Multicenter Controlled Clinical Trial Research Articles

Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial

BackgroundDiabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN.MethodsThis study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment.DiscussionThis study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect.Trial registrationClinicalTrials.gov. NCT05521737 Registered on 30 August 2022.International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b].

Efficacy comparison of 7- and 14-day P-CAB based bismuth-containing quadruple regimen with PPI based bismuth-containing quadruple regimen for Helicobacter pylori infection: rationale and design of an open-label, multicenter, randomized controlled trial

BackgroundOwing to its strong acid inhibition, potassium-competitive acid blocker (P-CAB) based regimens for Helicobacter pylori (H. pylori) eradication are expected to offer clinical advantages over proton pump inhibitor (PPI) based regimens. This study aims to compare the efficacy and adverse effects of a 7-day and a 14-day P-CAB-based bismuth-containing quadruple regimen (PC-BMT) with those of a 14-day PPI-based bismuth-containing quadruple regimen (P-BMT) in patients with high clarithromycin resistance.MethodsThis randomized multicenter controlled clinical trial will be performed at five teaching hospitals in Korea. Patients with H. pylori infection who are naive to treatment will be randomized into one of three regimens: 7-day or 14-day PC-BMT (tegoprazan 50 mg BID, bismuth subcitrate 300 mg QID, metronidazole 500 mg TID, and tetracycline 500 mg QID) or 14-day P-BMT. The eradication rate, treatment-related adverse events, and drug compliance will be evaluated and compared among the three groups. Antibiotic resistance testing by culture will be conducted during the trial, and these data will be used to interpret the results. A total of 366 patients will be randomized to receive 7-day PC-BMT (n = 122), 14-day PC-BMT (n = 122), or 14-day P-BMT (n = 122). The H. pylori eradication rates in the PC-BMT and P-BMT groups will be compared using intention-to-treat and per-protocol analyses.DiscussionThis study will demonstrate that the 7-day or 14-day PC-BMT is well tolerated and achieve similar eradication rates to those of 14-day P-BMT. Additionally, the 7-day PC-BMT will show fewer treatment-related adverse effects and higher drug compliance, owing to its reduced treatment duration.Trial registrationKorean Clinical Research Information Service registry, KCT0007444. Registered on 28 June 2022, https://cris.nih.go.kr/cris/index/index.do.

Low dose of liraglutide combined with metformin leads to a significant weight loss in Chinese Han women with polycystic ovary syndrome: a retrospective study

Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder with complex pathophysiological mechanism. It is reported that even a modest weight loss of 5–10% substantially may improve the reproductive and metabolic profile. This study aims to assess the efficacy of the low dose of liraglutide (0.6 mg QD) combined with metformin (0.85 mg BID) in weight loss in Chinese Han women with PCOS. Methods We included clinical data of 102 obese/overweight (≥18 years, body mass index ≥28 kg/m2 or ≥24 kg/m2) women who were diagnosed with PCOS from October 2016 to March 2018 in Wuhan Union Hospital initially. They were treated with dinae-35, low dose of liraglutide (0.6 mg QD) and metformin (0.85 mg BID) for 12 weeks. The demographic and clinical data were retrieved retrospectively, and weight loss was the main outcome measure. Student’s paired t-test and Wilcoxon rank sum test were used to compare the differences before and after therapy, p < 0.05 was considered statistically significant. Results Participants(n = 102)had lost a mean of 7.20 ± 3.42 kg of body weight (95%CI: 6.55–7.86, p < 0.001), and the mean reduction of BMI was 2.87 ± 1.36 kg/m2 (95%CI: 0.02–0.27, p < 0.001). A total of 88.24% of participants lost more than 5% of their body weight. Conclusion The combination of low dose of liraglutide and metformin was associated with significant reduction of body weight in Chinese Han women with PCOS. Additionally, a larger randomized double-blind multicenter controlled clinical trial is needed to confirm that. Trial registration The study was registered on http://www.chictr.org.cn as ChiCTR1900024384.

Effect of a specially formulated diet on progression of heart enlargement in dogs with subclinical degenerative mitral valve disease.

