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Background: Despite the implementation of various postoperative management strategies, the prevalence of postoperative fatigue syndrome (POFS) remains considerable among individuals undergoing laparoscopic radical gastrectomy. While the N-methyl-D-aspartic acid receptor antagonist esketamine has demonstrated efficacy in enhancing sleep quality and alleviating postoperative pain, its impact on POFS remains uncertain. Consequently, the objective of this study is to ascertain whether perioperative administration of esketamine can effectively mitigate the occurrence of POFS in patients undergoing laparoscopic radical gastrectomy. Methods: A total of 133 patients diagnosed with gastric cancer were randomly assigned to two groups, namely the control group (Group C) (n = 66) and the esketamine group (Group E) (n = 67), using a double-blind method. The Group C received standardized anesthesia, while the Group E received esketamine in addition to the standardized anesthesia. The primary outcome measure assessed was the Christensen fatigue score at 3 days after the surgical procedure, while the secondary outcomes included the disparities in postoperative fatigue, postoperative pain, sleep quality, and adverse reactions between the two groups. Results: In the group receiving esketamine, the fatigue scores of Christensen on the third day after surgery were significantly lower compared to the Group C (estimated difference, -0.70; 95% CI, -1.37 to -0.03; P = 0.040). Additionally, there was a significant decrease in the occurrence of fatigue in the Group E compared to the Group C on the first and third days following surgery (P < 0.05). Also, compared to individuals who had distal gastrectomy, those who had entire gastrectomy demonstrated a higher degree of postoperative tiredness reduction with esketamine. Furthermore, the Group E exhibited reduced postoperative pain and improved sleep in comparison to the Group C. Both groups experienced similar rates of adverse events. Conclusions: The use of esketamine during the perioperative period can improve POFS after laparoscopic radical gastrectomy, without adverse reactions. Trial registration: Registered in the Chinese Clinical Trial Registry (ChiCTR2300072167) on 05/06 /2023. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated whether using virtual reality (VR) could help reduce anxiety in women undergoing gynecological cancer surgery. Participants were split into two groups: one receiving VR therapy alongside usual care and the other receiving only usual care. Results showed that VR significantly decreased anxiety levels before surgery compared to the control group. This suggests that VR could be a valuable tool in preparing patients for surgery, potentially improving their experience and outcomes. Further research is needed to explore VR's benefits in other types of surgery and its long-term effects on patient recovery. Perioperative anxiety is common among patients undergoing surgery, potentially leading to negative outcomes. Immersive virtual reality (VR) has shown promise in reducing anxiety in various clinical settings. This study aimed to evaluate the effectiveness of VR in reducing perioperative anxiety in patients undergoing gynecological oncology surgery and was conducted as a single-center, double-arm, single-blinded randomized controlled trial at the Gold Coast University Hospital, Queensland, Australia. Participants were randomized into the VR intervention + care as usual (CAU) group (n = 39) and the CAU group (n = 41). Anxiety scores were assessed using a six-tier visual facial anxiety scale at baseline, after the intervention/CAU on the same day, and, several days up to weeks later, immediately before surgery. There was no significant difference in baseline anxiety scores, type of operation, or suspected cancer between the two groups. The VR intervention significantly reduced anxiety scores from baseline to preoperative assessment (p < 0.001). The median anxiety score in the VR intervention group decreased from 3 (interquartile range 2 to 5) at baseline to 2 (2 to 3) prior to surgery, while the control group's scores were 4 (2 to 5) and 4 (3 to 5), respectively. Multivariate analysis showed that group assignment was the sole outcome predictor, not age, type of procedure, or the time elapsed until surgery. Thus, VR exposure was effective in reducing perioperative anxiety in patients undergoing gynecological oncology surgery. The use of VR as a preparation tool may improve patient experience and contribute to better surgical outcomes, warranting further research into exploring the potential benefits of VR in other surgical specialties and its long-term impact on patient recovery. [ABSTRACT FROM AUTHOR]

Background: Although previous studies have showed that epidural morphine can be used as a complement to local anesthetics for analgesia after postcesarean delivery under spinal anesthesia, there is little known about the analgesic dosage of epidural morphine and hydromorphone for hemorrhoidectomy. Therefore, we conducted this study to examine the potency ratio of hydromorphone to epidural morphine as well as effective analgesic dose for 50% patients (ED50) undergoing elective hemorrhoidectomy. Methods: 80 patients under elective hemorrhoidectomy with combined spinal and epidural anesthesia(CSEA) in department of anesthesia, Dongguan Tungwah hospital. To assess the ED50, patients were treated with epidural morphine or epidural hydromorphone randomly using a biased coin method-determined dose with a sequential allocation procedure. Following surgery, standardized multimodal analgesia was administered to all patients. A pain response score of ≤ 3 (on a scale of 0–10) was determined to be the effective dose after 24 h following CSEA. The ED50 in both groups were determined using the probit regression and isotonic regression method. We also measured pain intensity by patient interview using a 10 point verbal numeric rating scale prospectively at 6, 12 and 24 h after CSEA, and adverse effects were also noted. Results: The ED50 was 0.350 mg (95% CI, 0.259–0.376 mg) in hydromorphone group and 1.129 mg (95% CI, 0.903–1.187 mg) in morphine group, respectively, estimated by isotonic regression method. Regression analysis with the probit, the ED50 of epidural hydromorphone was 0.366 mg (95% CI, 0.276–0.388 mg) and epidural morphine was 1.138 mg (95% CI, 0.910–1.201 mg). Exploratory findings showed that there was no difference between the most frequent dosages of epidural hydromorphone or epidural morphine in the occurrence of nausea, vomiting and pruritus. When administered with epidural opioids at ED50 doses or higher, 97.5% (39/40) of epidural morphine patients and 97.5% (39/40) epidural hydromorphone of patients were satisfied with their analgesia. Conclusion: Effective hemorrhoidectomy analgesia requires a 3:1 ratio of epidural morphine to epidural hydromorphone. Both drugs provide excellent patient satisfaction. [ABSTRACT FROM AUTHOR]

Background: In Traditional Chinese Medicine (TCM) theory, cold dampness obstruction is one of the common syndromes of osteoarthritis. Therefore, in clinical practice, the main treatment methods are to dispel wind, remove dampness, and dissipate cold, used to treat knee osteoarthritis (KOA). This report describes a mulitercenter clinical study to assess Zhuifeng Tougu Capsule's efficacy and safety in the treatment of patients who are cold dampness obstruction syndrome in KOA, and to provide evidence-based medical for the rational use of Zhuifeng Tougu Capsules in clinical practice. Methods: This randomized, parallel group controlled, double-blind, double dummy trial will include a total of 215 KOA patients who meet the study criteria. 215 patients underwent 1:1 randomisation, with 107 cases assigned the experimental group (Zhuifeng Tougu Capsules + Glucosamine Sulfate Capsules Simulator) and 108 assigned the control group (Glucosamine Sulfate Capsules + Zhuifeng Tougu Capsules Simulator). After enrolment, patients received 12 weeks of treatment. The main efficacy measure is the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score. Visual analogue scale (VAS) pain score, Self-condition assessment VAS score, WOMAC KOA score, TCM syndrome score and TCM syndrome efficacy, ESR level, CRP level, suprapatellar bursa effusion depth, use of rescue drugs, and safety indicators are secondary efficacy indicators. Results: Compared with before treatment, WOMAC pain score, VAS pain score, Self-condition assessment VAS score, WOMAC KOA score, and TCM syndrome score decreased significantly in both groups (P < 0.01). Also, the experimental group showed significant differences in the above indicators compared to control (P < 0.01). However, after treatment, no significant differences were showed in the ESR level, CRP level, and suprapatellar bursa effusion depth between the two groups (P > 0.05). No any serious adverse effects showed in the experimental group and control group. Conclusions: Zhuifeng Tougu Capsules can effectively improve knee joint function and significantly alleviate the pain of KOA. Trial registration: Clinical trial registration was completed with the China Clinical Trial Registration Center for this research protocol (No. ChiCTR2000028750) on January 2, 2020. [ABSTRACT FROM AUTHOR]

Objective: Limited studies have yet evaluated the effectiveness of topiramate in the treatment of amphetamine and methamphetamine addiction. Therefore, the aim of this study was to investigate the effectiveness of topiramate in the treatment of patients with this disorder. Methods: In this randomized, double-blind, placebo-controlled clinical trial, 52 patients with amphetamine and methamphetamine use disorder, within the age range of 16-60 years, were randomly divided into an intervention group (n = 26) and a placebo group (n = 26). The intervention group was treated with topiramate tablets with a starting dose of 50 mg, which was gradually increased to the target dose of 200 mg. The control group was treated with placebo. The duration of drug intervention in this clinical trial was 12 weeks, and all participants were evaluated before the intervention and 2, 4, 6, 8, 10, and 12 weeks after beginning the intervention. The Beck Depression Inventory, drug use temptation questionnaire, urine test, and side effects questionnaire were used as outcome measures to assess the patients. The data were analyzed using chi-square, independent t-test, and analysis of variance with repeated measurements. Results: There was no significant difference between the intervention and placebo groups in depression at the beginning of the treatment and at the 4th, 8th, and 12th weeks after the intervention (P > 0.05). The urine test also showed no significant difference between the two groups at any of the evaluation stages (P > 0.05). Although there was no significant difference between the two groups in the drug use temptation results at the beginning and the 2nd, 4th and 6th weeks (P > 0.05), the level of drug temptation in the intervention group was significantly lower than the placebo group in the 8th, 10th, and 12th weeks (P < 0.05). Conclusion: Topiramate can be effective in reducing the desire to use amphetamine and methamphetamine. However, further studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Background: The risk of postoperative cognitive dysfunction(POCD) in laparoscopic surgery should not be overlooked. Intravenous lidocaine can reduce perioperative inflammatory response in patients undergoing laparoscopic surgery, while the effect of intraoperative intravenous lidocaine on postoperative cognitive function in patients undergoing laparoscopic colorectal cancer surgery has not been well studied. We investigated whether intraoperative lidocaine improves postoperative cognitive function after laparoscopic radical resection for colorectal cancer. Methods: We conducted a prospective, randomized double blinded controlled trial to investigate the effect of intravenous lidocaine on rapid postoperative recovery in patients undergoing laparoscopic radical resection of colorectal cancer. The patients were randomly assigned to receive either intravenous lidocaine or saline. The primary outcome was cognitive dysfunction defined by a decrease from pre- to postoperative ≥ 2 of the Mini-Mental State Examination (MMSE) score, at the 3rd and the 7th postoperative days. Secondary outcomes were the MMSE raw score and parameters of the patients' postoperative recovery such as agitation and length of stay in the post-anaesthesia care unit (PACU), length of hospital stay, markers of inflammation (white blood cell count and CRP), and incidence of complications. Results: Seventy-three patients in the lidocaine group and 77 patients in the control group completed the trial. The rate of cognitive dysfunction was lower in the lidocaine group than that in the control group, both at the 3rd (18.57% vs. 63.64% for each group respectively; RR = 0.26, 95%CI = 0.19–0.32; p < 0.0001) and at the 7th postoperative day (12.33% vs. 53.25% for each group respectively; RR = 0.28, 95%CI = 0.22–0.35; P < 0.001). The postoperative MMSE scores were also higher in the lidocaine group than in the control group both at the 3rd (median 25 vs. 24 respectively) and at the 7th postoperative day (26 vs. 24 respectively). Also, patients in the lidocaine group displayed a lower white blood cell count than the control group at the 1st postoperative day (8.5 ± 2.7 vs. 10.4 ± 3.3; p < 0. 001). No differences were evidenced for the other secondary outcomes. Conclusions: Intraoperative intravenous lidocaine can significantly improve postoperative cognitive function in patients undergoing laparoscopic radical resection of colorectal cancer. Trial registration: Chinese Clinical Trial Registry (16/1/2022, registration number: ChiCTR2200055683) [ABSTRACT FROM AUTHOR]

