Safety and efficacy of myofascial release therapy in the treatment of patients with hemophilic ankle arthropathy. Single-blind randomized clinical trial.

BACKGROUND: Hemophilia is characterized by degenerative joint damage. Patients with hemophilic arthropathy present joint damage, reduced range of motion, and decreased strength and functional capacity. Myofascial release therapy aims to decrease pain and improve tissue mobility and functionality. OBJECTIVES: To evaluate the safety and efficacy of myofascial release therapy in patients with hemophilic ankle arthropathy. METHOD: Single-blind randomized controlled trial. Fifty-eight adult patients with hemophilia were randomly allocated to the experimental group (myofascial release therapy with foam roller) or the control group (no intervention whatsoever). The daily home protocol of myofascial release therapy for the lower limbs using a foam roller lasted eight consecutive weeks. The primary variable was the safety of myofascial release therapy (weekly telephone follow-up). The secondary variables were pain intensity (visual analog scale), range of motion (goniometer), functional capacity (2-Minute Walk Test) and muscle strength (dynamometer), at baseline and at 8 and 10 weeks. RESULTS: During the experimental phase, none of the patients in the experimental group developed ankle hemarthrosis. There were statistically significant changes in time*group interaction in ankle dorsal flexion (F[1.75] = 10.72; p < .001), functional capacity (F[1.16] = 5.24; p = .009) and gastrocnemius strength (F[2] = 26.01; p < .001). The effect size of the changes after the intervention was medium-large in pain intensity (d = -1.77), functional capacity (d = 1.34) and gastrocnemius strength (d = 0.76). CONCLUSION: Myofascial release therapy is a safe form of physical therapy for patients with hemophilia. Myofascial release therapy can effectively complement prophylactic pharmacological treatment in patients with hemophilic arthropathy, improving range of motion in dorsal flexion, functional capacity and gastrocnemius strength.

Treatments for painful temporomandibular disc displacement with reduction: a network meta-analysis of randomized clinical trials.

There is currently no consensus on the best treatment for painful temporomandibular disc displacement with reduction (DDwR), and no network meta-analysis of randomized clinical trials (RCTs) comparing all types of treatment for this condition has been conducted. The objective of this study was to compare and rank all treatments for DDwR, including conservative treatments, occlusal splints, low-level laser therapy (LLLT), manual therapy, no treatment (control), arthrocentesis (Arthro) alone, Arthro plus intra-articular injection of platelet-rich plasma (Arthro-PRP) or hyaluronic acid (Arthro-HA), and Arthro plus occlusal splint. Predictor variables were pain intensity and maximum mouth opening (MMO). The mean difference with 95% confidence interval was estimated using Stata software. The GRADE system was used to assess the certainty of the evidence. Twenty RCTs reporting 1107 patients were identified in the literature search; 980 of these patients were included in the network meta-analysis. Direct meta-analysis showed that Arthro-PRP significantly reduced pain intensity compared to Arthro alone, while occlusal splint and manual therapy were superior to conservative treatment (all very low quality evidence). Arthro with intra-articular injection of PRP/HA ranked as the most effective treatment in terms of pain reduction, whereas LLLT ranked the best choice for increasing MMO for patients with DDwR. However, it is important to note that the evidence for the superiority of these treatments is generally of very low quality. Therefore, further high-quality research is needed to confirm these findings and provide more reliable recommendations for the treatment of DDwR.

Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy.