Previous studies in dogs with degenerative mitral valve disease (DMVD) have identified altered myocardial energy metabolism and oxidation, which might contribute to cardiac hypertrophy. Diets rich in medium chain fatty acids and antioxidants are a potential means of treatment. A previous clinical study found significantly smaller left atrial diameter (LAD) and left atrium-to-aorta diameter ratio (LA : Ao) in dogs with subclinical DMVD fed a specially formulated diet vs control diet for 6 months. A specially formulated diet will slow or arrest left heart enlargement in dogs with subclinical DMVD over 365 days. One hundred twenty-seven dogs with unmedicated subclinical DMVD; 101 dogs in the per protocol cohort. Randomized double-blinded controlled multicenter clinical trial. The study's primary composite outcome measure was the sum of percentage change in LAD and left ventricular internal dimension at end-diastole (LVIDd) at day 365. In the per protocol cohort, the outcome measure increased by 8.0% (95% confidence interval [CI], 2.9%-13.1%) in dogs receiving the test diet vs 8.8% (95% CI, 5.1%-12.5%) in dogs receiving control diet (P = .79). Neither component of the primary outcome measure was significantly different between groups (LAD, P = .65; LVIDd, P = .92). No difference was found in mitral valve E wave velocity (P = .36) or the proportion of dogs withdrawn from the study because of worsening DMVD and heart enlargement (P = .41). Feeding a specially formulated diet for 365 days was not associated with a significantly different rate of change of left heart size in dogs with subclinical DMVD as compared to control.

Robotic versus Conventional Overground Gait Training in Subacute Stroke Survivors: A Multicenter Controlled Clinical Trial.

Although stroke survivors can benefit from robotic gait rehabilitation, stationary robot-assisted gait training needs further investigation. In this paper, we investigated the efficacy of this approach (with an exoskeleton or an end-effector robot) in comparison to the conventional overground gait training in subacute stroke survivors. In a multicenter controlled clinical trial, 89 subacute stroke survivors conducted twenty sessions of robot-assisted gait training (Robotic Group) or overground gait training (Control Group) in addition to the standard daily therapy. The robotic training was performed with an exoskeleton (RobotEXO-group) or an end-effector (RobotEND-group). Clinical outcomes were assessed before (T0) and after (T1) the treatment. The walking speed during the 10-Meter Walk Test (10 MWT) was the primary outcome of this study, and secondary outcomes were the 6-Minute Walk Test (6 MWT), Timed Up and Go test (TUG), and the modified Barthel Index (mBI). The main characteristics assessed in the Robotic and Control groups did not differ at baseline. A significant benefit was detected from the 10 MWT in the Robotic Group at the end of the study period (primary endpoint). A benefit was also observed from the following parameters: 6 MWT, TUG, and mBI. Moreover, patients belonging to the Robot Group outperformed the Control Group in gait speed, endurance, balance, and ADL. The RobotEND-group improved their walking speed more than the RobotEXO-group. The stationary robot-assisted training improved walking ability better than the conventional training in subacute stroke survivors. These results suggest that people with subacute stroke may benefit from Robot-Assisted training in potentiating gait speed and endurance. Our results also support that end-effector robots would be superior to exoskeleton robots for improving gait speed enhancement.

Effectiveness and Efficacy of Thermoformed and 3D Printed Aligners in Correcting Malocclusion (Spacing) and Its Impact on Periodontal Oral Health and Oral Microbiome: A Double-Blinded Parallel Randomized Controlled Multicenter Clinical Trial.