Objective Alcohol withdrawal syndrome (AWS) is a frequent and potentially life-threatening condition experienced in alcohol use disorder. Since hypomagnesemia is involved in AWS's severity, we conducted a multicenter double-blind randomized placebo-controlled trial to examine the efficacy of oral magnesium supplementation as an adjuvant therapy of AWS. Material and Methods Inpatients were recruited in six different centers if they had a baseline score higher than eight on the Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). The experimental treatment was magnesium lactate dehydrate, administrated three times per day providing a total of 426.6 mg per day and up to 15 days. The primary endpoint was the significant between-group difference of the CIWA-Ar total score change from baseline to 3 days later. The treatment group and baseline score were introduced as covariables in an analysis of covariance. Results A total of 98 inpatients were included {71.4% of men; mean age of 49.1 years [standard deviation (SD): 10.3]}. In the intention-to-treat population, the mean reduction of the CIWA-Ar score in the experimental group between baseline and 3 days later was 10.1 (SD: 5.2), whereas it was 9.2 (SD: 3.9) in the control group. The absolute difference of the adjusted mean in the experimental group compared with the control group was −0.69 (SD: 0.72), which did not correspond to a significant between-group difference (P  = 0.34). Per-protocol analysis and sensitivity analyses also supported this result. Supplementary analyses found no significant difference regarding benzodiazepine consumption, magnesium blood concentration, and satisfaction to care. Conclusions The present study does not support the rationale of systematic oral magnesium supplementation in patients with AWS. [ABSTRACT FROM AUTHOR]

Background: Dementia is characterized by neurocognitive decline which interferes with daily function and independence. Cognitive stimulation therapy (CST) is an evidence-based cognitive psychosocial intervention for people with dementia. Materials and Methods: A prospective interventional study of single-blind RCT design conducted in the Department of Neurology at ABVIMS and Dr RML Hospital amongst patients with DSM-V major neurocognitive disorder aged more than 50 years. Participants were randomized to CST and control groups using a block-randomized design. The control group participants received treatment as usual while the CST group delivered 45-min virtual group CST sessions for a total of 14 sessions over seven weeks. All participants in both groups were assessed at baseline and eight weeks using the Montreal Cognitive Assessment Scale (MoCA), Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog), neuropsychiatric inventory, instrumental activities of daily living, and Zarit Burden Interview for Caregiver Burden (ZBI) by a rater blind to group randomization. Results: Total MoCA scores improved significantly in the CST group, compared to the control group which showed a statistically significant decrease. The mean total ADAS-Cog score in the CST group improved significantly compared to controls. The Lawton Instrumental Activities of Daily Living Scale showed a statistically significant change in the control group compared to the intervention group. From the comparison of the mean total neuropsychiatric inventory scale, it was observed that there was a statistically significant decrease in the severity of Behavioural and Psychological Symptoms of Dementia (BPSD) symptoms in the CST group. The mean total ZBI score decreased significantly in the CST group favoring less caregiver burden. Conclusion: This study proved that CST has a significant impact on cognitive outcomes in dementia and it also proved its effectiveness in controlling the BPSD outcomes and caregiver burden in dementia. [ABSTRACT FROM AUTHOR]

Simple Summary: Effective and scalable diet, exercise, and weight management interventions are needed for primary cancer prevention in the general public, as well as for cancer control and tertiary prevention among the growing population of cancer survivors. A 6-month online intervention, entitled "Daughters, dUdes, mothErs, and others Together" (DUET), was designed to promote weight loss, a healthful diet, and increased physical activity among cancer survivors and their chosen partners. Fifty-six cancer survivor-partner dyads (n = 112 participants in total) were recruited into a randomized controlled trial that compared DUET to a waitlist control. The trial surpassed all feasibility endpoints with regard to uptake, retention, and safety; the DUET intervention also resulted in significant weight loss and reductions in caloric intake, as well as having a promising impact on physical activity and performance, blood glucose, and indicators of inflammation. (1) Background: A healthful diet, regular physical activity, and weight management are cornerstones for cancer prevention and control. Yet, adherence is low in cancer survivors and others, calling for innovative solutions. Daughters, dUdes, mothers, and othErs fighting cancer Together (DUET) is a 6-month, online, diet-and-exercise, weight-loss intervention to improve health behaviors and outcomes among cancer survivor-partner dyads. (2) Methods: DUET was tested in 56 dyads (survivors of obesity-related cancers and chosen partners) (n = 112), both with overweight/obesity, sedentary behavior, and suboptimal diets. After baseline assessment, dyads were randomized to DUET intervention or waitlist control arms; data were collected at 3- and 6-months and analyzed using chi-square, t-tests, and mixed linear models (α < 0.05). (3) Results: Retention was 89% and 100% in waitlisted and intervention arms, respectively. Dyad weight loss (primary outcome) averaged −1.1 (waitlist) vs. −2.8 kg (intervention) (p = 0.044/time-by-arm interaction p = 0.033). Caloric intake decreased significantly in DUET survivors versus controls (p = 0.027). Evidence of benefit was observed for physical activity and function, blood glucose, and c-reactive protein. Dyadic terms were significant across outcomes, suggesting that the partner-based approach contributed to intervention-associated improvements. (4) Conclusions: DUET represents a pioneering effort in scalable, multi-behavior weight management interventions to promote cancer prevention and control, calling for studies that are larger in size, scope, and duration. [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]

Objective Our main aim was to investigate the effect of a single oral dose of C21, a selective angiotensin II type 2 receptor agonist, on cold-induced vasoconstriction in SSc-related RP. Methods This was a phase IIa, randomized, double-blind, cross-over, single-dose, placebo-controlled, single-centre study. Twelve female patients with SSc (median age 58.5 years, median duration of RP 19.0 years) attended on four occasions: screening, treatment visits 1 and 2 (separated by 3–7 days) and follow-up. At the first treatment visit, patients were randomized to receive either a single oral dose of C21 (200 mg) or placebo, then the opposite treatment on the second visit. Forty min after each treatment, each patient underwent a standard hand cold challenge. The primary end point was the area under the curve (AUC) for rewarming for each finger (eight fingers) over 15 min. Secondary end points included the maximum finger temperature after rewarming (MAX). Statistical analyses were performed by multiplicative ANCOVA models. Results For all eight fingers combined, mean AUC for rewarming was higher after treatment with C21 than after placebo (geometric mean 20 046°C*s vs 19 558°C*s), but not significantly (P  = 0.380) and MAX (at 15 min) was also higher (geometric mean 23.5°C vs 22.5°C; P  = 0.036). C21 was well tolerated. Conclusion Despite the small trial size, a signal emerged suggesting that even in patients with established SSc, C21 may confer benefit for RP and deserves further investigation. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT04388176. [ABSTRACT FROM AUTHOR]

Background: Dietary fish-oil supplementation might attenuate the associations between fine particulate matter (PM2.5) and subclinical biomarkers. However, the molecular mechanisms remain to be elucidated. This study aimed to explore the molecular mechanisms of fish-oil supplementation against the PM2.5-induced health effects.Methods: We conducted a randomized, double-blinded, and placebo-controlled trial among healthy college students in Shanghai, China, from September 2017 to January 2018. A total of 70 participants from the Fenglin campus of Fudan University were included. We randomly assigned participants to either supplementation of 2.5-gram fish oil (n = 35) or sunflower-seed oil (placebo) (n = 35) per day and conducted four rounds of health measurements in the last two months of the trial. As a post hoc exploratory study, the present untargeted metabolomics analysis used remaining blood samples collected in the previous trial and applied a Metabolome-Wide Association Study framework to compare the effects of PM2.5 on the metabolic profile between the sunflower-seed oil and fish oil groups.Results: A total of 65 participants completed the trial (34 of the fish oil group and 31 of the sunflower-seed oil group). On average, ambient PM2.5 concentration on the day of health measurements was 34.9 µg/m3 in the sunflower-seed oil group and 34.5 µg/m3 in the fish oil group, respectively. A total of 3833 metabolites were significantly associated with PM2.5 in the sunflower-seed oil group and 1757 in the fish oil group. Of these, 1752 metabolites showed significant between-group differences. The identified differential metabolites included arachidonic acid derivatives, omega-3 fatty acids, omega-6 fatty acids, and omega-9 fatty acids that were related to unsaturated fatty acid metabolism, which plays a role in the inflammatory responses.Conclusion: This trial suggests fish-oil supplementation could mitigate the PM2.5-induced inflammatory responses via modulating fatty acid metabolism, providing biological plausibility for the health benefits of fish-oil supplementation against PM2.5 exposure.Trial Registration: This study is registered at ClinicalTrails.gov (NCT03255187). [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]

