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Objective: Determine efficacy of the novel WiiNWalk intervention on walking-related outcomes in older adults with lower limb amputation. Design: Multi-site, parallel, evaluator-masked randomized controlled trial. Setting: Home-setting in three Canadian cities. Participants: Community-dwelling lower limb prosthesis users over 50 years of age. Interventions: The WiiNWalk group (n = 38) used modified Wii Fit activities for prosthetic rehabilitation. The attention control group (n = 33) used Big Brain Academy: Wii Degree, comprising of cognitive activities. Both groups completed a 4-week supervised phase with three 1-h sessions/week in groups of three overseen by a clinician via videoconferencing and a 4-week unstructured and unsupervised phase. Main Measures: Primary outcome was walking capacity (2 min walk test); secondary outcomes were balance confidence (activities-specific balance confidence scale), dynamic balance (four-step square test), and lower limb functioning (short physical performance battery). Outcomes were compared across time points with repeated measures analysis of covariance, adjusting for baseline and age. Results: Mean age was 65.0 (8.4) years, with 179.5 (223.5) months post-amputation and 80% transtibial amputation. No group difference in a 2 min walk test with an effect size: 1.53 95% CI [−3.17, 6.23] m. Activities balance confidence was greater in the WiiNWalk group by 5.53 [2.53, 8.52]%. No group difference in the four-step square test −0.16 [−1.25, 0.92] s, nor short physical performance battery 0.48 [−0.65, 1.61]. A post-hoc analysis showed the greatest difference in balance confidence immediately after an unsupervised phase. Conclusions: The WiiNWalk intervention improved balance confidence, but not walking-related physical function in older adult lower limb prosthesis users. Future rehabilitation games should be specific to the amputation context. Clinical Trial Registration number, NCT 01942798. [ABSTRACT FROM AUTHOR]

Study Design: Randomized controlled trial.Objective: To evaluate the efficacy of adjunctive topical tranexamic acid (tTXA) in reducing postoperative blood loss and packed red cell (PRC) transfusion in patients who underwent palliative decompressive spinal metastasis surgery for malignant epidural spinal cord compression.Summary Of Background Data: Palliative decompressive spinal metastasis surgery is associated with massive postoperative blood loss and increased transfusion rate. tTXA reduces blood loss in traumatic or degenerative spinal surgery; however, the role of topical TXA in decompressive spinal metastasis surgery remains controversial.Method: A total of 65 patients who underwent palliative decompressive thoracolumbar spinal metastasis surgery were included in this study. In 33 patients, 1 g of tTXA (20 mL) was soaked in an absorbable gelatin sponge and placed lateral to the decompressive site. The remaining 32 patients in the control group received the same procedures with normal saline at the same volume, instead of TXA. All of the patients received standard 1 g intravenous TXA, just before initiating the operation. The primary outcome was postoperative blood loss, and the secondary outcomes were postoperative PRC transfusion and complications.Results: No differences were found in postoperative blood loss between tTXA and placebo group (P50 778 mL [IQR 347, 1,122 mL] versus P50 490 mL [IQR 295, 920 mL]; P = 0.238). The number of patients requiring postoperative PRC transfusion were quite similar in tTXA and placebo groups (PRC transfusion in 15 patients [45.45%] versus 16 patients [50%]; P = 0.585). No complications related to TXA and absorbable gelatin sponge were observed.Conclusion: We do not recommend tTXA as an adjunctive treatment for patients undergoing decompressive spinal metastasis surgery since it does not provide additional benefit to prophylactic intravenous TXA in postoperative blood loss and transfusion rate.Level of Evidence: 2. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical effects of interactive dynamic scalp acupuncture (IDSA), simple combination therapy (SCT), and traditional scalp acupuncture (TSA) on cognitive function, depression and anxiety in patients with post-stroke cognitive impairment. Methods: A total of 660 patients with post-stroke cognitive impairment who were admitted to 3 hospitals in Shenzhen City between May 2017 and May 2020 were recruited and randomly assigned to the IDSA (218 cases), SCT (222 cases) and TSA groups (220 cases) according to a random number table. All the patients received conventional drug therapy for cerebral stroke and exercise rehabilitation training. Scalp acupuncture and computer-based cognitive training (CBCT) were performed simultaneously in the IDSA group, but separately in the morning and in the afternoon in the SCT group. The patients in the TSA group underwent scalp acupuncture only. The course of treatment was 8 weeks. Before treatment (M0), 1 (M1) and 2 months (M2) after treatment, as well as follow-up at 1 (M3) and 2 months (M4), the cognitive function of patients was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA) Scales; depression, anxiety, sleep quality, and self-care ability of patients were assessed using Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Pittsburgh Sleep Quality Index (PSQI), and Modified Barthel Index (MBI), respectively. During this trial, all adverse events (AEs) were accurately recorded. Results: There were no significant differences in the MMSE, MoCA, HAMD, HAMA, PSQI, and MBI scores among the 3 groups at M0 (all P>0.05). In the IDSA group, the MMSE, MoCA and MBI scores from M2 to M4 were significantly higher than those in the SCT and TSA groups, while the HAMD, HAMA and PSQI scores were significantly reduced (all P<0.01). The changes of all above scores (M2-M0, M4-M0) were significantly superior to those in the SCT and TSA groups (all P<0.01, except M4-M0 of HAMD). At M2, the severity of MMSE, HAMD, HAMA, PSQI and MBI in the IDSA group was significantly lower than that in the SCT and TSA groups (all P<0.01). There was no serious AE during this trial. Conclusions: IDSA can not only significantly improve cognitive function, but also reduce depression, anxiety, which finally improves the patient's self-care ability. The effect of IDSA was significantly better than SCT and TSA. (Trial registration No. ChiCTR1900027206) [ABSTRACT FROM AUTHOR]

Background No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19. Methods Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. Results A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (−1.41 vs −1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (−3.37 vs −3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported. Conclusions In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care. [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]

