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Achieving the best possible outcomes requires the reliable implementation of best practices for every patient. Specifically, optimizing outcomes requires a spectrum of research spanning basic science, drug development, clinical efficacy and effectiveness, health services, quality improvement, and implementation research. However, our rapid increase in understanding the mechanisms of health and disease and their treatment has far outpaced our ability to reliably provide that care, resulting in poor reliability and enormous variation in care. T3 translational research studies attempt to answer questions surrounding reliable implementation of interventions, decreasing variations in care, and spreading effective therapies. To answer these questions, T3 research may use traditional research methodology such as randomized controlled trials (RCTs); however, various other approaches such as quasiexperimental designs (eg, time-series analysis) are often used. Although uncommon, T3 research has shown promise in not only improving process measures such as correct dosing of medications, but also outcome measures such as improved remission rates in patients with IBD. A more complete integration of T3 translational research into the more traditional research continuum is necessary if we are to achieve the best possible outcomes for our patients., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To confirm the efficacy and safety of Ganyushu Granule (GYSG) in treating premenstrual syndrome (PMS) in patients with Gan (Liver) depression and qi stagnation syndrome (GDQSS) and determine its effective dosage. Methods: From June 2018 to March 2021, a total of 240 PMS women with GDQSS were included and randomly divided into 3 groups in a 1:1:1 ratio using central block randomization: high-dose GYSG group (n=78, GYSG 2 packs/time), low-dose GYSG group (n=82, GYSG and its simulant 1 pack/time), and placebo group (n=80, GYSG simulant 2 packs/time). Treatment with GYSG or placebo was given thrice daily and for up to 3 menstrual cycles. Primary outcomes were PMS diary (PMSD) score and premenstrual tension syndrome self-rating scale (PMTS). Secondary outcomes were Chinese medicine (CM) syndrome efficacy. PMSD, PMTS, and efficacy of CM were evaluated with menstrual cycles during the treatment period. Outcome indicators were analyzed after each menstrual cycle. All analyses were performed using an intention-to-treat method, and clinical safety was assessed. Results: Of the 216 patients included in the effectiveness analysis, 70, 75, and 71 patients were in the high-, low-dose GYSG, and placebo groups, respectively. From the 2nd treatment cycle, the change in PMSD scores in the high- and low-dose groups was lower than that in the placebo group (P<0.05). PMTS scores in the high-dose GYSG group after the 1st treatment cycle was lower than that in the placebo group (P<0.05), while after the 3rd treatment cycle, that in the low-dose group was lower than that in the placebo group (P<0.05). After the 2nd treatment cycle, the high-dose GYSG group had the best CM syndrome efficacy (P<0.05). No serious adverse reactions were reported. Conclusions: GYSG was safe and well-tolerated at both doses for treating PMS patients with GDQSS. High-dose GYSG might be the optimal dose for a phase III trial. (Registration No. ChiCTR1800016595) [ABSTRACT FROM AUTHOR]

Objective: The fragility index (FI), which is the minimum number of changes in status from "event" to "non-event" resulting in a loss of statistical significance, serves as a significant supplementary indicator for clinical physicians in interpreting clinical trial results and aids in understanding the outcomes of randomized controlled trials (RCTs). In this systematic literature survey, we evaluated the FI for RCTs evaluating Chinese herbal medicine (CHM) for irritable bowel syndrome (IBS), and explored potential associations between study characteristics and the robustness of RCTs. Methods: A comprehensive search was conducted in four databases in Chinese and four databases in English from their inception to January 1, 2023. RCTs encompassed 1:1 ratio into two parallel arms and reported at least one binary outcome that demonstrated statistical significance were included. FI was calculated by the iterative reduction of a target outcome event in the treatment group and concomitant subtraction of a non-target event from that group, until positive significance (defined as P < 0.05 by Fisher's exact test) is lost. The lower the FI (minimum 1) of a trial outcome, the more fragile the positive result of the outcome was. Linear regression models were adopted to explore influence factors of the value of FI. Results: A total of 30 trials from 2 4118 potentially relevant citations were finally included. The median FI of total trials included was 1.5 (interquartile range [IQR], 1–5), and half of the trials (n = 15) had a FI equal to 1. In 12 trials (40%), the total number of participants lost to follow-up surpassed the respective FI. The study also identified that increased FI was significantly associated with no TCM syndrome differentiation for inclusion criteria of the patients, larger total sample size, low risk of bias, and larger numbers of events. Conclusions: The majority of CHM IBS RCTs with positive results were found to be fragile. Ensuring adequate sample size, scientifically rigorous study design, proper control of confounding factors, and a quality control calibration for consistency of TCM diagnostic results among clinicians should be addressed to increase the robustness of the RCTs. We recommend reporting the FI as one of the components of sensitivity analysis in future RCTs to facilitate the assessment of the fragility of trials. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system. More than 90,000 Canadians are affected; a cure is yet to be found. Available treatments to manage the disease course are only partially effective. For many years, persons with MS (PwMS) have used cannabis to relax, to reduce pain and spasticity, or to improve sleep and daily functioning, despite the lack of scientific evidence on the efficacy of specific cannabinoids [i.e., tetrahydrocannabinol (THC) and cannabidiol (CBD)] on these MS symptoms. The purpose of this clinical trial is to assess the effectiveness of different doses of these cannabinoids, alone or combined, on spasticity relief, compared to placebo. Moreover, we aim to determine which treatment is best effective to address other key MS conditions. Methods: A double-blinded, randomized, factorial, placebo-controlled trial will be performed. We intend to include up to 250 PwMS aged over 21 recruited from the Centre hospitalier de l’Université de Montréal MS Clinic. PwMS will be randomly assigned on a 1:1:1:1 ratio to one of the trial arms: THC alone, CBD alone, THC/CBD combination, or placebo, using stratified blocked randomization, with random blocks within each stratum. The primary outcome is a self-assessment of spasticity using the mean Numeric Rating Scale score over 7  days. The main outcome will be the difference in this score at 4  weeks compared to baseline. Secondary outcomes include assessments of spasticity as measured by a clinician, pain, fatigue, sleep, bowel, bladder, and sexual dysfunction, restless legs syndrome, mental health, quality of life, mobility, cognitive functioning, and adverse events. Treatment responders are eligible for a 12-week extension phase, using the same treatment allocation and assessments. Discussion: Previous clinical studies examined the efficacy of cannabis-based medicines in PwMS, mostly using products with 1:1 THC/CBD ratio. The major barrier to effectively use cannabis in real-world clinical settings is the lack of evidence on benefits of specific cannabinoids and information on possible related risks. The CANSEP study will contribute to overcome these limitations and identify the risks and benefits of cannabis-based treatments in PwMS. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. Methods: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18–80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). Results: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). Conclusions: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981) [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of Bufei Jiedu (BFJD) ranules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB). Methods: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups (1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months (6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life (QoL) of patients. Adverse reactions were monitored during and after the trial. Results: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as an adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo (58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion (5 months vs. 11 months). The cavity closure rate of the BFJD Granules group (50.6%, 43/85) was higher than that of the placebo group (32.1%, 26/81; P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group (all P<0.01). Overall, the death rates in the two groups were not significantly different; 5.1% (8/156) in the BFJD Granules group and 2.6% (4/156) in the placebo group. Conclusions: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rates, and rapidly improved QoL of patients with MDR-PTB (Registration No. ChiCTR-TRC-12002850) [ABSTRACT FROM AUTHOR]

Background Clinical trials of treatments for serious infections commonly use the primary endpoint of all-cause mortality. However, many trial participants survive their infection and this endpoint may not truly reflect important benefits and risks of therapy. The win ratio uses a hierarchical composite endpoint that can incorporate and prioritize outcome measures by relative clinical importance. Methods The win ratio methodology was applied post hoc to outcomes observed in the MERINO trial, which compared piperacillin-tazobactam with meropenem. We quantified the win ratio with a primary hierarchical composite endpoint, including all-cause mortality, microbiological relapse, and secondary infection. A win ratio of 1 would correspond to no difference between the 2 antibiotics, while a ratio <1 favors meropenem. Further analyses were performed to calculate the win odds and to introduce a continuous outcome variable in order to reduce ties. Results With the hierarchy of all-cause mortality, microbiological relapse, and secondary infection, the win ratio estimate was 0.40 (95% confidence interval [CI],.22–.71]; P =.002), favoring meropenem over piperacillin-tazobactam. However, 73.4% of the pairs were tied due to the small proportion of events. The win odds, a modification of the win ratio accounting for ties, was 0.79 (95% CI,.68–.92). The addition of length of stay to the primary composite greatly minimized the number of ties (4.6%) with a win ratio estimate of 0.77 (95% CI,.60–.99; P =.04). Conclusions The application of the win ratio methodology to the MERINO trial data illustrates its utility and feasibility for use in antimicrobial trials. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). Methods: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. Results: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. Conclusion: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331). [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy and safety of Keluoxin (KLX) capsules and provide validated evidence for the application of KLX in the treatment of diabetic kidney disease (DKD). Methods: A multicenter, randomized, double-blind, placebo-controlled trial design was used to screen 129 patients with DKD (urinary albumin-to-creatinine ratio [UACR]: male, 2.5–30 mg/mmol; female, 3.5–30 mg/mmol) and with Qi and Yin deficiency and blood stasis symptoms. Written informed consent was obtained from all patients. The patients were randomly divided into KLX and control groups. The KLX group was orally administered KLX (6 g/day) and irbesartan tablets (150 mg/day), whereas the control group was administered KLX placebo (6 g/day) and irbesartan tablets (150 mg/day). Patients were observed for 24 weeks to evaluate the natural logarithm of the UACR (log-UACR), the odds ratio (OR) for a sustained increase in the UACR of at least 30% and 40%, estimated glomerular filtration rate (eGFR), changes in symptoms and quality–of-life scores, and adverse events. Results: The changes of the natural log-UACR during the 24 weeks compared with baseline in the KLX group were better than those in the control group (LS mean ± standard error, −0.26 ± 0.10 vs. 0.01 ± 0.09, p = 0.0292). The incidence of a sustained increase in the UACR of at least 30% and 40% was found to be significantly lower in the KLX group (OR, 0.26; 95% confidence interval [CI], 0.09–0.75; OR, 0.29; 95% CI, 0.10–0.82). Changes in symptoms and quality-of-life scores in the KLX group were better than those in the control group. There was no statistically significant difference in eGFR or the incidence of adverse events between the groups. Conclusions: Overall, these results suggest that KLX capsules combined with irbesartan can reduce microalbuminuria, relieve the symptoms, and improve the quality of life for patients with type 2 early DKD compared with the use of irbesartan alone. Trial registration: Chinese Clinical Trial Registry, registration number: ChiCTR2100052764. [ABSTRACT FROM AUTHOR]