Objective: Sleep disturbance is one of the most prevalent problems in post-menopausal females. The current research intended to evaluate the effects of Dracocephalum on sleep disorder in post-menopausal females. Method: The current study is a randomized, double-blind controlled trial, in which 110 post-menopausal women were randomly allocated to Dracocephalum or placebo groups. The intervention group took Dracocephalum capsules containing 250 mg Dracocephalum extract twice daily for one month. While, the placebo group took the same capsule containing 250 mg of starch twice daily for one month. Pittsburgh Sleep Quality Index was completed by the participants of both groups before and after the treatment and the data obtained were analyzed with Chi-square, paired and independent t-test in SPSS (version 20). Results: The mean score of sleep quality before and after the treatment was 12.69 ± 3.98 and 8.58 ± 1.97 in the treatment group, respectively. Also, the score of sleep quality in the placebo group was 13.48 ± 2.60 and 11.21 ± 2.74 at the beginning and end of the research, respectively. The symptoms of sleep disorder in the intervention group significantly improved after the treatment (P < 0.001), while this was not the case with the placebo group (P = 0.155). Besides, there was a significant difference between the two groups in the mean score of sleep quality after the treatment (P = 0.012). Conclusion: Dracocephalum extracts are effective in reducing symptoms of sleep disorders in post-menopausal women. [ABSTRACT FROM AUTHOR]

Background: Axial involvement constitutes a specific domain of psoriatic arthritis (PsA). Interleukin (IL)-23 inhibitors have demonstrated improvement in axial PsA (axPsA) symptoms, but have not shown efficacy in treating ankylosing spondylitis (AS), suggesting differences in axPsA processes and treatments. In a post hoc, pooled analysis of patients with investigator- and imaging-confirmed sacroiliitis in two phase 3, randomized, placebo-controlled studies (DISCOVER-1 and DISCOVER-2), patients treated with guselkumab, an IL-23p19 inhibitor, had greater axial symptom improvements compared with placebo. Confirmatory imaging at baseline was restricted to the sacroiliac (SI) joints, occurred prior to/at screening, and was locally read.Methods: The STAR study will prospectively assess efficacy outcomes in PsA patients with magnetic resonance imaging (MRI)-confirmed axial inflammation. Eligible, biologic-naïve patients with PsA (N =  405) for ≥ 6 months and active disease (≥ 3 swollen and ≥ 3 tender joints, C-reactive protein [CRP] ≥ 0.3 mg/dL) despite prior non-biologic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs will be randomized (1:1:1) to guselkumab every 4 weeks (Q4W); guselkumab at week (W) 0, W4, then every 8 weeks (Q8W); or placebo with crossover to guselkumab at W24, W28, then Q8W. Patients will have Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4, spinal pain component score (0-10 visual analog scale) ≥ 4, and screening MRI-confirmed axial involvement (positive spine and/or SI joints according to centrally read Spondyloarthritis Research Consortium of Canada [SPARCC] score ≥ 3 in ≥ 1 region). The primary endpoint is mean change from baseline in BASDAI at W24; multiplicity controlled secondary endpoints at W24 include AS Disease Activity Score employing CRP (ASDAS), Disease Activity Index for PsA (DAPSA), Health Assessment Questionnaire - Disability Index (HAQ-DI), Investigator's Global Assessment of skin disease (IGA), and mean changes from baseline in MRI SI joint SPARCC scores. Centrally read MRIs of spine and SI joints (scored using SPARCC) will be obtained at W0, W24, and W52, with readers blinded to treatment group and timepoint. Treatment group comparisons will be performed using a Cochran-Mantel-Haenszel or chi-square test for binary endpoints and analysis of covariance, mixed model for repeated measures, or constrained longitudinal data analysis for continuous endpoints.Discussion: This study will evaluate the ability of guselkumab to reduce both axial symptoms and inflammation in patients with active PsA.Trial Registration: This trial was registered at ClinicalTrials.gov, NCT04929210 , on 18 June 2021.Protocol Version: Version 1.0 dated 14 April 2021. [ABSTRACT FROM AUTHOR]

Background: Gynecological malignant patients often have significant psychological and physical problems. The feasibility and generalizability of traditional intervention method is low due to the high time and labor cost, large number of gynecological malignant tumor patients in China, as well as shortage of health professionals. Therefore, it is necessary to design an alternative, innovative, and easily accessible intervention method. This study aims to evaluate the effect of WeChat-based intervention on anxiety, depression and disease-related symptoms of patients with gynecological malignant tumors during rehabilitation.Methods: A single-blinded, randomized, controlled, parallel-group pre-test and repeated post-test design will be conducted. A total of 76 participants will be randomly divided into the intervention group and control group. Anxiety and depression, disease-related symptoms, coping ability, benefit finding and quality of life will be measured at baseline and repeated immediately after the intervention (test 1), 3 months (test 2) and 6 months (test 3) after the intervention.Discussion: As the first randomized controlled trial with rigorous research design for patients with gynecological malignant tumors in the rehabilitation stage in China, this study will provide evidences for the effectiveness of the WeChat platform during intervention of patients with gynecological malignant tumors in the rehabilitation stage. The results are helpful to further explore the effect of WeChat-based intervention on improving patients' anxiety and depression, disease-related symptoms, and quality of life.Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100053450, Registered 21 November 2021, http://www.chictr.org.cn/searchproj.aspx. [ABSTRACT FROM AUTHOR]

Background and Objective: Zishen Pingchan granule (ZPG), a traditional Chinese herbal recipe for treating Parkinson's disease (PD), is usually used as an add-on drug with some antiparkinsonian drugs in China. The objectives of this study were to evaluate the efficacy, safety, and tolerability of ZPG combined with pramipexole in the treatment of depression in PD (dPD).Methods: A 12-week, multicenter, randomized, double-blind, and placebo-controlled study on ZPG was performed on a total of 200 patients who were treated with pramipexole but still had mild to moderate depressive symptoms. Patients were randomly divided into ZPG (n = 100) or placebo (n = 100). The primary effective result was the mean change from the baseline on the Hamilton Depression Scale 17 items (HAM-D-17) over 12 weeks and the clinical efficacy rate. Secondary endpoints were the mean change from the baseline in the Geriatric Depression Scale (GDS-15), Unified Parkinson's disease rating scale Part III (UPDRS III), Parkinson's quality of life scale (PDQ-8), and Parkinson's disease sleep scale (PDSS-2) over 12 weeks.Results: After 12 weeks of treatment, ZPG significantly reduced the mean [95% confidence interval] HAMD score vs. placebo (- 1.43 scores [- 2.50, - 0.36]; p = 0.009). The clinical remission rate and responders of the ZPG group were higher than those of the placebo (46.1% vs. 31.0%; p = 0.041; 34.8% vs. 18.4%; p = 0.014). A significant improvement in the PDSS-2 score was also observed in the ZPG group compared with that in the placebo group (- 3.56 scores [- 5.77, - 1.35]; p = 0.002). A total of 7 patients (7.1%) in the ZPG group had mild adverse events (AEs) vs 9 patients (9%) in the placebo group. No severe AEs were observed in either group. The randomization and controlled clinical study revealed that ZPG was effective, safe, and well-tolerated.Conclusion: ZPG combined with pramipexole further reduced the depressive symptoms and improved the sleeping quality of PD patients. Trial registration The protocol was retrospectively registered at the Chinese Clinical Trial Registry, Unique identifier: ChiCTR1800019942, date of registration: December 9, 2018; http://www.chictr.org.cn/showproj.aspx?proj=30432. [ABSTRACT FROM AUTHOR]

Background: To summarize the up-to-date empirical evidence on trial-level characteristics of randomized controlled trials associated with treatment effect estimates.Methods: A systematic review searched three databases up to August 2020. Meta-epidemiological (ME) studies of randomized controlled trials on intervention effect were eligible. We assessed the methodological quality of ME studies using a self-developed criterion. Associations between treatment effect estimates and trial-level characteristics were presented using forest plots.Results: Eighty ME studies were included, with 25/80 (31%) being published after 2015. Less than one-third ME studies critically appraised the included studies (26/80, 33%), published a protocol (23/80, 29%), and provided a list of excluded studies with justifications (12/80, 15%). Trials with high or unclear (versus low) risk of bias on sequence generation (3/14 for binary outcome and 1/6 for continuous outcome), allocation concealment (11/18 and 1/6), double blinding (5/15 and 2/4) and smaller sample size (4/5 and 2/2) significantly associated with larger treatment effect estimates. Associations between high or unclear risk of bias on allocation concealment (5/6 for binary outcome and 1/3 for continuous outcome), double blinding (4/5 and 1/3) and larger treatment effect estimates were more frequently observed for subjective outcomes. The associations between treatment effect estimates and non-blinding of outcome assessors were removed in trials using multiple observers to reach consensus for both binary and continuous outcomes. Some trial characteristics in the Cochrane risk-of-bias (RoB2) tool have not been covered by the included ME studies, including using validated method for outcome measures and selection of the reported results from multiple outcome measures or multiple analysis based on results (e.g., significance of the results).Conclusions: Consistently significant associations between larger treatment effect estimates and high or unclear risk of bias on sequence generation, allocation concealment, double blinding and smaller sample size were found. The impact of allocation concealment and double blinding were more consistent for subjective outcomes. The methodological and reporting quality of included ME studies were dissatisfactory. Future ME studies should follow the corresponding reporting guideline. Specific guidelines for conducting and critically appraising ME studies are needed. [ABSTRACT FROM AUTHOR]