Aligners are the common devices used in orthodontics for the correction of malocclusion. Various materials and techniques are employed to fabricate aligners. One of those includes thermoformed and 3D aligners. These aligners can be worn for several days, and their impact on periodontal health is not known. Therefore, the aim of our protocol is to determine the effectiveness of these aligners in correcting malocclusion and their impact on periodontal health and oral microbiome. A double-blinded randomized controlled clinical trial with a total of n = 60 patients will be included with n = 30 in each group (Test: 3D printed aligners and Control: Thermoformed). The evaluation of oral health indices such as basic periodontal examination (BPE), periodontal screening and recording (PSR) that provide the status of periodontal health will be recorded. The oral microbiome assessment will be conducted with polymerase chain reaction (PCR). The primary endpoint will be the correction of malocclusion, and the secondary end point will be the status of periodontal health and oral microbiome. The duration of follow-up for each group will be 7 days for periodontal health and oral microbiome and 6 months for the space closure of 5 mm by 3D and thermoformed aligners.

A Prospective Randomized Controlled Multicenter Clinical Trial Comparing Paste-Type Acellular Dermal Matrix to Standard Care for the Treatment of Chronic Wounds.

The treatment of chronic wounds remains challenging. Acellular dermal matrix (ADM) has been shown to be effective for various types of wound healing. This study was designed to compare the wound size reduction rate after 12 weeks between patients receiving paste-type ADM and standard wound care. Patients over 19 years old with chronic wounds, deeper than full-thickness skin defects, more than 4 cm2 in size that did not heal over the 3 weeks before the study were included. After a screening period of 7 days, patients were randomized to receive either paste-type ADM or standard wound care. The wound status was evaluated at baseline, 1, 2, 4, 8, and 12 weeks. A total of 86 patients were enrolled in this study. The wounds continuously and constantly reduced in size from week 1, and the reduction rate was significantly greater in the study group from week 2 until the end (week 12). In the study group, wound healing was achieved in 29 of 38 wounds (76.3%). Paste-type ADM might be a useful option for wound healing and can be applied safely and efficiently for advanced wound care.

The Role of Individual Characteristics in Predicting Short- and Long-Term Cognitive and Psychological Benefits of Cognitive Stimulation Therapy for Mild-to-Moderate Dementia

Introduction: This study examined the role of individual characteristics in predicting short- and long-term benefits of the Italian version of Cognitive Stimulation Therapy (CST-IT), an evidence-based intervention for people with mild-to-moderate dementia.Materials and Methods: Data were drawn from a sample (N = 123) of people with dementia (PwD) who took part in a multicenter controlled clinical trial of CST-IT. Assessments at pre-test, immediately after completing the treatment, and 3 months later investigated the following outcomes: general cognitive functioning and language, mood and behavior, everyday functioning, and quality of life. Age, education and baseline (pre-test) cognitive functioning, mood (depression) and behavioral and neuropsychiatric symptoms were considered as predictors of any short- and long-term benefits.Results: Linear mixed-effects models showed that different individual characteristics -particularly education and age- influenced the benefits of CST-IT, depending on the outcome measures considered. Higher education predicted larger gains in general cognitive functioning and, along with less severe depressive symptoms, in language (magnification effects). Older age was associated with positive changes in mood (compensation effects). Albeit very modestly, older age was also associated with larger gains in everyday functioning (compensation effects). Gains in quality of life were predicted by older age and lower education (compensation effects). Baseline cognitive functioning, mood and/or behavioral symptoms broadly influenced performance too, but their role again depended on the outcomes considered.Discussion: These findings underscore the importance of considering and further exploring how psychosocial interventions like CST are affected by individual characteristics in order to maximize their efficacy for PwD.

Feasibility of Using Daily Home High-Flow Nasal Therapy in COPD Patients Following a Recent COPD Hospitalization.

High-flow nasal therapy (HFNT) has beneficial effects in patients hospitalized with acute hypoxemic respiratory failure. HFNT has not been extensively studied following hospitalization for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We explored the feasibility of conducting a multicentered trial to evaluate the use of HFNT to increase the time to next moderate/ severe exacerbation in patients recently hospitalized for a COPD exacerbation. In this pilot study we measured the hours of home daily HFNT use, maximally tolerated flow rates and temperature, and side effects for a period of 90 days. Patients were enrolled in a 90-day, open-labeled pilot study of HFNT to determine the safety and feasibility of home use for daily outpatient COPD management. Patients ≥ 40 years of age with prior hospitalization within the past 12 weeks for an AECOPD were enrolled. COPD was the primary diagnosis in all patients. Thirty patients presented for HFNT titration. Two dropped out; 1 after receiving a lung transplant and the other was lost to follow-up. The remaining 28 patients completed 90 days of HFNT. None withdrew from HFNT due to intolerance. Use of HFNT averaged 6.8 (2.1) hours daily. Daily home HFNT for up to 3 months is feasible in COPD patients following hospitalization for AECOPD. Improvements observed in disease-specific quality of life, respiratory symptoms, and 6-minute walk distance suggest the need for a prospective multicenter controlled clinical trial.