Nearly four years after its first appearance, and having gone from pandemic to endemic, the SARS-CoV-2 remains out of control globally. The purpose of this study was to evaluate the clinical efficacy of vitamin D (VD) in COVID-19 and long COVID-19, explain the discrepancy in clinical outcomes and highlight the potential impact of metformin on VD efficacy in recent articles. Articles from January 2022 to August 2023 were selected for this review. The objective of this study was achieved by reviewing, analyzing, and discussing articles demonstrating (1) the mechanism of action of VD (2) observational or randomized clinical trials (RCTs) that support or not the beneficial clinical effects of VD in COVID-19 or long COVID. (3) genetic and non-genetic reasons for the variation in the effects of VD. Articles were collected from electronic databases such as PubMed, Scopus, MEDLINE, Google Scholar, Egyptian Knowledge Bank, Science Direct, and Cochrane Database of Systematic Reviews. Twenty three studies conducted in vitro or in animal models indicated that VD may act in COVID-19 through protecting the respiratory system by antimicrobial peptide cathelicidins, reducing lung inflammation, regulating innate and adaptive immune functions and up regulation of autophagy gene activity. Our review identified 58 clinical studies that met the criteria. The number of publications supporting a beneficial clinical activity of VD in treating COVID-19 was 49 (86%), including 12 meta-analyses. Although the total patients included in all articles was 14,071,273, patients included in publications supporting a beneficial role of VD in COVID-19 were 14,029,411 (99.7%). Collectively, extensive observational studies indicated a decisive relationship between low VD levels and the severity of COVID-19 and mortality outcomes. Importantly, evidence from intervention studies has demonstrated the effectiveness of VD supplements in treating COVID-19. Furthermore, the results of 4 observational studies supported the beneficial role of VD in alleviating symptoms of long COVID-19 disease. However, eight RCTs and one meta-analysis of RCTs may contain low-grade evidence against a beneficial role of VD in COVID-19. Twenty-five articles have addressed the association between VDR and DBP genetic polymorphisms and treatment failure of VD in COVID-19. Impaired VDR signaling may underlie the variability of VD effects as non-genetic mechanisms. Interestingly, in recent studies, metformin has a beneficial therapeutic role in COVID-19 and long COVID-19, possibly by improving AMPK signaling of the VDR and enhancing the efficacy of the VD. In conclusion, evidence has been significantly strengthened over the past 18 months, with several meta-analyses and RCTs reporting conclusive beneficial effects of VD supplementation against COVID-19 and highlighting metformin to improve VDR sensitivity and efficacy in treating COVID-19 and long COVID-19.

The remote intercessory prayer, during the clinical evolution of patients with COVID -19, randomized double-blind clinical trial.

The objective of this study was to evaluate the effect of intercessory prayer performed by a group of spiritual leaders on the health outcomes of hospitalized patients with Novel Coronavirus (COVID-19) infection, specifically focusing on mortality and hospitalization rates. DESIGN: This was a double-blinded, controlled, and randomized trial conducted at a private hospital in São Paulo, Brazil. INTERVENTIONS: Both groups continued to receive their usual medical care in accordance with HCor Hospital's institutional patient care protocol for COVID-19 patients. INTERVENTION: Both groups received their regular medical care according to HCor's institutional patient care protocol for COVID-19 patients. The intervention group, in addition to standard treatment, received intercessory prayers performed by a group of spiritual leaders. MAIN OUTCOME MEASURES: The primary endpoint was in-hospital mortality. Secondary endpoints included the need for mechanical ventilation during hospitalization, duration of mechanical ventilation, length of ICU stay, and length of hospital stay. RESULTS: A total of 199 participants were randomly assigned to the groups. The primary outcome, in-hospital mortality, occurred in 8 out of 100 (8.0 %) patients in the intercessory prayer group and 8 out of 99 (8.1 %) patients in the control group (HR 0.86 [0.32 to 2.31]; p = 0.76). Additionally, there were no significant differences between the groups in terms of secondary outcomes. CONCLUSION: The study found no evidence of an effect of intercessory prayer on the primary outcome of mortality or on the secondary outcomes of hospitalization time, ICU time, and mechanical ventilation time.

Comparative effects of nutraceuticals on body weight in adults with overweight or obesity: A systematic review and network meta-analysis of 111 randomized clinical trials.

There is no research on the comparative effects of nutraceuticals on weight loss in adults with overweight or obesity. This study aimed at quantifying and ranking the effects of different nutraceuticals on weight loss. We searched PubMed, Scopus, and Web of Science to November 2022. We included randomized trials evaluating the comparative effects of two or more nutraceuticals, or compared a nutraceutical against a placebo for weight loss in adults with overweight or obesity. We conducted random-effects network meta-analysis with a Frequentist framework to estimate mean difference [MD] and 95% confidence interval [CI] of the effect of nutraceuticals on weight loss. One hundred and eleven RCTs with 6171 participants that investigated the effects of 18 nutraceuticals on body weight were eligible. In the main analysis incorporating all trials, there was high certainty of evidence for supplementation of spirulina (MD: -1.77 kg, 95% CI: -2.77, -0.78) and moderate certainty of evidence that supplementation of curcumin (MD: -0.82 kg, 95% CI: -1.33, -0.30), psyllium (MD: -3.70 kg, 95% CI: -5.18, -2.22), chitosan (MD: -1.70 kg, 95% CI: -2.62, -0.78), and Nigella sativa (MD: -2.09 kg, 95%CI: -2.92, -1.26) could result in a small improvement in body weight. Supplementations with green tea (MD: -1.25 kg, 95%CI: -1.68, -0.82) and glucomannan (MD: -1.36 kg, 95%CI: -2.17, -0.54) demonstrated small weight loss, also the certainty of evidence was rated low. Based on our findings, supplementations with nutraceuticals can result in a small weight loss in adults with overweight or obesity.

