Search

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

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: 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]

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: 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]

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]

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]

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]

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]

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]

Although swallowing exercises are a fundamental treatment for dysphagia, few studies have evaluated the effectiveness of swallowing training in patients with Alzheimer's disease. We recruited 93 patients with Alzheimer's disease from three hospitals in Guangdong, China. This was a parallel armed randomized controlled trial that randomly assigned patients to intervention (n = 48) and control (n = 45) groups. The intervention group adopted systematic stepwise swallowing training for four weeks based on routine dysphagia care. The control group implemented routine dysphagia care, including diet and posture management and health education about swallowing dysfunction. The swallowing function was the primary outcome, which was assessed using the Water Swallowing Test and Standard Swallowing Assessment. An abnormal eating behavior questionnaire was used to assess the incidence of aberrant eating behavior in patients with Alzheimer's disease. The Mini-Nutritional Assessment Short Form and Barthel index were adopted to evaluate the nutritional status and ability to carry out daily activities between groups. SPSS software was used to perform the chi-square test, t -test, and generalized estimation equation for data analysis. We analyzed the effects of the stepwise swallowing training program using the generalized estimating equation method. The intervention group exhibited greater improvements in their swallowing function (Water Swallowing Test: β = − 3.133, 95 % CI: − 4.113, − 2.154, P < 0.001; Standard Swallowing Assessment: β = − 5.813, 95 % CI: − 7.782, − 3.844, P < 0.001), abnormal eating behaviors (abnormal eating behavior questionnaire: β = − 13.324, 95 % CI: − 21.643, − 5.005, P = 0.002), daily function (Barthel index: β = 11.280, 95 % CI: 4.021, 18.540, P = 0.002), and nutritional status (Mini-Nutritional Assessment Short Form: β = 2.402, 95 % CI: 1.313, 3.490, P < 0.001) over time than the routine-care group in the fourth week. Stepwise swallowing training is a safe and effective intervention for managing dysphagia and other related symptoms in patients with Alzheimer's disease. [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]