Objective: To examine the feasibility and preliminary efficacy of a group behavioral parenting intervention for emotional and behavioral problems (EBPs) in young autistic children.Method: This was a feasibility pilot randomized controlled trial comparing a 12-week group behavioral parenting intervention (Predictive Parenting) to an attention control (Psychoeducation). Parents of 62 autistic children 4 to 8 years of age were randomized to Predictive Parenting (n = 31) or Psychoeducation (n = 31). The primary outcome was a blinded observational measure of child behaviors that challenge. Secondary outcomes were observed child compliance and parenting behaviors; parent- and teacher-reported child EBPs; self-reported parenting practices, stress, self-efficacy, and well-being. Cost-effectiveness was also explored.Results: Recruitment, retention, completion of measures, treatment fidelity, and parental satisfaction were high for both interventions. There was no group difference in primary outcome: mean log of rate 0.18 lower (d, 90% CI = -0.44 to 0.08) in Predictive Parenting. Differences in rates of child compliance (0.44, 90% CI = 0.11 to 0.77), facilitative parenting (0.63, 90% CI = 0.33 to 0.92) and parent-defined target symptom change (-0.59, 90% CI -0.17 to -1.00) favored Predictive Parenting. There were no differences on other measures. Predictive Parenting was more expensive than Psychoeducation, with a low probability of being more cost-effective.Conclusion: Feasibility was demonstrated. There was no evidence from this pilot trial that Predictive Parenting resulted in reductions in child EBPs beyond those seen following Psychoeducation; in addition, the effect size was small, and it was more expensive. However, it showed superiority for child compliance and facilitative parenting with moderate effect sizes. Future, definitive studies should evaluate whether augmented or extended intervention would lead to larger improvements.Clinical Trial Registration Information: Autism Spectrum Treatment and Resilience (ASTAR); https://www.isrctn.com/; 91411078. [ABSTRACT FROM AUTHOR]

Background: Spinal cord stimulation (SCS) is a well‐established treatment for chronic intractable pain of the trunk and/or limbs; however, low back pain (LBP) is difficult to treat using traditional SCS. Differential Target Multiplexed spinal cord stimulation (DTM SCS) is an advanced approach inspired from animal studies demonstrating improved pain‐related behavior and pain‐relevant biological processes. Objective: The purpose of this study was to compare the effectiveness of DTM SCS and traditional SCS in treating chronic LBP and leg pain (LP). Methods: This prospective, postmarket randomized controlled trial compared DTM SCS to traditional SCS in patients with chronic LBP and LP. Primary end point was LBP responder rate (percentage of subjects with ≥ 50% relief) at 3 months. Noninferiority and superiority were assessed. Other outcomes included mean change in back and leg pain, responder rates, disability, global health, satisfaction, and safety profile throughout the 12‐month follow‐up. Results: One hundred twenty‐eight subjects were randomized across 12 centers (67 DTM SCS and 61 traditional SCS). Of the 94 patients implanted, 46 subjects in each group completed the 3‐month assessment. LBP responder rate of 80.1% with DTM SCS was superior to 51.2% with traditional SCS (p = 0.0010). Mean LBP reduction (5.36 cm) with DTM SCS was greater than reduction (3.37 cm) with traditional SCS (p < 0.0001). These results were sustained at 6 months and 12 months. Safety profiles were similar between treatment groups. Conclusion: Superiority of DTM SCS compared with traditional SCS for chronic LBP was demonstrated. Clinical improvements provided by DTM SCS were sustained over 12 months and are expected to significantly impact the management of chronic LBP. [ABSTRACT FROM AUTHOR]

Objective: To investigate the combined anti-inflammatory effect of activating blood circulation and detoxifying Chinese medicines in unstable angina (UA) patients. Methods: This study was an open-labeled, randomized controlled trial conducted in 5 centers in Beijing. A total of 154 patients were randomized into two groups at a 1:1 ratio by random numbers. Based on the conventional treatment, patients in the activating blood circulation (ABC) group were treated with Guanxin Danshen Droping Pill (冠心丹参滴丸, 0.4 g, thrice daily), and patients in the activating blood circulation and detoxifying (ABCD) group were treated with Guanxin Danshen Droping Pill (0.4 g, thrice daily) and Andrographis tablet (0.2 g, thrice daily) for 4 weeks. The primary outcome was the serum level of high sensitive C reaction protein (hs-CRP), and the secondary outcome index included the serum levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), soluble CD40 ligand (sCD40L), thrombomodulin (TM), the score of angina pectoris, the score of blood stasis syndrome, and the score of Chinese medicine symptoms, observed at week 0 and week 4. Results: A total of 144 patients completed the trial (ABC group, n=70; ABCD group, n=74). There were no significant differences in the clinical baseline characteristics between the two groups. When compared with the ABC group, ABCD group showed better performance in reducing the level of inflammatory factors, especially hs-CRP (P<0.05), IL-6 (P<0.01) and TNF-α (P<0.01). In term of clinical symptoms, ABCD group played a better role in improving the scores of angina pectoris and blood stasis syndrome than ABC group (all P<0.05). Conclusions: The combination of Guanxin Danshen Dropping Pill and Andrographis tablet exert significant anti-inflammatory effect on UA patients, which is superior to single Guanxin Danshen Dropping Pill. (Registration No. ChiCTR-TRC-13004072) [ABSTRACT FROM AUTHOR]

Abstract: Chronic low back pain can be caused by impaired control and degeneration of the multifidus muscles and consequent functional instability of the lumbar spine. Available treatment options have limited effectiveness and prognosis is unfavorable. We conducted an international randomized, double-blind, sham-controlled trial at 26 multidisciplinary centers to determine safety and efficacy of an implantable, restorative neurostimulator designed to restore multifidus neuromuscular control and facilitate relief of symptoms (clinicaltrials.gov identifier: NCT02577354). Two hundred four eligible participants with refractory mechanical (musculoskeletal) chronic LBP and a positive prone instability test indicating impaired multifidus control were implanted and randomized to therapeutic (N = 102) or low-level sham (N = 102) stimulation of the medial branch of the dorsal ramus nerve (multifidus nerve supply) for 30 minutes twice daily. The primary endpoint was the comparison of responder proportions (≥30% relief on the LBP visual analogue scale without analgesics increase) at 120 days. After the primary endpoint assessment, participants in the sham-control group switched to therapeutic stimulation and the combined cohort was assessed through 1 year for long-term outcomes and adverse events. The primary endpoint was inconclusive in terms of treatment superiority (57.1% vs 46.6%; difference: 10.4%; 95% confidence interval, -3.3% to 24.1%, P = 0.138). Prespecified secondary outcomes and analyses were consistent with a modest but clinically meaningful treatment benefit at 120 days. Improvements from baseline, which continued to accrue in all outcome measures after conclusion of the double-blind phase, were clinically important at 1 year. The incidence of serious procedure- or device-related adverse events (3.9%) compared favorably with other neuromodulation therapies for chronic pain. [ABSTRACT FROM AUTHOR]