Background: Reducing current clinical symptoms and the risks of future exacerbations is the main goal of stable COPD management. Traditional Chinese medicine has unique advantages in chronic disease management. YuPingFeng (YPF), as a classical prescription, has been proven to reduce the risk of exacerbations, but there is a lack of high-quality evidence for the assessment of clinical symptoms and quality of life, particularly for the assessment of treatment response of microecology and immunity. Methods/design: This is a prospective, multicentre, randomized, double-blind, placebo-controlled clinical trial. A total of 316 eligible subjects with moderate to severe COPD will be randomized 1:1 to receive YPF or placebo. Participants will receive either YPF or a placebo at 5 g three times daily for 52 weeks. The primary outcome will be the change in the COPD Assessment Test (CAT) score after 52 weeks of treatment. Secondary outcomes will include changes in the St George's Respiratory Questionnaire (SGRQ) score and clinical symptom score, among others. Outcomes will be measured at each visit. The study will continue for 52 weeks and will include six visits to each subject (at day 0 and weeks 4,12,24,36 and 52). In the event of exacerbations, subjects will be required to go back to the hospital once on the first day of exacerbation or when their condition permits. Discussion: This trial will provide research methods to evaluate the clinical efficacy, safety, and the possible mechanism of YPF in the treatment of stable moderate-to-severe COPD patients. In addition, we hope to provide more possibilities for TCM to participate in the management of stable COPD. Trial registration: The trial was registered at the Chinese Clinical Trials Registry on 3 June 2022 (ChiCTR2200060476; date recorded: 3/6/2022, https://www.chictr.org.cn/). [ABSTRACT FROM AUTHOR]

Aim of the study: To evaluate the clinical efficacy and safety of commonly used oral Chinese patent medicines for the treatment of coronary heart disease combined with hyperlipidemia in clinical practice through a network meta-analysis. Materials and methods: PubMed, Embase, Cochrane Library, Web of Science, Wanfang, VIP, SinoMed, and CNKI databases were searched for all published randomized controlled trials (RCTs) on the treatment of coronary heart disease combined with hyperlipidemia using Chinese patent medicines. NoteExpress software was used to screen the literature obtained from the databases according to the inclusion and exclusion criteria. The Cochrane risk of bias assessment tool was used to evaluate the quality of the included studies. A network meta-analysis was performed using R 4.2.1. Subgroup analyses of outcome indicators were made based on conventional treatment (CT) methods. The incidence of adverse events in the included RCTs was statistically analyzed. A funnel plot was drawn using RevMan 5.4.1 software for the assessment of bias in the total clinical effectiveness rate. Finally, the quality of evidence for interventions with statistically significant differences was evaluated using the GRADE system. Results: A total of 78 RCTs were included, involving 7,955 cases and 8 types of Chinese patent medicines, which were Tongxinluo Capsule, Naoxintong Capsule, Compound Danshen Dripping Pill, Shexiangbaoxin Pill, Songling Xuemaikang Capsule, Xuezhikang Capsule, Yindan Xinnaotong Capsule, and Zhibitai Capsule. A total of 24 RCTs reported the incidence of adverse events, but no statistically significant difference in the incidence of adverse events was found between the experimental and control groups in each study (P > 0.05). There was no obvious publication bias in all studies, but the overall quality of evidence in the included RCTs was low. Comparison of different intervention measures showed that Naoxintong Capsule + CT improved the cardiac index and cardiac output, and lowered the low-density lipoprotein cholesterol and total cholesterol levels. Tongxinluo Capsule + CT raised high-density lipoprotein cholesterol levels and reduced triglyceride levels. Xuezhikang Capsule + CT improved the total clinical effectiveness rate. Subgroup analyses showed that differences in CT did not cause heterogeneity in the results. Conclusion: Compared with the use of CT alone, the combined use of Chinese patent medicines with CT can effectively improve the symptoms in patients with both coronary heart disease and hyperlipidemia. [ABSTRACT FROM AUTHOR]

Background and Aims: There is little RCT evidence that brief interventions improve treatment seeking in individuals with severe alcohol use disorder (AUD) or treatment seeking reduces alcohol use. The aim was to test the efficacy of a brief intervention to increase treatment seeking in treatment naïve adults with severe AUD and measure its effects on alcohol use. Design: Parallel group, non‐pharmacologic RCT with intervention (n = 197) and active control (n = 203) conditions, with blinded assessors conducting follow‐ups at 1, 3 and 6 months. Setting: Online recruitment in a 17‐county region of upstate New York, USA. Participants: Inclusion criteria consisted of ages ≥18 years, Alcohol Use Disorders Identification Test score ≥16, exceeds recommended limits for alcohol use and no history of AUD treatment. n = 400; 50% female; 79% white; mean age, 40.7; mean education, 14.6 years. Intervention and comparator: One‐session telephone‐delivered interventions: Cognitive‐Behavioral Therapy for Treatment Seeking (CBT‐TS; intervention), review of a National Institute on Alcohol Abuse and Alcoholism pamphlet on AUD treatment (control). Measurements Self‐report of any AUD treatment use over 3 months (primary outcome) and two standard measures of alcohol use over 6 months (secondary outcomes). Findings Intent‐to‐treat analyses were used. Assessment follow‐up rates were ≥93%. Any alcohol‐related treatment use over 3‐month follow‐up was obtained by 38 (19%) intervention participants and 36 (18%) control participants, a non‐significant difference, χ2 [1] = 0.16, P = 0.689. Secondary analysis showed a significant interaction term between sex and intervention assignment (β = −1.197, P = 0.027). The interaction suggested CBT‐TS was effective in men (22% vs 13%), although the evidence was somewhat weak (P = 0.071), and it was not effective in women (17% vs 24%). Conclusions: A one‐session cognitive‐behavioral therapy intervention to increase treatment seeking in treatment naïve adults with severe alcohol use disorder did not increase treatment seeking. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the preventive effect and safety of Chinese medicinal application at KI1 (Yongquan) acupoint on intermittent migraine. Methods: A double-blind randomized controlled clinical study was designed. Patients were randomly divided into the treatment group and control group with 29 cases in each group. Patients in the treatment group (n = 29) received the treatment of Chinese medicinal application at KI1 (Yongquan) acupoint for 4 weeks. Patients in the control group (n = 29) received placebo for 4 weeks. Both groups were followed up for 4 weeks after drug withdrawal. The frequency of headache attack, headache duration, severity of headache and Patient-reported Outcome Rating Scale (PRO Scale) score of migraine were compared between the two groups. Safety indicators were adverse events. Results: In addition to the number of analgesics used, the frequency of headache attack, headache duration and severity of headache in the treatment group were lower than those in the control group after treatment, and the differences were statistically significant (P < 0.05). Differences in decrease of the frequency of headache attack and headache duration between the two groups did not persist into the follow-up period (P > 0.05). After treatment and during the follow-up period, the total score of migraine PRO scale in the treatment group was significantly lower than that in the control group, and the difference was statistically significant (P < 0.05). Moreover, scores of the 4 evaluation dimensions all decreased to varying degrees. No adverse reactions were reported during the study period. Conclusion: The Chinese medicinal application at KI1 (Yongquan) acupoint used in this study can prevent migraine. It can reduce the frequency of migraine attack, reduce the total duration of attack and decrease the severity of headache. [ABSTRACT FROM AUTHOR]

Rationale: Inadequate responses to current schizophrenia treatments have accelerated research into novel therapeutic approaches. Objectives: This study investigated the efficacy and tolerability of adjunctive L-theanine, an ingredient with neuroimmunomodulatory and neuroprotective properties, for chronic schizophrenia. Methods: Eighty chronic schizophrenia inpatients were equally assigned to receive risperidone (6 mg/day) plus either L-theanine (400 mg/day) or matched placebo in this 8-week, randomized, parallel-group, double-blind, placebo-controlled trial. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS) by recording the results of subscales at baseline and weeks 4 and 8 to measure treatment efficacy. Additionally, the participants were assessed for the Hamilton Depression Rating Scale (HDRS) and adverse events, including the Extrapyramidal Symptom Rating Scale (ESRS). Results: Sixty patients, 30 in each group, were included in the analyses. All baseline demographic and clinical characteristics were comparable between the groups (p-values > 0.05). The reduction rates from baseline to endpoint in negative, general psychopathology, and total scores of PANSS were greater in the L-theanine group (p-values = 0.03, 0.01, and 0.04, respectively). Regarding general psychopathology scores, the reduction in the L-theanine group was also greater until week 4 (p-value < 0.01). The time × treatment interaction effect was significant on negative (p-value = 0.03), general psychopathology (p-value < 0.01), and total (p-value = 0.04) scores of PANSS, indicating additional improvements in the L-theanine group. The HDRS and side effects were comparable between the groups (p-values > 0.05). Conclusions: L-Theanine adjunct to risperidone safely and tolerably outperformed adjunctive placebo for schizophrenia, and promising evidence indicated its effects on primary negative symptoms, which need to be scrutinized in further studies. Trial registration: The study protocol was registered and published prospectively in the Iranian Registry of Clinical Trials (http://www.irct.ir; registration number: IRCT20090117001556N133) on 2020–12-12. [ABSTRACT FROM AUTHOR]