Background: Colorectal adenomas (CRAs) are precancerous lesions of the large intestine presenting as colorectal polyps. At present, the conventional treatment methods for CRA mainly include high-frequency electrocoagulation and electroexcision, biopsy forceps polypectomy, cauterization by laser and microwave, and other endoscopic interventions. The principal advantages conferred by these treatment strategies include less trauma, quick postoperative recovery, and simplicity to perform. However, the higher recurrence rates and insignificant improvement of postoperative symptoms after endoscopic surgery are considerable drawbacks to this approach. Besides, there is currently no effective pharmacotherapy to prevent the recurrence of CRA. Jianpi Lishi Jiedu (JLJ) granules are a form of traditional Chinese medicine (TCM) used to manage postoperative patients with CRA, which has shown a certain degree of efficacy in clinical practice. However, its effectiveness and safety profile have not been convincingly evaluated. The purpose of this study is to evaluate the clinical efficacy and safety profile of JLJ granules in the management of postoperative patients with CRA and to observe the recurrence rate of adenoma in these patients.Methods: A randomized, double-blind, and placebo-controlled clinical trial is performed in this study. A total of 80 postoperative patients with CRA will be randomly classified into the Jianpi Lishi Jiedu granules group or the placebo control group. Patients in both groups shall receive 3 months of intervention, after which medical follow-up and safety evaluation will be performed for all of the patients. The primary outcome is the recurrence rate of adenomas within 12 months. The secondary outcomes are the cardinal TCM symptom scores, minor TCM symptom scores, Bristol Stool Scale, efficacy of TCM symptoms, safety indicators, and blinding assessment.Discussion: In this study, the impact on the recurrence of adenomas and the efficacy and safety of JLJ granules in terms of improving the clinical symptoms of postoperative patients with CRA will be evaluated.Trial Registration: Trial registration Chinese Clinical Trial Registry ChiCTR 2100044297. Registered on March 16, 2021. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of Ludangshen oral liquid for treatment of convalescent patients with coronavirus disease 2019 (COVID-19) with randomized, double-blind, placebo-controlled multicenter method. Methods: 200 convalescent COVID-19 patients who had symptoms related to decreased digestive and respiratory function were randomly divided to either receive Ludangshen oral liquid or placebo for 2 weeks. The severity of clinical symptoms including fatigue, anorexia, abdominal distension, loose stools, and shortness of breath were assessed by visual analogue scale and observed at before and after treatment. The improvement and resolution rates of clinical symptoms were evaluated. Full analysis set (FAS) and per-protocol set (PPS) were used for statistical analyses. Adverse events were recorded during the study. Results: 8 patients did not complete the study. After 2 weeks of treatment, both FAS and PPS results showed that patients in Ludangshen group had significantly lower score of fatigue, anorexia, loose stools, and shortness of breath than placebo group (P < 0.05), while there was no significant difference in distention (P > 0.05). The improvement rate of fatigue, anorexia, distension, loose stools and shortness of breath were significantly higher in Ludangshen group (P < 0.05), as well as the resolution rates (P < 0.05) except for shortness of breath (P > 0.05). There were two cases of adverse events, with one nose bleeding in Ludangshen group and one headache in placebo group. Conclusion: The study suggested that two weeks of Ludangshen oral liquid treatment may have certain effects for convalescent COVID-19 patients on improving digestive and respiratory symptoms including fatigue, anorexia, loose stools and shortness of breath, which may be one of the choices for management of convalescent COVID-19 patients with digestive and respiratory symptoms. [ABSTRACT FROM AUTHOR]

Background: To investigate the analgesic effect of perioperative use of duloxetine in patients received total knee arthroplasty (TKA).Method: This prospective randomized, double-blind, placebo-controlled trial study was registered in the Chinese Clinical Trial Registry (ChiCTR2000033910). 100 patients were finally enrolled. The hospital pharmacy prepared small capsules containing either duloxetine or starch (placebo) which were all identical in appearance and weight (50:50). The 100 enrolled patients were given a capsule (containing either 60 mg duloxetine or 60 mg placebo) every night before sleep since preoperative day 2 till postoperative day 14 (17 days in all) by a nurse who were not involved in this trial. Other perioperative managements were the same in the two groups. The primary outcome was the VAS score, including rVAS (visual analogue scale at rest) and aVAS (visual analogue scale upon ambulation) throughout the perioperative period. The secondary outcomes included opioid consumption, range of motion, including both active range of motion (aROM) and passive range of motion (pROM) and adverse events. The patients were followed up everyday until 7 days after TKA, afterwards, they were followed up at the time of 3 weeks and 3 months after TKA.Result: rVAS in duloxetine group were significantly less than placebo group throughout the postoperative period: 4.7 ± 2.3 vs 5.9 ± 2.6 (P = 0.016) at 24 h postoperative; 2.1 ± 1.6 vs 2.8 ± 1.7 (P = 0.037) at 7 days postoperative. In terms of aVAS, similarly, duloxetine group had less aVAS than placebo group throughout the postoperative period: 6.2 ± 2.1 vs 7.1 ± 2.2 (P = 0.039) at 24 h postoperative; 3.3 ± 1.7 vs 4.1 ± 2.0 (P = 0.034) at 7 days postoperative. Patients in duloxetine group consumed significantly less opioids per day than the placebo group: 24.2 ± 10.1 g vs 28.5 ± 8.3 g (P = 0.022) at 24 h postoperative; 2.7 ± 2.5 g vs 4.1 ± 2.6 g (P = 0.007) at 7 days postoperative. aROM in duloxetine group were significantly better than placebo group until postoperative day 6, the aROM became comparable between the two groups: 110.2 ± 9.9° in duloxetine group vs 107.5 ± 11.5° in control group (P = 0.211). In terms of pROM, duloxetine group had significantly better pROM until postoperative day 5, the pROM became comparable between the two groups: 103.8 ± 12.1° in duloxetine group vs 99.5 ± 10.8° in control group (P = 0.064). No significant difference was found between the two groups in the rates of dizziness, bleeding, sweating, fatigue and dryness of mouth. In the placebo group, more patients got nausea/vomiting and constipation (P < 0.05). However, in terms of drowsiness, duloxetine group was reported higher rate (P < 0.05).Conclusion: Several other RCTs have already mentioned the analgesic effect of duloxetine, but not in the immediate postoperative period. In this study, we found duloxetine could reduce acute postoperative pain in the immediate postoperative period and decrease the opioids consumption as well as accelerating postoperative recovery, without increasing the risk of adverse medication effects in patients undergoing TKA. Duloxetine could act as a good supplement in multimodal pain management protocol for patients undergoing TKA.Trial Registration Statement: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000033910). The date of registration was 06/16/2020. [ABSTRACT FROM AUTHOR]

Background: Existing recommended treatment options for personality disorders (PDs) are extensive and costly. There is emerging evidence indicating that trauma-focused treatment using eye movement desensitization and reprocessing (EMDR) therapy aimed at resolving memories of individuals' adverse events can be beneficial for this target group within a relatively short time frame. The primary purpose of the present study is to determine the effectiveness of EMDR therapy versus waiting list in reducing PD symptom severity. Furthermore, the effects of EMDR therapy on trauma symptom severity, loss of diagnosis, personal functioning, quality of life, and mental health outcomes will be determined. In addition, the cost-effectiveness of EMDR therapy in the treatment of PDs is investigated. Moreover, predictors of treatment success, symptom deterioration and treatment discontinuation will be assessed. Lastly, experiences with EMDR therapy will be explored.Method: In total, 159 patients with a PD will be included in a large multicentre single-blind randomized controlled trial. The Structured Clinical Interview for DSM-5 Personality Disorders will be used to determine the presence of a PD. Participants will be allocated to either a treatment condition with EMDR therapy (ten biweekly 90-min sessions) or a waiting list. Three months after potential treatment with EMDR therapy, patients can receive treatment as usual for their PD. All participants are subject to single-blinded baseline, post-intervention and 3-, 6- and 12-month follow-up assessments. The primary outcome measures are the Assessment of DSM-IV Personality Disorders and the Clinician-Administered PTSD Scale for DSM-5. For cost-effectiveness, the Treatment Inventory of Costs in Patients with psychiatric disorders, EuroQol-5D-3L, and the Mental Health Quality of Life Questionnaire will be administered. The PTSD Checklist for DSM-5, Brief State Paranoia Checklist and Difficulties in Emotion Regulation Scale will be used to further index trauma symptom severity. Type of trauma is identified at baseline with the Childhood Trauma Questionnaire-SF and Life Events Checklist for the DSM-5. Personal functioning and health outcome are assessed with the Level of Personality Functioning Scale-BF 2.0, Outcome Questionnaire-45 and Mental Health Quality of Life Questionnaire. Experiences with EMDR therapy of patients in the EMDR therapy condition are explored with a semi-structured interview at post-intervention.Discussion: It is expected that the results of this study will contribute to knowledge about the effectiveness, and cost-effectiveness of trauma-focused treatment using EMDR therapy in individuals diagnosed with a PD. Follow-up data provide documentation of long-term effects of EMDR therapy on various outcome variables, most importantly the reduction of PD symptom severity and loss of diagnoses.Trial Registration: Netherlands Trial Register NL9078 . Registered on 31 November 2020. [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: Vulvovaginal candidiasis is the second most common cause of vulvovaginal infections. Due to the increasing resistance to synthetic antifungal drugs, the use of drugs with a natural origin is a priority. The aim of the present study was to compare the effectiveness of Arnebia euchroma with vaginal cream clotrimazole 1% United States Pharmacopeia (USP) for the treatment of vulvovaginal candidiasis. Materials and Methods: This triple-blind trial study was performed on 112 women with diagnosed Candida vaginitis clinically and by a laboratory test, patients were randomly divided into two groups receiving Arnebia euchroma and vaginal clotrimazole (56 people per group) in clinics and medical centers Ahvaz (Iran) from April 2018 to April 2019. Clinical and laboratory symptoms were recorded at the beginning of the study and 1 week after the end of treatment by a researcher-made questionnaire. Data analysis were performed using SPSS software v-23. p < 0.05 was considered significant. Results: After the intervention, vaginal culture was negative in terms of Candida in 17 (36.17%) patients of the Amoeba euchroma group and 37 (69.81%) patients of the clotrimazole group. The Chi-square showed that there was a significant difference between the culture results in both groups (χ² = 10.10, df = 1, p = 0.001). No differences were observed between the two groups in terms of vaginal symptoms based on adjustment for age and using a logistic regression model. Conclusions: A vaginal cream containing Arnebia euchroma could reduce the complaints of vulvovaginal candidiasis. But, future studies with larger sample sizes and different dosages are recommended. [ABSTRACT FROM AUTHOR]