Objectives: Currently, there are no approved treatments for early disease stages of COVID-19 and few strategies to prevent disease progression after infection with SARS-CoV-2. The objective of this study is to evaluate the safety and efficacy of convalescent plasma (CP) or camostat mesylate administered within 72 h of diagnosis of SARS-CoV-2 infection in adult individuals with pre-existing risk factors at higher risk of getting seriously ill with COVID-19. Camostat mesylate acts as an inhibitor of the host cell serine protease TMPRSS2 and prevents the virus from entering the cell. CP represents another antiviral strategy in terms of passive immunization. The working hypothesis to be tested in the RES-Q-HR study is that the early use of CP or camostat mesylate reduces the likelihood of disease progression to (modified) WHO stages 4b-8 in SARS-CoV-2-positive adult patients at high risk of moderate or severe COVID-19 progression.Trial Design: This study is a 4-arm (parallel group), multicenter, randomized (2:2:1:1 ratio), partly double-blind, controlled trial to evaluate the safety and efficacy of convalescent plasma (CP) or camostat mesylate with control or placebo in adult patients diagnosed with SARS-CoV-2 infection and high risk for progression to moderate/severe COVID-19. Superiority of the intervention arms will be tested.Participants: The trial is conducted at 10-15 tertiary care centers in Germany. Individuals aged 18 years or above with ability to provide written informed consent with SARS-CoV-2 infection, confirmed by PCR within 3 days or less before enrolment and the presence of at least one SARS-CoV-2 symptom (such as fever, cough, shortness of breath, sore throat, headache, fatigue, smell/and or taste disorder, diarrhea, abdominal symptoms, exanthema) and symptom duration of not more than 3 days. Further inclusion criteria comprise: Presence of at least one of the following criteria indicating increased risk for severe COVID-19: Age > 75 years Chronic obstructive pulmonary disease (COPD) and/or pulmonary fibrosis BMI > 40 kg/m2 Age > 65 years with at least one other risk factor (BMI > 35 kg/m2, coronary artery disease (CAD), chronic kidney disease (CKD) with GFR < 60 ml/min but ≥ 30 ml/min, diabetes mellitus, active tumor disease) BMI > 35 kg/m2 with at least one other risk factor (CAD, CKD with GFR < 60 ml/min but ≥ 30 ml/min, diabetes mellitus, active tumor disease) Exclusion criteria: 1. Age < 18 years 2. Unable to give informed consent 3. Pregnant women or breastfeeding mothers 4. Previous transfusion reaction or other contraindication to a plasma transfusion 5. Known hypersensitivity to camostat mesylate and/or severe pancreatitis 6. Volume stress due to CP administration would be intolerable 7. Known IgA deficiency 8. Life expectancy < 6 months 9. Duration SARS-CoV-2 typical symptoms > 3 days 10. SARS-CoV-2 PCR detection older than 3 days 11. SARS-CoV-2 associated clinical condition ≥ WHO stage 3 (patients hospitalized for other reasons than COVID-19 may be included if they fulfill all inclusion and none of the exclusion criteria) 12. Previously or currently hospitalized due to SARS-CoV-2 13. Previous antiviral therapy for SARS-CoV-2 14. ALT or AST > 5 x ULN at screening 15. Liver cirrhosis > Child A (patients with Child B/C cirrhosis are excluded from the trial) 16. Chronic kidney disease with GFR < 30 ml/min 17. Concurrent or planned anticancer treatment during trial period 18. Accommodation in an institution due to legal orders (§40(4) AMG). 19. Any psycho-social condition hampering compliance with the study protocol. 20. Evidence of current drug or alcohol abuse 21. Use of other investigational treatment within 5 half-lives of enrolment is prohibited 22. Previous use of convalescent plasma for COVID-19 23. Concomitant proven influenza A infection 24. Patients with organ or bone marrow transplant in the three months prior to screening visit INTERVENTION AND COMPARATOR: Participants will be randomized to the following 4 groups: 1) Convalescent plasma (CP), 2 units at screening/baseline visit (day 0) or day 1; CP is defined by the presence of neutralizing anti-SARS-CoV-2 antibodies with titers ≥ 1:160; individuals with body weight ≥ 150 kg will receive a third unit of plasma on day 3 2) Camostat mesylate (200 mg per capsule, one capsule taken each in the morning, afternoon and evening on days 1-7) 3) Standard of care (SOC, control for CP) 4) Placebo (identical in appearance to camostat mesylate capsules, one capsule taken each morning, afternoon and evening on days 1-7; for camostat mesylate control group) Participants will be monitored after screening/baseline on day 3, day 5, day 8, and day 14. On day 28 and day 56, telephone visits and on day 90, another outpatient visit are scheduled. Adverse events and serious adverse events will be monitored and reported until the end of the study. An independent data safety monitoring committee will review trial progression and safety.Main Outcomes: The primary endpoint of the study is the cumulative number of individuals who progress to or beyond category 4b on the modified WHO COVID-19 ordinal scale (defined as hospitalization with COVID-19 pneumonia and additional oxygen demand via nasal cannula or mask) within 28 days after randomization.Randomization: Participants will be randomized using the Alea-Tool ( aleaclinical.com ) in a 2:2:1:1 ratio to the treatment arms (1) CP, (2) camostat mesylate, (3) standard of care (SoC), and (4) placebo matching camostat mesylate. Randomization will be stratified by study center.Blinding (masking): The camostat mesylate treatment arm and the respective placebo will be blinded for participants, caregivers, and those assessing outcomes. The treatment arms convalescent plasma and standard of care will not be blinded and thus are open-labeled, unblinded.Numbers To Be Randomized (sample Size): Overall, n = 994 participants will be randomized to the following groups: n = 331 to convalescent plasma (CP), n = 331 to camostat mesylate, n = 166 to standard of care (SoC), and n = 166 to placebo matching camostat mesylate.Trial Status: The RES-Q-HR protocol (V04F) was approved on the 18 December 2020 by the local ethics committee and by the regulatory institutions PEI/BfARM on the 2 December 2020. The trial was opened for recruitment on 26 December 2020; the first patient was enrolled on 7 January 2021 and randomized on 8 January 2021. Recruitment shall be completed by June 2021. The current protocol version RES-Q HR V05F is from 4 January 2021, which was approved on the 18 January 2021.Trial Registration: EudraCT Number 2020-004695-18 . Registered on September 29, 2020. ClinicalTrial.gov NCT04681430 . Registered on December 23, 2020, prior to the start of the enrollment (which was opened on December 26, 2020).Full Protocol: The full protocol (V05F) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to determine the effect of using three‐dimensional videos with virtual reality glasses and distraction cards including optical illusion pictures on patients' pain and satisfaction levels during intramuscular benzathine penicillin injection. Design: A randomized controlled trial. Method: The study population consisted of 91 patients who were prescribed intramuscular benzathine penicillin medication. The participants were stratified by gender and assigned to three groups (control, virtual reality and distraction cards groups). The visual analogue scale was used to assess pain and patient satisfaction. A one‐way analysis of variance and Dunnett's post hoc tests were used to compare the pain and satisfaction levels by group. Results: The mean pain was 6.67 (2.17) in the control group, 4.4 (2.71) in the distraction cards group and 4.93 (3.07) in the virtual reality group and the difference was statistically significant (F = 5.84, p ˂.01). The average of the satisfaction levels in the groups was 3.57 (2.23) in the control group, 7.13 (2.86) in the distraction cards group and 8.07 (2.55) in the virtual reality group. The difference between the satisfaction levels was statistically significant (F = 25.77, p ˂.01). Conclusion: The three‐dimensional videos with virtual reality glasses and distraction cards including optical illusion pictures were effective in reducing pain associated with intramuscular benzathine penicillin injection and increasing patient satisfaction. Impact: The results of this study will contribute to evidence‐based nursing practices for the pain associated with intramuscular benzathine penicillin injection. Clinical Trial Registry: NCT04420559. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to review the effects of robot-assisted therapy (RT) for improving poststroke upper extremity motor impairment. Methods The PubMed, Embase, Medline, and Web of Science databases were searched from inception to April 8, 2020. Randomized controlled trials that were conducted to evaluate the effects of RT on upper extremity motor impairment poststroke and that used Fugl-Meyer assessment for upper extremity scores as an outcome were included. Two authors independently screened articles, extracted data, and assessed the methodological quality of the included studies using the Physiotherapy Evidence Database (PEDro) scale. A random-effects meta-analysis was performed to pool the effect sizes across the studies. Results Forty-one randomized controlled trials with 1916 stroke patients were included. Compared with dose-matched conventional rehabilitation, RT significantly improved the Fugl-Meyer assessment for upper extremity scores of the patients with stroke, with a small effect size (Hedges g  = 0.25; 95% CI, 0.11-0.38; I 2 = 45.9%). The subgroup analysis revealed that the effects of unilateral RT, but not that of bilateral RT, were superior to conventional rehabilitation (Hedges g  = 0.32; 95% CI, 0.15-0.50; I 2 = 55.9%). Regarding the type of robot devices, the effects of the end effector device (Hedges g  = 0.22; 95% CI, 0.09–0.36; I 2 = 35.4%), but not the exoskeleton device, were superior to conventional rehabilitation. Regarding the stroke stage, the between-group difference (ie, RT vs convention rehabilitation) was significant only for people with late subacute or chronic stroke (Hedges g  = 0.33; 95% CI, 0.16-0.50; I 2 = 34.2%). Conclusion RT might be superior to conventional rehabilitation in improving upper extremity motor impairment in people after stroke with notable upper extremity hemiplegia and limited potential for spontaneous recovery. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the effectiveness of a Computer-based Cognitive Behavioral Therapy (CCBT) and identify the characteristics of depressed adolescents that participated in the CCBT program.Methods: Screening tests for depression and help-seeking variables were conducted in school-aged Korean adolescents (n= 376, mean age=15.71 years, 53.7% female). The number of adolescents that scored above the threshold for mild depression (PHQ-9, CES-D) was 139. Fifty adolescents agreed to participate in the randomized controlled trial (RCT) of CCBT program. Twenty-five adolescents were randomly assigned to the treatment group, and the other 25 to the waitlist control group. The treatment group engaged in CCBT with therapeutic support. To identify variables affecting the outcomes, the quality of their homework compliance also was assessed.Results: Participants (n=50) who agreed to participate in the CCBT program demonstrated different help-seeking attitudes - a greater recognition of the need for help and lower interpersonal openness - compared to the adolescents (n=87) who did not participate (t = -2.93, p < .01; t = 3.50, p < .001). The treatment group showed significant improvements in depression, self-esteem, and quality of life compared to the waitlist group. Adolescents with high homework compliance showed a significant decrease in the depression scores compared to adolescents with low homework compliance.Limitations: Small sample size, no follow-up assessments.Conclusion: CCBT could be an effective alternative for depressed adolescents, especially those who tend to have low interpersonal openness. To improve the effects of CCBT, therapeutic support needs to be provided. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of Yugengtongyu granules on reducing the incidence of adverse cardiovascular events and improving quality of life (QOL) in patients with stable coronary artery disease (SCAD). Methods: A double-blind randomized controlled trial was conducted among SCAD population. One hundred fourteen patients were randomly assigned to experimental group (n = 57) and control group (n = 57) following randomized block design. Combined with the basis of standard treatment of SCAD, the experimental group and control group received Yugengtongyu granules or placebo, respectively, twice daily for 6 months and were followed for another 1 year (18 months in total from enrollment). Major outcomes (any occurrence of cardiovascular death, nonfatal myocardial infarction, or coronary revascularization), minor outcomes (any occurrence of all-cause death, ischemic stroke, readmission due to unstable angina, heart failure, or malignant arrhythmia), and composite outcomes (union of major and minor outcomes) were used to evaluate prognosis; Seattle Angina Questionnaire (SAQ) was applied to evaluate QOL, and levels of low density lipoprotein-cholesterol (LDL-C) and high sensitive C reacting protein (HS-CRP) in serum were tested. Results: The incidence of composite outcomes in the experimental group was significantly lower than that in the control group (3 [5.2%] vs. 11 [19.2%], hazard ratio: 0.273, 95% confidence interval: 0.080–0.926, p = 0.022); major outcomes, minor outcomes, and independent events such as nonfatal myocardial infarction showed lowering trend in experimental group. Experimental group scored significantly higher than control group in four dimensions of SAQ: physical limitation, angina frequency, treatment satisfaction, and disease perception at the third- and sixth-month follow-up; there was no significant difference in serum level of LDL or HS-CRP at all scheduled timepoints. Conclusion: The addition of Yugengtongyu granules based on current standard treatment reduced the incidence of composite outcomes and improved QOL in patients with SCAD. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-13004370). [ABSTRACT FROM AUTHOR]