Background: Animal and human studies have revealed reciprocal association between exercise and gut-brain axis. However, the clinical evidence from randomized controlled trials (RCT) are still limited to directly assess the effects of aerobic exercise on gut microbiota. To fill this gap, we conducted this 12-week RCT in both groups of adolescents with and without sub-threshold mood symptoms.Methods: A total of 224 adolescents were randomized to the aerobic exercise intervention or psychoeducation-controlled arm. 49 adolescents with subthreshold symptoms and 142 clinically-well adolescents provided the sample for microbiota assessed by metagenomic sequencing. Aerobic exercise of running at the moderate-intensity for 30 min per day, 5 days a week, were conducted for 12 weeks.Results: Adolescents with subthreshold symptoms had significantly lower beta diversity than clinically-well adolescents in both the exercise intervention and psychoeducation-controlled arms (p<0.05). After intervention, no difference in gut microbiota diversity, phylum, genus, species level abundancies or gut microbial functions were found in both of the symptomatic or non-symptomatic groups. Metagenome-wide association study analysis showed no significant difference in metagenomic linkage groups.Limitations: The sample size is relatively small. The exercise intensity we employed may be insufficient to result in observable effects on intestinal microbiota.Conclusion: We conclude that a 12-week moderate-intensity aerobic exercise intervention showed no significant beneficial effect on the gut microbiota in clinically-well adolescents as well as in adolescents with subthreshold symptoms. The beta diversity of gut microbiota in adolescents with subthreshold mood syndromes may be impaired when compared with clinically-well adolescents. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of shared decision-making (SDM) intervention among patients with lumbar degenerative diseases (LDDs) in terms of decision self-efficacy, control preferences, SDM process, decision satisfaction, and conflict.Methods: A total of 130 outpatients with LDDs recruited from orthopedic or rehabilitation clinics were randomly assigned to the SDM intervention (n = 67) or comparison (n = 63) groups. Patients in the intervention group received decision aids (DAs) with decision coaching and those in controlled group received standard educational materials from a health educator. The primary outcome was decision self-efficacy, and secondary outcomes were control preference, SDM process, conflict, and satisfaction.Results: The SDM intervention significantly improved decision self-efficacy (mean difference [MD] = 7.1, 95% confidence interval [CI]: 1.7-12.5, partial η2 = 0.05) and reduced conflict (MD = -7.0, 95% CI: -12.2 to -1.9, partial η2 = 0.06), especially in patients without family involvement, compared with the health education group. However, no significant between-group differences were observed in other outcomes.Conclusion: SDM intervention improved SDM self-efficacy and reduced conflict in patients with LDDs.Practice Implications: Clinicians can integrate DAs and decision coaching in SDM conversations. SDM intervention seems to engage patients in decision-making, especially those without family involvement. [ABSTRACT FROM AUTHOR]

Study Question: Does ultra-long downregulation with a GnRH agonist (triptorelin depot) in previously operated patients with endometriosis improve the rate of clinical pregnancy with positive fetal heart beat (CPHB) in the subsequent initiated fresh ART cycle?Summary Answer: Ultra-long downregulation with a GnRH agonist prior to ART did not improve the rate of CPHB in the subsequent fresh ART cycle in previously completely operated patients but the trial was underpowered due to early termination.What Is Known Already: Administration of GnRH agonists for a period of 3-6 months prior to ART in women with endometriosis may increase the odds of clinical pregnancy. However, the quality of the studies on which this statement is based is questionable, so these findings need confirmation.Study Design, Size, Duration: A controlled, randomized, open label trial was performed between 1 June 2013 and 31 December 2016 (start and end of recruitment, respectively). Patients with prior complete laparoscopic treatment of any type or stage of endometriosis and an indication for ART were randomized (by a computer-generated allocation sequence) into two groups: the control group underwent ART stimulation in a classical long agonist protocol using preparation with oral contraceptives, the ultra-long group first underwent at least 3 months downregulation followed by a long agonist protocol for ART stimulation. The sample size was calculated to detect a superiority of the ultra-long downregulation protocol, based on the hypothesis that baseline CPHB rate in the control group of 20% would increase to 40% in the ultra-long group. For a power of 20% at a significance level of 5%, based on two-sided testing, including 5% of patients lost to follow-up, the necessary sample size was 172 patients (86 per group).Participants/materials, Setting, Methods: This trial was conducted at the Leuven University Fertility Center, a tertiary care center for endometriosis and infertility, and a total of 42 patients were randomized (21 in the control group and 21 in the ultra-long group).Main Results and the Role Of Chance: Baseline characteristics were similar in both groups. The primary outcome studied-CPHB after the initiated ART treatment-did not differ and was 25% (5/20) in the control group, and 20% (4/20) in the ultra-long group (P > 0.999; relative risk (RR) 1.25, 95% CI 0.41-3.88). Cumulative (fresh + associated frozen) CPHB rates were also similar in the control versus ultra-long group (8/20, 40% vs 6/20, 30%, P = 0.7411; RR = 1.33, 95% CI 0.57-3.19). When other secondary outcomes were compared with the ultra-long group, patients from the control group had a shorter duration of stimulation (mean 11.8 days (SD ± 2.4) versus 13.2 days (SD ± 1.5), P = 0.0373), a lower total dose of gonadotrophins used (mean 1793 IU/d (SD ± 787) vs 2329 (SD ± 680), P = 0.0154), and a higher serum estradiol concentration (ng/ml) at the end of ovarian stimulation on the day of ovulation triggering or cycle cancellation (mean1971 (SD ± 1495) vs 929 (± 548); P = 0.0326), suggesting a better ovarian response in the control group.Limitations, Reasons For Caution: Due to a strong patient preference, nearly exclusively against ultra-long downregulation (even though patients were thoroughly informed of the potential benefits), the targeted sample size could not be achieved and the trial was stopped prematurely.Wider Implications Of the Findings: Conditional power analysis revealed that the probability of confirming the study hypothesis if the study were completed would be low. We hypothesize that in patients with prior complete surgical treatment of endometriosis, the ultra-long protocol does not enhance ART-CPHB rates. Patient's concerns and preferences regarding possible side-effects, and delay of ART treatment start with the ultra-long protocol should be taken into account when considering this type of treatment in women with endometriosis.Study Funding/competing Interest(s): C.T. was during 2 years funded by a grant from the Clinical research Foundation of UZ Leuven (KOF) and during 2 years by the Research Foundation-Flanders (FWO grant number: 1700816N). C.T. reports grants from Clinical Research Foundation of the University Hospitals of Leuven (KOF), grants from Fund for Scientific Research Flanders (FWO), during the conduct of the study; grants, non-financial support and other from Merck SA, non-financial support and other from Gedeon Richter, non-financial support from Ferring Pharmaceuticals, outside the submitted work. T.D. is vice president and head of Global Medical Affairs Fertility, Research and Development, Merck KGaA, Darmstadt, Germany. He is also a professor in Reproductive Medicine and Biology at the Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven (University of Leuven), Belgium and an adjunct professor at the Department of Obstetrics and Gynecology in the University of Yale, New Haven, USA. Neither his corporate role nor his academic roles represent a conflict of interest with respect to the work done by him for this study. A.C. reports personal fees from Merck S.p.A., outside the submitted work. The other co-authors have no conflict of interest.Trial Registration Number: UZ Leuven trial registry SS55300, EudraCT number 2013-000993-32, clinicaltrials.gov NCT02400801.Trial Registration Date: Registration for EudraCT on 1 March 2013.Date Of First Patient’s Enrolment: 4 September 2013. [ABSTRACT FROM AUTHOR]

