Flavonoids for viral acute respiratory tract infections: protocol for a systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: Herbal and 'natural' products are a growing industry in today's society because they reportedly help with numerous diseases and ailments. To date, there are some randomised controlled trials (RCTs) conducted on patients concerning the efficacy of flavonoids against viral acute respiratory tract infection (ARTI) showing inconsistent results. On this basis, we will summarise the available evidence to investigate the efficacy of flavonoids on viral ARTI by conducting a systematic review and meta-analysis. METHODS AND ANALYSIS: This protocol has been registered. The systematic review and meta-analysis will be conducted by Cochrane guidelines and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. RCTs comparing the flavonoids group with the control group for treating virus-induced ARTI will be included. RCTs published with relative outcomes will be searched through 12 databases. Data were searched from inception to 25 March 2022. Relevant literature search, data extraction and quality assessment will be performed by pairs of reviewers independently, and the third researcher will be involved in a discussion for disagreements. Stata V.16.0 software will be used for statistical analysis. Dichotomous data will use the ORs with 95% CIs. Continuous data will use the weighted mean difference with 95% CIs. Heterogeneity will be tested by χ2-based Cochran Q statistic and I2 statistic. Sensitivity analyses and subgroup analyses will be used to observe the heterogeneity between included studies. The funnel plot, Egger's test and Begg's test will be used to judge the publication bias. A p<0.05 will be considered to indicate a statistically significant result. TRAIL REGISTRATION NUMBER: INPLASY202180107.

Flavonoid-containing supplements for preventing acute respiratory tract infections: A systematic review and meta-analysis of 20 randomized controlled trials.

BACKGROUND: This systematic review and meta-analysis was conducted to investigate the efficacy and safety of flavonoid-containing supplements in preventing acute respiratory tract infection (ARTI). METHODS: Randomized controlled trials (RCTs) investigating the effects of flavonoid-containing supplements on ARTI prevention in the aspects of ARTI incidence, mean ARTI sick days, symptoms, bio-immune markers, and adverse effects were searched in 5 databases. Data were searched from inception to November 26, 2021. Stata 16.0 was used to perform the meta-analysis. RESULTS: Twenty RCTs (n = 4521) were included in this systematic review and meta-analysis. Pooled results showed that in the flavonoid-containing supplement group, the ARTI incidence and mean ARTI sick days were significantly decreased compared to those in the control group (RR = 0.81, 95% CI: 0.74-0.89, p < 0.001; WMD = -0.56, 95% CI: -1.04 to -0.08, p = 0.021; respectively). In 8 RCTs, flavonoids were singly used for interventions, ARTI incidence in the experimental group significantly decreased compared to that in the control group (RR = 0.85, 95% CI: 0.72-1.00, p = 0.047). In ten RCTs, flavonoid-containing mixtures were applied for interventions, and ARTI incidence in the experimental group significantly decreased compared to that in the control group (RR = 0.79, 95% CI: 0.71-0.89, p < 0.001). Furthermore, the ARTI incidence and mean ARTI sick days were significantly decreased in the experimental group compared to those in the control group in the flavan-3-ols subgroup (RR = 0.79, 95% CI: 0.67-0.92, p = 0.002; WMD = -2.75, 95% CI: -4.30 to -1.21, p < 0.001; respectively) and the multiple subclasses subgroup (RR = 0.75, 95% CI: 0.63-0.88, p = 0.001; WMD = -0.56, 95% CI: -1.11 to -0.01, p = 0.046; respectively). However, the bio-immune markers including interleukin-6, hypersensitive-c-reactive-protein, tumor necrosis factor-α, and interferon-γ did not differ between the flavonoid group and the control group. Moreover, in the flavonoid-containing supplement group, the incidence of adverse reactions did not increase compared to that in the control group (RR = 1.16, 95% CI: 0.78-1.73, p = 0.469). CONCLUSIONS: This systematic review and meta-analysis showed that flavonoid-containing supplements were efficacious and safe in preventing ARTIs. The most important limitations result from the small number of trials, poor quality of some included RCTs, differences in the composition and types of interventions, principal subclasses of flavonoids, methods of administration, and methodology. Moreover, only a few RCTs conducted independent verification of the flavonoid supplements used in the trial in terms of purity and potency, which may lead to a potential source of bias. Thus, larger and better-designed studies are needed to further verify this conclusion.

Flavonoids for Treating Viral Acute Respiratory Tract Infections: A Systematic Review and Meta-Analysis of 30 Randomized Controlled Trials.

