (average activity of the least active 5-h period) were associated with higher HbA1c, while other sleep variables were not related to HbA1c. Multiple stepwise regression analysis adjusting for age, sex, body mass index and sleep duration revealed that lower relative amplitude, but not L5, was independently associated with higher HbA1c (B = -0.027, p = 0.031). In summary, among patients with prediabetes, an abnormal circadian rhythm was associated with higher HbA1c, implying a greater risk of developing diabetes. These results support the role of circadian rhythmicity in glucose control among those with prediabetes.

New anti-diabetic agents for the treatment of non-alcoholic fatty liver disease: a systematic review and network meta-analysis of randomized controlled trials.

Objectives: This network meta-analysis aims to compare the efficacy and safety of new anti-diabetic medications for the treatment of non-alcoholic fatty liver disease (NAFLD). Materials and methods: PubMed and Scopus were searched from inception to 27th March 2022 to identify all randomized controlled trials (RCTs) in NAFLD patients. Outcomes included reductions in intrahepatic steatosis (IHS) and liver enzyme levels. The efficacy and safety of DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, and other therapies were indirectly compared using a NMA approach. Unstandardized mean difference (USMD) with 95% confidence intervals (CI) were calculated. Results: 2,252 patients from 31 RCTs were included. "Add-on" GLP-1 agonists with standard of care (SoC) treatment showed significantly reduced IHS compared to SoC alone [USMD (95%CI) -3.93% (-6.54%, -1.33%)]. Surface under the cumulative ranking curve (SUCRA) identified GLP-1 receptor agonists with the highest probability to reduce IHS (SUCRA 88.5%), followed by DPP-4 inhibitors (SUCRA 69.6%) and pioglitazone (SUCRA 62.2%). "Add-on" GLP-1 receptor agonists were also the most effective treatment for reducing liver enzyme levels; AST [USMD of -5.04 (-8.46, -1.62)], ALT [USMD of -9.84 (-16.84, -2.85)] and GGT [USMD of -15.53 (-22.09, -8.97)] compared to SoC alone. However, GLP-1 agonists were most likely to be associated with an adverse event compared to other interventions. Conclusion: GLP-1 agonists may represent the most promising anti-diabetic treatment to reduce hepatic steatosis and liver enzyme activity in T2DM and NAFLD patients. Nevertheless, longer-term studies are required to determine whether this delays progression of liver cirrhosis in patients with NAFLD and T2DM. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021259336.1.