Background: Despite widespread use of long-lasting insecticidal nets (LLINs) and other tools, malaria caused 409,000 deaths worldwide in 2019. While indoor residual spraying (IRS) is an effective supplement, IRS is moderately expensive and logistically challenging. In endemic areas, IRS requires yearly application just before the main rainy season and potential interim reapplications. A new technology, insecticide-treated wall liner (ITWL), might overcome these challenges.Methods: We conducted a 44-cluster two-arm randomized controlled trial in Muheza, Tanzania from 2015 to 2016 to evaluate the cost and efficacy of a non-pyrethroid ITWL to supplement LLINs, analyzing operational changes over three installation phases. The estimated efficacy (with 95% confidence intervals) of IRS as a supplement to LLINs came mainly from a published randomized trial in Muleba, Tanzania. We obtained financial costs of IRS from published reports and conducted a household survey of a similar IRS program near Muleba to determine household costs. The costs of ITWL were amortized over its 4-year expected lifetime and converted to 2019 US dollars using Tanzania's GDP deflator and market exchange rates.Results: Operational improvements from phases 1 to 3 raised ITWL coverage from 35.1 to 67.1% of initially targeted households while reducing economic cost from $34.18 to $30.56 per person covered. However, 90 days after installing ITWL in 5666 households, the randomized trial was terminated prematurely because cone bioassay tests showed that ITWL no longer killed mosquitoes and therefore could not prevent malaria. The ITWL cost $10.11 per person per year compared to $5.69 for IRS. With an efficacy of 57% (3-81%), IRS averted 1162 (61-1651) disability-adjusted life years (DALYs) per 100,000 population yearly. Its incremental cost-effectiveness ratio (ICER) per DALY averted was $490 (45% of Tanzania's per capita gross national income).Conclusions: These findings provide design specifications for future ITWL development and implementation. It would need to be efficacious and more effective and/or less costly than IRS, so more persons could be protected with a given budget. The durability of a previous ITWL, progress in non-pyrethroid tools, economies of scale and competition (as occurred with LLINs), strengthened community engagement, and more efficient installation and management procedures all offer promise of achieving these goals. Therefore, ITWLs merit ongoing study.First Posted: 2015 ( NCT02533336 ). [ABSTRACT FROM AUTHOR]

Background: In treating patients with cervical ossification of the posterior longitudinal ligament (COPLL), a novel surgery technique - anterior controllable antedisplacement and fusion (ACAF) suggested promising clinical benefits in recent exploratory studies.Methods: This is a multicentre, randomized, open-label, parallel-group, active controlled trial that will compare the clinical benefits of ACAF versus conventional posterior laminoplasty (LAMP) in severe COPLL patients. A total of 164 patients will be enrolled and randomized in a 1:1 ratio to either ACAF or LAMP group. The primary efficacy measure is cervical- Japanese Orthopaedic Association (C-JOA) recovery rate at 12 months post operation, which is to be derived by Hirabayashi's method from JOA data (range, 0 [worst] to 17 [normal condition]). Other important secondary efficacy endpoints include visual analogue scale (VAS) pain score (range, 0 [no pain] to 10 [most severe]), 10-item neck disability index (NDI, a total range of 0 to 50 points, the highest index the worst) and 6-level Nurick disability grade (range, 0 [mild] to 5 [severe]). Safety endpoints including adverse events, perioperative complications, and adverse events of special interest will also be assessed in this study. Full analysis set for baseline and efficacy data analyses according to the intention-to-treat principle will be established as the primary analysis population. Analysis of covariance (ANCOVA) will be used to analyze the C-JOA recovery rate, with random stratification factors (if appropriate) and the treatment group as fixed factors, and the baseline level of C-JOA score as covariate.Discussion: This study is designed to demonstrate the clinical benefits of ACAF as compared to conventional LAMP in COPLL patients. It will provide clinical evidence that the novel surgery technique - ACAF might be more favorable in treating patients with severe cervical ossification of the posterior longitudinal ligament. (Words: 290).Trial Registration: ClinicalTrials.gov number, NCT04968028 . [ABSTRACT FROM AUTHOR]

Background: Experts recommend us to keep a safety guidewire during the process of upper urinary tract endoscopy, though there is a lack of high-level evidence to support  the efficacy and safety of  this opinion. This study conducted to compare the outcome of ureteral stone breakage in the presence or absence of safety guidewire.Materials and Methods: Patients candidate for endoscopic breakage of ureteral stone using a semi-rigid ureteroscope, were randomly assigned in  two groups based on keeping a safety guidewire (group1)  or removing the guidewire (group2) before the process of breaking ureteral stone by lithoclast. Demographic factors, history of previous stone treatment, kidney function, stone location, symptoms duration and severity were recorded for each patient. Primary outcomes include success rate of stone treatment and secondary outcomes include number of attempts to enter to ureter, success rate of ureteral entry, success rate of stone achievement, stone migration rate and success rate of ureteral stent insertion. The recorded data were entered to the SPSS software and descriptive statistical analysis including power calculation and non-inferiority design for the primary and secondary outcomes, was performed. P-value less than 0.05 was considered significant.Results: From January 2016 till May 2018, 320 patients were randomized with 160 patients in each arm. Considering the cases who were missed due to follow-up loss, there were 153 patients in group 1 and 147 patients in group 2 at the end of the study. Baseline data were equally distributed in both groups. Based on the initial analysis, the studied variables had no significant difference between two groups; though, according to the subgroup analysis of patients with proximal ureter stones, patients in Group 1 had higher rates of ureteral injury comparing to the patients in Group 2 (p=0.03).Conclusion: According to our findings, keeping the safety guidewire through the process of endoscopic stone breakage (stone size: less than 1.5Cm) seems to add no significant benefit to the procedure outcome, while it increases the ureteral injuries in the proximal ureter stones, but not in mid or distal ureter stones. [ABSTRACT FROM AUTHOR]