Efficacy and safety of acupuncture in post-stroke constipation: a systematic review and meta-analysis.

Background and objective: Post-stroke constipation (PSC) is a common complication of strokes that seriously affects the recovery and quality of life of patients, and effective treatments are needed. Acupuncture is a viable treatment option, but current evidence is insufficient to support its efficacy and safety. This study aims to evaluate the efficacy and safety of acupuncture in the treatment of PSC. Methods: A systematic search of eight databases was conducted to identify PSC-related randomized clinical trials from the inception of each database through May 2023. Methodological quality assessment was conducted by RoB 2.0, meta-analysis was conducted by RevMan 5.3 and Stata 15.1, and evidence quality was evaluated by GRADE. Moreover, reporting quality of acupuncture interventions was assessed using the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Results: Thirty RCTs involving 2,220 patients were identified. We found that acupuncture was superior to conventional treatment (CT) in improving total responder rate [risk ratio (RR): 1.16, 95% confidence interval (CI): 1.09 to 1.25, p < 0.0001], decreasing constipation symptom scores [standardized mean difference (SMD): -0.65, 95% CI: -0.83 to -0.46, p < 0.00001], increasing serum P substance (SP) levels (SMD: 1.92, 95% CI: 0.47 to 3.36, p = 0.009), reducing the time to first bowel movement (BM) (SMD: -1.19, 95% CI: -2.13 to -0.25, p = 0.01), and lowing serum vasoactive intestinal peptide (VIP) levels (SMD: -2.11, 95% CI: -3.83 to -0.38, p = 0.02). Furthermore, acupuncture plus CT was superior regarding total responder rate (RR: 1.26, 95% CI: 1.17 to 1.35, p < 0.00001), serum SP levels (SMD: 2.00, 95% CI: 1.65-2.35, p < 0.00001), time to first BM (SMD: -2.08, 95% CI: -2.44 to -1.71, p < 0.00001), and serum VIP levels (SMD: -1.71, 95% CI: -2.24 to -1.18, p < 0.00001). However, regarding Bristol Stool Scale (BSS) score, acupuncture plus CT was superior to CT (SMD: -2.48, 95% CI: -3.22 to -1.73, p < 0.00001), while there was no statistically significant difference between acupuncture and CT (SMD: 0.28, 95% CI: -0.02 to 0.58, p = 0.07). Acupuncture causes fewer AEs than CT (RR: 0.13, 95% CI: 0.06 to 0.26, p < 0.00001), though there was no statistically significant difference between acupuncture plus CT vs. CT (RR: 1.30, 95% CI: 0.60 to 2.84, p = 0.51). Conclusion: Acupuncture may be an effective and safe therapy for PSC. However, given the inferior quality of clinical data, additional well-designed RCTs are required to confirm these findings.

Effects of berberine and barberry on selected inflammatory biomarkers in adults: A systematic review and dose-response meta-analysis of randomized clinical trials.