Regenerative Endodontic Procedure of Immature Permanent Teeth with Leukocyte and Platelet-rich Fibrin: A Multicenter Controlled Clinical Trial

IntroductionThe aim of this nonrandomized, multicenter controlled clinical trial was to evaluate the impact of leukocyte–platelet-rich fibrin (LPRF) on regenerative endodontic procedures (REPs) of immature permanent teeth in terms of periapical bone healing (PBH) and further root development (RD). MethodsHealthy patients between 6–25 years with an inflamed or necrotic immature permanent tooth were included and divided between the test (= REP + LPRF) and control (= REP-LPRF) group depending on their compliance and the clinical setting (university hospital or private practice). After receiving REP ± LPRF, the patients were recalled after 3, 6, 12, 24, and 36 months. At each recall session, the teeth were clinically and radiographically (by means of a periapical radiograph [PR]) evaluated. A cone-beam computed tomographic (CBCT) imaging was taken preoperatively and 2 and 3 years postoperatively. PBH and RD were quantitatively and qualitatively assessed. ResultsTwenty-nine teeth with a necrotic pulp were included, from which 23 (9 test and 14 control) were analyzed. Three teeth in the test group had a flare-up reaction in the first year after REP. Except for 2 no shows, all the analyzed teeth survived up to 3 years after REP, and, in case of failure, apexification preserved them. Complete PBH was obtained in 91.3% and 87% of the cases based on PR qualitative and quantitative evaluation, respectively, with no significant difference between the groups with respect to the baseline. The PR quantitative change in RD at the last recall session with respect to the baseline was not significant (all P values > .05) in both groups. The qualitative assessment of the type of REP root healing was nonuniform. In the test group, 55.6% of the teeth presented no RD and no apical closure. Only 50% of the 14 teeth assessed with CBCT imaging presented complete PBH. Regarding volumetric measurements on RD 3 years after REP for the change with respect to the baseline in root hard tissue volume, mean root hard tissue thickness, and apical area, the control group performed significantly in favor of RD than the test group (P = .03, .003, and 0.05 respectively). For the volumetric change 3 years after REP with respect to the baseline in root length and maximum root hard tissue thickness, no significant difference (P = .72 and .4, respectively) was found between the groups. The correlation between the PR and CBCT variables assessing RD was weak (root lengthening) to very weak (root thickening). ConclusionsREP-LPRF seems to be a viable treatment option to obtain PBH and aid further RD of necrotic immature permanent teeth. Caution is needed when evaluating REP with PR.

Osseodensification effect on implants primary and secondary stability: Multicenter controlled clinical trial

BackgroundOsseodensification (OD) has shown to improve implant stability; however, the influences of implant design, dimensions, and surgical site characteristics are unknown.PurposeTo compare the insertion torque (IT) and temporal implant stability quotients (ISQ) of implants placed via OD or subtractive drilling (SD).Materials and MethodsThis multicenter controlled clinical trial enrolled 56 patients, whom were in need of at least 2 implants (n = 150 implants). Patients were treated with narrow, regular, or wide implants and short, regular, or long implants in the anterior or posterior region of the maxilla or in the posterior region of the mandible. Osteotomies were performed following manufacturers recommendation. IT was recorded with a torque indicator. ISQ was recorded with resonance frequency analysis immediately after surgery, 3 and 6 weeks.ResultsData complied as a function of osteotomy indicated significantly higher IT for OD relative to SD. OD outperformed conventional SD for all pairwise comparisons of arches (maxilla and mandible) and areas operated (anterior and posterior), diameters and lengths of the implants, except for short implants. Overall, ISQ data also demonstrated significantly higher values for OD compared to SD regardless of the healing period. Relative to immediate readings, ISQ values significantly decreased at 3 weeks, returning to immediate levels at 6 weeks; however, ISQ values strictly remained above 68 throughout healing time for OD. Data as a function of arch operated and osteotomy, area operated and osteotomy, implant dimensions and osteotomy, also exhibited higher ISQ values for OD relative to SD on pairwise comparisons, except for short implants.ConclusionsOD demonstrated higher IT and temporal ISQ values relative to SD, irrespective of arch and area operated as well as implant design and dimension, with an exception for short implants. Future studies should focus on biomechanical parameters and bone level change evaluation after loading.