Drugs are the most widely used therapeutic tool for treatment of diseases. However, misuse can lead to an adverse drug event (ADE) in susceptible individuals such as those that are severely obese. This study aimed to describe the frequency of ADEs, the associations of ADEs with anatomical therapeutic chemical classes and their respective frequency, estimate the prevalence of ADEs, and analyse factors associated with ADE in adults with severe obesity. Cross-sectional analysis of baseline data from a randomized clinical trial in the central-western region of Brazil. A total of 150 individuals aged 18-65 years with a Body Mass Index of 35 kg/m2 were included. The outcome variable was the presence of ADE and the explanatory variables were socio-demographic factors, lifestyle, health, and medication use. ADEs were associated with use of drugs for the digestive tract and metabolism (p < 0.001) and the cardiovascular system (p < 0.001). The prevalence of ADEs was 32.67% (n = 49) and associated with the age range 40 to 49 years (p = 0.033), diabetes (p = 0.004), multimorbidities 4 (p = 0.009), self-medication (0.031), and presence of potential drug interactions (0.017). The prevalence of ADEs was high and was associated with drugs commonly used in treatment of obesity-related morbidities and self-medication. The introduction of a pharmacist to multi-professional teams can improve medication safety for severely obese patients. [ABSTRACT FROM AUTHOR]

Objective: The benefit of bibloc over monobloc appliances in treating obstructive sleep apnoea (OSA) has not been evaluated in randomized trials. We hypothesized that these types of appliances would be equally effective.Material and methods: In this multicentre, randomized equivalence trial, patients with OSA received one type of bibloc or one type of monobloc treatment. At baseline, a 1-night polygraphy study was done, and this was repeated after 1 year. The outcome was any change in the apnoea-hypopnoea index (AHI) and the limits of equivalence between the two devices were set at ±5 AHI units.Results: Of 302 patients, 146 were randomly assigned to bibloc and 156 to monobloc appliances. In 88 and 104 patients, respectively, there were significant reductions in the AHI (p < .001) with a mean change of -16.7 (95% CI -19.4 to -14.1) in the bibloc and -11.8 (-14.9 to -8.7) in the monobloc groups. The proportions of responders defined as having an AHI <10 were 68% and 65% for the bibloc and monobloc groups, respectively. Treatment-related adverse events were mild, transient and the dropouts were more frequent in the bibloc group.Conclusions: Both types of treatments positively and significantly reduced respiratory disturbances, but at the 1-year follow-up, they were not significantly different in treating OSA, with a numerically greater reduction of the AHI value with the bibloc appliance. However, the higher proportion of treatment-related adverse events and higher proportion of dropouts among bibloc users should be balanced against the advantage of a greater reduction in the AHI. [ABSTRACT FROM AUTHOR]