BACKGROUND: This meta-analysis aimed to investigate the efficacy and safety of flavonoids in treating viral acute respiratory tract infections (ARTIs). METHODS: Randomized controlled trials (RCTs) were entered into meta-analyses performed separately for each indication. Efficacy analyses were based on changes in disease-specific symptom scores. Safety was analyzed based on the pooled data from all eligible trials, by comparing the incidence of adverse events between flavonoids and the control. RESULTS: In this study, thirty RCTs (n = 5,166) were included. In common cold, results showed that the flavonoids group decreased total cold intensity score (CIS), the sum of sum of symptom intensity differences (SSID) of CIS, and duration of inability to work vs. the control group. In influenza, the flavonoids group improved the visual analog scores for symptoms. In COVID-19, the flavonoids group decreased the time taken for alleviation of symptoms, time taken for SARS-CoV-2 RT-PCR clearance, the RT-PCR positive subjects at day 7, time to achievement of the normal status of symptoms, patients needed oxygen, patients hospitalized and requiring mechanical ventilation, patients in ICU, days of hospitalization, and mortality vs. the control group. In acute non-streptococcal tonsillopharyngitis, the flavonoids group decreased the tonsillitis severity score (TSS) on day 7. In acute rhinosinusitis, the flavonoids group decreased the sinusitis severity score (SSS) on day 7, days off work, and duration of illness. In acute bronchitis, the flavonoids group decreased the bronchitis severity score (BSS) on day 7, days off work, and duration of illness. In bronchial pneumonia, the flavonoids group decreased the time to symptoms disappearance, the level of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). In upper respiratory tract infections, the flavonoids group decreased total CIS on day 7 and increased the improvement rate of symptoms. Furthermore, the results of the incidence of adverse reactions did not differ between the flavonoids and the control group. CONCLUSION: Results from this systematic review and meta-analysis suggested that flavonoids were efficacious and safe in treating viral ARTIs including the common cold, influenza, COVID-19, acute non-streptococcal tonsillopharyngitis, acute rhinosinusitis, acute bronchitis, bronchial pneumonia, and upper respiratory tract infections. However, uncertainty remains because there were few RCTs per type of ARTI and many of the RCTs were small and of low quality with a substantial risk of bias. Given the limitations, we suggest that the conclusions need to be confirmed on a larger scale with more detailed instructions in future studies.Systematic Review Registration: inplasy.com/inplasy-2021-8-0107/, identifier: INPLASY20218010.

Gender-differential effects on blood glucose levels between acarbose and metformin in Chinese patients with newly diagnosed type 2 diabetes: a sub-analysis of the MARCH trial.

Using the data from the trial of Metformin and AcaRbose in Chinese as the initial Hypoglycemic treatment (MARCH), this study was performed to compare the differential effects of acarbose and metformin on glucose metabolism after stratification by gender. Six hundred and forty patients who had finished the whole 48-week follow-up were included. The reduction of haemoglobin A1c (HbA1c) was comparable between acarbose- and metformin-treated patients among either females or males, and it was also similar between males and females treated with either acarbose or metformin for 24 and 48 weeks. The dropping of fasting plasma glucose (FPG) in acarbose-treated females was significantly less than that in metformin-treated females at both 24 and 48 weeks. Furthermore, the decrease of 2-hour postprandial glucose (2hPPG) in acarbose-treated males was significantly greater than that in metformin-treated males at both 24 and 48 weeks. Multiple linear regression analysis showed that drug selection was an independent factor affecting the decrease of FPG in female patients while it independently influenced 2hPPG in males at week 24 and 48. The reductions of FPG and 2hPPG at week 24 and 48 were also significantly different between metformin-treated females and metformin-treated males although gender was not an independent regulating factor. Our study indicates that there might be gender-differential effects on FPG and 2hPPG reduction when the comparisons are made between acarbose and metformin treatments.

Effectiveness and safety of acupuncture in post-stroke depression (PSD): Protocol for a Bayesian analysis.