The previous meta-analysis showed an advantageous effect of berberine supplementation on interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and serum C-reactive protein (CRP) concentrations; however, it is unknown the dosage that this component influences inflammatory biomarkers. A comprehensive search was done in Scopus, PubMed, and Web of Science until September 2022 to find randomized controlled trials (RCT) that assessed the effects of berberine/barberry on IL-6, TNF-α, and CRP in adults but not trials without a control group. Studies bias was assessed using RoB 2. A random-effects model was performed to calculate the weighted mean difference (WMD). A dose-dependent effect was calculated. Eighteen clinical trials with 1600 participants were included in the current meta-analysis. These interventions significantly mitigate IL-6 levels (-1.18 pg/mL), TNF-α levels (-3.72 pg/mL), and CRP levels (-1.33 mg/L). In addition, the non-linear analysis showed a significant lowering effect of berberine/barberry on IL-6 and TNF-α levels in doses <1000 mg/day and less than 5 weeks of intervention. There are limitations to our findings, including low-quality studies and significant heterogeneity. These interventions might be considered adjunct therapy to managing inflammation status. However, more investigation and high-quality evidence must be conducted to obtain more comprehensive and generalizable results.

Switching Biological Therapies in Severe Asthma.

Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment of severe asthma: anti-IgE (Omalizumab), anti-IL-5/anti-IL-5Rα (Mepolizumab and Benralizumab), and anti-IL-4Rα (Dupilumab). Numerous randomized controlled trials (RCTs) and real-life studies have been conducted to define their efficacy and identify baseline patients' characteristics potentially predictive of favorable outcomes. Switching to another monoclonal antibody is recommended in case of a lack of benefits. The aim of this work is to review the current knowledge on the impact of switching biological therapies in severe asthma as well as on predictors of treatment response or failure. Almost all of the information about switching from a previous monoclonal antibody to another comes from a real-life setting. In the available studies, the most frequent initial biologic was Omalizumab and patients who were switched because of suboptimal control with a previous biologic therapy were more likely to have a higher baseline blood eosinophil count and exacerbation rate despite OCS dependence. The choice of the most suitable treatment may be guided by the patient's clinical history, biomarkers of endotype (mainly blood eosinophils and FeNO), and comorbidities (especially nasal polyposis). Due to overlapping eligibility, larger investigations characterizing the clinical profile of patients benefiting from switching to different monoclonal antibodies are needed.

Effectiveness of "Centaurea behen" root on quality of life in patients with systolic heart failure: A randomized clinical trial.

Introduction: The effect of Centaurea behen (Cb) on patients with systolic heart failure is not known academically. This study was conducted to evaluate the effect of Cb on improving the quality of life (QoL) and echocardiographic and biochemical blood parameters in patients with systolic heart failure. Methods: This study was a parallel double-blind, placebo-controlled randomized trial of 60 patients with systolic heart failure, was conducted from May 2018 up to August 2019. Intervention group received 150 mg twice daily Cb capsules for two months + Guideline directed medical therapy (GDMT), and control group received GDMT + placebo capsules for two months. The main aim of the present study were to assess the QoL based on the 6-minute walk test (6MWT) and the Minnesota living with heart failure questionnaire (MLHFQ). Independent T-test, paired T-test, and ANOVA were used for the analysis. Results: At the beginning of the present study there were no significant differences between study groups in terms of QoL and clinical results. After treatment, the average values of QoL based on MLHFQ and 6MWT instruments were significantly improved 15.5 and 36.18, respectively (P<0.05). Conclusion: Based on the MLHFQ, and 6MWT tests, the consumption of Centaurea behen root extract was associated with significant improvement in the quality of life of patients with systolic heart failure.

Relationship between vitamin D and asthma from gestational to adulthood period: a meta-analysis of randomized clinical trials.

BACKGROUND: Despite numerous studies investigating vitamin D, its impact on asthma is still unknown. The aim of our meta-analysis is to analyze the vitamin D supplementation influence on asthma prevention and treatment ranging from gestational to adulthood period. METHODS: Fifteen randomized clinical trials were included after database search. Studies contained the analyzed endpoints: the number of asthma and wheezing occurrence in gestational and infantile periods, the change of childhood/adult asthma control test score and forced expiratory volume in one second (FEV1) in childhood and adulthood periods. Random effects model was used to calculate effect sizes. RESULTS: Supplementation by women during pregnancy period decreased the wheezing occurrence in their children by 23% (RR = 0.77; 95% CI [0.64; 0.92]; p < 0.0049, I2 = 0%); whereas had no effect on given asthma parameters during the infantile period. Moreover, vitamin D administration had negative effect on the FEV1 change in children (MD = -3.84; 95% CI [-7.68; -0.01]; p = 0.0497; I2 = 95%), but had positive effect on the change of ACT score in adults (MD = 1.80; 95% CI [0.12; 3.49]; p = 0.0359; I2 = 99%). CONCLUSIONS: Our meta-analysis showed the varying results depending on patient's life period. It is important to further investigate the role of vitamin D supplementation in asthma management.