Background: Colonic diverticular disease has been increasing in prevalence due to the rapidly aging global population, but standard treatment has not changed dramatically in recent years. Daiobotanpito (DBT; Da Huang Mu Dan Tang in Chinese) has been used in medical treatment of acute abdominal abscesses, such as appendicitis or diverticulitis in traditional Japanese (Kampo) medicine for many years, based on more than 3000 years of experience. Prior to this study, a retrospective open-label trial was conducted to compare patients with acute diverticulitis who received oral DBT combined with intravenous antibiotics with those who received intravenous antibiotic alone; it showed a positive effect of DBT on acute diverticulitis. We aim to investigate whether moderate to severe acute diverticulitis shows greater improvement with intravenous antibiotics plus orally administered DBT compared with intravenous antibiotics plus placebo.Methods: This is a two-group, randomized, double-blind, placebo-controlled, multi-center trial, which is designed to evaluate the efficacy and safety of DBT in patients with moderate to severe diverticulitis treated with intravenous antibiotics. Eligible participants will be randomized to either a treatment group receiving a 10-day oral DBT regimen plus conventional therapy or a control group receiving a 10-day placebo regimen plus conventional therapy. The primary outcome will be success in treating diverticulitis: the success rate will be defined as elimination of abdominal pain within 4 days in all patients, and in patients with fever (body temperature ≧ 37.5 °C) on inclusion into this study, fever relief with reduction in body temperature to < 37.5 °C within 3 days. Secondary endpoints will include the number of hospitalization days, changes in inflammatory response (C-reactive protein (CRP), white blood cell (WBC) and neutrophil counts), fever type, number of days before beginning food intake, recurrence rate (observation for 1 year after registration), and adverse event expression rate. Assessments will be performed at baseline and on the day of discharge. The recurrence rate will be recorded at 1 year after registration.Discussion: This study is expected to provide evidence to support the clinical benefits of DBT in the treatment of acute diverticulitis. It may also provide evidence on the efficacy and safety of DBT in the recurrence of acute diverticulitis.Trial Registration: UMIN-CTR: UMIN000027381. Registered on 27 April 2017. https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000031377, and changed to jRCTs041180063, registered on 30 July 2019; as a result of the revision of the domestic law in 2018 in Japan. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatitis C virus (HCV) genotype (GT) 4 infection is prevalent in sub‐Saharan Africa and the Middle East, particularly in Egypt. This study evaluated the safety and efficacy of elbasvir/grazoprevir administered for 8 and 12 weeks in participants with HCV GT4 infection. Methods: In this partially randomized, open‐label multicentre study conducted in France (NCT03111108; Protocol MK5172‐096), treatment‐naive participants with GT4 infection and F0‐F2 fibrosis were randomized 2:1 to elbasvir (50 mg)/grazoprevir (100 mg) for 8 or 12 weeks. Treatment‐naive participants with F3‐F4 fibrosis and all treatment‐experienced participants (F0‐F4) were assigned to elbasvir/grazoprevir for 12 weeks. The primary endpoint was sustained virologic response (SVR) 12 weeks after the end of therapy. Results: One hundred and seventeen participants were enrolled. Among treatment‐naive participants with F0‐F2 fibrosis, SVR was achieved by 94% (50/53) and 96% (26/27) of those receiving elbasvir/grazoprevir for 8 or 12 weeks, respectively, and four participants relapsed. In the 12‐week arm, 95% (35/37) achieved SVR and two participants relapsed. NS5A resistance‐associated substitutions were present at baseline and virologic failure in five of the participants with relapse. Drug‐related adverse events occurred in 42% (n = 22) and 50% (n = 32) of participants receiving 8 and 12 weeks of treatment, respectively. No participant discontinued treatment owing to an adverse event. Conclusion: These data confirm the efficacy of elbasvir/grazoprevir administered for 12 weeks in treatment‐experienced individuals with HCV GT4 infection and those with advanced fibrosis. Treatment‐naive individuals with mild fibrosis can be treated effectively with an 8‐week regimen. [ABSTRACT FROM AUTHOR]

Objectives: This research investigates the healing practices of modern Paganism using a randomized controlled trial. Paganism is a burgeoning belief system in the United Kingdom, within which healing is a key aspect. However, Pagan spell-casting practices have received little attention from distance healing researchers. This study aims to address this gap in the literature. Design: This study utilized a randomized, double-blind, delayed intervention design. Settings/Location: Research took place at the University of Northampton. Subjects: Forty-four participants (30 females, 14 males) were recruited using snowball sampling (mean age = 24.30; range = 18–55). Procedure: Participants were randomly allocated to either Group A or B. Participants made written requests to the practitioner about changes they would like to see in their lives and provided a photograph and personal item to be used during the intervention. Participants attended meetings once a week during which they would take part in a guided body scan meditation before completing a quality-of-life measure. Healing practices were conducted for Group A between weeks 1 and 2 and for Group B between weeks 2 and 3. Outcome Measure: Well-being was measured using the 26-item WHOQOL-BREF. Results: Multivariate analysis of variance (MANOVA) showed a significant, positive change in general health from weeks 1 to 4 (F = 4.02, p = 0.025, η2 = 0.149). Separate analysis of variances of the four WHOQOL domains showed significant improvements across the study in the physical and psychologic domains only; there was no significant group difference on any of the outcomes. Conclusion: All participants showed an increase in health and well-being domains directly related to their spell requests. However, there are no group differences to suggest that the spell-casting intervention was responsible. [ABSTRACT FROM AUTHOR]