Intravenous immunoglobulin treatment for chronic inflammatory demyelinating polyneuropathy usually starts with a 2.0 g/kg induction dose followed by 1.0 g/kg maintenance doses every 3 weeks. No dose-ranging studies with intravenous immunoglobulin maintenance therapy have been published. The Progress in Chronic Inflammatory Demyelinating polyneuropathy (ProCID) study was a prospective, double-blind, randomized, parallel-group, multicentre, phase III study investigating the efficacy and safety of 10% liquid intravenous immunoglobulin (Panzyga®) in patients with active chronic inflammatory demyelinating polyneuropathy. Patients were randomized 1:2:1 to receive the standard intravenous immunoglobulin induction dose and then either 0.5, 1.0 or 2.0 g/kg maintenance doses every 3 weeks. The primary end point was the response rate in the 1.0 g/kg group, defined as an improvement ≥1 point in adjusted Inflammatory Neuropathy Cause and Treatment score at Week 6 versus baseline and maintained at Week 24. Secondary end points included dose response and safety. This trial was registered with EudraCT (Number 2015-005443-14) and clinicaltrials.gov (NCT02638207). Between August 2017 and September 2019, the study enrolled 142 patients. All 142 were included in the safety analyses. As no post-infusion data were available for three patients, 139 were included in the efficacy analyses, of whom 121 were previously on corticosteroids. The response rate was 80% (55/69 patients) [95% confidence interval (CI): 69-88%] in the 1.0 g/kg group, 65% (22/34; CI: 48-79%) in the 0.5 g/kg group, and 92% (33/36; CI: 78-97%) in the 2.0 g/kg group. While the proportion of responders was higher with higher maintenance doses, logistic regression analysis showed that the effect on response rate was driven by a significant difference between the 0.5 and 2.0 g/kg groups, whereas the response rates in the 0.5 and 2.0 g/kg groups did not differ significantly from the 1.0 g/kg group. Fifty-six per cent of all patients had an adjusted Inflammatory Neuropathy Cause and Treatment score improvement 3 weeks after the induction dose alone. Treatment-related adverse events were reported in 16 (45.7%), 32 (46.4%) and 20 (52.6%) patients in the 0.5, 1.0 and 2.0 g/kg dose groups, respectively. The most common adverse reaction was headache. There were no treatment-related deaths. Intravenous immunoglobulin (1.0 g/kg) was efficacious and well tolerated as maintenance treatment for patients with chronic inflammatory demyelinating polyneuropathy. Further studies of different maintenance doses of intravenous immunoglobulin in chronic inflammatory demyelinating polyneuropathy are warranted. [ABSTRACT FROM AUTHOR]

Background: Long-term exposure to high concentrations of PM2.5 may cause immune system dysfunction and damage to the respiratory and cardiovascular systems. PM2.5 may cause CD4 + T helper cells to polarize toward TH1 or TH2 cell types, which may be associated with the onset and progression of many human diseases. Recent studies have shown that omega-3 fatty acids can regulate human immune function and reduce physiological damage caused by air pollution; however, only limited research has examined the therapeutic effects of omega-3 fatty acids on subjects with high exposure to PM2.5 in mass transit systems such as subways.Methods: This study was designed as a prospective, randomized, double-blinded (to participants and researchers), placebo-controlled clinical trial. The research plan is to randomly select 120 eligible adults based on the difference in PM2.5 exposure in the Chengdu subway station. They should be aged 20-65 years old and work in the subway station more than or equal to 3 times a week, each time greater than or equal to 8 h, and had worked continuously in the subway station for more than 2 years. All participants will receive omega-3 fatty acids or placebo for 8 weeks. The primary outcomes will be changes in the TH1/TH2 cell polarization index and changes in serum cytokine concentrations. Secondary outcomes will be changes in early indicators of atherosclerosis, pulmonary function, COOP/WONCA charts, and scores on the Short-Form 36 Health Survey for quality of life. Results will be analyzed to evaluate differences in clinical efficacy between the two groups. A 6-month follow-up period will be used to assess the long-term value of omega-3 fatty acids for respiratory and cardiovascular disease endpoints.Discussion: We will explore the characteristics of the TH1/TH2 cell polarization index in a population with high exposure to PM2.5. Omega-3 fatty acids and placebo will be compared in many ways to test the effect on people exposed to PM2.5 subway stations. This study is expected to provide reliable evidence to support the promotion of omega-3 fatty acids in clinical practice to protect individuals who are highly exposed to PM2.5.Trial Registration: Chinese Clinical Trial Registry ChiCTR2000038065 . Registered on September 9, 2020. [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]

Objective: to evaluate the effect of the Self-Instructional Guide for Clinical Reasoning on the diagnostic accuracy of undergraduate Nursing students. Method: a randomized, parallel and double-blind (researchers and outcome evaluators) clinical trial, carried out with undergraduate Nursing students. Validated case studies were applied in two phases to identify the patient's Nursing diagnosis/problem, etiology and clues, using the Guide with the intervention group in the second phase. The outcomes - diagnostic and etiological accuracy and number of clues - were evaluated using validated rubrics. Descriptive statistics were used to analyze demographic data; Fisher's exact test for similarities in prior education and confidence; Mann-Whitney's test for age; and non-parametric ANOVA test in the evaluation of the hypothesis of differences in performance. Results: final sample composed of 24 students in the control group and 27 in the intervention group; no difference as to gender, age and schooling. There was a difference in diagnostic (p=0.041) and etiological (p=0.0351) accuracy in the intervention group, showing a negative effect of using the Guide. Conclusion: the one-time selfinstruction was not effective in impacting the diagnostic accuracy of students solving case studies. Repeated application of the Guide as a teaching tool can be effective in improving such outcome. [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]

Background: Variability in the 25-hydroxyvitamin D [25(OH)D] response to prenatal and postpartum vitamin D supplementation is an important consideration for establishing vitamin D deficiency prevention regimens.Objectives: We aimed to examine interindividual variation in maternal and infant 25(OH)D following maternal vitamin D supplementation.Methods: In a randomized trial of maternal vitamin D supplementation (Maternal Vitamin D for Infant Growth Trial), healthy pregnant women (n = 1300) received a prenatal cholecalciferol (vitamin D-3) dose of 0, 4200, 16,800, or 28,000 IU/wk from 17 to 24 wk of gestation followed by placebo to 6 mo postpartum. A fifth group received 28,000 IU cholecalciferol/wk both prenatally and postpartum. In a subset of participants, associations of 25(OH)D with hypothesized explanatory factors were estimated in women at delivery (n = 655) and 6 mo postpartum (n = 566), and in their infants at birth (n = 502) and 6 mo of age (n = 215). Base models included initial 25(OH)D and supplemental vitamin D dose. Multivariable models were extended to include other individual characteristics and specimen-related factors. The model coefficient of determination (R2) was used to express the percentage of total variance explained.Results: Supplemental vitamin D intake and initial 25(OH)D accounted for the majority of variance in maternal 25(OH)D at delivery and postpartum (R2 = 70% and 79%, respectively). Additional characteristics, including BMI, contributed negligibly to remaining variance (<5% increase in R2). Variance in neonatal 25(OH)D was explained mostly by maternal delivery 25(OH)D and prenatal vitamin D intake (R2 = 82%). Variance in 25(OH)D in later infancy could only partly be explained by numerous biological, sociodemographic, and laboratory-related characteristics, including feeding practices (R2 = 43%).Conclusions: Presupplementation 25(OH)D and vitamin D supplemental dose are the major determinants of the response to maternal prenatal vitamin D intake. Vitamin D dosing regimens to prevent maternal and infant vitamin D deficiency should take into consideration the mean 25(OH)D concentration of the target population. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced nausea and vomiting (CINV) is considered as the most common complications of chemotherapy which has a detrimental influence on the quality of life of patients with cancer. We assessed the efficacy of Apple (Malus domestica) syrup for reducing CINV. Materials and Methods: This study was a randomized, double-blind, placebo-controlled trial carried out in a Hematooncology Clinic affiliated to Mazandaran University of Medical Sciences, Sari, Iran (from October 2017 to August 2018). Subjects were randomly allocated to receive apple syrup or placebo along with their previous antiemetic treatment and chemotherapy regimen, three times a day. Thirty-four patients received apple syrup (n = 16) or placebo (n = 18). Statistical analysis was conducted using SPSS software Version 21® (SPSS Inc., Chicago, IL, USA). A P < 0.05 indicated statistical significance. Results: Both acute and delayed nausea grades were significantly lower in M. domestica syrup in comparison to placebo syrup (P = 0.001 and 0.001, respectively). The duration of nausea (P = 0.04) was lower in intervention group compared to placebo group. Conclusion: These findings demonstrated that M. domestica syrup can reduce the severity and duration of nausea in cancer patients who received chemotherapy. [ABSTRACT FROM AUTHOR]

To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk of worsening. We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: need for supplemental oxygen, age ≥75 years, age between 60 and 74 years and presence of at least one co-morbidity. Severely ill patients requiring oxygen therapy >3 L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on day 0 followed by 400 mg per day for 8 days or a placebo. The primary end point was a composite of death or start of invasive mechanical ventilation within 14 days following randomization. Secondary end points included mortality and clinical evolution at days 14 and 28, and viral shedding at days 5 and 10. The trial was stopped after 250 patients were included because of a slowing down of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years (interquartile range 58–86 years) and 151/250 (60.4%) patients required oxygen therapy. The primary end point occurred in 9/124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group (relative risk 1.12; 95% CI 0.45–2.80). The rates of positive SARS-CoV-2 RT-PCR tests at days 5 and 10 were 72.8% (75/103) and 57.1% (52/91) in the hydroxychloroquine group, versus 73.0% (73/100) and 56.6% (47/83) in the placebo group, respectively. No difference was observed between the two groups in any of the other secondary end points. In this underpowered trial involving mainly older patients with mild to moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo. ClinicalTrials.gov Identifier: NCT04325893 (https://clinicaltrials.gov/ct2/show/NCT04325893). [ABSTRACT FROM AUTHOR]