Objective: Youth with sickle cell disease (SCD) are at risk for neurocognitive deficits including problems with working memory (WM), but few interventions to improve functioning exist. This study sought to determine the feasibility and efficacy of home-based, digital WM training on short-term memory and WM, behavioral outcomes, and academic fluency using a parallel group randomized controlled trial design.Methods: 47 children (7-16 years) with SCD and short-term memory or WM difficulties were randomized to Cogmed Working Memory Training at home on a tablet device (N = 24) or to a standard care Waitlist group (N = 23) that used Cogmed after the waiting period. Primary outcomes assessed in clinic included performance on verbal and nonverbal short-term memory and WM tasks. Secondary outcomes included parent-rated executive functioning and tests of math and reading fluency.Results: In the evaluable sample, the Cogmed group (N = 21) showed greater improvement in visual WM compared with the Waitlist group (N = 22; p = .03, d = 0.70 [CI95 = 0.08, 1.31]). When examining a combined sample of participants, those who completed ≥10 training sessions exhibited significant improvements in verbal short-term memory, visual WM, and math fluency. Adherence to Cogmed was lower than expected (M = 9.07 sessions, SD = 7.77), with 19 participants (41%) completing at least 10 sessions. Conclusions: Visual WM, an ability commonly affected by SCD, is modifiable with cognitive training. Benefits extended to verbal short-term memory and math fluency when patients completed a sufficient training dose. Additional research is needed to identify ideal candidates for training and determine whether training gains are sustainable and generalize to real-world outcomes. [ABSTRACT FROM AUTHOR]

Objective: To observe the clinical effect of high suspension and low incision (HSLI) surgery on mixed haemorrhoids, compared with Milligan-Morgan haemorrhoidectomy. Methods: A multi-centre, randomized, single-blind, non-inferiority clinical trial was performed. Participants with mixed haemorrhoids from Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing Rectum Hospital, Air Force Medical Center of People's Liberation Army of China, and Puyang Hospital of Traditional Chinese Medicine were enrolled from September 2016 to March 2018. By using a blocked randomization scheme, participants were assigned to two groups. The experimental group was treated with HSLI, while the control group was treated with Milligan-Morgan haemorrhoidectomy. The primary outcome was the clinical effect evaluated at 12 weeks after operation. The secondary outcomes included the number of haemorrhoids treated during the operation, pain scores, use of analgesics, postoperative oedema, wound healing, incidence of anal stenosis, anorectal manometry after operation, as well as surgical duration, length of stay and total hospitalization expenses. A safety evaluation was also conducted. Results: In total, 246 eligible participants were enrolled, with 123 cases in each group. There was no significant difference in the clinical effect between the two groups (100.00% vs. 99.19%, P>0.05). Compared with the control group, the number of external haemorrhoids treated during the operation and the pain scores after operation were significantly reduced in the experimental group (P<0.05 or P<0.01); the patient number with wound healing at 2 weeks after operation and the functional length of anal canal at 12 weeks after operation were significantly increased in the experimental group (P<0.05). There was no significant difference in the incidence of anal stenosis, the numbers of patients using analgesics and patients with postoperative oedema between the two groups after operation (P>0.05). The surgical duration and length of stay in the experimental group were significantly longer than those in the control group, and the total hospitalization expense was significantly higher than that in the control group (all P<0.05). No adverse events were reported in either group during the whole trial or follow-up period. Conclusion: HSLI had the advantages of preserving the skin of anal canal completely, alleviating postsurgical pain and promoting rapid recovery after operation. (Registration No. ChiCTR1900022883) [ABSTRACT FROM AUTHOR]

Aims This randomized controlled trial sought to determine the financial impact of an initial diagnostic strategy of coronary computed tomography angiography (CCTA) in patients with heart failure (HF) of unknown aetiology. Invasive coronary angiography (ICA) is used to investigate HF patients. CCTA may be a non-invasive cost-effective alternative to ICA. This randomized controlled trial sought to determine the financial impact of an initial diagnostic strategy of coronary computed tomography angiography (CCTA) in patients with heart failure (HF) of unknown aetiology. Methods and results This multicentre, international trial enrolled patients with HF of unknown aetiology. The primary outcome was the cost of CCTA vs. ICA strategies at 12 months. Clinical outcomes were also collected. An 'intention-to-diagnose' analysis was performed and a secondary 'as-tested' analysis was based on the modality received. Two hundred and forty-six patients were randomized (age = 57.8 ± 11.0 years, ejection fraction = 30.1 ± 10.1%). The severity of coronary artery disease was similar in both groups. In the 121 CCTA patients, 93 avoided ICA. Rates of downstream ischaemia and viability testing were similar for both arms. There were no significant differences in the composite clinical outcomes or quality of life measures. The cost of CCTA trended lower than ICA [CDN −$871 (confidence interval, CI −$4116 to $3028)]. Using an 'as-tested' analysis, CCTA was associated with a decrease in healthcare costs (CDN −$2932, 95% CI −$6248 to $746). Conclusion In patients with HF of unknown aetiology, costs were not statistically different between the CCTA and ICA strategies. Clinical Trials.gov NCT01283659 [ABSTRACT FROM AUTHOR]

There are currently no approved pharmacological treatments to improve social reciprocity and limit repetitive and rigid behaviors in autism spectrum disorder (ASD). We describe the design of two Phase III studies evaluating the efficacy/safety of bumetanide oral liquid formulation in ASD. These are international, multicenter, randomized, double-blind, placebo-controlled studies in children and adolescents with ASD aged 7 to 17 years (n = 200; study 1), or younger children with ASD aged 2 to 6 years (n = 200; study 2). The primary endpoint of each is change in Childhood Autism Rating Scale 2 total raw score after 6 months. These studies could contribute to the first pharmacological treatment to improve social reciprocity and limit repetitive and rigid behaviors in children and adolescents with ASD. [ABSTRACT FROM AUTHOR]