Background: Alcohol use and its related consequences are a public health problem among young adults. Building upon efficacious personalized normative feedback interventions, dynamic norms can be used to highlight the decreasing prevalence of alcohol use over time among young adults' peers, thereby increasing their motivation to change drinking consistent with the trend. Because limited research has examined dynamic norms feedback interventions for alcohol use, we examined the acceptability and initial efficacy of such an intervention, and potential iatrogenic effects of showing norms feedback about drinking to light drinkers and nondrinkers. Methods: Participants were 546 unvaccinated young adults ages 18–24 who completed a baseline survey, intervention, and 1‐month follow‐up assessment. Participants were block randomized to receive a brief web‐based dynamic norms intervention, with feedback content focused on either (a) alcohol‐related behaviors (intervention) or (b) COVID‐19 vaccine behaviors (the attention‐matched control for the present study). Results: On average, participants who received the alcohol intervention rated it as generally engaging, helpful, and acceptable, with the majority (90.8%) indicating that they would recommend it to a friend. Supporting initial efficacy, in generalized linear models controlling for demographics and baseline alcohol outcomes, at 1‐month follow‐up the alcohol intervention was associated with statistically and clinically significant reductions in all indices of perceived drinking norms, drinking quantity, drinking frequency, and driving after drinking occasions. Lighter drinkers showed no adverse iatrogenic effects. Conclusions: Presenting alcohol‐related personalized normative feedback using dynamic trends is a promising intervention for reducing alcohol use in a community sample of young adults. Further research clarifying the optimal presentation of dynamic norms is needed. [ABSTRACT FROM AUTHOR]

Acute gastroenteritis is one of the most common diseases in children and an important cause of morbidity and mortality worldwide. No specific treatment is available; therefore, management is exclusively symptomatic. Xyloglucan has been approved in Europe as a class IIa medical device for restoration of the physiological functions of the intestinal wall. Our objective was to assess efficacy and safety of xyloglucan for the treatment of acute gastroenteritis in children. We performed a triple‐blind, randomized placebo‐controlled clinical trial in four primary care centers and one continued care hospital center. The study population comprised children with acute gastroenteritis aged >3 months and <5 years. Our primary endpoint was time (in hours) of resolution of diarrhea, defined as the time to resolution of stool consistency (Bristol Stool Form Scale ≤5 or Amsterdam Stool Form Scale B or C) or time until deposition frequency resumes to normality, whichever occurred first. We also recorded intravenous rehydration, hospitalization, stools per day, Vesikari scale, vomiting, relapse, weight loss, drugs prescribed, and adverse events. Eighty children were included in the intention‐to‐treat population (43 xyloglucan and 37 placebo) and 74 (93%) in the per‐protocol population. Time to resolution of diarrhea was similar in both groups with (median, 95% CI) 24, 17–24 h in the xyloglucan group versus 24, 19–24 h in the placebo group, p =.680. Significant differences were observed for patients with moderate‐to‐severe diarrhea (Vesikari scale ≥9): xyloglucan group (20 [15–24] h) versus placebo group (85 [51–120] h) (p =.04). No other significant differences were found. Xyloglucan can be considered safe and other studies should be performed to confirm the usefulness in patients with moderate‐to‐severe diarrhea. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect and safety of Reyanning Mixture (RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. Methods: This is a prospective, open-label, randomized controlled trial. Patients aged 1–17 years and diagnosed with asymptomatic or mild coronavirus disease-2019 (COVID-19) were assigned to an intervention group (RYN plus standard care) and a control group (standard care) according to a randomization list. The primary outcomes were SARS-CoV-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold (Ct) values of ORF1ab or N genes were also tested. Results: A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days (interquartile range (IQR): 5–6) vs. 7 days (IQR: 6–7), P<0.01]. By days 3 and 7, the negative conversion rates were significantly higher in the intervention group (day 3: 32.7% vs. 21.2%, P=0.007; day 7: 75.2% vs. 60.8%, P=0.001). Ct values significantly increase on day 2 [ORF1ab gene: 35.62 (IQR: 29.17–45.00) vs. 34.22 (IQR: 28.41–39.41), P=0.03; N gene: 34.97 (IQR: 28.50–45.00) vs. 33.51 (IQR: 27.70–38.25), P=0.024] and day 3 [ORF1ab gene: 38.00 (IQR: 32.72–45.00) vs. 35.81 (IQR: 29.96–45.00), P=0.003; N gene: 37.16 (IQR: 32.01–45.00) vs. 35.26 (IQR: 29.09–45.00), P=0.01]. No significant difference was found in hospital length of stay between the two groups (P>0.05). Symptoms of cough were significantly improved (82.2% vs. 70.0%, P=0.02) and wheezing was significantly reduced (0.7% vs. 12.9%, P<0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported. Conclusion: Adding RYN to standard care may be a safe and effective treatment for children with asymptomatic and mild SARS-CoV-2 infection. (Registration No. ChiCTR2200060292) [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy and safety of arbidol hydrochloride tablets as a treatment for influenza-like diseases. Methods: In this multicenter, randomized, controlled, open label study, a total of 412 influenza-like cases were collected from 14 hospitals in seven regions of Hebei Province from September 2021 to March 2022. Patients were randomly divided into two groups. The control group (n = 207) were administered oseltamivir phosphate capsules for five days and the experimental group (n = 205) were administered arbidol hydrochloride tablets for five days. The primary endpoint was the time to normal body temperature, and the secondary endpoints included the time to remission of influenza symptoms, incidence of influenza-like complications, and incidence of adverse reactions. Results: Before treatment, there was no significant difference between the two groups in general conditions, blood routine, body temperature, or symptom severity. After treatment, there was no significant difference between the groups in the mean time to fever remission (59.24 h ± 25.21 vs. 61.05 h ± 29.47) or the mean time to remission of influenza symptoms (57.31 h ± 30.19 vs. 62.02 h ± 32.08). Survival analyses using Log-rank and Wilcoxon bilateral tests showed that there was no significant difference in fever relief time or influenza symptom relief time between the two groups. Regarding the incidence of complications and adverse events, there was only one case of tracheitis, one case of nausea, one case of vomiting, and one case of dizziness in the control group. In the experimental group, there was one case of nausea, one case of vomiting, and one case of drowsiness. In addition, one patient in the control group was hospitalized for urinary calculi. Conclusion: There was no significant difference between the patients with influenza-like cases treated with arbidol hydrochloride tablets and those treated with oseltamivir phosphate capsules. Further, the patients treated with arbidol hydrochloride tablets had fewer adverse reactions, and thus, the tablets were safe to use. [ABSTRACT FROM AUTHOR]

Objective: To analyze the efficacy of Biejiajian Pill (BJJP) on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis, and explore its relationship with liver fibrosis. Methods: This was a prospective, randomized double-blind controlled trial. Using the stratified block randomization method, 35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned (1:1) to receive entecavir (0.5 mg/d) combined with BJJP (3 g/time, 3 times a day) or placebo (simulator as control, SC group, simulator 3 g/time, 3 times a day) for 48 weeks. Blood and stool samples were collected from patients at baseline and week 48 of treatment, respectively. Liver and renal functions as well as hematological indices were detected. Fecal samples were analyzed by 16S rDNA V3–V4 high-throughput sequencing, and intestinal microbiota changes in both groups before and after treatment were compared, and their correlations with liver fibrosis were analyzed. Results: Compared with the SC group, there was no significant difference in liver function, renal function and hematology indices in the BJJP group, however, the improvement rate of liver fibrosis was higher in the BJJP group (94.4% vs. 64.7%, P=0.041). Principal coordinate analysis (PCoA) based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment (P<0.01 and P=0.003), respectively. After 48 weeks' treatment, the abundance levels of beneficial bacteria (Bifidobacteria, Lactobacillus, Faecalibacterium and Blautia) increased, whereas the abundance levels of potential pathogenic bacteria, including Escherichia coli, Bacteroides, Ruminococcus, Parabacteroides and Prevotella decreased, among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis (r=0.34, P=0.04; r=0.38, P=0.02), respectively. The microbiota in the SC group did not change significantly throughout the whole process of treatment. Conclusion: BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis (ChiCTR1800016801). [ABSTRACT FROM AUTHOR]

Background: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults. Methods: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 sites in the USA through the Pediatric Emergency Care Applied Research Network (PECARN). Enrollment began in 2021 and will continue for 5 years. Within 12 h of receiving their first dose of intravenous opioids, enrolled participants are randomized 1:1 to receive either (1) a one-time loading dose of L-arginine (200 mg/kg with a maximum of 20 g) administered intravenously followed by a standard dose of 100 mg/kg (maximum 10 g) three times a day or (2) a one-time placebo loading dose of normal saline followed by normal saline three times per day at equivalent volumes and duration as the study drug. Participants, research staff, and investigators are blinded to the participant's randomization. All clinical care is provided in accordance with the institution-specific standard of care for SCD-VOE based on the 2014 National Heart, Lung, and Blood Institute guidelines. The primary outcome is time to SCD-VOE pain crisis resolution, defined as the time (in hours) from study drug delivery to the last dose of parenteral opioid delivery. Secondary outcomes include total parental opioid use and patient-reported outcomes. In addition, the trial will characterize alterations in the arginine metabolome and mitochondrial function in children with SCD-VOE. Discussion: Building on the foundation of established relationships between emergency medicine providers and hematologists in a multicenter research network to ensure adequate participant accrual, the STArT Trial will provide definitive information about the efficacy of intravenous arginine for the treatment of SCD-VOE for children. Trial registration: The STArT Trial was registered in ClinicalTrials.gov on April 9, 2021, and enrollment began on June 21, 2021 (NCT04839354). [ABSTRACT FROM AUTHOR]