Objectives:Bupleurum chinense (BC; Radix Bupleuri) formulae are widely used in herbal medicine clinical practice for major depressive disorder (MDD). This study provides an up-to-date and comprehensive systematic review and meta-analysis of BC formula for MDD. Design: Randomized controlled trials were retrieved from English and Chinese databases, from their inceptions to March 2019. Included studies compared BC formula alone or as integrative medicine to selective serotonin reuptake inhibitor (SSRI) antidepressants. Studies included adults 18–65 years of age. People with other types of depression or physical comorbidities, such as poststroke depression, bipolar, and other mental or physical disorders, were excluded. Meta-analysis was performed using STATA software. Grading of Recommendations Assessment, Development, and Evaluation was also conducted to assess the quality of evidence. Results: Thirty studies compared BC formula to antidepressants and 25 studies compared BC formula plus antidepressants to antidepressants alone. BC formula was more effective than antidepressants at improving depression severity measured on the Hamilton Rating Scale for Depression (HRSD) (standardized mean difference [SMD] −0.35, 95% confidence interval [CI] −0.52 to −0.18, I2 = 81.2%). Integrative use of BC formula plus SSRIs was also superior to SSRIs alone at improving HRSD scores (SMD −1.03, 95% CI −1.43 to −0.62, I2 = 94.2%). However, heterogeneity of the included studies was high and quality was low. The total number and severity of adverse events in the BC formula groups were less than that in the antidepressant groups. Conclusions: BC formula alone or given as integrative medicine with antidepressants reduced depression severity. However, the evidence is low quality and at risk of bias. Well-designed studies are needed to validate the results we identified in this review. [ABSTRACT FROM AUTHOR]

Objective: Toutongning (TTN) capsule, a Chinese patent medicine, is used as a prophylactic treatment for migraine. The present study was conducted as a postmarketing evaluation of the efficacy and safety of TTN capsule. Design: A randomized, double-blind, placebo-controlled trial. Location: Patients recruited from 14 medical centers in China from May 2014 to August 2015. Subjects: Patients between 18 and 65 years of age with a diagnosis of migraine. Interventions: The patients were randomly assigned to receive either TTN (1200 mg, three times daily) or a matched placebo (1:1) for 4 weeks. Outcome measures: The primary outcome measured was a minimum 50% reduction in the frequency of headaches from the 4-week baseline period to the last 4 weeks of the 12-week trial. Secondary outcomes included duration, days, and visual analog score of headache attack, interval between headache attacks, usage of acute analgesics, and score on the Headache Impact Test-6. In addition, all patients were evaluated for adverse events (AEs). Results: This study initially enrolled 400 patients; a total of 378 participants completed the experiment while fulfilling all study requirements. TTN had a superior effect compared with the placebo on both the primary and secondary outcome measures without any serious AEs or unexpected side effects. Conclusion: TTN can effectively prevent the occurrence of migraine headaches and is well-tolerated and safe. TTN may exhibit a persistent therapeutic effect even after cessation of use. Trial Registration number: ChiCTR-IPR-15007058. [ABSTRACT FROM AUTHOR]

Background The population effects of influenza vaccination in children have not been extensively studied, especially in tropical, developing countries. In rural Senegal, we assessed the total (primary objective) and indirect effectiveness of a trivalent inactivated influenza vaccine (IIV3). Methods In this double-blind, cluster-randomized trial, villages were randomly allocated (1:1) for the high-coverage vaccination of children aged 6 months through 10 years with either the 2008–09 northern hemisphere IIV3 or an inactivated polio vaccine (IPV). Vaccinees were monitored for serious adverse events. All village residents, vaccinated and unvaccinated, were monitored for signs and symptoms of influenza illness using weekly home visits and surveillance in designated clinics. The primary outcome was all laboratory-confirmed symptomatic influenza. Results Between 23 May and 11 July 2009, 20 villages were randomized, and 66.5% of age-eligible children were enrolled (3918 in IIV3 villages and 3848 in IPV villages). Follow-up continued until 28 May 2010. There were 4 unrelated serious adverse events identified. Among vaccinees, the total effectiveness against illness caused by the seasonal influenza virus (presumed to all be drifted A/H3N2, based on antigenic characterization data) circulating at high rates among children was 43.6% (95% confidence interval [CI] 18.6–60.9%). The indirect effectiveness against seasonal A/H3N2 was 15.4% (95% CI -22.0 to 41.3%). The total effectiveness against illness caused by the pandemic influenza virus (A/H1N1pdm09) was -52.1% (95% CI -177.2 to 16.6%). Conclusions IIV3 provided statistically significant, moderate protection to children in Senegal against circulating, pre-2010 seasonal influenza strains, but not against A/H1N1pdm09, which was not included in the vaccine. No indirect effects were measured. Further study in low-resource populations is warranted. Clinical Trials Registration NCT00893906. [ABSTRACT FROM AUTHOR]

Background and Aims: Irritable bowel syndrome (IBS) is a chronic relapsing disorder characterized by abdominal pain-discomfort and altered bowel habits. The IBS-diarrhoea predominant subtype (IBS-D) is defined as >25% of bowel movements representing type 6 or 7 of the Bristol Stool Form Scale. Management of IBS-D is mainly symptomatic, including lifestyle modification. Due to absence of standard treatment, multiple drugs are used. A controlled release (CR) form of mebeverine, recommended for spasmodic gastrointestinal disorders (including IBS) has recently been introduced in Indian market. We have conducted a placebo-controlled double blind randomized controlled trial [CTRI/2018/03/012897] to evaluate the effectiveness and safety of this product. Methods: 40 patients of IBS-D were recruited from medicine out-patient department (OPD) of a tertiary care hospital and randomized to two parallel groups. One received mebeverine 200 mg CR tablets twice daily for 8 weeks, while other received matching placebo. Outcome parameters were number of bowel movements per day over past 7 days (NoBM7d), severity of abdominal cramps and IBS quality of life (IBSQoL) score. Medication adherence record and treatment emergent adverse events were captured. Results: Mebeverine group showed modest but statistically significant improvement in NoBM7d, cramps and IBSQoL from baseline to 4 and 8 weeks. The changes within the placebo group were not statistically significant. Also, the intergroup differences at both 4 and 8 weeks were not statistically significant. Adherence was better in mebeverine group and both interventions were well tolerated. Conclusions: Mebeverine 200 mg CR twice daily has modest effect in IBS-D and therefore will not be a good choice for patients with severe symptoms. [ABSTRACT FROM AUTHOR]