Is the \u201cBrainwork Intervention\u201d effective in reducing sick leave for non-permanent workers with psychological problems? Results of a controlled clinical trial

BackgroundBoth the presence of psychological problems and the absence of an employment contract are related to long-term sickness absence, prolonged work disability and unemployment. Studies researching the effectiveness of return-to-work interventions on these non-permanent workers, including unemployed and temporary agency workers and workers with an expired fixed-term contract, are lagging behind. Therefore, a return-to-work intervention called “Brainwork” was developed. The aim of this study was to assess the effectiveness of the ‘Brainwork Intervention’ in reducing the duration of sick leave compared to usual care over a 12-month follow-up.MethodsIn a multicenter controlled clinical trial, using a quasi-randomization procedure, we compared the Brainwork Intervention (n = 164) to usual care (n = 156). The primary outcome was the duration of sick leave. Secondary outcomes were the duration of sick leave starting from Social Security Agency transfer; the proportion of workers returned to work; the number of hours of paid employment during the follow-up period; the degree of worker participation; the level of psychological complaints; and the self-efficacy for return to work. Protocol adherence (Brainwork Intervention) was considered sufficient when at least three of the five protocol steps were followed. Cox regressions, linear and ordinal regression, and Mixed Model analyses were performed.ResultsAll 320 participants were analyzed. The Brainwork Intervention resulted in a non-significant reduction of the duration of sick leave compared to usual care (269 days versus 296 days; HR = 1.29; 95% CI 0.94–1.76; p = 0.11). For those working (46%) during the 12-month follow-up, the mean number of hours of paid employment was non-significantly higher in the usual care group (682 h versus 493 h; p = 0.053). No significant differences were found for other secondary outcomes. Protocol adherence was 10%.ConclusionsThe Brainwork Intervention as performed with a low protocol adherence did not result in a significant reduction of the duration of sick leave compared to usual care. It remains unclear what the results would have been if the Brainwork Intervention had been executed according to protocol.Trial registrationThe Netherlands Trial Register (NTR); NTR3976 (old registration number NTR4190). Registered September 27th 2013.

Efficacy of WC03 in treating radiotherapy-induced oral mucositis (RIOM): A multicenter nonrandomized controlled clinical trial.