Clinical practice guidelines support cognitive rehabilitation for people with a history of mild traumatic brain injury (mTBI) and cognitive impairment, but no class I randomized clinical trials have evaluated the efficacy of self-administered computerized cognitive training. The goal of this study was to evaluate the efficacy of a self-administered computerized plasticity-based cognitive training programmes in primarily military/veteran participants with a history of mTBI and cognitive impairment. A multisite randomized double-blind clinical trial of a behavioural intervention with an active control was conducted from September 2013 to February 2017 including assessments at baseline, post-training, and after a 3-month follow-up period. Participants self-administered cognitive training (experimental and active control) programmes at home, remotely supervised by a healthcare coach, with an intended training schedule of 5 days per week, 1 h per day, for 13 weeks. Participants (149 contacted, 83 intent-to-treat) were confirmed to have a history of mTBI (mean of 7.2 years post-injury) through medical history/clinician interview and persistent cognitive impairment through neuropsychological testing and/or quantitative participant reported measure. The experimental intervention was a brain plasticity-based computerized cognitive training programme targeting speed/accuracy of information processing, and the active control was composed of computer games. The primary cognitive function measure was a composite of nine standardized neuropsychological assessments, and the primary directly observed functional measure a timed instrumental activities of daily living assessment. Secondary outcome measures included participant-reported assessments of cognitive and mental health. The treatment group showed an improvement in the composite cognitive measure significantly larger than that of the active control group at both the post-training [+6.9 points, confidence interval (CI) +1.0 to +12.7, P = 0.025, d = 0.555] and the follow-up visit (+7.4 points, CI +0.6 to +14.3, P = 0.039, d = 0.591). Both large and small cognitive function improvements were seen twice as frequently in the treatment group than in the active control group. No significant between-group effects were seen on other measures, including the directly-observed functional and symptom measures. Statistically equivalent improvements in both groups were seen in depressive and cognitive symptoms. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is the most common joint disorder in the United States of America (USA) with a fast-rising prevalence. Current treatment modalities are limited, and total knee replacement surgeries have shown disadvantages, especially for grade II/III OA. The interest in the use of biologics, including umbilical cord (UC)-derived Wharton's jelly (WJ), has grown in recent years. The results from a preliminary study demonstrated the presence of essential components of regenerative medicine, namely growth factors, cytokines, hyaluronic acid (HA), and extracellular vesicles, including exosomes, in WJ. The proposed study aims to evaluate the safety and efficacy of intra-articular injection of UC-derived WJ for the treatment of knee OA symptoms. Methods: A randomized, controlled, single-blind, multi-center, prospective study will be conducted in which the safety and efficacy of intra-articular administration of UC-derived WJ are compared to HA (control) and saline (placebo control) in patients suffering from grade II/III knee OA. A total of 168 participants with grade II or III knee OA on the KL scale will be recruited across 53 sites in the USA with 56 participants in each arm and followed for 1 year post-injection. Patient satisfaction, Numeric Pain Rating Scale, Knee Injury and Osteoarthritis Outcome Score, 36-Item Short Form Survey (SF-36), and 7-point Likert Scale will be used to assess the participants. Physical exams, X-rays, and MRI with Magnetic Resonance Observation of Cartilage Repair Tissue score will be used to assess improvement in associated anatomy. Discussion: The study results will provide valuable information into the safety and efficacy of intra-articular administration of Wharton's jelly for grade II/III knee osteoarthritis. The results of this study will also add to the treatment options available for grade II/III OA as well as help facilitate the development of a more focused treatment strategy for patients. Trial registration: ClinicalTrials.gov, NCT04711304. Registered on January 15, 2021 [ABSTRACT FROM AUTHOR]

Background: Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response.Objectives: This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI.Methods: The ASSAIL-MI trial was a randomized, double-blind, placebo-controlled trial conducted at 3 high-volume PCI centers in Norway. Patients admitted with STEMI within 6 h of symptom onset were eligible. Consenting patients were randomized in a 1:1 fashion to promptly receive a single infusion of 280 mg tocilizumab or placebo. The primary endpoint was the myocardial salvage index as measured by magnetic resonance imaging after 3 to 7 days.Results: We randomized 101 patients to tocilizumab and 98 patients to placebo. The myocardial salvage index was larger in the tocilizumab group than in the placebo group (adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04). Microvascular obstruction was less extensive in the tocilizumab arm, but there was no significant difference in the final infarct size between the tocilizumab arm and the placebo arm (7.2% vs. 9.1% of myocardial volume, p = 0.08). Adverse events were evenly distributed across the treatment groups.Conclusions: Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703). [ABSTRACT FROM AUTHOR]

Background: Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by diastolic dysfunction. Despite the increasing incidence of HFpEF, there is no available therapy that reduces the mortality rate of HFpEF. Zhigancao Tang has been used traditionally for the treatment of cardiovascular diseases in China. The use of traditional Chinese medicine (TCM) is associated with improvements in clinical syndromes and quality of life of patients. A randomized clinical trial should be conducted to provide clear evidence regarding the efficacy and safety of Zhigancao Tang granules for the treatment of HFpEF.Methods: A randomized, double-blinded, placebo-controlled clinical trial was proposed. A total of 122 patients with HFpEF will be randomly assigned to receive Zhigancao Tang granules or placebo for 12 weeks. The primary outcome measure is cardiac function. The secondary outcomes include measurement of the integral TCM syndrome score, echocardiography, 6-min walk test, N-terminal-pro hormone B-type natriuretic peptide level, atrial natriuretic peptide level, Minnesota Living with Heart Failure scale, and Lee's scale. The outcome measures will be evaluated at baseline, 4 weeks, and 12 weeks. Adverse events will be evaluated from baseline till the 12-week follow-up period.Discussion: The results of this trial will demonstrate whether Zhigancao Tang granules are effective and safe for treating HFpEF.Trial Registration: ClinicalTrials.gov NCT04317339 . Registered on 23 March 2020. [ABSTRACT FROM AUTHOR]

Background: The potential of a ketone monoester (β-hydroxybutyrate; KEβHB) supplement to rapidly mimic a state of nutritional ketosis offers a new therapeutic possibility for diabetes prevention and management. While KEβHB supplementation has a glucose-lowering effect in adults with obesity, its impact on glucose control in other insulin-resistant states is unknown.Objectives: The primary objective was to investigate the effect of KEβHB-supplemented drink on plasma glucose in adults with prediabetes. The secondary objective was to determine its impact on plasma glucoregulatory peptides.Methods: This randomized controlled trial [called CETUS (Cross-over randomizEd Trial of β-hydroxybUtyrate in prediabeteS)] included 18 adults [67% men, mean age = 55 y, mean BMI (kg/m2) = 28.4] with prediabetes (glycated hemoglobin between 5.7% and 6.4% and/or fasting plasma glucose between 100 and 125 mg/dL). Participants were randomly assigned to receive KEβHB-supplemented and placebo drinks in a crossover sequence (washout period of 7-10 d between the drinks). Blood samples were collected from 0 to 150 min, at intervals of 30 min. Paired-samples t tests were used to investigate the change in the outcome variables [β-hydroxybutyrate (βHB), glucose, and glucoregulatory peptides] after both drinks. Repeated measures analyses were conducted to determine the change in concentrations of the prespecified outcomes over time.Results: Blood βHB concentrations increased to 3.5 mmol/L within 30 minutes after KEβHB supplementation. Plasma glucose AUC was significantly lower after KEβHB supplementation than after the placebo [mean difference (95% CI): -59 (-85.3, -32.3) mmol/L × min]. Compared with the placebo, KEβHB supplementation led to significantly greater AUCs for plasma insulin [0.237 (0.044, 0.429) nmol/L × min], C-peptide [0.259 (0.114, 0.403) nmol/L × min], and glucose-dependent insulinotropic peptide [0.243 (0.085, 0.401) nmol/L × min], with no significant differences in the AUCs for amylin, glucagon, and glucagon-like peptide 1.Conclusions: Ingestion of the KEβHB-supplemented drink acutely increased the blood βHB concentrations and lowered the plasma glucose concentrations in adults with prediabetes. Further research is needed to investigate the dynamics of repeated ingestions of a KEβHB supplement by individuals with prediabetes, with a view to preventing new-onset diabetes. This trial was registered at www.clinicaltrials.gov as NCT03889210. [ABSTRACT FROM AUTHOR]

Background: Outcomes data for a durable-polymer everolimus-eluting stent (EES) at extended long-term follow-up in patients with ST-segment elevation myocardial infarction (STEMI) are unknown.Objectives: The aim of this study was to assess the 10-year outcomes of patients enrolled in the EXAMINATION (A Clinical Evaluation of Everolimus Eluting Coronary Stents in the Treatment of Patients With ST-Segment Elevation Myocardial Infarction) trial.Methods: The EXAMINATION-EXTEND (10-Years Follow-Up of the EXAMINATION Trial) study is an investigator-driven 10-year follow-up of the EXAMINATION trial, which randomly assigned 1,498 patients with STEMI in a 1:1 ratio to receive either EES (n = 751) or bare-metal stents (n = 747). The primary endpoint was a patient-oriented composite endpoint of all-cause death, any myocardial infarction, or any revascularization. Secondary endpoints included a device-oriented composite endpoint of cardiac death, target vessel myocardial infarction, or target lesion revascularization; the individual components of the combined endpoints; and stent thrombosis.Results: Complete 10-year clinical follow-up was obtained in 94.5% of the EES group and 95.9% of the bare-metal stent group. Rates of the patient-oriented composite endpoint and device-oriented composite endpoint were significantly reduced in the EES group (32.4% vs. 38.0% [hazard ratio: 0.81; 95% confidence interval: 0.68 to 0.96; p = 0.013] and 13.6% vs. 18.4% [hazard ratio: 0.72; 95% confidence interval: 0.55 to 0.93; p = 0.012], respectively), driven mainly by target lesion revascularization (5.7% vs. 8.8%; p = 0.018). The rate of definite stent thrombosis was similar in both groups (2.2% vs. 2.5%; p = 0.590). No differences were found between the groups in terms of target lesion revascularization (1.4% vs. 1.3%; p = 0.963) and definite or probable stent thrombosis (0.6% vs. 0.4%; p = 0.703) between 5 and 10 years.Conclusions: At 10-year follow-up, EES demonstrated confirmed superiority in combined patient- and device-oriented composite endpoints compared with bare-metal stents in patients with STEMI requiring primary percutaneous coronary intervention. Between 5- and 10-year follow-up, a low incidence of adverse cardiovascular events related to device failure was found in both groups. (10-Years Follow-Up of the EXAMINATION Trial; NCT04462315). [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method. Methods: Sixty cases from Shanghai Changzheng Hospital from April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6 weeks, 12 weeks, 6 months, and 12 months after intervention. MORCART scores were assessed at pre-operation and 12 months after intervention. Results: Twenty-nine cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P > 0.05). The WOMAC total and WOMAC function scores of the experiment group were significantly lower than those of the control group 6 months and 12 months after surgery (P < 0.05). The VAS rest and VAS motion scores of the experiment group were found significantly lower than those of the control group 12 months after surgery (P < 0.05). The MOCART scores of the experiment group were found significantly higher compared with the control group 12 months after surgery (P < 0.05). No significant difference in WOMAC stiffness scores were found between the two groups. Conclusions: The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe and provides assistance in reducing pain and improving function in patients with knee cartilage lesions. Trial registration: ChiCTR1800015379. Registered on 27 March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25901. [ABSTRACT FROM AUTHOR]