Background: Various therapeutic agents have been described for alopecia areata but none is satisfactory. The use of ultraviolet A phototherapy in phototoxic regimens has emerged lately with promising results. Objective: To determine the efficacy and safety of phototoxic regimen of psoralen ultraviolet A (PUVA) in comparison to conventional therapy with intralesional corticosteroids in patients with alopecia areata. Methods: In this randomized controlled clinical trial, 40 patients were randomized to either phototoxic regimen of psoralen ultraviolet A group or potent intralesional corticosteroids group for three months. Study ended at six months. The primary outcome was treatment success: sustained regrowth of hair in ≥80% of the affected areas at six months. Tissue cytokines were assessed at zero and three months. Results: At six months, treatment success was achieved by 45% of patients, similarly in both groups. Tissue cytokine expression correlated well with clinical response. Conclusion: Phototoxic regimen of topical PUVA deserves a place among therapeutic tools used in management of alopecia areata especially in more extensive conditions where intralesional corticosteroids would not be suitable. Trial registration: [ABSTRACT FROM AUTHOR]

Summary: Treatment effects of combining teriparatide and whole-body vibration exercise (WBV) vs teriparatide alone in twelve months were compared using bone mineral density (BMD), bone microarchitecture, and bone turnover markers. We found an increased effect in lumbar spine BMD by adding WBV to teriparatide in postmenopausal osteoporotic women. Introduction: The parathyroid hormone (PTH) analogue teriparatide is an effective but expensive anabolic treatment for osteoporosis. Whole-body vibration exercise (WBV) has been found to stimulate muscle and bone strength in some studies. Animal data demonstrate a beneficial effect on bone when combining PTH with mechanical loading. The aim of this study was to investigate if combining WBV exercise and teriparatide treatment gives additional beneficial effects on bone compared to teriparatide alone in postmenopausal women with osteoporosis. Methods: The PaVOS study is a randomized controlled trial where postmenopausal osteoporotic women starting teriparatide 20 μg/day were randomized to WBV + teriparatide or teriparatide alone. WBV consisted of three sessions a week (12 min, including 1:1 ratio of exercise:rest). Bone mineral density (BMD) and bone microarchitecture, bone turnover markers, and sclerostin measurements were obtained. Data were analyzed using a linear mixed regression model with adjustment for baseline values or robust cluster regression in an intention-to-treat (ITT) analysis. Results: Thirty-five women were randomized (17 in teriparatide + WBV group and 18 in teriparatide group). At 12 months, both groups increased significantly in BMD at the lumbar spine. The teriparatide + WBV group increased by (mean ± SD) 8.90% ± 5.47 and the teriparatide group by 6.65% ± 5.51. The adjusted treatment effect of adding WBV to teriparatide was statistically significant at 2.95% [95% CI = 0.14–5.77; P = 0.040]. Markers of bone turnover increased significantly in both groups at three and six months with no significant difference between groups. No other treatment effects were observed in hip BMD, bone microarchitecture parameters, or sclerostin levels in either group. Conclusion: Twelve months of WBV and teriparatide had a significant clinically relevant treatment effect in lumbar spine BMD compared to teriparatide alone in postmenopausal osteoporotic women. ClinicalTrials.gov:(NCT02563353). [ABSTRACT FROM AUTHOR]