Therapeutic massage/Tuina for treatment of functional dyspepsia: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: A systematic review of randomized controlled trials (RCTs) was conducted to assess the potential effect of therapeutic massage/Tuina on functional dyspepsia (FD) patients. METHOD: Twelve databases and three clinical trial registries were searched until December 2021, for RCTs that compared Tuina combined with or without conventional therapy versus conventional therapy in FD. We assessed the methodological quality of included trials by the Cochrane Risk of Bias tool, and graded the quality of the evidence. The data were presented as risk ratio (RR) or mean difference (MD) respectively with their 95% confidence interval (CI). RESULTS: In total, 14 RCTs with 1128 FD participants were included. Compared with conventional therapy, Tuina showed significant beneficial effects on improving overall symptom (RR = 1.12, 95% CI 1.06 to 1.19, low certainty evidence), and early satiation (MD -0.44 scores, 95% CI -0.72 to -0.16, very low certainty evidence). Compared with conventional therapy, Tuina plus conventional therapy also significantly improved overall symptom (RR = 1.14, 95% CI 1.06-1.23, low certainty evidence), quality of life (MD 10.44 scores, 95% CI 7.65-13.23, low certainty evidence), and epigastric pain (MD -0.76 scores, 95% CI -1.11 to -0.41, low certainty evidence). No adverse events related to Tuina and cost-effectiveness were reported. CONCLUSION: Low certainty evidence showed that Tuina significantly improved overall symptom of FD participants compared with conventional therapy. Low certainty evidence showed that Tuina plus conventional therapy obviously improved overall symptom and quality of life of FD participants compared with conventional therapy.

Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 134000 Individuals in 29 Randomized Clinical Trials and 157000 Individuals in 30 Prospective Cohort Studies: An Updated Systematic Review and Meta-analysis.

BACKGROUND: According to the findings from observational studies and clinical trials assessing the effect of vitamin D supplements on cardiovascular diseases (CVDs), there are still contradictory results. This systematic review aimed to assess the effect of vitamin D supplements on CVDs considering cohort studies and clinical trials. Study Design: A systematic review. METHODS: MEDLINE/PubMed, Science Direct, Embase, and Cochrane Library databases were reviewed by two reviewers independently until 2022. The study effect is risk ratio (RR) and 95% confidence interval (CI) according to Mantel Haenszel's random-effects model. Then, Stata version 14 was used for statistical analysis. RESULTS: In clinical trial studies, the incidence of CVDs among the vitamin D-consuming group was not significantly different from that in the placebo group (RR: 0.99, 95% CI: 0.95-1.03; P=0.77; I 2=0%). CVD mortality was also not significantly different between the two groups (RR: 0.97, 95% CI: 0.90-1.05; P=0.72; I2=0%). In cohort studies, circulating 25 (OH) D increased the risk of CVD incidence by 31% (RR: 1.31, 95% CI: 1.19-1.45) and CVD mortality by 37% (RR: 1.37, 95% CI: 1.17-1.61). CONCLUSION: According to current evidence from clinical trials, vitamin D supplementation should not be recommended for CVD prevention. However, there is a direct association between vitamin D deficiency and the incidence of CVDs as well as its mortality. According to the results of clinical trial studies carrying higher levels of scientific evidence, it can be concluded that vitamin D supplementation does not exert a significant effect on the incidence, mortality, and reduction of CVDs.

Effect of flavonoid intake on circulating levels of adiponectin and leptin: A systematic review and meta-analysis of randomized controlled clinical trials.