BACKGROUND: Post-stroke depression (PSD) is the most common emotional problem after stroke. It can lower the quality of life and increase the recurrence and mortality. Pharmacological agents have been shown to treat PSD. However, the benefits of pharmacotherapy are debatable and the side-effects are significant. More and more clinical trials suggest that acupuncture plays an important role in patients with PSD. The primary purposes of the study are to conduct a Bayesian analysis of randomized trials to determine the effect of acupuncture and investigate the effect of several acupuncture therapies on PSD. METHODS: We will retrieve articles from 5 English databases [PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials, and WHO International Clinical Trials Registry (TCTRP)] and 4 Chinese databases [Chinese National Knowledge Infrastructure (CNKI), Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database (CBM)]. The publication period will be from inception to January 2019. All randomized controlled trials that evaluate the safety and efficacy of acupuncture on PSD will be included. The primary outcomes will be the change in the degree of depression as measured by the Hamilton Depression Scale and Beck Depression Inventory. Two reviewers will separately extract the data and assess the risk of bias by using the Cochrane Collaboration's risk of bias tool. Bayesian analysis will be conducted to pool the effects of several acupunctures. The ranking probabilities for several acupunctures (simple acupuncture, fire needle, warm acupuncture, auriculo-acupuncture, or electroacupuncture) will be estimated by the surface under the cumulative ranking curve. RESULT: This study will provide reliable evidence for acupuncture on PSD. CONCLUSION: The results of this review will introduce a safe and effective treatment and provide reliable evidence to evaluate the effectiveness of several acupuncture therapies on PSD. TRIAL REGISTRATION NUMBER: CRD42019132725.

Efficacy and safety of Shen-Song-Yang-Xin capsule for treating arrhythmia in the elderly patients with coronary heart disease: Protocol for a systematic review and meta-analysis.

BACKGROUND: Coronary heart disease (CHD) is a major cause of mortality worldwide. Shen-Song-Yang-Xin capsule (SSYXC) has received extensive attention as an alternative therapy in improving myocardial ischemia and hypoxia effectively. In addition, there has been no systematic review or meta-analysis of SSYXC in the treatment of the elderly patients with cardiac arrhythmias in coronary heart disease (CHD). Therefore, we carry out a protocol of a proposed study based on the referred Reporting Items for Systematic Reviews and Meta-Analyses guidelines that aims to systematically evaluate the efficacy and safety of SSYXC in the elderly patients with cardiac arrhythmias in CHD. METHODS: Two researchers will search 9 electronic databases (PubMed, Medline, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese VIP Information, Wanfang Database, and Chinese Biomedical Database) to identify all studies that meet the inclusion criteria and were published before October 2018. The literature selection process will be reported in accordance with the PRISMA guidelines. After information extraction and methodological quality evaluation, we will use Stata 12.0 software (STATA Corporation, College Station, TX) to synthesize the data. The primary outcomes will include effective rates of treatment and improvements of electrocardiogram or 24 hours dynamic electrocardiogram result, and secondary outcomes will include improvement of relevant serological indexes, heart function classification and adverse events. RESULTS: The data synthesis results will objectively illustrate the efficacy and safety of SSYXC in the elderly patients with cardiac arrhythmias in CHD. CONCULSION: The findings will provide a reference for the use of SSYXC in the treatment of the elderly patients with cardiac arrhythmias in CHD. REGISTRATION: PROS-PERO CRD42018112570.

Associations between changes in glucagon-like peptide-1 and bodyweight reduction in patients receiving acarbose or metformin treatment.

BACKGROUND: The present post hoc analysis investigated whether changes in endogenous glucagon-like peptide-1 (∆GLP-1) levels are associated with weight loss in newly diagnosed diabetes patients. METHODS: In all, 784 subjects from the Metformin and AcaRbose in Chinese as initial Hypoglycemic treatment (MARCH) study were stratified according to ∆GLP-1. Changes in clinical and physiological parameters were evaluated across ∆GLP-1 subgroups (low, medium, and high) to assess correlations between ∆GLP-1 and weight loss in acarbose- versus metformin-treated groups. RESULTS: After 24 weeks treatment, greater ∆GLP-1 was associated with significantly greater weight loss (-2 vs -1 kg in the medium/high vs low ∆GLP-1 groups, respectively) and reduction in body mass index (BMI; -0.88, -0.83, and -0.69 kg/m2 in the high, medium, and low ∆GLP-1 groups, respectively). In the acarbose-treated group, there was a significant association between ∆GLP-1 and BMI reductions, and greater ∆GLP-1 across the high, medium, and low ∆GLP-1 groups was correlated with greater weight loss (-2.8, -2.1, and -1.9 kg, respectively) and reductions in fasting plasma glucose (-1.57, -1.28, and -1.02 mmol/L, respectively) at Week 24. No significant differences were found across ∆GLP-1 subgroups in metformin-treated patients (P > 0.05). Multivariate linear regression analysis revealed that gender, baseline BMI, and ∆GLP-1 at Week 24 were associated with weight loss. Baseline BMI and ∆GLP-1 in the acarbose-treated group and baseline BMI in the metformin-treated group predicted weight loss at Week 24. CONCLUSION: Changes in GLP-1 levels are associated with weight loss in newly diagnosed Chinese diabetes patients receiving acarbose.

Efficacy of acarbose and metformin in newly diagnosed type 2 diabetes patients stratified by HbA1c levels.