Background: Throwing injuries of the shoulder and elbow are common among youth baseball players. Hypothesis: A prevention program will reduce the incidence of throwing injuries of the shoulder and elbow by 50% among youth baseball players. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: The authors block randomized 16 youth baseball teams consisting of 237 players aged 9 to 11 years into an intervention group (8 teams, 117 players) and a control group (8 teams, 120 players). The intervention program consisted of 5 stretching, 2 dynamic mobility, and 2 balance training exercises performed during warm-up. Both groups were followed up for 12 months, during which the incidence of shoulder and elbow injuries was recorded. In addition, ball speed during pitching as a performance-related factor and variables of physical function (passive range of motion of the elbow, shoulder and hip, dynamic balance, and thoracic kyphosis angle) were assessed during the pre- and postintervention periods. Results: The incidence of shoulder and elbow injuries in the intervention group (1.7 per 1000 athlete-exposures) was significantly lower than that in the control group (3.1 per 1000 athlete-exposures) (hazard ratio, 1.940; 95% CI, 1.175-3.205; P =.010). The factors related to pitching performance, as assessed by ball speed, tended to increase in the intervention group as compared with the control group (P =.010). The program also improved shoulder horizontal adduction deficits on the dominant side, hip internal rotation on the nondominant side, and the thoracic kyphosis angle. Conclusion: A prevention program decreases throwing injuries of the shoulder and elbow and enhances the parameter of pitching performance in youth baseball players. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether XueBiJing injection improves clinical outcomes in critically ill patients with severe community-acquired pneumonia.Design: Prospective, randomized, controlled study.Setting: Thirty-three hospitals in China.Patients: A total of 710 adults 18-75 years old with severe community-acquired pneumonia.Interventions: Participants in the XueBiJing group received XueBiJing, 100 mL, q12 hours, and the control group received a visually indistinguishable placebo.Measurements and Main Results: The primary outcome was 8-day improvement in the pneumonia severity index risk rating. Secondary outcomes were 28-day mortality rate, duration of mechanical ventilation and total duration of ICU stay. Improvement in the pneumonia severity index risk rating, from a previously defined endpoint, occurred in 203 (60.78%) participants receiving XueBiJing and in 158 (46.33%) participants receiving placebo (between-group difference [95% CI], 14.4% [6.9-21.8%]; p < 0.001). Fifty-three (15.87%) XueBiJing recipients and 84 (24.63%) placebo recipients (8.8% [2.4-15.2%]; p = 0.006) died within 28 days. XueBiJing administration also decreased the mechanical ventilation time and the total ICU stay duration. The median mechanical ventilation time was 11.0 versus 16.5 days for the XueBiJing and placebo groups, respectively (p = 0.012). The total duration of ICU stay was 12 days for XueBiJing recipients versus 16 days for placebo recipients (p = 0.004). A total of 256 patients experienced adverse events (119 [35.63%] vs 137 [40.18%] in the XueBiJing and placebo groups, respectively [p = 0.235]).Conclusions: In critically ill patients with severe community-acquired pneumonia, XueBiJing injection led to a statistically significant improvement in the primary endpoint of the pneumonia severity index as well a significant improvement in the secondary clinical outcomes of mortality, duration of mechanical ventilation and duration of ICU stay. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of diacerein in patients with rheumatoid arthritis (RA) who are methotrexate inadequate responders (MTX-IR). Method: In this pilot, multicenter, double-blind, placebo-controlled trial, MTX-IR RA patients were randomized to either diacerein or matching placebo as add-on treatment to MTX for 24 weeks. Efficacy and safety were evaluated every 4 weeks until week 28. Primary and secondary efficacy endpoints were the percentage of patients achieving the ACR20 criteria and a moderate EULAR response at week 24, respectively. Results: Forty patients were equally randomized to both study treatments; 16 and 19 participants completed the study in the diacerein and the placebo arms, respectively. Baseline characteristics were similar in both groups, except that tender joint count, DAS28-ESR score, and non-steroidal anti-inflammatory drug consumption were higher in the placebo arm. The ACR20 response at week 24 was similar in the diacerein and placebo groups (65% vs 45%, P =.20). However, treatment response according to the EULAR criteria was better in patients taking diacerein (75% vs 25% of moderate response, P =.002). In the 35 patients with assessments through week 28, diacerein was superior to placebo in ACR20 at weeks 24 and 28 (both 81% vs 47%, P =.04). Incidence of adverse events was comparable in both arms, with only chromaturia being more common with diacerein than placebo (40% vs 10%, P =.03). Conclusions: These preliminary results show the potential benefits of diacerein on pain, joint function, and disease activity in MTX-IR RA patients. Trial registration: ClinicalTrials.gov Identifier: NCT01264211 Key Points • Diacerein has shown positive effects on rheumatoid arthritis symptoms. • A good safety profile of diacerein has been observed when it was administered as add-on therapy to methotrexate in patients with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

This study aimed to provide an updated systematic review and meta‐analysis of randomized controlled trials (RCT) investigating the effectiveness of lifestyle interventions on weight loss and the impact on the severity of obstructive sleep apnoea (OSA). A systematic search of five databases between 1980 and May 2018 was used to identify all RCT which employed a lifestyle intervention (i.e. diet‐only, exercise‐only or combination of the two) aiming to reduce the severity of OSA (assessed using the apnoea–hypopnoea index (AHI)). Random‐effects meta‐analyses followed by meta‐regression were conducted. Ten RCT involving 702 participants (Intervention group: n = 354; Control group: n = 348) were assessed in two meta‐analyses. The weighted mean difference in AHI (−8.09 events/h, 95% CI: −11.94 to −4.25) and body mass index (BMI, −2.41 kg/m2, 95% CI: −4.09 to −0.73) both significantly favoured lifestyle interventions over control arms. Subgroup analyses demonstrated that all interventions were associated with reductions in the AHI, but only the diet‐only interventions were associated with a significant reduction in BMI. No association was found between the reduction in AHI or BMI and the length of the intervention, or with baseline AHI and BMI levels. All lifestyle interventions investigated appear effective for improving OSA severity and should be an essential component of treatment for OSA. Future research should be directed towards identifying subgroups likely to reap greater treatment benefits as well as other therapeutic benefits provided by these interventions. See relatedEditorial [ABSTRACT FROM AUTHOR]

Background: A larger defect in the annulus fibrosus following lumbar discectomy is a well-known risk factor for reherniation. Procedures intended to prevent reherniation by sealing or occluding the annular defect warrant study in high-risk patients. This study sought to determine 3-year results of lumbar discectomy with a bone-anchored annular closure device (ACD) or lumbar discectomy only (controls) in patients at high risk for reherniation. Methods: This multicenter randomized trial enrolled patients with sciatica due to lumbar intervertebral disc herniation who failed conservative treatment. Patients with large annular defects after lumbar limited microdiscectomy were intraoperatively randomly assigned to receive ACD or control. Clinical and imaging follow-up was performed at routine intervals over 3 years. Main outcomes included rate of reherniations, reoperations, and endplate changes; leg and back pain scores on a visual analogue scale; Oswestry Disability Index (ODI); Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the SF-36; and adverse events adjudicated by a data safety monitoring board. Results: Among 554 randomized patients, the modified intent-to-treat population consisted of 272 patients in which ACD implantation was attempted and 278 receiving control; device implantation was not attempted in 4 patients assigned to ACD. Outcomes at 3 years favored ACD for symptomatic reherniation (14.8% vs. 29.5%; P < 0.001), reoperation (11.0% vs. 19.3%; P = 0.007), leg pain (21 vs. 30; P < 0.01), back pain (23 vs. 30; P = 0.01), ODI (18 vs. 23; P = 0.02), PCS (47 vs. 44; P < 0.01), and MCS (52 vs. 49; P < 0.01). The frequency of all-cause serious adverse events was comparable between groups (42.3% vs. 44.5%; P = 0.61). Conclusions: The addition of a bone-anchored ACD in patients with large annular defects following lumbar discectomy reduces the risk of reherniation and reoperation, and has a similar safety profile over 3-year follow-up compared with lumbar limited discectomy only. Trial registration: ClinicalTrials.gov NCT01283438 [ABSTRACT FROM AUTHOR]