Behavioral and psychological symptoms of dementia are a major factor in the burden of care and medical expenses. Conventional pharmacological treatments do not exert a distinct effect on the benefits versus the risks. The herbal medicine woohwangchungsimwon is frequently prescribed for neuropsychiatric disorders. An effect of woohwangchungsimwon on behavioral and psychological symptoms of dementia has been previously reported; however, no clinical studies have been conducted. We aim to evaluate the efficacy and safety of woohwangchungsimwon combined with donepezil for alleviating these symptoms in probable Alzheimer's disease. In this randomized, assessor-blinded, parallel-group clinical trial, 74 participants with probable Alzheimer's disease will be divided via block randomization into a woohwangchungsimwon + donepezil combination group (n = 37) or a donepezil single group (n = 37). Participants will include patients under donepezil treatment for at least a month. We will perform the study for 24 weeks. The Neuro-Psychiatric Inventory subscale scores will be the primary outcome. Secondary outcomes will include cognitive function, dementia severity, physical function, quality of life, depression, anxiety, and insomnia. For safety evaluation, we will assess adverse reactions, measure vital signs, and conduct laboratory tests. This is the first trial aiming to confirm the efficacy and safety of woohwangchungsimwon combined with donepezil for alleviating behavioral and psychological symptoms of dementia. Its findings could provide a basis for their co-administration to control these symptoms in probable Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The therapeutic decision whether or not to systematically supplement vitamin D in all children aged 0 to 5 years is a question that remains difficult to answer. In France, a multicenter epidemiological study shows that rickets is not very prevalent even though compliance with vitamin D intake is not known and can be considered imperfect because it is restrictive. Children under 5 with pigmented skin, immigrants or adopted children, as well as those exclusively breastfed are at risk of deficiency rickets. A better knowledge of the risk factors could make it possible to define a priority target population for supplementation. [ABSTRACT FROM AUTHOR]

Background: There is still a large demand for effective treatments to delay disease deterioration in amyotrophic lateral sclerosis (ALS). Typical symptoms of ALS are considered "flaccidity syndrome" in traditional Chinese medicine (TCM). Huoling Shengji Granule (HLSJ) is a TCM formula used to treat flaccidity syndrome. Results of preclinical tests and a previous clinical study support HLSJ as a novel drug for ALS patients. This trial proposed to examine whether a 48-week course of HLSJ is effective and safe for ALS patients diagnosed with the Chinese medicine syndrome of spleen qi insufficiency and kidney yang deficiency. Methods and analysis: In this phase II, multicenter, randomized, double-blind, riluzole parallel-controlled, superiority-design study, eligible participants had the equal opportunity to be assigned to receive either HLSJ or riluzole randomly. Eleven specialized ALS centers in Mainland China will recruit 144 patients for this trial. The primary and secondary outcomes included the change in the ALSFRS-R score and the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) from baseline to Week 48. Discussion: Here, we endeavored to evaluate TCM for ALS using a standard evidence-based approach for the first time. In addition, the ROADS, a self-report linear-weighted questionnaire, was selected as a secondary outcome measure. We expect to offer a new reference for the outcome evaluation of ALS trials. [ABSTRACT FROM AUTHOR]

Background: Adult nephropathy is mainly caused by idiopathic membranous nephropathy (IMN). In cases of proteinuria, Modified Ponticelli Regimens (MPR) are often successful. However, it can cause adverse side effects. Oral Sanqi Qushi Granule (SQG) with MPR is effective in patients with IMN. However, whether it can improve the remission rate of IMN and shorten the remission time is unknown. In this trial, SQG with MPR on IMN will be evaluated clinically for its efficacy and safety. Methods: We will randomly assign IMN patients who meet the criteria to receives SQG plus cyclical Cyclophosphamide (CTX)/steroids or with placebo plus cyclical CTX/steroids for 6 months. A 12-month follow-up will be conducted on them. Status of remission will be used to assess treatment efficacy. Discussion: This study aims to appraise whether treatment with SQG plus cyclical CTX/steroids is superior to placebo plus cyclical CTX/steroids in the remission rate of patients with adult IMN. Adverse events of SQG plus MPR will be also evaluated for further researches about Chinese Medicine and MPR on whether it can improve the remission rate of IMN in half a year and shorten the remission time and relieve adverse effects will also be clarified. Trial registration: Chinese Clinical Trial Registry ChiCTR2200061953. Registered on 13 July 2022. [ABSTRACT FROM AUTHOR]

Background: The incidence of non-alcoholic fatty liver disease (NAFLD) has been on the rise in recent years, and there are no effective drugs to treat NAFLD; therefore, effective prevention and treatment of NAFLD have become a new challenge. Danggui Shaoyao Powder (DGSY) is a classic prescription commonly used in clinical practice and has been shown to reduce hepatic steatosis in patients with NAFLD. In addition, previous studies have shown that DGSY can alleviate hepatic steatosis and inflammation in NAFLD mice. Although clinical practice and basic studies have shown that DGSY is effective in NAFLD, high levels of clinical evidence are lacking. Therefore, a standardized RCT study protocol is required to evaluate its clinical efficacy and safety. Methods and analysis: This study will be a randomized, double-blind, placebo-controlled, and single-center trial. According to the random number table, NAFLD participants will be randomly divided into the DGSY or placebo group for 24 weeks. The follow-up period will be 6 weeks after drug withdrawal. The primary outcome is the relative change in MRI-proton density fat fraction (MRI-PDFF) from baseline to 24 weeks. Absolute changes in serum alanine aminotransferase (ALT), liver stiffness measurement (LSM), body mass index (BMI), blood lipid, blood glucose, and insulin resistance index will be selected as secondary outcomes to comprehensively evaluate the clinical efficacy of DGSY in the treatment of NAFLD. The safety of DGSY will be evaluated by renal function, routine blood and urine tests, and electrocardiogram. Discussion: This study will provide evidence-based medical corroboration for the clinical application of DGSY and promote the development and application of this classic prescription. Trial registration: http://www.chictr.org.cn. Trial number: ChiCTR2000029144. Registered on 15 Jan 2020. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer survivors often experience decline in physical performance and poor quality of life after surgery and during adjuvant therapies. In these patients, preserving skeletal muscle mass and high-quality nourishment are essential to reduce postoperative complications and improve quality of life and cancer-specific survival. Digital therapeutics have emerged as an encouraging tool for cancer survivors. However, to the best of our knowledge, randomized clinical trials applying personalized mobile application and smart bands as a supportive tool to several colorectal patients remain to be conducted, intervening immediately after the surgical treatment. Methods: This study is a prospective, multi-center, single-blinded, two-armed, randomized controlled trial. The study aims to recruit 324 patients from three hospitals. Patients will be randomly allocated to two groups for one year of rehabilitation, starting immediately after the operation: a digital healthcare system rehabilitation (intervention) group and a conventional education-based rehabilitation (control) group. The primary objective of this protocol is to clarify the effect of digital healthcare system rehabilitation on skeletal muscle mass increment in patients with colorectal cancer. The secondary outcomes would be the improvement in quality of life measured by EORTC QLQ C30 and CR29, enhanced physical fitness level measured by grip strength test, 30-sec chair stand test and 2-min walk test, increased physical activity measured by IPAQ-SF, alleviated pain intensity, decreased severity of the LARS, weight, and fat mass. These measurements will be held on enrollment and at 1, 3, 6 and 12 months thereafter. Discussion: This study will compare the effect of personalized treatment stage-adjusted digital health interventions on immediate postoperative rehabilitation with that of conventional education-based rehabilitation in patients with colorectal cancer. This will be the first randomized clinical trial performing immediate postoperative rehabilitation in a large number of patients with colorectal cancer with a tailored digital health intervention, modified according to the treatment phase and patient condition. The study will add foundations for the application of comprehensive digital healthcare programs focusing on individuality in postoperative rehabilitation of patients with cancer. Trial registration: NCT05046756. Registered on 11 May 2021. [ABSTRACT FROM AUTHOR]

Abstract Background Antiretroviral therapy (ART) adherence is still suboptimal among some key populations, highlighting the need for innovative tailored strategies. This randomized controlled trial (RCT) aimed to evaluate the effect of a differentiated digital intervention on ART adherence among men who have sex with men (MSM) living with HIV in China. Methods The two-armed parallel RCT was conducted at one HIV clinic in Jinan of China from October 19, 2020, to June 31, 2021. Men were referred by health providers to join the study and then choose one of three digital strategies—text message, only instant message, or instant message plus social media. They were assigned in a 1:1 ratio to the intervention arm or control arm using block randomization, and inside each arm, there were three groups depending on the type of delivering the message. The groups were divided according to participants’ preferred digital strategies. The intervention arm received ART medication messages, medication reminders, peer education, and involved in online discussion. The control arm received messages on health behavior and nutrition. The primary outcome was self-reported optimal ART adherence, defined as not missing any doses and not having any delayed doses within a one-month period. Secondary outcomes included CD4 T cell counts, viral suppression, HIV treatment adherence self-efficacy, and quality of life. Intention-to-treat analysis with generalized linear mixed models was used to evaluate the intervention’s effect. Results A total of 576 participants were enrolled, including 288 participants assigned in the intervention arm and 288 assigned in the control arm. Most were ≤ 40 years old (79.9%) and initiated ART ≤ 3 years (60.4%). After intervention, the proportion of participants achieving optimal ART adherence in the intervention arm was higher than in the control arm (82.9% vs 71.1%). The differentiated digital intervention significantly improved ART adherence (RR = 1.74, 95%CI 1.21–2.50). Subgroup analysis showed one-to-one instant message-based intervention significantly improved ART adherence (RR = 2.40, 95% CI 1.39–4.17). Conclusions The differentiated digital intervention improved ART adherence among MSM living with HIV in China, which could be integrated into people living with HIV (PLWH) management and further promoted in areas where PLWH can access text messaging and instant messaging services. Trial registration ChiCTR2000041282. Retrospectively registered on 23 December 2020.