e24127 Background: RIOM is a common side effect of radiotherapy for head and neck cancer patients, however, no standard and effective treatment existed so far. WC03 is an oily Traditional Chinese Herbal Medicine recipe for external-use in mouth, which had been utilized to treat RIOM in China-Japan Friendship Hospital for more than ten years. This trial aimed to investigate the safety and efficacy of WC03 in treating RIOM. Methods: Between May 2017 and June 2018, we conducted a multicenter, non-randomized controlled trial within 7 hospitals in China. Inclusion criteria included head and neck cancer patients who developed RIOM (≥ grade II) undergoing radiotherapy or after radiotherapy (within 6 months). They were assigned to different groups based on their willingness. Patients in treatment group were treated by WC03, which was daily applied to the oral mucosa for 30 min twice a day. Patients in control group were treated with Kangfuxin (Periplaneta americana) Lotion combined with conventional treatment such as vitamin B12 and rhGM-CSF. The interventions lasted for 2 weeks. The primary outcome was overall effective rate, which was calculated through changes of radio-induced oral mucositis grade before and after interventions (according to National Cancer Institute Common Toxicity Criteria). Secondary outcome was oral pain which was measured by Numeric Pain Rating Scale. Results: 48 eligible participants were enrolled, 24 in treatment group and 24 in control group, respectively. 2 patients in treatment group were withdrawn from the study in the first week because of developing secondary infection and treatment got changed. Thus, 22 were included at the terminal of the study. All the 24 participants in control group were included. After the intervention, the overall effective rate was 95.45%(21/22) in the treatment group, which was significantly higher than that of 70.83% (17/24) in the control group (p = 0.049). Similarly, 86.36%(19/22) of the participants in treatment group got cured, which was significantly higher than that of 45.83%(11/24) in the control group(p = 0.007). There is a trend that oral pain relief rate in the treatment group was higher than that of the control group, but not statistically significant (100.00% vs. 87.50%, p = 0.210). Patients in treatment group used less time to get relieved from RIOM than control group (5 vs. 8 days, p &lt; 0.001). No adverse event had been observed in both two groups. Conclusions: WC03 is safe and effective in treating radiotherapy-induced oral mucositis. RCT is necessary in future studies.

ПЛАцентарная Циркуляция и исходы прЕэклампсии под влияНием Терапии Аргинином (ПЛАЦЕНТА): мультицентровое рандомизированное контролируемое исследование

The objective: to evaluate the effectiveness of L-arginine in the correction of dysfunction in the utero-placental-fetal complex, intrauterine development of the fetus and the condition of the newborn in the early period of adaptation. Materials and methods. A prospective double-blind, randomized, multicenter controlled clinical trial was carried out at the Republican Specialized Scientific and Practical Medical Center of Obstetrics and Gynecology, II Clinic of the Tashkent Medical Academy and the Republican Perinatal Center of the Ministry of Health of the Republic of Uzbekistan. Results. Treatment with L-arginine in women at the end of the second and beginning of the third trimester of pregnancy with chronic diseases complicated by placental dysfunction improves perinatal outcomes, leads to a decrease in the number of premature births and asphyxiation of newborns. Conclusion. The use of L-arginine in the treatment of preeclampsia and correction of disorders in the utero-placental-fetal complex significantly improves the utero-placental-fetal blood flow. This allows to prolong the pregnancy to the optimal term of delivery. Key words: utero-placental-fetal blood flow, placental dysfunction, fetoplacental insufficiency, pregnant women, newborns, correction, therapy, L-arginine, Tivortin.

Berberine Hydrochloride for the Prevention of Colorectal Adenomas: A Double-Blind, Randomised Controlled Multicenter Clinical Trial

Background: Chemoprevention of colorectal adenoma and cancer remains its importance in public health. The rate of adenoma recurrence in the first year after polypectomy is very high in East Asian populations. We aimed to investigate the clinical potential and safety of Berberine hydrochloride for colorectal adenoma recurrence. Methods: This double-blind, randomised, placebo-controlled clinical trial was done in seven hospital centers across six provinces in China. Patients with recently diagnosed adenomas and after complete polypectomy were recruited and randomized into a BBR group (Berberine hydrochloride 0.3g, twice daily) or a placebo group. They were anticipated for at least one follow-up colonoscopy until a diagnosis of CRA/CRC or the last enrolled patient reached the 2-year follow-up. The primary efficacy endpoint was the recurrence of adenomas at any follow-up colonoscopy. The secondary outcomes were the recurrences of polypoid lesions as well as advanced adenomas or CRC. Findings: Between Nov 14, 2014 and Dec 29, 2018, 1136 patients were screened for eligibility, and 1108 underwent randomization. 553 patients were assigned to receive Berberine hydrochloride and 555 to placebo. An unadjusted RR for recurrent adenomas and all polypoid lesions were 0.77 (95% CI, 0.66 to 0.91) and 0.77 (95% CI, 0.67 to 0.89), representing a decrease of 22.72% and 22.70%, respectively. No CRC occurred during the whole trial. Interaction test showed taking BBR was effective in female with unadjusted RR for recurrent adenomas of 0.58 (95% CI, 0.41 to 0.81); P=0.07 (Alpha = 0.10). No serious adverse events were reported. Interpretation: Although the mechanism has not been fully elucidated yet, Berberine hydrochloride was effective to reduce colorectal adenoma recurrence after polypectomy. Trial Registration: This trial is registered with ClinicalTrials.gov number NCT02226185. Funding Statement: This project was supported by grants from the National Natural Science Foundation of China (81421001, 81530072, 81830081 and 8177100232), the funds from Shanghai Shenkang Center (SHDC12018121), from Shanghai Municipal Key Clinical Specialty, and from Innovative research team of high-level local universities in Shanghai. The project was also partially supported by Top-Notch project of China and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20152514). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Approval for this study was obtained from the Ethics Committee of Renji Hospital, Shanghai Jiao-Tong University School of Medicine on 13th August 2014. The protocol and informed consent forms were also approved by the institutional ethics committees at each of the participating clinical centers.