Aim: To assess the efficacy of a commercially available adjunctive phototherapy protocol ("Perio‐1") in treatment of periodontitis. Materials and Methods: In an examiner‐blind, randomized, controlled, split‐mouth, multicentre study, 60 periodontitis patients received root surface debridement (RSD) in sextants either alone (control sextants) or with the adjunctive phototherapy protocol (test sextants). Re‐evaluation was performed at 6, 12 and 24 weeks. Results: No statistically significant differences in mean (± standard deviation) clinical attachment level (CAL) change from baseline to week 24 were observed between test (−1.00 ± 1.16 mm) and control sextants (−0.87 ± 0.79 mm) at sites with probing pocket depths (PPDs) ≥5 mm ("deep sites") at baseline (p =.212). Comparisons between test and control sextants for all other parameters (CAL change at all sites, PPD change at deep sites/all sites, bleeding on probing, plaque scores), and for all change intervals, failed to identify any statistically significant differences. Conclusions: The phototherapy protocol did not provide any additional clinical benefits over those achieved by RSD alone. (German Clinical Trials Register DRKS00011229). [ABSTRACT FROM AUTHOR]

Objective: Unintentional injuries are the leading cause of death for children under 19 years of age. For preschoolers, many injuries occur in the home. Addressing this issue, this study assessed if a storybook about home safety could be effective to increase preschoolers' safety knowledge and reduce their injury-risk behaviors.Methods: Applying a randomized controlled trial design, normally developing English speaking preschool children (3.5-5.5 years) in Southwestern Ontario Canada were randomly assigned to the control condition (a storybook about healthy eating, N = 30) or the intervention condition (a storybook about home hazards, N = 29). They read the assigned storybook with their mother for 4 weeks; time spent reading was tracked, and fidelity checks based on home visits were implemented.Results: Comparing postintervention knowledge, understanding score, and risk behaviors across groups revealed that children who received the intervention were able to identify more hazards, provide more comprehensive safety explanations, and demonstrate fewer risky behaviors compared with children in the control group (ηp2 = 0.13, 0.19, and 0.51, respectively), who showed no significant changes over time in safety knowledge, understanding, or risk behaviors. Compliance with reading the safety book and fidelity in how they did so were very good.Conclusions: A storybook can be an effective resource for educating young children about home safety and reducing their hazard-directed risk behaviors. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect and safety of bloodletting puncture at hand twelve Jing-Well points (HTWPs) in acute stroke patients with conscious disturbance. Methods: In this multi-center and randomized controlled trial, 360 patients suffered from ischemic or hemorrhagic stroke with conscious disturbance within 48 h from the onset of symptom were divided into bloodletting (180 cases) and control (180 cases) groups using a block randomization. Patients in both groups received routine Western medicine, and patients in the bloodletting group received additional bloodletting puncture at HTWPs on admission immediately before conventional treatment. The primary outcome measure was Glasgow Coma Scale (GCS) score and the secondary outcomes included blood pressure, respiratory rate and pulse rate. All variables were evaluated at baseline (before bloodletting), 0 (after bloodletting immediately), 15, 30, 50 and 80 min post bloodletting. Results: At 80 min post bloodletting, the proportion of patients with improved consciousness in the bloodletting group was greater than the control group (P<0.05). In the separate analysis of moderate consciousness disturbance subgroup, bloodletting therapy benefited ischemic patients, and improved the eye and language response of GCS score at 15, 30, 50, 80 min post bloodletting (P<0.05 or P<0.01). No significant differences were observed regarding the secondary outcomes between two groups (P>0.05). Conclusion: The bloodletting puncture at HTWPs was safe and could improve conscious levels of ischemic stroke patients, highlighting a first-aid intervention for acute stroke. (Registration No. ChiCTR-INR-16009530) [ABSTRACT FROM AUTHOR]

Background: Physical exercise is suggested to be effective for preventing cognitive decline in older adults, but the relative efficacy of different types of exercise have yet to be clarified.Objective: This single-blinded randomized controlled trial was designed to investigate the differential effects of aerobic exercise training (AT), resistance exercise training (RT), and combined exercise training (CT) on cognition in older adults with subjective memory complaints (SMC).Methods: Community-dwelling older adults with SMC (n = 415; mean age = 72.3 years old) were randomly assigned to one of the four groups: AT, RT, CT, or control group. The study consisted of two phases: a 26-week intervention and a 26-week follow-up. The participants were evaluated at baseline, 26 weeks (postintervention), and 52 weeks (follow-up). The primary outcome of this study was memory function, which was assessed using the Logical Memory II subtest of the Wechsler Memory Scale-Revised (WMS-R) score. The secondary outcomes included global cognitive function, verbal fluency, working memory, processing speed, and executive functions.Results: Intention-to-treat analysis by a mixed-effect model repeated measure showed that the AT group had significantly improved performance on the WMS-R Logical Memory II test (2.74 [1.82-3.66] points) than the control group (1.36 [0.44-2.28] points) at the postintervention assessment (p = 0.037). The effect was more pronounced in those without amnesia than those with amnesia. No significant improvement was observed in the RT and CT groups.Conclusion: This study suggests that AT intervention can improve delayed memory in community-dwelling older adults, particularly in individuals without objective memory decline. [ABSTRACT FROM AUTHOR]

Background: Most currently used surgical robots have no force feedback; the next generation displays forces visually. A novel single-port robotic surgical system called FLEXMIN has been developed. Through an outer diameter of 38 mm, two instruments are teleoperated from a surgeon's control console including true haptic force feedback. One additional channel incorporates a telescope, another is free for special instrument functions.Methods: This randomized cross-over study analyzed the effect of haptic feedback on the application of intracorporeal forces. In a standardized experiment setup, the subjects had to draw circles with the surgical robot as gently as possible. The applied forces, the required time spans, and predefined error rates were measured.Results: Without haptic feedback, the maximum forces (median/IQR) were 6.43 N/2.96 N. With haptic feedback, the maximum forces were lower (3.57 N/1.94 N, p < 0.001). Also, the arithmetic means of the force progression (p < 0.001) and their standard deviations (p < 0.001) were lower. Not significant were the shorter durations and lower error rates. No sequence effect of force or duration was detected. No characteristic learning or fatigue curve was observed.Conclusions: In the experiment setup, the true haptic force feedback can reduce the applied intracorporeal robotic force to one-half when considering the aspects maximum, means, and standard deviation. Other test tasks are needed to validate the influence of force feedback on surgical efficiency and safety. [ABSTRACT FROM AUTHOR]