Objectives Digital therapeutics (DTx) are software-based therapeutic interventions based on clinical evidence. Randomized clinical trials (RCTs) are often the source of clinical evidence, similar to conventional drugs or medical devices. However, novel approaches such as the use of real-world data or digital biomarkers are also utilized. This article aimed to review how DTx products have been clinically evaluated. Methods DTx products approved by the US Food and Drug Administration as of 2020 were reviewed and products with sufficient published information were selected. Pivotal clinical trials were analyzed according to the elements of the Consolidated Standards of Reporting Trials (CONSORT) guideline. Case reviews were presented for other clinical evaluation strategies, considering the small number of publications. Results Most approved DTx products used RCTs for clinical evaluations. Similar to conventional RCTs, parallel-group designs with statistical hypothesis testing were adopted. However, DTx trials were often not blinded due to practical issues and involved various comparator groups. In addition, DTx products could be readily evaluated in home-based settings and delivered through the internet. Other evaluation approaches included retrospective analyses using insurance claims data or usage data, which enabled long-term evaluations of effectiveness. Digital biomarkers obtained from real-time and continuous log data were also used to improve the objectiveness of endpoints. Conclusions RCTs accounted for the majority of DTx evaluations. The designs of DTx trials were comparable to those of drug or device trials, but blinding and comparator elements were often different. Furthermore, the use of real-world data and digital biomarkers are also being tried.

Background': India is ranked second in the world in terms of tobacco use and tops the list of eight high-burden countries that account for two-thirds of the new tuberculosis (TB) cases globally. As tobacco smoking among TB patients is associated with unsuccessful TB treatment outcomes, effective smoking cessation interventions for TB patients is essential to combat this double pandemic. Aim: The study determined the effectiveness of nicotine replacement therapy (NRT) on smoking reduction and cessation among pulmonary TB patients. Settings and Design: The study included 300 pulmonary TB patients undergoing antitubercular treatment in government health care centers of Dakshina Kannada district in southern India. Materials and Methods: The participants in this two-armed, single-blinded, placebo-controlled, block-randomized trial were divided equally (n = 150) for experimental arm (brief advice + NRT) and control arm (brief advice + placebo). The total duration of treatment and follow-up was 6 months. Unadjusted relative risk (URR) and adjusted relative risk (ARR) were calculated for treatment outcomes at 95% confidence interval (CI). Generalized linear regression analysis was performed upon variables with P value less than 0.2. Results: After 6 months of intervention including follow up, there was a significant reduction in self-reported smoking (ARR = 1.08, 95% CI 1.01-1.17, P = 0.03) in the experimental arm compared with the control arm. Biochemically verified smoking abstinence was not significantly different between the two arms (ARR = 1.01, 95% CI 0.72-1.38, P = 0.97). Conclusion: The study showed statistically significant effectiveness of NRT for self-reported smoking reduction. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that may lead to bone erosion and disability. Although there are many biological therapies in RA treatment nowadays, such as etanercept and tofacitinib, there are still a considerable number of patients who cannot achieve clinical deep remission, which makes patients feel pain and stiffness of joints. As a traditional Chinese medicine preparation, Wangbi granule showed a synergistic role with methotrexate in the treatment of RA patients with "kidney deficiency and dampness" or "stasis blocking channels". Therefore, it is a promising therapeutic strategy for the clinical deep remission of RA. In this study, Wangbi granule will be used as the test drug. The investigators conduct this study to evaluate the efficacy and safety of Wangbi granule in the treatment of patients who have not achieved deep remission despite the use of methotrexate and tofacitinib. Methods and analysis: Two parallel randomized, triple-blind, placebo-controlled trials will be conducted. In six study centers, 340 eligible RA patients will be recruited and randomly allocated to either the intervention group or the control group (in a 1:1 ratio). They will receive Wangbi granule or Wangbi placebo 12.0 g each time, three times a day for 12 weeks. The primary outcome is the disease activity score derivative for 28 joints (DAS28). Secondary outcomes are patient-reported outcomes, American College of Rheumatology 50% response criteria (ACR50), fatigue scale-14 (FS-14), visual analogue scale for pain (VAS), health assessment questionnaire disability index (HAQ-DI) and biomarkers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Expected outcomes: The success of this study will provide strong evidence to confirm the efficacy and safety of Wangbi granule in the treatment of RA. Trial registration The trial has been registered in the ClinicalTrials Registry (NCT05540938, Date: 09/15/2022, https://clinicaltrials.gov/ct2/show/NCT05540938) [ABSTRACT FROM AUTHOR]

Background: Peripheral atherosclerosis is a common macrovascular complication of diabetes, but the treatment is limited. Chinese herbal medicine is the complementary and alternative therapy to delay the progression of atherosclerosis and reduce blood glucose and lipids. Shen-Qi Xiao-Tan (SQXT) formula is one of the prescriptions commonly used to treat diabetic peripheral atherosclerosis, but there is still a lack of high-quality evidence-based evidence. Methods: This is a randomized, double-blind, placebo-controlled add-on trial that is expected to enroll 114 diabetic patients with peripheral atherosclerosis. After a 2-week run-in period, participants will been randomly assigned in a 1:1 ratio and receive 12 weeks of usual treatment and SQXT formula (treatment group) or usual treatment and placebo (control group). The primary outcome is the change in carotid intima-media thickness from baseline to endpoint. The secondary outcomes are the structure and function of peripheral arteries, blood glucose and lipids, traditional Chinese medicine syndrome score, and quality of life, and safety and endpoint events are evaluated. To explore the therapeutic mechanism through oxidative stress, inflammation, and advanced glycation end products, and lipidomics will be used to screen for biomarkers for diagnosis and efficacy evaluation. Discussion: The objective of this trial is to evaluate the efficacy, safety and therapeutic mechanism of SQXT formula in the treatment of diabetic peripheral atherosclerosis. It will obtain high-quality evidence-based evidence and promote the treatment of diabetic macroangiopathy and the research and development of new drugs. Trial registration: This trial is registered on Chinese Clinical Trials.gov with number ChiCTR2100047189 on 10 Jun 2021, and has been approved by the Ethical Review Committee of Hospital of Chengdu University of Traditional Chinese Medicine with number 2020KL-080. [ABSTRACT FROM AUTHOR]

Background: Balance function provides a physiological link between the physical and cognitive function, and is a potential predictor for cognitive frailty. As a gentle mind–body exercise, Baduanjin can develop flexibility and co-ordination, thus would be is helpful for the improvement of balance function. This trial will evaluate the effect of Baduanjin on balance function in older adults with CF. Methods/design: A total of 72 community-dwelling older adults with CF will be recruited and randomly allocated (1:1) into the Baduanjin exercise group or usual physical activity control group. All participants will undergo a health education program on nutrition and diet-related knowledge for 6 sessions (30 min per session) during the intervention period. Moreover, participants in the Baduanjin exercise group will receive a 24-week Baduanjin training course of 60 min per session and 3 sessions per week, while those in the usual physical activity control group will be required to maintain their original physical activity. Primary and secondary outcomes will be measured at baseline and after the 24-week intervention period. A mixed linear model will be constructed to analyse the intervention effects. Discussion: This protocol presents an objective design of a randomized, single-blind trial that will evaluate the effectiveness and safety of traditional Chinese mind–body exercise Baduanjin training on the balance ability of community-dwelling older adults with cognitive frailty. If the results are as expected, this trial will provide evidence of the effect of Baduanjin exercise on balance in an older community-based population. Trial registration: This trial was registered in the Chinese Clinical Trial Registry with code ChiCTR2100050857 and was approved on 5 September 2021. [ABSTRACT FROM AUTHOR]

Background: Pneumonia, caused by infection or other factors, seriously endangers the health of children. Meropenem is an effective broad-spectrum antibiotic using in the treatment of infectious diseases. In the therapy of pneumonia, meropenem is mostly employed for the treatment of moderate to severe pneumonia. Previously, we established a population pharmacokinetics (PPK) model for meropenem in pediatric severe infection and simulated the control rate of the time during which the free plasma concentration of meropenem exceeds theminimum inhibitory concentration (MIC) is 70% of the dosing interval (70% fT > MIC). Therefore, we plan to conduct a multicenter randomized controlled trial (RCT) to compare the efficacy and safety between conventional regimen and model regimen for meropenem in pediatric severe pneumonia. Methods: One hundred patients (aged 3 months to 15 years)will be recruited in this RCT. They will be assigned randomly (at a 1:1 ratio) to a conventional treatment group (20 mg/kg, q8h, with 0.5-1 h infusion) and a model treatment group (20mg/kg, q8 h, with 4 h infusion). The primary outcome will be 70% fT > MIC. Secondary outcomes will be the prevalence of meropenem therapy failure, duration of antibiotic therapy, changes in levels of inflammatory indicators, changes in imaging examination results, and prevalence of adverse events. Ethical approval of our clinical trial has been granted by the ethics committee of Beijing Children's Hospital ([2022]-E-133-Y). This trial has been registered in the Chinese Clinical Trial Registry (ChiCTR2200061207). Discussion: Based on our previous PPK data, we have designed this RCT. It is hoped that it will promote rational use of antibacterial drugs in children suffering from severe pneumonia. [ABSTRACT FROM AUTHOR]

Objective: A recent academic-government partnership demonstrated the feasibility of utilizing Emergency Departments (ED) as a primary site for subject enrollment in clinical trials and achieved high rates of recruitment in two U.S. EDs. Given the ongoing need to test new therapeutics for influenza and other emerging infections, we sought to describe the historical rates of participant recruitment into influenza Phase III therapeutic RCTs in various clinical venues, including EDs.Study Design: A cross-sectional study was performed of influenza therapeutic Phase III RCTs published in PubMed, Embase, Scopus, and Clinicaltrials.gov from January 2000 to June 2019.Main Outcome: To estimate the weighted-average number of influenza-positive participants enrolled per site per season in influenza therapeutic RCT conducted in clinical settings, and to describe basic trial site characteristics.Results: 47 (0.7%) of 7008 articles were included for review of which 43 of 47 (91%) included information regarding enrollment sites; of these, 2 (5%) recruited exclusively from EDs with the remainder recruiting from mixed clinical settings (inpatient, outpatient, and ED). The median enrollment per study was 326 (IQR: 110, 502.5) with a median of 11 sites per study (IQR: 2, 59.5). Included studies reported a median of 201 (IQR: 74, 344.5) confirmed influenza-positive participants per study. The pooled number of participants enrolled per site per season was 11 (95% CI: 10, 12). The pooled enrollment numbers per clinical site after excluding the two 'ED only recruitment' studies were less [10.7 (95% CI: 9.9, 11.6)] than the pooled enrollment numbers per clinical site for the two 'ED only recruitment' studies [89.5 (95% CI 89.2-89.27)].Conclusion and Relevance: Published RCTs evaluating influenza therapeutics in clinical settings recruit participants from multiple sites but enroll relatively few participants, per site, per season. The few ED-based studies reported recruited more subjects per site per season. Untapped opportunities likely exist for EDs to participate and/or lead therapeutic RCTs for influenza or other emerging respiratory pathogens. [ABSTRACT FROM AUTHOR]