This meta-analysis of randomized controlled trials (RCTs) was conducted to explore the effects of flavonoid intake on adiponectin and leptin levels. The PubMed, EMBASE, and Cochrane Library databases were searched on March 1, 2021. Random-effects, subgroup, sensitivity, and meta-regression analyses were conducted on 40 publications. Flavonoid intake significantly increased circulating adiponectin (0.54 µg/ml, 95% CI [0.20, 0.88], p = .002; I2  = 86.4%) and significantly reduced leptin levels (weighted mean difference: -0.79 ng/ml, 95% CI [-1.33, -0.25], p = .004; I2  = 87.7%). Subgroup analysis demonstrated that flavonoid intervention produced a significant elevation in adiponectin levels only in studies that lasted more than 12 weeks, conducted in Asian regions, were parallel-designed, involved obese or overweight participants and participants with type 2 diabetes mellitus (T2DM) or cardiovascular diseases, used tea catechins, and used a dietary supplement intervention. A significantly negative effect on leptin levels was observed in studies conducted in Asian countries, with healthy participants and participants with T2DM, used whole food interventions, and involved participants with lower baseline leptin levels. In conclusion, flavonoid intake significantly increased circulating adiponectin and decreased leptin levels; however, study heterogeneity was very high. Future well-designed trials are required to address heterogeneous study designs and clarify the efficacy of plants in regulating adiponectin and leptin levels.

The Systemic Lupus Erythematosus Interventional Trials in Mainland China: A Continuous Challenge.

Objectives: More than a quarter of single-country systemic lupus erythematosus (SLE) interventional randomized clinical trials (RCTs) were conducted in China. To help develop management guidelines and set benchmarks for future SLE research, a systematic review of current trials is needed. Methods: We searched systematically three databases and four registries to summarize the interventional RCTs in mainland China and identify factors associated with participant loss. The internal validity of trials was assessed using the Cochrane risk-of-bias tool for assessing risk of bias. The odds ratio (OR) was defined as the ratio of the odds of less than 10% loss to follow-up in the presence or absence of different factors. Results: A total of 188 trials met our inclusion criteria, and 15·5% of trials conducted in mainland China ranked low risk of bias. Participant loss was significantly higher among trials that had a defined primary outcome or were registered {primary outcome identification (0·02 [0·00-0·23]) and registration (0·14 [0·03-0·69])}. Trials examining traditional Chinese medicine (TCM) pharmacological treatments had an 8·16-fold (8·16 [1·28-51·98]) higher probability of having low participant loss than trials examining non-TCM pharmacological treatment trials, and trials that did not report masking status had a 15·95-fold (15·95 [2·45-103·88]) higher probability of having low participant loss than open-label trials. In addition, published articles in Chinese also had higher probability of having low participant loss (5·39 [1·10-26·37]). Conclusion: SLE trials conducted in mainland China were of relatively poor quality. This situation, including nonrigorous design, lack of registration, and absence of compliance reporting, needs to be ameliorated. To maintain the fundamental repeatability and comparability of mainland China SLE RCTs, transparency of the clinical trial process and complete reporting of the trial data are crucial and urgently needed.

Chinese herbal medicine for myasthenia gravis: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Myasthenia Gravis (MG) is a disorder of neuromuscular transmission bringing mild ocular weakness to severe generalized muscle weakness and disability. The conventional treatments have long-term side effects, and Chinese herbal medicines (CHM) have shown possible effect and safety for MG patients, but the existing evidence was not robust enough and the results were out of date. METHODS: Searching for randomized controlled trials (RCTs) was conducted in 7 databases and clinical trial registries until July 2021. The ROB 2 tool was used to assess the study quality and GRADE was used to assess the quality of whole evidence. Meta-analyses were conducted and the results were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). RESULTS: Nineteen RCTs (1283 participants) testing 13 kinds of CHM with adequate randomization were included and six RCTs investigating Compound Huangqi were included in the meta-analyses. In addition to conventional treatment, nine CHMs reduced symptom scores of MG. Compound Huangqi plus conventional treatment (pyridostigmine bromide or prednisone or both) reduced the symptom scores compared with conventional treatment (MD = -3.56, 95%CI -4.86 to -2.26). Less adverse events happened in the CHM groups (3/247 in the CHM groups, 52/245 in the control groups, RR = 0.13, 95%CI 0.06 to 0.30, 9 RCTs, a total of 492 participants). The effect on quality of life was inconsistent. CONCLUSION: Nine CHMs could probably bring benefit for MG symptom improvement. Moderate to low certainty of evidence supported Compound Huangqi added-on conventional treatment probably bring extra benefit of improving MG symptoms. Adding CHMs could be safer than giving only conventional treatment. STUDY REGISTRATION: The protocol was registered in PROSPERO (ID: 32718).