Background: Diabetes and its sequelae such as diabetic foot ulcer are rising health hazards not only in western countries but all over the world. Effective, yet safe treatments are desperately sought for by physicians, healthcare providers, and of course patients.Methods/design: APOSEC, a novel, innovative drug, is tested in the phase I/II study MARSYAS II, where its efficacy to promote healing of diabetic foot ulcers will be determined. To this end, the cell-free secretome of peripheral blood mononuclear cells (APOSEC) blended with a hydrogel will be applied topically three times weekly for 4 weeks. APOSEC is predominantly effective in hypoxia-induced tissue damages by modulating the immune system and enhancing angiogenesis, whereby its anti-microbial ability and neuro-regenerative capacity will exert further positive effects. In total, 132 patients will be enrolled in the multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-ranging phase I/II study and treated with APOSEC at three dose levels or placebo for 4 weeks, followed by an 8-week follow-up period to evaluate safety and efficacy of the drug. Wound area reduction after 4 weeks of treatment will serve as the primary endpoint.Conclusion: We consider our study protocol to be suitable to test topically administered APOSEC in patients suffering from diabetic foot ulcers in a clinical phase I/II trial.Trial Registration: EudraCT 2018-001653-27 . Registered on 30 July 2019. ClinicalTrials.gov NCT04277598 . Registered on 20 February 2020.Title: "A randomized, placebo-controlled, double-blind study to evaluate safety and dose-dependent clinical efficacy of APO-2 at three different doses in patients with diabetic foot ulcer (MARSYAS II)". [ABSTRACT FROM AUTHOR]

Objective: to evaluate the effectiveness of the 50 IU/mL heparin solution compared to the 0.9% isotonic saline solution in preventing occlusion of the double lumen Hickman® catheter, 7 and 9 French, in patients undergoing hematopoietic stem cell transplantation. Method: a triple-blind randomized clinical trial. 17 double-lumen catheters (heparin group: n = 7 and 0.9% isotonic saline group: n = 10) were analyzed in which the two catheter routes were evaluated separately, totaling 34 lumens. The outcome variables were occlusion without reflux and complete occlusion. Descriptive analyses were performed using the Chi-square test and, of survival, according to the Kaplan-Meier test. Results: the mean number of days until the occlusion outcome was 52 in the heparin group and 13.46 in the 0.9% isotonic saline group in the white catheter route (p<0.001). In the red route, the mean follow- up days in the heparin group were 35.29, with no occlusion and 22.30 in the 0.9% isotonic saline group until the first occlusion (p=0.030). Conclusion: blocking with 50 IU/mL heparin solution is more effective than 0.9% isotonic saline in preventing occlusion of the Hickman® catheter. Brazilian Registry of Clinical Trials: RBR-3ht499. [ABSTRACT FROM AUTHOR]

Objective: Major depressive disorder (MDD) is predicted to be one of the biggest disease burden in the future. The antidepressant activity of gemfibrozil has been recently considered. In this study, we assessed the effectiveness of gemfibrozil as a sertraline adjunct in treating patients with MDD. Method: In this study, 46 patients with MDD based on the DSM-V criteria with a minimum score of 22 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were divided into two groups. One group was treated with 300 mg of gemfibrozil daily and the other group treated with placebo. Each group was treated simultaneously with 100 mg of sertraline daily for 8 weeks. The trial was randomized and double-blind. To assess the response to treatment, patients were evaluated at baseline and then at weeks 2, 4 and 8 using the HAM-D score. Results: The study was completed by 45 patients up to the final stages and follow-up visits. Repeated measure ANOVA with a Greenhouse-Geisser correction showed a significant difference for timextreatment interaction on within-subjects HAM-D scores [p-value= 0.026]. A notable difference was seen in time [p-value < 0.001]. The test of between-subject effects also represented a remarkable consequence of treatment on HAM-D scores at weeks 2, 4, and 8 [p-value = 0.07]. Using Kaplan-Meier estimate curves, time to remission periods were notable different between the 2 trial groups [Log-Rank p-value = 0.003]. Conclusion: Gemfibrozil is an effective adjunctive treatment in MDD and can be used to reduce depression symptoms. [ABSTRACT FROM AUTHOR]

Background: Diets inducing high fluctuations in plasma glucose levels are linked to type 2 diabetes. L-arabinose and D-xylose have been hypothesized to inhibit intestinal sucrase activity, delay sucrose digestion, and reduce glycaemic and insulinaemic responses. However, few human studies have assessed this using realistic foods. Objective: We investigated the effects of the addition of L-arabinose and D-xylose on glucose homeostasis using a fruit-based drink and the effect of L-arabinose using a muffin. Design: Fifteen males participated in two double-blind, randomized cross-over experiments. In experiment A, three drinks were tested: (1) L-arabinose, (2) D-xylose and (3) control drink. In experiment B, two muffins were tested: (1) L-arabinose and (2) control muffin. All products consisted of ~50 g available carbohydrates, and L-arabinose or D-xylose was added as 10% of sucrose. Pre- and post-ingestive plasma glucose and insulin levels were measured at fixed time points up to 180 min after consumption. Results: Glucose and insulin peaks were lower after the L-arabinose and D-xylose drink than the control drink (P < 0.01). After consumption of the muffin, glucose responses were not significantly different; however, the insulin peak and incremental area under the curve (iAUC) tended to be lower for the L-arabinose muffin. Conclusion: L-arabinose and D-xylose are functional ingredients that can potentially lower the post-ingestive glycaemic and insulinaemic responses when added to realistic foods. However, the efficacy of applying L-arabinose appears to depend on the food matrix. Addition of these compounds needs further testing in other foods and in other populations, such as pre-diabetics. [ABSTRACT FROM AUTHOR]

Background: Gastroenteritis is a common and impactful disease in childhood. Probiotics are often used to treat acute gastroenteritis (AGE); however, in a large multicenter randomized controlled trial (RCT) in 971 children, Lactobacillus rhamnosus GG (LGG) was no better than placebo in improving patient outcomes.Objectives: We sought to determine whether the effect of LGG is associated with age, weight z score and weight percentile adjusted for age and sex, or dose per kilogram administered.Methods: This was a preplanned secondary analysis of a multicenter double-blind RCT of LGG 1 × 1010 CFU twice daily for 5 d or placebo in children 3-48 mo of age with AGE. Our primary outcome was moderate to severe gastroenteritis. Secondary outcomes included diarrhea and vomiting frequency and duration, chronic diarrhea, and side effects. We used multivariable linear and nonlinear models testing for interaction effects to assess outcomes by age, weight z score and weight percentile adjusted for age and sex, and dose per kilogram of LGG received.Results: A total of 813 children (84%) were included in the analysis; 413 received placebo and 400 LGG. Baseline characteristics were similar between treatment groups. There were no differential interaction effects across ranges of age (P-interaction = 0.32), adjusted weight z score (P-interaction = 0.43), adjusted weight percentile (P-interaction = 0.45), or dose per kilogram of LGG received (P-interaction = 0.28) for the primary outcome. Whereas we found a statistical association favoring placebo at the extremes of adjusted weight z scores for the number of vomiting episodes (P-interaction = 0.02) and vomiting duration (P-interaction = 0.0475), there were no statistically significant differences in other secondary outcome measures (all P-interactions > 0.05).Conclusions: LGG does not improve outcomes in children with AGE regardless of the age, adjusted weight z score, and adjusted weight percentile of participants, or the probiotic dose per kilogram received. These results further strengthen the conclusions of low risk of bias clinical trials which demonstrate that LGG provides no clinical benefit in children with AGE.This trial was registered at clinicaltrials.gov as NCT01773967. [ABSTRACT FROM AUTHOR]

Background: While magnetic resonance imaging (MRI) plays a major role in the lives of people with multiple sclerosis (pwMS), studies have shown that MRI-specific knowledge in pwMS is limited. Moreover, poor knowledge was associated with negative feelings towards MRI (e.g. anxiety concerning MRI scan). Because information sources about MRI in MS for pwMS are not available, we designed and evaluated an evidence-based online educational platform about MRI in MS called "Understanding MRI in MS" (UMIMS). Based on a pilot study in n= 79 subjects, an educational intervention was found to be feasible and effective. We hypothesize that MRI-specific knowledge can be increased by using UMIMS and that, subsequently, negative feelings towards MRI will be reduced and shared decision-making competences increased.Methods: This randomized, controlled, double-blinded trial (RCT) will recruit n = 120 pwMS. The intervention group will receive access to UMIMS. The control group will get access to a specifically developed control website, which visually imitates UMIMS and contains the standard information available by several MS self-help organizations. The change in MRI-specific knowledge assessed via the MRI-risk knowledge questionnaire (MRI-RIKNO) after the intervention is the primary endpoint at 2 weeks. Several secondary endpoints will be assessed at different timepoints throughout the study, e.g. emotions towards MRI, autonomy preferences, threat by MS and shared decision-making competences. The study includes a process evaluation.Discussion: The aim of this RCT is to prove that access to an education tool on MRI in MS will increase pwMS' MRI-specific knowledge and enhance shared decision-making when discussing decisions involving MRI results during patient-physician encounters.Trial Registration: Clinicaltrials.gov NCT03872583 . Registered on 13 March 2019. [ABSTRACT FROM AUTHOR]