Background: Since the outbreak of COVID-19 in 2019, the global economy, culture, politics, and people's lives and health have been severely damaged and threatened. Although western modern medical treatment has made great efforts, the treatment of COVID-19 has not achieved ideal clinical efficacy with severe sequelae. Qingfei Paidu (QFPD), an important herbal prescription for COVID-19 treatment, has shown remarkable therapeutic effects in China's fight against the epidemic. Materials and methods: We searched seven databases up to 7 September 2022, including PubMed, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, World Scientific and SpringerLink. We used the Cochrane Risk of Bias tool to assess the quality of randomized controlled trials. All analysis results were conducted by RevMan 5.4.1 to carry out a meta-analysis. Results: Fifteen studies with 10390 patients were included. QFPD could not only significantly improve the cure rate and lung CT of COVID-19, reduce the number of patients turning to critical condition and death, shorten the time for nucleic acid conversion and the length of hospital stay, but change laboratory indexes and relieve body symptoms quickly without adverse effects. Conclusions: Compared with patients only treated by conventional western treatment (CWM), QFPD combined with CWM could be more effective for patients. It is worth spreading to other countries in the global battle against COVID-19. [ABSTRACT FROM AUTHOR]

Background: Sterile water injections can provide effective pain relief during childbirth, particularly for low back pain related to childbirth. However, the pain associated administering the injections can negatively impact women's impressions of the procedure. It may discourage women from considering repeat doses despite the quality of analgesia experienced. Determining strategies to reduce the pain related to the administration of sterile water injections would improve the acceptability of the technique. Therefore, the aim of this study was to evaluate the effect of topical local anesthesia on the pain associated with administration of sterile water injections. Methods: The study was designed as a multi-arm single-blind, randomized, controlled trial and 120 female healthy students were randomly divided according to one of four groups. The Intervention group received sterile water injections with topical local anesthesia. Control group 1 received sterile water injections without topical local anesthesia, control group 2 received injections of isotonic saline 0.9% with topical local anesthesia and control group 3 received injections of isotonic saline 0.9% without topical local anesthesia. Pain Immediately after the injections and subsidence in pain were recorded using a visual analogue scale. Sensations in the injection area were reported 15 min and the day after the injections. Results: The main finding of this study was that local anesthesia with EMLA® reduces the pain associated with the administration of intracutaneous sterile water injections. There was a significant difference in the self-assessed pain score immediately following the injections between the control (73.3 mm) and intervention groups (50.0 mm), p = 0.001. No adverse side effects were reported. Conclusion: Local anesthesia with EMLA® reduces the pain associated with intracutaneous administration of sterile water injections. Trial registration: The study was registered 08/07/2014 at ClinicalTrials.gov Identifier: NCT02213185. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) adherence is still suboptimal among some key populations, highlighting the need for innovative tailored strategies. This randomized controlled trial (RCT) aimed to evaluate the effect of a differentiated digital intervention on ART adherence among men who have sex with men (MSM) living with HIV in China.Methods: The two-armed parallel RCT was conducted at one HIV clinic in Jinan of China from October 19, 2020, to June 31, 2021. Men were referred by health providers to join the study and then choose one of three digital strategies-text message, only instant message, or instant message plus social media. They were assigned in a 1:1 ratio to the intervention arm or control arm using block randomization, and inside each arm, there were three groups depending on the type of delivering the message. The groups were divided according to participants' preferred digital strategies. The intervention arm received ART medication messages, medication reminders, peer education, and involved in online discussion. The control arm received messages on health behavior and nutrition. The primary outcome was self-reported optimal ART adherence, defined as not missing any doses and not having any delayed doses within a one-month period. Secondary outcomes included CD4 T cell counts, viral suppression, HIV treatment adherence self-efficacy, and quality of life. Intention-to-treat analysis with generalized linear mixed models was used to evaluate the intervention's effect.Results: A total of 576 participants were enrolled, including 288 participants assigned in the intervention arm and 288 assigned in the control arm. Most were ≤ 40 years old (79.9%) and initiated ART ≤ 3 years (60.4%). After intervention, the proportion of participants achieving optimal ART adherence in the intervention arm was higher than in the control arm (82.9% vs 71.1%). The differentiated digital intervention significantly improved ART adherence (RR = 1.74, 95%CI 1.21-2.50). Subgroup analysis showed one-to-one instant message-based intervention significantly improved ART adherence (RR = 2.40, 95% CI 1.39-4.17).Conclusions: The differentiated digital intervention improved ART adherence among MSM living with HIV in China, which could be integrated into people living with HIV (PLWH) management and further promoted in areas where PLWH can access text messaging and instant messaging services.Trial Registration: ChiCTR2000041282. Retrospectively registered on 23 December 2020. [ABSTRACT FROM AUTHOR]

Background: Transdiagnostic group cognitive-behavioral therapy (tCBT) is a delivery model that could help overcome barriers to large-scale implementation of evidence-based psychotherapy for anxiety disorders. The aim of this study was to assess the effectiveness of combining group tCBT with treatment-as-usual (TAU), compared to TAU, for the treatment of anxiety disorders in community-based mental health care. Methods: In a multicenter single-blind, two-arm pragmatic superiority randomized trial, we recruited participants aged 18–65 who met DSM-5 criteria for principal diagnoses of generalized anxiety disorder, social anxiety disorder, panic disorder, or agoraphobia. Group tCBT consisted of 12 weekly 2 h sessions. There were no restrictions for TAU. The primary outcome measures were the Beck Anxiety Inventory (BAI) and clinician severity rating from the Anxiety and Related Disorders Interview Schedule for DSM-5 (ADIS-5) for the principal anxiety disorder at post-treatment, with intention-to-treat analysis. Results: A total of 231 participants were randomized to either tCBT + TAU (117) or TAU (114), with outcome data available for, respectively, 95 and 106. Results of the mixed-effects regression models showed superior improvement at post-treatment for participants in tCBT + TAU, compared to TAU, for BAI [ p < 0.001; unadjusted post-treatment mean (s.d.): 13.20 (9.13) v. 20.85 (10.96), Cohen's d = 0.76] and ADIS-5 [ p < 0.001; 3.27 (2.19) v. 4.93 (2.00), Cohen's d = 0.79]. Conclusions: Our findings suggest that the addition of group tCBT into usual care can reduce symptom severity in patients with anxiety disorders, and support tCBT dissemination in routine community-based care. [ABSTRACT FROM AUTHOR]

Objective: To observe the efficacy and safety of Guihuang Formula (GHF) in treating patients with type III prostatitis and Chinese medicine syndrome of dampness-heat and blood stasis. Methods: Sixty-six patients diagnosed with type III prostatitis with dampness-heat and blood stasis syndrome were randomly divided into the treatment group (GHF) and the control group (tamsulosin) using a random number table, with 33 cases each group. The treatment group received GHF twice a day, and the control group received tamsulosin 0.2 mg once daily before bedtime. Patients in both groups received treatment for 6 weeks and was followed up for 2 weeks. The outcomes included the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, Chinese Medicine Symptoms Score (CMSS), expressed prostatic secretions (EPS) and adverse events (AEs). Results: After treatment, the NIH-CPSI total score and domain scores of pain discomfort, urination and quality of life decreased significantly from the baseline in both groups (P<0.05). The CMSS score decreased in both groups (P<0.05). The WBC count decreased and lecithin body count increased in both groups (P<0.05). GHF showed a more obvious advantage in reducing the pain discomfort and quality of life domain scores of NIH-CPSI, reducing the CMSS score, increasing the improvement rate of the WBC and lecithin body counts, compared with the control group (P<0.05). There were no significant differences in decreasing urination domain score of NIH-CPSI between two groups (P>0.05). In addition, no serious AEs were observed. Conclusion: GHF is effective in treating type III prostatitis patients with dampness-heat and blood stasis syndrome without serious AEs. (Registration No. ChiCTR1900026966) [ABSTRACT FROM AUTHOR]

Aims: Filgotinib is a potent, oral, JAK1‐preferential inhibitor for the treatment of rheumatoid arthritis (RA). This report describes exposure‐response (ER) analyses of filgotinib for dose confirmation based on three phase 3 and two phase 2 studies in moderate to severe RA patients. Methods: The pharmacokinetic exposures used in ER analyses were derived from population pharmacokinetic analysis. The exposure‐efficacy relationships were assessed for efficacy endpoints (ACR20/50/70 and DAS28) over effective area under curve (AUCeff), the combined exposures of filgotinib and GS‐829845 (major, active metabolite), with nonlinear logistic regression models developed. Also, a t‐test was performed to compare the exposure between subjects who achieved response and those who did not. For the ER analyses of safety, exposures were examined between subjects who experienced and who did not experience the evaluated safety events, which was conducted separately for filgotinib and GS‐829845. Results: The nonlinear logistic regression showed increasing response with increasing exposure, with exposures at 200 mg dose primarily residing on the curve plateau. Also, AUCeff was significantly higher in the subjects who achieved responses compared to those who did not (10 900 vs 9900 h*ng/mL for ACR20, P value <.0001). For exposure‐safety analyses, filgotinib and GS‐829845 exposures were similar irrespective of the presence/absence of the evaluated safety endpoints, indicating no exposure‐safety relationship for common treatment‐emergent adverse events (TEAEs)/laboratory abnormalities and serious TEAEs/infections. Conclusions: ER analyses confirmed that filgotinib produced more robust therapeutic effects across the exposure range observed at 200 mg once daily compared to lower doses, and collectively with the lack of exposure‐safety relationship, the 200 mg once daily dose was supported for commercialization. [ABSTRACT FROM AUTHOR]