BACKGROUND: The aim of the present study was to investigate whether the therapeutic efficacy of acarbose and metformin is correlated with baseline HbA1c levels in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: Data for 711 subjects were retrieved from the MARCH (Metformin and AcaRbose in Chinese as initial Hypoglycemic treatment) trial database and reviewed retrospectively. Patients were grouped according to baseline HbA1c levels (<7%, 7%-8%, and >8%) and the results for these three groups were compared between acarbose and metformin treatments. RESULTS: Acarbose and metformin treatment significantly improved T2DM-associated parameters (weight, fasting plasma glucose [FPG], postprandial glucose [PPG], glucagon-like peptide-1 [GLP-1], HOMA-IR, and total cholesterol) across all HbA1c levels. Acarbose decreased PPG and HOMA-ß significantly more than metformin, but only in subjects with lower baseline HbA1c (PPG in the <7% and 7%-8%, HOMA-ß in the <7% groups; all P < 0.05). Acarbose decreased triglyceride (TG) levels, and the areas under the curve (AUC) for insulin and glucagon more than metformin at all HbA1c levels (P < 0.05). After 24 weeks treatment, metformin decreased FPG levels significantly more than acarbose for all baseline HbA1c groups (all P < 0.001). With the exception of FPG, PPG, and TG levels, differences between the two treatment groups observed at 24 weeks were not detected at 48 weeks. CONCLUSIONS: Acarbose decreased PPG and TG and spared the AUC for insulin more effectively in patients with low-to-moderate baseline HbA1c levels, whereas metformin induced greater reductions in FPG. These results may help guide selection of initial therapy based on baseline HbA1c.

Factors that influence the efficacy of acarbose and metformin as initial therapy in Chinese patients with newly diagnosed type 2 diabetes: a subanalysis of the MARCH trial.

OBJECTIVE: To conduct a subanalysis of the randomized MARCH (Metformin and AcaRbose in Chinese as the initial Hypoglycemic treatment) trial to investigate whether specific characteristics are associated with the efficacy of either acarbose or metformin as initial therapy. RESEARCH DESIGN AND METHODS: A total of 657 type 2 diabetes patients who were randomly assigned to 48 weeks of therapy with either acarbose or metformin in the MARCH trial were divided into two groups based upon their hemoglobin A1c (HbA1c) levels at the end of follow-up: HbA1c <7% (<53 mmol/mol) and ≥7% (≥53 mmol/mol). Univariate, multivariate, and stepwise linear regression analyses were applied to identify the factors associated with treatment efficacy. MAIN OUTCOME MEASURES: Because this was a subanalysis, no measurement was performed. RESULTS: Univariate analysis showed that the efficacy of acarbose and metformin was influenced by HbA1c, fasting blood glucose (FBG), and 2 hour postprandial venous blood glucose (2hPPG) levels, as well as by changes in body mass index (BMI) (p ≤ 0.006). Multivariate analysis and stepwise linear regression analyses indicated that lower baseline 2hPPG values and greater changes in BMI were factors that positively influenced efficacy in both treatment groups (p ≤ 0.05). Stepwise regression model analysis also revealed that a lower baseline homeostasis model assessment-estimated insulin resistance (HOMA-IR) and higher serum insulin area under the curve (AUC) were factors positively influencing HbA1c normalization in all patients (p ≤ 0.032). CONCLUSIONS: Newly diagnosed type 2 diabetes patients with lower baseline 2hPPG and HOMA-IR values are more likely to achieve glucose control with acarbose or metformin treatment. Furthermore, the change in BMI after acarbose or metformin treatment is also a factor influencing HbA1c normalization. A prospective study with a larger sample size is necessary to confirm our results as well as measure ß cell function and examine the influence of the patients' dietary habits.

Acarbose compared with metformin as initial therapy in patients with newly diagnosed type 2 diabetes: an open-label, non-inferiority randomised trial.