Effect of zinc supplementation on mortality in under 5-year children: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Several clinical trials evaluated the effect of zinc supplementation on mortality in children, but the results were inconsistent. We aimed to conduct a systematic review and meta-analysis on the impact of zinc supplementation on mortality in under 5-year children. METHODS: A comprehensive search was conducted using the electronic (PubMed, Scopus, Web of Science) databases, and Google Scholar, up to June 2020. Randomized clinical trials (RCTs) that reported the effect of zinc supplementation on death incidence in under 5-year children were included in the analysis. Screening was performed based on title/abstract and full-text. A random effects model was applied to calculate the summary relative risk (SRR). Risk of Bias 2.0 tool was used to rate the quality of trials. The body of evidence was assessed by the GRADE approach. RESULTS: Combining 30 RRs from 28 RCTs including 237,068 participants revealed that zinc supplementation has significantly reduced the risk of all-causes mortality by 16% in children (SRR: 0.84, 95% CI: 0.74, 0.96). A follow-up duration of less than 1 year after supplementation resulted in 54% reduced risk of mortality (0.46; 0.33, 0.63) with no heterogeneity between investigations. Subgroup analysis by zinc dosage showed that assigning ≥ 10 mg/d zinc to under five children and duration of less than 11 months of intervention decreased the risk of all-cause mortality by 44% (0.56; 0.42, 0.75) and 48% (0.52; 0.38, 0.72), respectively. In low birth weight (LBW) infants, zinc supplementation was reduced all-cause mortality by 52% (0.48; 0.23, 1.00). Zinc supplementation significantly reduced the risk of death from pneumonia (0.70: 0.64, 0.98) and infection (0.54; 0.39, 0.76), also changed the risk of mortality from diarrhea by 15% (0.85; 0.70, 1.03) and sepsis by 57% (0.43; 0.18, 1.02). CONCLUSION: This meta-analysis on RCTs revealed that zinc supplementation in under 5-year children has significantly reduced the risk of all-cause mortality. Notable decreases were found in trials with a dose of 10 mg/d or more zinc supplementation, a maximum of 11 months of supplementation, a follow-up less than one year and especially in LBW infants.

Efficacy of Brain-Computer Interface and the Impact of Its Design Characteristics on Poststroke Upper-limb Rehabilitation: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Background. A number of recent randomized controlled trials reported the efficacy of brain-computer interface (BCI) for upper-limb stroke rehabilitation compared with other therapies. Despite the encouraging results reported, there is a significant variance in the reported outcomes. This paper aims to investigate the effectiveness of different BCI designs on poststroke upper-limb rehabilitation. Methods. The effect sizes of pooled and individual studies were assessed by computing Hedge's g values with a 95% confidence interval. Subgroup analyses were also performed to examine the impact of different BCI designs on the treatment effect. Results. The study included 12 clinical trials involving 298 patients. The analysis showed that the BCI yielded significant superior short-term and long-term efficacy in improving the upper-limb motor function compared to the control therapies (Hedge's g = 0.73 and 0.33, respectively). Based on our subgroup analyses, the BCI studies that used the intention of movement had a higher effect size compared to those used motor imagery (Hedge's g = 1.21 and 0.55, respectively). The BCI studies using band power features had a significantly higher effect size than those using filter bank common spatial patterns features (Hedge's g = 1.25 and - 0.23, respectively). Finally, the studies that used functional electrical stimulation as the BCI feedback had the highest effect size compared to other devices (Hedge's g = 1.2). Conclusion. This meta-analysis confirmed the effectiveness of BCI for upper-limb rehabilitation. Our findings support the use of band power features, the intention of movement, and the functional electrical stimulation in future BCI designs for poststroke upper-limb rehabilitation.

Efficacy of near infrared dental lasers on dentinal hypersensitivity: a meta-analysis of randomized controlled clinical trials.