Purpose: The present study aimed to investigate fish oil plus vitamin D3 (FO + D) supplementation on biomarkers of non-alcoholic fatty liver disease (NAFLD). Methods: In a 3-month randomized controlled trial, 111 subjects with NAFLD, aged 56.0 ± 15.9 y, were randomized into FO + D group (n = 37), fish oil group (FO, n = 37) or corn oil group (CO, n = 37). The subjects consumed the following capsules (3 g/day), which provided 2.34 g/day of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3 (FO + D group), or 2.34 g/day of EPA + DHA (FO group), or 1.70 g/d linoleic acid (CO group). Results: Using multivariable-adjusted general linear model, there were significant net reductions in serum alanine aminotransferase (ALT), and triacylglycerol (TAG) and TNF-α levels in the FO + D and FO groups, compared with the control group (P < 0.05). The supplemental FO + D also showed significant reductions in insulin (− 1.58 ± 2.00 mU/L vs. − 0.63 ± 1.55 mU/L, P = 0.050) and IL-1β (− 6.92 ± 7.29 ng/L vs. 1.06 ± 5.83 ng/L, P < 0.001) in comparison with control group. Although there were no significant differences between FO + D and FO groups regarding biochemical parameters, supplemental FO + D showed decreases in ALT (from 26.2 ± 13.5 U/L to 21.4 ± 9.6 U/L, P = 0.007), aspartate aminotransferase (AST, from 22.5 ± 7.0 U/L to 20.2 ± 4.0 U/L, P = 0.029), HOMA-IR (from 3.69 ± 1.22 to 3.38 ± 1.10, P = 0.047), and TNF-α (from 0.43 ± 0.38 ng/L to 0.25 ± 0.42 ng/L, P < 0.001) levels following the intervention. Conclusion: The present study demonstrated that groups supplemented with FO + D and FO had similar beneficial effects on biomarkers of hepatocellular damage and plasma TAG levels in subjects with NAFLD, while in the FO + D group, there were some suggestive additional benefits compared with FO group on insulin levels and inflammation. Trial registration: ChiCTR1900024866. [ABSTRACT FROM AUTHOR]

Chinese herbal medicine is increasingly used as complementary therapy to manage nausea and vomiting in different cultures. One such herbal recipe is the Hezhong granules, which contain classical antiemetic formulations, and are commonly used to prevent chemotherapy-induced nausea and vomiting (CINV). Modern pharmacological studies have shown that the key components of Hezhong granules, including Pinellia ternata (Thunb.), Evodia rutaecarpa (Juss.), and Zingiber officinale exhibit significant antiemetic and antitumor properties. Despite this promising evidence, controlling CINV remains a significant challenge in cancer treatment. Moreover, there is a lack of scientifically designed clinical trials to validate the efficacy and safety of classical antiemetic formulas for CINV interventions. To investigate the efficacy and safety of Hezhong granules in preventing CINV in patients with advanced colorectal cancer (CRC). This study was conducted between October 2020 and February 2022 in 12 hospital wards in Southwest China. In this multicenter, randomized controlled trial, we enrolled patients with advanced CRC who received fluorouracil-based chemotherapy. The patients were randomly assigned in a 1:1 ratio to either the Hezhong granule group (receiving a 5-HT3-receptor antagonist, dexamethasone, and Hezhong granules) or the placebo group (receiving a 5-HT3-receptor antagonist, dexamethasone, and placebo) during the first and second courses of chemotherapy. A 5-day diary was provided to all patients. Acute and delayed CINV were defined as CINV occurring within 24 h or between 24 and 120 h after the start of treatment. The primary endpoints were complete response rate (CRR, defined as the proportion of patients without nausea/vomiting) and objective response rate (ORR, defined as the proportion of patients without nausea/vomiting plus mild nausea/vomiting) for both acute and delayed CINV. Secondary endpoints were the daily rates of CINV events and Functional Living Index-Emesis (FLIE). To identify the predictors of CINV, we conducted multivariate ordered logistic regression analysis. This study was registered with the Chinese Clinical Trial, number ChiCTR2100041643. A total of 120 participants were randomly assigned, of whom 112 (56/56) completed two cycles and were included in the full analysis. In the acute phase, there were minor improvements in the Hezhong granule group, but there were no significant differences in the CRRs for nausea and vomiting (mean difference:10.7 %, P = 0.318, 0.324), while the ORRs increased by approximately 17.5 % (mean difference:16.1 %, P = 0.051; 17.9 %, P = 0.037, respectively). In the delayed phase, significant improvements of approximately 20 % were observed in both the CRRs (mean difference:19.6 %, P = 0.053; 21.4 %, P = 0.035) and ORRs (mean difference:17.9 %, P = 0.037, 0.043) for nausea and vomiting. Additionally, the daily rate of CINV events showed a mean difference of 19 % (P < 0.05). According to FLIE scores, approximately 70 % of patients who received Hezhong granules reported an improvement in their quality of life, with CINV symptoms having"no impact on daily life (NIDL)". No serious adverse events were attributed to herbal medicine. Hezhong granules proved to be both effective and well-tolerated in preventing CINV in patients with advanced CRC, with notable benefits in preventing delayed CINV. These promising results set the stage for subsequent phase III clinical trials and experimental research on Hezhong Granules. [Display omitted] • Hezhong granule can increase the complete response rate of CINV by about 10 %–20 %. • Hezhong granule can increase the objective response rate of CINV by about 16 %–18 %. • Hezhong granule show better efficacy in preventing delayed CINV. • Hezhong granule is well tolerated and can significantly improve the quality of life of patients. [ABSTRACT FROM AUTHOR]

Background': India is ranked second in the world in terms of tobacco use and tops the list of eight high-burden countries that account for two-thirds of the new tuberculosis (TB) cases globally. As tobacco smoking among TB patients is associated with unsuccessful TB treatment outcomes, effective smoking cessation interventions for TB patients is essential to combat this double pandemic. Aim: The study determined the effectiveness of nicotine replacement therapy (NRT) on smoking reduction and cessation among pulmonary TB patients. Settings and Design: The study included 300 pulmonary TB patients undergoing antitubercular treatment in government health care centers of Dakshina Kannada district in southern India. Materials and Methods: The participants in this two-armed, single-blinded, placebo-controlled, block-randomized trial were divided equally (n = 150) for experimental arm (brief advice + NRT) and control arm (brief advice + placebo). The total duration of treatment and follow-up was 6 months. Unadjusted relative risk (URR) and adjusted relative risk (ARR) were calculated for treatment outcomes at 95% confidence interval (CI). Generalized linear regression analysis was performed upon variables with P value less than 0.2. Results: After 6 months of intervention including follow up, there was a significant reduction in self-reported smoking (ARR = 1.08, 95% CI 1.01–1.17, P = 0.03) in the experimental arm compared with the control arm. Biochemically verified smoking abstinence was not significantly different between the two arms (ARR = 1.01, 95% CI 0.72–1.38, P = 0.97). Conclusion: The study showed statistically significant effectiveness of NRT for self-reported smoking reduction.

OBJECTIVE: Cerebral palsy seriously affects children's physical and mental health due to its high morbidity and disability rate. Ankle-foot orthoses are an important treatment for this disease. However, it is not very clear about the clinical effect of ankle-foot orthoses on the motor function of children with cerebral palsy. Therefore, this paper systematically assesses the clinical effect of ankle-foot orthoses on the improvement of motor function in children with cerebral palsy. METHODS: Literature retrieval was carried out in the electronic databases of PubMed, EMbase, Web of Science, Cochrane Library, CBM, CNKI, WanFang, and VIP. The time limit for retrieval was from the establishment of these databases to September 9, 2020. According to the inclusion and exclusion criteria, randomized controlled trials of ankle-foot orthoses in the treatment of children with cerebral palsy were included. At least two evaluators extracted the data independently and used Cochrane 5.1.0 bias risk assessment tool to evaluate the quality of included studies. The data were analyzed by Revman 5.3 software. RESULTS: In the end, a total of 12 randomized controlled trials with high quality, involving 480 children with cerebral palsy, were included in this study. Among them, 239 patients in the ankle-foot orthosis group wore ankle-foot orthosis; 241 patients in the control group did not wear ankle-foot orthosis. The treatment course was 0-48 weeks. Meta-analysis results showed that the improvement of Gross Motor Function Measure-88-D/E score (mean difference (MD)=6.26, 95% confidence interval (CI):3.54-8.98, P < 0.000 01), modified Ashworth scale score (MD=-0.60, 95%CI: -0.80 to -0.40, P < 0.000 01), dorsiflexion mean in swing (MD=14.96, 95%CI: 12.03-17.90, P < 0.000 01), effectiveness in improving motor function (MD=2.99, 95%CI: 1.19-7.50, P=0.02), and stride length (MD=0.06, 95%CI: 0.04-0.09, P < 0.000 01) in the ankle-foot orthosis group was better than that in the control group. CONCLUSION: Evidence from these 12 randomized controlled trials indicates that no matter walking with ankle-foot orthosis, or walking without ankle-foot orthosis after wearing for a certain period of time, in the short time, it has remarkable clinical value in improving motor function. However, further studies on the long-term recovery of motor function are required. [ABSTRACT FROM AUTHOR]