Background: Obesity accelerates age-related cognitive decline, which is partly mediated by vascular dysfunction.Objective: The aim was to test the hypothesis that supplementation with fish oil and curcumin can enhance cognitive performance by improving cerebral circulatory function in overweight or obese middle-aged to older adults.Methods: In a 16-wk double-blind, placebo-controlled intervention trial, adults [50-80 y; BMI (kg/m2): 25-40] were randomly assigned to either fish oil (2000 mg/d DHA + 400 mg/d EPA), curcumin (160 mg/d), or a combination. Effects on cerebrovascular function (primary outcome) and cardiovascular risk factors were reported previously. Effects on cognitive performance and cerebrovascular responsiveness (CVR) to cognitive stimuli are reported herein. One-factor ANOVA with post hoc analyses was conducted between groups in the whole cohort and in males and females separately. Two-factor ANOVA was conducted to assess independent effects of fish oil and curcumin and a potential interaction. Correlations between outcomes (those obtained herein and previously reported) were also examined.Results: Compared with placebo, fish oil improved CVR to a processing speed test (4.4% ± 1.9% vs. -2.2% ± 2.1%; P = 0.023) and processing speed in males only (Z-score: 0.6 ± 0.2 vs. 0.1 ± 0.2; P = 0.043). Changes in processing speed correlated inversely with changes in blood pressure (R = -0.243, P = 0.006) and C-reactive protein (R = -0.183, P = 0.046). Curcumin improved CVR in a working memory test (3.6% ± 1.2% vs. -0.2% ± 0.2%, P = 0.026) and, in males only, performance of a verbal memory test compared with placebo (Z-score: 0.2 ± 0.1 vs. -0.5 ± 0.2, P = 0.039). Combining fish oil with curcumin did not produce additional benefits.Conclusions: Improvements in processing speed following fish-oil supplementation in middle-aged to older males might be mediated by improvements in circulatory function. Mechanisms underlying the cognitive benefit seen with curcumin are unknown. As cognitive benefits were found in males only, further evaluation of sex differences in responsiveness to supplementation is warranted. This trial was registered at the Australian and New Zealand Clinical Trial Register at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370788 as ACTRN12616000732482p. [ABSTRACT FROM AUTHOR]

Background: Cancer-related fatigue represents one major cause of reduced quality of life in cancer patients and can seriously affect the physical, emotional, and cognitive functioning impeding coping with the disease. Options for effective treatment of cancer-related fatigue are limited, consisting only of non-pharmacologic interventions like physical activity, psychosocial, and mind-body interventions. Recent evidence suggests that vitamin D3 supplementation might alleviate cancer-related fatigue. However, confirmation in a randomized controlled trial is needed.Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 456 colorectal cancer (CRC) patients aged 18 years and older are being recruited in three German rehabilitation clinics. Study inclusion requires hospitalization of at least 3 weeks at such a clinic, a diagnosis of non-metastatic CRC (stage I-III), surgical removal of the tumor within the past 9 months, and season-adapted vitamin D insufficiency or deficiency. Eligible patients are randomly assigned to a personalized regimen of vitamin D3 or placebo for 12 weeks. In the intervention group, a loading dose of 20,000 or 40,000 IU vitamin D3 will be administered daily during the first 11 days, followed by a maintenance dose of 2000 IU daily. Patients will complete questionnaires for secondary outcomes (fatigue subdomains, quality of life and subdomains, depression, functional well-being, and infection frequency). Blood and urine samples will be collected for analyses of safety parameters (hypervitaminosis D, hypercalcemia, hypercalciuria, and renal impairment) and efficacy biomarkers (25-hydroxyvitamin D, HbA1c, white blood cell count, leukocyte subtype counts, serum C-reactive protein, uric acid, creatinine, triglycerides, total, low- and high-density lipoprotein cholesterol).Discussion: This trial tests whether a personalized vitamin D3 dosing regimen reduces or prevents fatigue among non-metastatic CRC patients by treating the underlying vitamin D deficiency/insufficiency. If efficacy can be confirmed, personalized vitamin D3 supplementation could be used as a tertiary prevention measure in addition to non-pharmacological treatments of cancer-related fatigue in CRC patients. We expect to detect an effect of vitamin D3 supplementation on secondary outcomes like quality of life, depression, functional well-being, infections, inflammatory biomarkers, diabetes mellitus, and dyslipidemia.Trial Registration: European Clinical Trials Database: EudraCT-No: 2019-000502-30, January 21, 2019; German Clinical Trials Register (DRKS): DRKS00019907 , April 30, 2019. [ABSTRACT FROM AUTHOR]

Background: Postherpetic neuralgia (PHN) is one of the most common types of chronic neuropathic pain, which seriously affects quality of the life because of pain severity and poor response to the currently available treatments. The main strategies for PHN management are medication and invasive interventional therapies; however, these approaches have many adverse effects, so it is important to find another effective and safe treatment for PHN.Methods: A single-center, single-blind randomized clinical trial will evaluate 98 study participants randomized in a 1:1 ratio into control and experimental groups. The control group will receive conventional treatment including medication therapy and invasive interventional therapy. The experimental group will receive extracorporeal shockwave therapy (ESWT) in addition to conventional therapy. The primary outcome is pain intensity assessed on a visual analogue scale (VAS); the secondary outcomes are the following: quality of life assessed by the 36-Item Short-Form Health Survey (SF-36), psychological state for anxiety and depression measured by the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), and sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI). Assessors blinded to the randomization will collect data during the intervention period at baseline and weeks 1, 4, and 12. The plasma levels of tumor necrosis factor-α and interleukin-6 will be assessed before and after ESWT to explore the biochemical mechanisms of ESWT in the treatment of PHN.Discussion: This randomized controlled trial will evaluate the effectiveness and safety of ESWT in patients with PHN and thus will provide clinical evidence for its use in the management of PHN and explore the potential biochemical mechanisms of this treatment.Trial Registration: www.ChiCTR.org.cn , identifier: ChiCTR1900025828. Registered on 10 September 2019. [ABSTRACT FROM AUTHOR]

Background: Elevated cholesterol levels and systemic inflammation are considered relevant risk factors for cardiovascular disease (CVD) development and progression. Increasing evidence suggests that cholesterol-lowering and inflammation-lowering nutraceuticals are useful in the management of moderate hypercholesterolemia. Here, we describe the study protocol of a clinical trial aimed to evaluate the cholesterol and inflammatory lowering effect of an innovative dietary supplement (BruMeChol™, Mivell S.r.l., Italy), composed of a mixture of extracts of bergamot and olive fruits in association with vitamin K2 in subjects with mild hypercholesterolemia.Methods: The study was planned as a randomized, double-blind, placebo-controlled, parallel group clinical trial for 12 weeks at the Cardiology Unit of the IRCCS INRCA of Ancona, Italy. A total of 125 subjects (age ≥ 40 years) with mild hypercholesterolemia (total serum cholesterol levels ≥ 200 and ≤ 250 mg/dl) will be recruited. Intervention arm participants will take one capsule of dietary supplement two times a day, 15 min before the main meal. Control arm participants will receive one capsule of placebo in the same way. The dietary supplement capsule contains the following ingredients: phytosterols, flavonoid-rich extract of bergamot fruit (Citrus bergamia), flavonoid-rich extract of olive fruit (Olea europaea), and vitamin K2. Participants will undergo a medical evaluation and chemical-clinical examinations, which include lipid profile, glycemia, biomarkers of renal, liver and cardiac/muscular functions, interleukins (IL 6, IL-32, IL-37, and IL-38), and innovative mediators of inflammation such as inflamma-miRs (miR-21 and miR-146a), at baseline, and after 6 and 12 weeks of treatment. The decrease in total cholesterol levels and inflammatory biomarkers will be the primary and secondary endpoints of the study.Discussion: This protocol study, planned to verify the effects of BruMeChol™ dietary supplementation in subjects with mild hypercholesterolemia, could also contribute to new study designs for next large-scale multicenter clinical trials.Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12619000170123 . Retrospectively registered on 5 February 2019. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders characterized by recurrent abdominal pain associated with defecation or a change in bowel habits. Leading to significant negative effect on patients' quality of life and huge financial burden to health system, the management of IBS is a great challenge. Probiotics are considered as an effective therapy; however, in a lack of high-quality evidence of efficacy, no strain- and dose-specific probiotics were recommended in clinical guidelines. This study aims to evaluate the efficacy of the Bifidobacterium quadruple viable tablet in the treatment of IBS-D.Methods/design: A multicenter randomized controlled trial will be performed in fourteen hospitals. A total of three hundred patients who fulfill the eligibility criteria will be stratified divided into an experimental group and a control group randomly in a ratio of 1:1. The experimental group is treated with the Bifidobacterium quadruple viable tablet while the control group is treated with placebo. All the patients will receive a 4-week treatment and a 2-week follow-up. The primary outcome is the effectiveness in improving abdominal pain and stool consistency; the secondary outcome includes evaluation of overall symptom relief, frequency of defecation, bloating, urgency of defecation, remedial medication, score of IBS-QOL, and changes of microbiota and metabonomics. Physical examination, vital signs, laboratory tests, adverse events, and concomitant medication will be taken into account for intervention safety assessment during the trial.Discussion: This multicenter randomized controlled trial may provide high-quality evidence on the efficacy of the Bifidobacterium quadruple viable tablet for IBS-D on both physical and mental dimensions in China. To fill the gap of previous probiotic intervention studies, in addition, this study will also present safety assessment which will be a significant emphasis.Trial Registration: ChiCTR1800017721 . Registered on 10 August 2018. [ABSTRACT FROM AUTHOR]