Conventional therapies have aimed to try to help individuals suffering with dentine hypersensitivity (DH/DHS). A relatively new approach, laser therapy claims to be beneficial while having immediate and long-lasting effect. Therefore, our analysis aims to explore the immediate and 1-month efficacy of near-infrared laser (NIR) therapy in treating dentinal hypersensitivity. A systematic literature search conducted in databases, and analysis was undertaken utilizing a meta-analysis approach. Randomized controlled clinical trials comparing near-infrared lasers and placebo/no treatment in patients (> 18 years) were included. The risk of bias for included studies was assessed using Cochrane RoB tool (for randomized studies). Random effects meta-analyses model of standardized mean differences and 95% confidence intervals were performed using RevMan 5.4 software. A comprehensive electronic and manual search yielded a total of 1081 potential articles. Following the implementation of the inclusion and exclusion criteria, a total of 6 studies were included in the analysis. Near-infrared laser therapy led to statistical significant reduction in immediate and 1-month follow-up VAS (visual analog scale) scores compared to placebo/no treatment (p < 0.05). Statistical heterogeneity across the studies was high (I2-96%). The findings suggest that near-infrared laser therapy does have a significant immediate effect in reducing dentine hypersensitivity compared to placebo/no treatment. Furthermore, this effect is not diminished and endured at 1-month follow-up.

Looking for Crumbs in the Obesity Forest: Anti-obesity Interventions and Obesity-Associated Cardiometabolic Traits in the Mexican Population. History and Systematic Review With Meta-Analyses.

Mexicans and Mexican Americans share culture, genetic background, and predisposition for chronic complications associated with obesity and diabetes making imperative efficacious treatments and prevention. Obesity has been treated for centuries focused-on weight loss while other treatments on associated conditions like gout, diabetes (T2D), and hypertriglyceridemia. To date, there is no systematic review that synthesizes the origin of obesity clinics in Mexico and the efforts to investigate treatments for obesity tested by randomized clinical trials (RCT). We conducted systematic searches in Pubmed, Scopus, and Web of Science to retrieve anti-obesity RCT through 2019 and without an inferior temporal limit. The systematic review included RCT of anti-obesity treatments in the Mexican adult population, covering alternative medicine, pharmacological, nutritional, behavioral, and surgical interventions reporting metabolism-associated traits such as BMI, weight, waist circumference, triglycerides, glucose, among others. Only the studies with at least 3 months of treatment were included in the meta-analyses in order to reduce placebo effects. We found 634 entries, after removal of duplicates and screening the studies based on eligibility criteria, we analyzed 43 national, and 2 multinational-collaborative studies. Most of the national studies had small sample sizes, and the implemented strategies do not have replications in the population. The nutrition/behavioral interventions were difficult to blind, and most studies have medium-to-high risk of bias. Nutritional/behavioral interventions and medications showed effects on BMI, waist circumference, and blood pressure. Simple measures like pure water instead of sweet beverages decrease triglycerides and systolic blood pressure. Dark chocolate showed the highest effect for BMI and high blood pressure, and treatment with insulin increased weight in those with T2D. The study of obesity in Mexico has been on-going for more than four decades, the interest on RCT just increased until this millennium, but with small sample sizes and lack of replication. The interventions affect different cardiometabolic associated traits, which should be analyzed in detail in the population living near the Mexico-U.S. border; therefore, bi-national collaboration is desirable to disentangle the cultural effects on this population's treatment response. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020221436, identifier: CRD42020221436.

Nutraceutical Combinations in Hypercholesterolemia: Evidence from Randomized, Placebo-Controlled Clinical Trials.

There is an increasing number of nutraceutical combinations (NCs) on the market for hypercholesterolemia, although clinical trials to verify their safety and efficacy are scarce. We selected fourteen randomized, placebo-controlled clinical trials (RCTs) on different lipid-lowering NCs in hypercholesterolemic subjects. We described each compound's mechanism of action and efficacy in the mixtures and summarized the clinical trials settings and NCs safety and efficacy results. Almost all NCs resulted efficient against hypercholesterolemia; only one reported no changes. Interestingly, red yeast rice (RYR) was present in eleven mixtures. It is not clear whether the lipid-lowering efficacy of these combinations derives mainly from the RYR component monacolin K "natural statin" single effect. Up to now, few RCTs have verified the efficacy of every single compound vs. NCs to evaluate possible additive or synergistic effects, probably due to the complexity and the high resources request. In conclusion, to manage the arising nutraceutical tide against hypercholesterolemia, it could be helpful to increase the number and robustness of clinical studies to verify the efficacy and safety of the new NCs.