Background: Constipation is a common problem among advanced cancer patients; however, many of them find limited effective from current therapies. Thus, we aimed to test the effect of a traditional Chinese herbal formula, modified MaZiRenWan (MZRW), by comparing with placebo among palliative cancer patients with constipation. Methods: This is a randomized, double-blind, placebo-controlled trial. Participants aged over 18 were recruited and randomized to MZRW or placebo group in addition to current prescriptions (including ongoing laxatives treatment) for two weeks. Exclusion criteria included cognitive impairment, presence of a colostomy or gastrointestinal obstruction and estimated life expectancy of less than one month. Individualized modification of MZRW was allowed according to the traditional Chinese medicine (TCM) pattern of patient. The primary outcome was the global assessment of improvement, which reflected whether the constipation had improved, remained the same or worsened. Results: Sixty patients, with mean age 75.2 years (range 47–95 years), were randomized to MZRW or placebo group. Among the MZRW group, 59.3% (16/27) had improvement in the global assessment score, as compared with 28.6% (8/28) of the placebo group (p-value = 0.022). Besides, the MZRW group had significant increase in stool frequency, and reduction in constipation severity and straining of defecation (p-value < 0.05). No serious adverse event was reported due to the research medication. Conclusion: This pilot trial suggests modified MZRW is well-tolerated and effective for relief of constipation in patients with advance cancer. It could be considered as a potential treatment option for constipation in palliative care. Trial registration: The trial had been registered in ClinicalTrials.gov with identifier number NCT02795390 [https://clinicaltrials.gov/ct2/show/NCT02795390] on June 10, 2016. [ABSTRACT FROM AUTHOR]

Objective: To explore the therapeutic effect of Bushen Yiqi Huoxue Decoction BYHD) in patients with diminished ovarian reserve (DOR). Methods: A total of 180 patients with DOR diagnosed from December 2013 to December 2014 were equally assigned into progynova and duphaston (E+D) group, Zuogui Pill group and BYHD group with 60 cases in each by computerized randomization. Patients received E+D, Zuogui Pill or BYHD for 12 months, respectively. Follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), antral follicle count (AFC), ovarian volume, endometrial thickness, and the resistance indices (RIs) of ovarian arteries and uterine arteries were observed before and after treatment. Results: Nine women (4 from the E+D group, 3 from the Zuogui Pill group, and 2 from the BYHD group) withdrew from the study. After 6 months, Zuogui Pill and BYHD significantly decreased FSH and LH and increased endometrial thickness and AMH (all P<0.01). BYHD also resulted in E2 elevation (P<0.05), ovary enlargement (P<0.05), AFC increase (P<0.01), and RI of ovarian arteries decrease (P<0.05). After 12 months, further improvements were observed in the Zuogui Pill and BYHD groups (all P<0.01), but BYHD showed better outcomes, with lower FSH, larger ovaries and a thicker endometrium compared with the Zuogui Pill group (all P<0.01). However, E+D only significantly increased endometrial thickness (P<0.01) and no significant improvements were observed in the RI of uterine arteries in the three groups. Conclusions: BYHD had a favorable therapeutic effect in patients with DOR by rebalancing hormone levels, promoting ovulation, and repairing the thin endometrium. The combination of tonifying Shen (Kidney), benefiting qi and activating blood circulation may be a promising therapeutic strategy for DOR. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal functional disease. Adults with IBS may experience abdominal pain, change of bowel habits, and abnormal stool form without organic disease. IBS can seriously affect their work productivity and quality of life, especially diarrhea-predominant irritable bowel syndrome (IBS-D). The Chinese medicine JCM-16021 has been shown to be potentially effective in improving the symptoms of IBS-D based on a small scale clinical trial. Hence, a large scale clinical study is designed to further evaluate the efficacy and safety of the Chinese medicine JCM-16021 for IBS-D with traditional Chinese medicine (TCM) pattern of Liver Stagnation and Spleen Deficiency (LSSD). Methods: This study is a multi-center, randomized, double-blind, placebo-controlled clinical trial. 392 eligible participants will be enrolled with 2-week run-in, 8-week treatment and 8-week follow-up. After run-in period, participants will be randomized to receive either the Chinese medicine JCM-16021 or placebo for 8 weeks, and will have post-treatment follow up for another 8 weeks. The primary outcome is the improvement rate on the global assessment of improvement (GAI) at week 10. The secondary outcomes consist of changes of IBS-D symptoms, TCM pattern improvement, IBS-Quality of Life (IBS-QoL), IBS-Symptom Severity Score (IBS-SSS), safety, etc. Results: A standard protocol has been developed for the study. The protocol will provided a detailed procedure to conduct a clinical trial and verify if the Chinese medicine JCM-16021 would significantly improve the overall symptoms of IBS-D with LSSD pattern of TCM by relieving abdominal pain, reducing stool frequency, improving the stool consistency and improving quality of life. The consolidated evidence from the study can shed light on the treatment of IBS-D with Chinese medicine. Conclusion: The protocol will provide details for investigators about the study following SPIRIT Statement. High-quality evidence on the efficacy and safety of Chinese medicine JCM-16021 for IBS-D will be provided through strict compliance with the protocol. Trial registration: ClinicalTrial.gov identifier: NCT03457324. Registered 8 February 2018, https://clinicaltrials.gov/ct2/show/NCT03457324?term=NCT03457324&draw=2&rank=1 [ABSTRACT FROM AUTHOR]

Purpose: This study aims to determine the feasibility of thread-embedding acupuncture (TEA) for the treatment of shoulder instability. Patients and Methods: This is a patient-assessor blinded, randomized, sham-controlled trial with two parallel arms. A total of 40 patients with shoulder instability aged between 13 and 43 years will be recruited and screened using set inclusion and exclusion criteria. After screening, they will be randomly allocated to the TEA or sham TEA group. Patients in both groups will then receive TEA or sham TEA treatment on six acupoints once a week for 8 weeks, which will be followed by additional follow-up assessments at 4 and 8 weeks after the end of treatment. Changes in shoulder pain and disability will be assessed as the primary outcome, whereas 100-mm pain visual analogue scale, shoulder range of motion, rotator cuff quality of life index, EuroQol 5-dimension 5-levels, treatment satisfaction, economic evaluation, and safety will all be measured as secondary outcomes of the study. Outcome assessment will be conducted at baseline and at 4, 8, and 16 weeks after screening. Conclusion: The results from this trial will help to design further clinical trials on the efficacy, safety, and cost-effectiveness of performing TEA for shoulder instability. Trial Registration Number: KCT0005921 (Clinical Research Information Service of the Republic of Korea). [ABSTRACT FROM AUTHOR]

Background: Traditional Chinese medicine (TCM) has gained widespread application in treating chronic heart failure (CHF) secondary to coronary heart disease (CHD). However, the sound clinical evidence is still lacking. Corresponding clinical trials vary considerably in the outcome measures assessing the efficacy of TCM, some that showed the improvement of clinical symptoms are not universally acknowledged. Rational outcome measures are the key to evaluate efficacy and safety of each treatment and significant elements of a convincing clinical trial. We aimed to summarize and analyze outcome measures in randomized controlled trials (RCTs) of TCM in treating CHF caused by CHD, subsequently identify the present problems and try to put forward solutions. Methods: We systematically searched databases including Embase, PubMed, Cochrane Library, CBM, CNKI, VIP and Wanfang from inception to October 8, 2018, to identify eligible RCTs using TCM interventions for treating CHF patients caused by CHD. Cochrane Database of Systematic Reviews (CDSR) was searched to include Cochrane systematic reviews (CSRs) of CHF. Two authors independently assessed the risk of bias of the included RCTs according to the Cochrane Handbook. Outcome measures of each trial were extracted and analyzed those compared with the CSRs. We also evaluated the reporting quality of the outcome measures. Results: A total of 31 RCTs were included and the methodology quality of the studies was generally low. Outcome measures in these RCTs were mortality, rehospitalization, efficacy of cardiac function, left ventricular ejection fraction (LVEF), 6 min' walk distance (6MWD) and Brain natriuretic peptide (BNP), of which mortality and rehospitalization are clinical end points while the others are surrogate outcomes. The reporting rate of mortality and rehospitalization was 12.90% (4/31), the other included studies reported surrogate outcomes. As safety measure, 54.84% of the studies reported adverse drug reactions. Two trials were evaluated as high in reporting quality of outcomes and that of the other 29 studies was poor due to lack of necessary information for reporting. Conclusions: The present RCTs of TCM in treating CHF secondary to CHD did not concentrate on the clinical end points of heart failure, which were generally small in size and short in duration. Moreover, these trials lacked adequate safety evaluation, had low quality in reporting outcomes and certain risk of bias in methodology. For objective assessment of the efficacy and safety of TCM in treating CHF secondary to CHD, future research should be rigorous designed, set end points as primary outcome measures and pay more attention to safety evaluation throughout the trial. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of Taohong Siwu Decoction (桃红四物汤, TSD), a Chinese herbal compound prescription, in patients with angina pectoris (AP). Methods: Randomized clinical trials (RCTs) comparing TSD plus conventional treatment (CT) with CT plus placebo or CT only in the patients with AP were searched in PubMed, Cochrane Library, Excerpta Medica Database, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Database, Chinese Scientific Journal Database, Chinese Clinical Trial Registry and International Clinical Trial Registry from their inception to March 2017. The primary outcomes include a composite event of death, acute myocardial infarction (AMI), and target vessel revascularization. The secondary outcomes include angina symptom, electrocardiogram (ECG) improvement and serum high-sensitivity C-reactive protein (hs-CRP), endothelin-1 (ET-1), triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. The methodological quality of included studies and extracted available data were assessed. RevMan 5.3 software was used to conduct statistical analysis. The relative risk (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) was calculated. A funnel plot was used to evaluate the publication bias. Results: Among 204 studies identified in the literature search, 12 trials including 959 patients with AP met the inclusion criteria. No studies reported the primary outcome including death, AMI and target vessel revascularization. TSD combined with CT showed significant improvement in relieving angina symptom [RR=3.70, 95% CI (2.42, 5.67)] and ECG [RR=3.20, 95% CI (2.20, 4.65)] compared with CT alone. TSD combined with CT reduced the serum hs-CRP, TG, TC and LDL-C levels compared with CT alone. No serious adverse events were reported in TSD combined with CT. Conclusions: TSD combined with CT has a potential benefit on relieving AP without significant adverse events. However, the efficacy on the cardiovascular events needs to be assessed by more rigorously-designed, largescale, and multi-center RCTs in future. [ABSTRACT FROM AUTHOR]