Nonsurgical and Surgical Management of Osteoporotic Vertebral Body Fractures: Recommendations of the Spine Section of the German Society for Orthopaedics and Trauma (DGOU).

Study Design:Prospective clinical cohort study (data collection); expert opinion (recommendation development).Objectives:Treatment options for nonsurgical and surgical management of osteoporotic vertebral body fractures are widely differing. Based on current literature, the knowledge of the experts, and their classification for osteoporotic fractures (OF classification) the Spine Section of the German Society for Orthopaedics and Trauma has now introduced general treatment recommendations.Methods:a total of 707 clinical cases from 16 hospitals were evaluated. An OF classification–based score was developed to guide in the option of nonsurgical versus surgical management. For every classification type, differentiated treatment recommendations were deduced. Diagnostic prerequisites for reproducible treatment recommendations were defined: conventional X-rays with consecutive follow-up images (standing position whenever possible), magnetic resonance imaging, and computed tomography scan. OF classification allows for upgrading of fracture severity during the course of radiographic follow-up. The actual classification type is decisive for the score.Results:A score of less than 6 points advocates nonsurgical management; more than 6 points recommend surgical management. The primary goal of treatment is fast and painless mobilization. Because of expected comorbidities in this age group, minimally invasive procedures are being preferred. As a general rule, stability is more important than motion preservation. It is mandatory to restore the physiological loading capacity of the spine. If the patient was in a compensated unbalanced state at the time of fracture, reconstruction of the individual prefracture sagittal profile is sufficient. Instrumentation technique has to account for compromised bone quality. We recommend the use of cement augmentation or high purchase screws. The particular situations of injuries with neurological impairment; necessity to fuse; multiple level fractures; consecutive and adjacent fractures; fractures in ankylosing spondylitis are being addressed separately.Conclusions:The therapeutic recommendations presented here provide a reliable and reproducible basis to decide for treatment choices available. However, intermediate clinical situations remain with a score of 6 points allowing for both nonsurgical and surgical options. As a result, individualized treatment decisions may still be necessary. In the next step, the recommendations presented will be further evaluated in a multicenter controlled clinical trial.

Applicability Evaluation of Simplified Cognitive Behavioral Therapy.

BackgroundWe have developed a structured cognitive behavioral therapy manual for anxiety disorder in China, and the present study evaluated the applicability of simplified cognitive behavioral therapy based on our previous research.AimsTo evaluate the applicability of simplified cognitive behavioral therapy (SCBT) on generalized anxiety disorder (GAD) by conducting a multi-center controlled clinical trial.MethodsA multi-center controlled clinical trial of SCBT was conducted on patients with GAD, including institutions specializing in mental health and psychiatry units in general hospitals. The participants were divided into 3 groups: SCBT group, SCBT with medication group and medication group. The drop-out rates of these three groups, the therapy satisfaction of patients who received SCBT and the evaluation of SCBT from therapists were compared.Results(1) There was no significant difference among the drop-out rates in the three groups. (2) Only the duration and times of therapy were significantly different between the two groups of patients who received the SCBT, and the therapy satisfaction of the SCBT group was higher than that of the SCBT with medication group. (3) Eighteen therapists who conducted the SCBT indicated that the manual was easy to comprehend and operate, and this therapy could achieve the therapy goals.ConclusionThe applicability of SCBT for patients with GAD is relatively high, and it is hopeful that SCBT can become a psychological treatment which can be applied in medical institutions of various levels.