To identify the rehabilitative effects of robot-assisted therapy on balance function among stroke patients. A systematic review and meta-analysis of randomized controlled trials. Thirteen electronic databases were systematically searched from inception to March 2018: Web of Science, PubMed, EMBase, The Cochrane Library, Science Direct, CINAHL, MEDLINE, AMED, Physiotherapy Evidence Database, SPORTDiscus, WanFang Data, China National Knowledge Infrastructure and Chinese Scientific Journal Database. Randomized controlled trials were retrieved for identifying the effects of robot-assisted therapy on balance function among stroke patients. Two authors independently searched databases, screened studies, extracted data, and evaluated the methodological quality and risk bias of each included study. A standardized protocol and data-collection form were used to extract information. Effect size was evaluated by mean difference with corresponding 95% confidence intervals. Methodological quality and risk bias evaluation for each included study followed the quality appraisal criteria for randomized controlled trials that were recommended by Cochrane Handbook. Meta-analysis was conducted by utilizing Review Manager 5.3, a Cochrane Collaboration tool. Data was synthesized with descriptive analysis instead of meta-analysis where comparisons were not possible to be conducted with a meta-analysis. Thirty-one randomized controlled trials with a total of 1249 participants were included. The majority of the included studies contained some methodological flaws. The results of the meta-analysis indicated that robot-assisted therapy produced positive effects on balance function, as shown by an increase in the Berg balance scale score [random effects model, mean difference = 4.64, 95%CI = 3.22–6.06, P ＜0.01], as well as Fugl-Meyer balance scale scores [fixed effects model, mean difference = 3.57, 95%CI = 2.81–4.34, P ＜0.01]. After subgroup and sensitivity analyses, the positive effects were not influenced by different types of robotic devices, by whether robot-assisted therapy was combined with another intervention or not, or by differences in duration and intensity of intervention. Evidence in the present systematic review indicates that robot-assisted therapy may produce significantly positive improvements on balance function among stroke patients compared with those not using this method. More multi-center, high-quality and large-scale randomized controlled trials following the guidelines of CONSORT are necessary to generate high-quality evidence in further research. [ABSTRACT FROM AUTHOR]

Objective: Adolescents and young adults (AYAs) with cancer are at high risk of negative psychosocial outcomes. Promoting Resilience in Stress Management (PRISM), a novel, brief, skill-based intervention, has demonstrated efficacy in improving psychosocial well-being for AYAs. We utilized data from a recent randomized trial of PRISM versus usual care (UC) to categorize and explore group differences in change trajectories of patient reported outcomes (PROs) over time.Methods: One hundred English-speaking AYAs (aged 12-25 years old) with cancer were randomized to PRISM versus UC. At enrollment and 6 months later, AYAs completed validated PROs measuring resilience (Connor-Davidson Resilience Scale [CDRISC-10]), hope (Hope Scale), benefit finding (Benefit and Burden Scale for Children), cancer-specific quality of life (Pediatric Quality of Life [PedsQL] Cancer Module), and distress (Kessler-6). Patient response trajectories were categorized as "improved," "consistently well," "consistently at risk," or "deteriorated" using minimal clinically important differences (MCIDs) or established measure cutoffs for all PROs. Positive response trajectories consisted of the first two categories ("improved" and "consistently well"), and negative response trajectories consisted of the latter two categories ("consistently at risk" and "deteriorated").Results: Across all PROs, more patients in the PRISM arm "improved" in psychosocial well-being over time, and fewer PRISM recipients "deteriorated" over time. Across all PROs, a greater proportion of PRISM participants (vs UC) experienced positive response trajectories. Across all PROs, a greater proportion of UC participants experienced negative response trajectories.Conclusions: PRISM shows evidence of both a prevention effect and an intervention effect. Thus, PRISM may serve as a viable prevention and early intervention model for psychosocial care. [ABSTRACT FROM AUTHOR]

Background: Post-prostatectomy urinary incontinence is an adverse event leading to significant distress. Our aim was to evaluate immediate urinary continence (UC) recovery in a single-surgeon prospective randomized comparative study between the traditional robot-assisted laparoscopic radical prostatectomy (TR-RALP) and the Retzius-sparing RALP (RS-RALP), for the treatment of the clinically localized prostate cancer (PCa).Methods: 102 consecutive PCa patients were prospectively randomized to TR-RALP (57) or RS-RALP (45). Postoperative continence was defined as patient-reported absence of leakage or use of 0 pads/day. The immediate continence rate and 95% confidence interval (CI 95%) were calculated for each treatment. Univariable and multivariate logistic regressions were used to assess predictors of immediate continence following RALP. Continence rates from 1 to 6 months were calculated by Kaplan-Meier curves; log-rank test was used for the curve comparison. Two analyses were performed, considering a per-protocol (PP) population regarding all randomized patients that received nerve-sparing RALP and an Intention-To-Treat (ITT) population regarding all randomized patients that received RALP.Results: In the PP analysis, the rates of immediate continence were 12/40 (30%) (CI 95% 17-47%) for the TR-RALP and 20/39 (51.3%) (CI 95% 35-68%) for the RS-RALP (p = 0.05). In the ITT analysis, the corresponding rates were 12/57 (21%) (CI 95% 11-34%) for the TR-RALP and 23/45 (51%) (CI 95% 36-66%) for the RS-RALP (p = 0.001). Median time to continence was 21 days for the TR-RALP and 1 day for RS-RALP, respectively (p = 0.02). The relative Kaplan-Meier curves regarding continence resulted statistically different when compared with the log rank test (p = 0.02). In the multivariate analysis, lower age and the Retzius-sparing approach were significantly associated to earlier continence recovery.Conclusions: The Retzius-sparing approach significantly reduces time to continence following RALP. Further studies are required to confirm the reproducibility of our results and investigate the role of the RS-RALP as an additional "protective" factor for postoperative continence in the elderly population. [ABSTRACT FROM AUTHOR]