Objective: Increasing meaning in life (MiL) among people experiencing disease or adversity may improve coping and resilience. The purpose of this review is to characterize the effects of MiL interventions.Data Source: A systematic search of PubMed, PsycInfo, and Google Scholar was conducted encompassing the following parameters: meaning in life, purpose in life, or sense of purpose with randomized controlled trials.Study Inclusion& Exclusion Criteria: Randomized controlled trials (RCTs) of interventions with at least one outcome that measured improvement in MiL and were published in English between January 2000 and January 2020.Data Extraction& Synthesis: 33 randomized controlled trials (k = 35) were identified. Data were coded by authors and a research assistant for intervention type, control group type, and risk of bias. The random effects model of Review Manager 5.3 was used to produce SMD and evaluate heterogeneity.Results: The effect size for studies with a passive control group was SMD = 0.85 (95% CI 0.54 to 1.17) and for studies with an active control group was SMD = .032 (95% CI 0.09 to 0.55). Mindfulness programs produced the largest effect size (1.57) compared to passive controls, while narrative programs produced the largest effect relative to active controls (0.61). There was considerable heterogeneity in most estimates.Conclusion: Several interventions increase MiL, including some that are relatively brief and do not require licensed professionals. [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: The completion rate of Advance Directives (ADs) has been low. This study aims to examine the effectiveness of two interventions 1) active counseling sessions coupled with passive patient education pamphlets, and 2) patient education pamphlets alone, compared with 3) control group (usual care), in increasing the completion rates of ADs in the primary care setting. Methods: Multicenter randomised controlled trial in four public primary care clinics in Singapore under Singapore Health Services. Randomization was performed via block randomization with Sequential Numbered Opaque Sealed Envelopes. Participants were randomized into 1) active intervention group (both counseling by primary care physicians and patient education pamphlets) or 2) passive intervention group (only patient education pamphlets), and 3) control group (usual care) with follow-up at 6 weeks. The main outcome measure is the proportion of participants who completed / planned to complete) ADs six weeks post-intervention. Results: Four hundred five participants were eligible to participate in the study. One hundred eighty-eight participants were recruited into the study (response rate = 46.4%), of which 158 completed the study. There was no significant difference between the control group, passive intervention group, and active intervention group, in terms of completion rates of ADs (29.4, 36.4, and 30.8% respectively). Conclusions: This randomized controlled trial did not support the use of patient education pamphlets with or without active counseling sessions in increasing the completion of ADs in a primary care setting in Singapore. The optimal intervention strategy depends on each health system's context and resources, taking into consideration patients' profiles, which deserves further studies. Trial registration: Registered on April 17, 2018 clinicaltrials.gov (NCT03499847). [ABSTRACT FROM AUTHOR]

Background: The plasma fraction GRF6019 shows multiple benefits on brain aging in mice, including enhanced cognition, neurogenesis, and synaptic density, as well as reduced neuroinflammation.Objective: To evaluate the safety, tolerability, and preliminary efficacy of GRF6019 in patients with severe Alzheimer's disease (AD).Methods: A phase II, double-blind, placebo-controlled study in patients with severe AD (Mini-Mental State Examination score 0-10). Patients were randomized 2 : 1 to GRF6019 (N = 18) or placebo (N = 8) and received daily 250 mL intravenous infusions over 5 days. The primary endpoints were the rates of adverse events (AEs) and the tolerability of GRF6019 as assessed by the number of patients completing the study. Change from baseline in cognitive and functional assessments was also evaluated.Results: All patients completed 100%of study visits and infusions. The rate of AEs was similar in the GRF6019 (8/18 patients [44.4%]) and placebo (3/8 patients [37.5%]) groups, and there were no deaths or serious AEs. The most common AEs considered related to treatment were mild, transient changes in blood pressure in the GRF6019 group (hypotension: 2 patients [11.1%]; hypertension: 1 patient [5.6%]); there were no related AEs in the placebo group. The trial was not powered to detect statistically significant differences between treatment groups. At the end of the study, patients in both treatment groups remained stable or improved on all cognitive and functional endpoints.Conclusion: GRF6019 demonstrated excellent safety, feasibility, and tolerability. Future trials designed to characterize the potential functional benefits of GRF6019 and related plasma fractions in severe AD are warranted. [ABSTRACT FROM AUTHOR]

Background: Acupuncture has been used for treating vascular cognitive impairment, but evidence for its effectiveness remains limited.Objective: This single-center, patient-accessor blinded, randomized controlled trial was designed to assess whether acupuncture could improve the cognitive function of patients with vascular cognitive impairment with no dementia (VCIND).Methods: 120 VCIND patients were randomly assigned to the electro-acupuncture (EA) or sham acupuncture (SA) group at a 1 : 1 ratio, with treatment conducted thrice weekly for 8 weeks. The primary outcome was the changes of cognitive function measured by the Montreal Cognitive Assessment (MoCA) from baseline to week 8. The secondary outcomes included the scores of the Mini-Mental State Examination (MMSE), the Modified Barthel Index (MBI) and the Self-rating Depression Scale (SDS). Follow-up assessments were performed with MoCA and MMSE at week 16 and 32. Linear mixed-effects models were used for analysis and all statistical tests were two-sided.Results: The results showed that patients in the EA group had a significantly greater improvement in MoCA score (23.85±4.18) than those in the SA group (21.48±4.44) at week 8 (95% CI = 0.80, 3.92, p = 0.04), as well as higher MoCA scores over time (p < 0.001 for interaction). Patients who received EA showed a greater increase in MMSE scores (26.41±3.47) than those who received SA (24.40±3.85) along 8 weeks (95% CI = 0.69, 3.34, p = 0.004). However, results diminished over time. No serious adverse events occurred during the trial.Conclusion: EA is a safe and effective technique to improve cognition over the short term of 8 weeks in VCIND patients. [ABSTRACT FROM AUTHOR]