Short-course Regimen for Subsequent Treatment of Pulmonary Tuberculosis: A Prospective, Randomized, Controlled Multicenter Clinical Trial in China

PurposeWe designed a prospective, multicenter, randomized, controlled study to assess a 5-month regimen compared with the standard regimen on previously treated patients with pulmonary tuberculosis (TB). MethodsWe enrolled 917 sputum smear–positive patients undergoing additional treatment in 27 major tuberculosis hospitals in China. Patients were randomly assigned to a test group (n = 626)treated with a 5-month regimen of moxifloxacin, pasiniazid, rifabutin, ethambutol, and pyrazinamide or a reference group (n = 291) treated with an 8-month regimen of isoniazid, rifampicin, and streptomycin. All patients with a favorable response were followed up for 5 years after the end of treatment. FindingsOf the study patients, 61 in the test group and 19 in the reference group had multidrug-resistant (MDR) TB. The treatment success rate in the study group was 74.12%, which was significantly higher than the 67.70% in the reference group (P = 0.04), whereas the treatment success rate of patients with MDR-TB was not significantly different between the test and reference groups (70.5% vs 63.1%, P =0.79). The adverse effects rates in the test and reference groups were 7.4% and 3.1%, respectively (P = .01). The difference in the TB recurrence rates between the group arm (9.6%) and the reference group (21.8%) was statistically significant (P < 0.001). ImplicationsThe moxifloxacin, pasiniazid, rifabutin, ethambutol, and pyrazinamide test regimen yielded higher success and lower recurrence rates than the currently recommended isoniazid, rifampicin, and streptomycin regimen, but the rate of adverse effects was higher. ClinicalTrials.gov identifier: NCT02331823.

Treatment of auditory hallucinations with bilateral theta burst stimulation (cTBS): protocol of a randomized, double-blind, placebo-controlled, multicenter trial.

ClinicalTrials.gov identifier: NCT02670291.

Comparison between over-glasses patching and adhesive patching for children with moderate amblyopia: a prospective randomized clinical trial.

To investigate efficacy of over-glasses patching treatment for amblyopic children using visual function improvement and Amblyopia Treatment Index (ATI) changes. In a randomized multi-center controlled clinical trial, 107 children aged 3-7years with moderate amblyopia (visual acuity in the range of 20/40 to 20/100) were included to receive treatment with either an adhesive skin patch or a fabric over-glasses patch. The patients were prescribed 2h of patching per day for the sound eye. Best-corrected visual acuity (BCVA) was investigated and ATI questionnaires were collected from parents at 5weeks and 17weeks after the initiation of treatment. ATI identifies barriers and problems associated with amblyopia treatment. We compared the changes of visual acuity of amblyopic eyes and ATI scores in two groups. At 17weeks, the mean visual acuity of the amblyopic eye using Snellen chart improved 3.2 lines in the adhesive patching group and 2.7 lines for an over-glasses patching method that fit over eyeglasses (p = 0.345). A similar proportion of subjects in each group had improvement of ≥2 lines (adhesive patching group 67% vs over-glasses patching group 67%, p = 0.372). There was also no difference in treatment burden in each group as measured with the Amblyopia Treatment Index. The only item to demonstrate a significant difference between groups was that related to "Treatment makes the eye or eyelids red" (mean 4.0 ± 1.1 vs 3.0 ± 1.0 at 17weeks, p = 0.001, for adhesive vs over-glasses patch). Over-glasses patching treatment is a useful option for amblyopia treatment when the patients suffer from adverse effects of using adhesive skin patching.