BACKGROUND: Metformin is the only first-line oral hypoglycaemic drug for type 2 diabetes recommended by international guidelines with proven efficacy, safety, and cost-effectiveness. However, little information exists about its use in Asian populations. We aimed to ascertain the effectiveness of the α-glucosidase inhibitor acarbose, extensively adopted in China, compared with metformin as the alternative initial therapy for newly diagnosed type 2 diabetes. METHODS: In this 48-week, randomised, open-label, non-inferiority trial, patients who were newly diagnosed with type 2 diabetes, with a mean HbA1c of 7·5%, were enrolled from 11 sites in China. After a 4-week lifestyle modification run-in, patients were assigned to 24 weeks of monotherapy with metformin or acarbose as the initial treatment, followed by a 24-week therapy phase during which add-on therapy was used if prespecified glucose targets were not achieved. Primary endpoints were to establish whether acarbose was non-inferior to metformin in HbA1c reduction at week 24 and week 48 timepoints. The non-inferiority margin was 0·3%, with an expected null difference in the change from baseline to week 48 in HbA1c. Analysis was done on a modified intention-to-treat population. This study was registered with Chinese Clinical Trial Registry, number ChiCTR-TRC-08000231. FINDINGS: Of the 788 patients randomly assigned to treatment groups, 784 patients started the intended study drug. HbA1c reduction at week 24 was -1·17% in the acarbose group and -1·19% in the metformin group. At week 48, the HbA1c reduction was -1·11% (acarbose) and -1·12% (metformin) with difference 0·01% (95% CI -0·12 to 0·14, p=0·8999). Six (2%) patients in the acarbose group and seven (2%) patients in the metformin group had serious adverse events, and two (1%) and four (1%) had hypoglycaemic episodes. INTERPRETATION: This study provides evidence that acarbose is similar to metformin in efficacy, and is therefore a viable choice for initial therapy in Chinese patients newly diagnosed with type 2 diabetes. FUNDING: Bayer Healthcare (China) and Double Crane Phama.

[Efficacy of tianmaixiaoke tablets in the treatment of newly diagnosed type 2 diabetes mellitus in China].

OBJECTIVE: To explore the efficacy and influencing factors of chromium picolinate (tianmaixiaoke tablet) in the treatment of newly diagnosed type 2 diabetes mellitus in China. METHODS: A total of 84 outpatients with newly diagnosed type 2 diabetes mellitus visiting 4 hospitals in Beijing were randomly divided into two equal groups: study group receiving tianmaixiaoke tablet 240 mg bid for 24 weeks (n = 42) and control group sitagliptin 100 mg qd for 24 weeks (n = 42). The levels of fasting plasma glucose (FPG), plasma glucose 2 h after meal (PG2 h) and glycated hemoglobin (HbA1c) were detected before and 24 weeks after treatment. The serum levels of chromium and insulin were detected. RESULTS: Study was completed in 76 patients. The serum level of chromium was significantly lower in the diabetes group than in the normal group at baseline ((56 ± 28) µg/L vs (112 ± 21) µg/L, P = 0.00). At 24 weeks after treatment, the levels of HbA1c, FPG and PG2 h decreased while the serum level of chromium increased significantly in both groups. There were 11 patients with changed HbA1c from baseline (ΔHbA1c) ≥ 1% in the study group. At 24 weeks after treatment, HbA1c decreased by 1.61% (from 8.38% ± 0.72% to 6.77% ± 0.62%) and serum level of chromium increased by 35.14 µg/L in the ΔHbA1c ≥ 1% group with a low baseline serum level of chromium ((36.2 ± 18.0) µg/L). Both study group and control group were divided into three subgroups according to baseline serum level of chromium. ΔHbA1c reduced with the increase in baseline serum level of chromium in study group, while in control group, ΔHbA1c was unrelated with baseline serum level of chromium. At 24 weeks after treatment, insulin resistance index (HOMA-IR) reduced, ß cell function index (HOMA-ß) and insulinogenic index (IGI) increased in both groups. Multiple linear regression showed that the variables significantly associated with ΔHbA1c were baseline HbA1c and the baseline serum level of chromium. CONCLUSIONS: Chromium is commonly deficient in the newly diagnosed type 2 diabetics in China. HbA1c decreases and serum chromium increases significantly after chromium supplementation in the patients with a low baseline serum level of chromium.

[Clinical application of acupuncture for treatment of heroin withdrawal syndrome].

OBJECTIVE: To make technical standard of acupuncture manipulation for acupuncture treatment of heroin withdrawal syndrome. METHODS: Two hundred and twenty cases of heroin withdrawal syndrome were randomly divided into an acupuncture group of 111 cases and a control group of 109 cases. They were respectively treated with acupuncture and oral administration of lofexidine hydrochloride, and their therapeutic effects were observed. RESULTS: The heroin dependence (acute stage) were effectively withdrawn in the two groups. The treatment group in change of total scores for withdrawal symptoms before and after treatment, the total scores for withdrawal symptoms at the 4th and 5th days, treatment of insomnia and the score for self-Hamilton Anxiety Scale and the score after at the 4th day was superior to the control group (P < 0.05, P < 0.01, P < 0.001). CONCLUSION: Acupuncture has a satisfactory, rapid, safe and reliable clinical therapeutic effect.