Background: Many surgeons utilize biologic mesh for elective complex ventral hernia repair (VHR; large hernias, contaminated fields, or patients with comorbid conditions). However, no randomized controlled trials (RCTs) have compared biologic and synthetic mesh. We hypothesize biologic mesh would result in fewer major complications at one-year post-operative compared with synthetic mesh. Patients and Methods: We performed a single-center, pilot RCT. All eligible patients undergoing complex, open VHR were randomly assigned to receive biologic or synthetic mesh placed in the retromuscular position. Primary outcome was major complications, namely, a composite of mesh infection, recurrence, or re-operation at one-year post-operative. Secondary outcomes included surgical site infections (SSI), seromas, hematomas, wound dehiscence, re-admissions, and Clavien-Dindo complication grade. Outcomes were assessed using Fisher exact test and Bayesian generalized linear models. Results: Of 87 patients, 44 were randomly assigned to biologic mesh and 43 to synthetic mesh. Most cases were wound class 2-4 (68%) and 75% had a hernia width >4 cm. Most patients were obese (70%) and had an American Society of Anesthesiogists (ASA) score of 3-4 (53%). Compared with patients in the synthetic mesh group, patients in the biologic mesh group had a higher percentage of: major complications at one-year post-operative (42.4% vs. 21.6%; relative risk [RR] = 1.96 [95% confidence interval {CI} = 0.94-4.08]; number needed to harm = 4.8; p = 0.071); SSI (15.9% vs. 9.3%; RR = 1.71 [95% CI = 0.54-5.42]; p = 0.362); wound dehiscence (25.0% vs. 14.0%; RR = 1.79 [95% CI = 0.73-4.41]; p = 0.205); and re-admissions (22.7% vs 9.3%; RR = 2.44 [95% CI = 0.83-7.20]; p = 0.105). Bayesian analysis demonstrated that compared with synthetic mesh, biologic mesh had a 95% probability of increased risk of major complications at one-year post-operative. No clear evidence of a difference was found on seromas, hematomas, or Clavien-Dindo complication grade. Conclusions: In elective complex open VHR, biologic mesh demonstrated no benefit compared with synthetic mesh in one-year outcomes. Moreover, Bayesian analysis suggests that biologic mesh may have an increased probability of major complications. [ABSTRACT FROM AUTHOR]

Background: International oncology societies recommend early palliative care. Specific models to integrate early palliative care efficiently into clinical practice are debated. The authors designed a study to look at the quantitative and qualitative outcomes of an early palliative care intervention in oncological care to decrease stress and improve quality of life. Aims: To compare a single structured early palliative care intervention added to a usual oncology care in terms of distress and health-related quality of life at baseline compared to 6 months after enrollment. Design: This multicenter randomized controlled trial (NCT01983956) enrolled adult patients with advanced cancer. Participants were either randomly assigned to usual oncology care alone or usual care plus a structured early palliative care intervention. Setting/participants: One hundred fifty adult patients with a variety of advanced cancer diagnoses were randomized. Seventy-four participants were in the intervention and 76 participants in the control group. The primary outcome was the change in patient distress assessed by the National Comprehensive Cancer Network distress thermometer at 6 months. Health-related quality of life, the secondary outcome, was assessed by the Functional Assessment of Cancer Therapy–General Questionnaire. Results: The results showed no significant effect of the early palliative care intervention neither on patient distress nor on health-related quality of life. Conclusion: The addition of an early intervention to usual care for patients with advanced cancer did not improve distress or quality of life. Thus, patients may need more intensive early palliative care with continuous professional support to identify and address their palliative needs early. [ABSTRACT FROM AUTHOR]

Background: Awareness for the importance of psychological and spiritual needs in patients with terminal diseases has increased in recent years, but randomized trials on the effects of psychosocial interventions are still rare. Aim: To investigate the efficacy of the "Song of Life" music therapy intervention regarding the emotional and psycho-spiritual dimensions of quality of life. Design: Patients were randomly assigned to either "Song of Life" or a relaxation intervention. "Song of Life" is a novel three-session music therapy intervention working with a biographically meaningful song. Primary outcome was the improvement in psychological quality of life. Secondary outcomes included spiritual well-being, ego-integrity, momentary distress, and global quality of life and the explorative assessment of treatment satisfaction (patient and family member version). Intention-to-treat analysis was conducted including adjustment for multiple testing in secondary outcomes. Setting/participants: Between December 2018 and August 2020, 104 patients receiving specialized palliative care were recruited from two palliative care wards. Results: No significant differences were found regarding psychological and global quality of life, but "Song of Life" participants reported significantly higher spiritual well-being (p = 0.04) and ego-integrity (p < 0.01), as well as lower distress (p = 0.05) than patients in the control group. Both patients' and family members' treatment satisfaction was higher after "Song of Life" with large between-group effect sizes on items asking for meaningfulness (d = 0.96) and importance (d = 1.00). Conclusions: Our findings provide evidence that "Song of Life" is an effective and meaningful biographical music therapy intervention to facilitate psycho-spiritual integration in terminally ill patients. Trial Registration: German Clinical Trials Register (DRKS)—DRKS00015308 (date of registration: September 7th 2018). [ABSTRACT FROM AUTHOR]

Background: Target lesion failure remains an issue with contemporary drug-eluting stents. Thus, the dual-therapy sirolimus-eluting and CD34+ antibody-coated Combo stent (DTS) was designed to further improve early healing. This study aimed to investigate whether the DTS is noninferior to the sirolimus-eluting Orsiro stent (SES) in an all-comers patient population.Methods: The SORT OUT X (Combo Stent Versus Orsiro Stent) trial, was a large-scale, randomized, multicenter, single-blind, 2-arm, noninferiority trial with registry-based follow-up. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction, or target lesion revascularization within 12 months, analyzed using intention-to-treat. The trial was powered for assessing target lesion failure noninferiority of the DTS compared with the SES with a predetermined noninferiority margin of 0.021.Results: A total of 3146 patients were randomized to treatment with the DTS (1578 patients; 2008 lesions) or SES (1568 patients; 1982 lesions). At 12 months, intention-to-treat analysis showed that 100 patients (6.3%) assigned the DTS and 58 patients (3.7%) assigned the SES met the primary end point (absolute risk difference, 2.6% [upper limit of 1-sided 95% CI, 4.1%]; P (noninferiority)=0.76). The SES was superior to the DTS (incidence rate ratios for target lesion failure, 1.74 [95% CI, 1.26-2.41]; P=0.00086). The difference was explained mainly by a higher incidence of target lesion revascularization in the DTS group compared with the SES group (53 [3.4%] vs. 24 [1.5%]; incidence rate ratio, 2.22 [95% CI, 1.37-3.61]; P=0.0012).Conclusions: The DTS did not confirm noninferiority to the SES for target lesion failure at 12 months in an all-comer population. The SES was superior to the DTS mainly because the DTS was associated with an increased risk of target lesion revascularization. However, rates of death, cardiac death, and myocardial infarction at 12 months did not differ significantly between the 2 stent groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03216733. [ABSTRACT FROM AUTHOR]

Background: The success of coronary artery bypass grafting surgery (CABG) is dependent on long-term graft patency, which is negatively related to early wall thickening. Avoiding high-pressure distension testing for leaks and preserving the surrounding pedicle of fat and adventitia during vein harvesting may reduce wall thickening.Methods: A single-centre, factorial randomized controlled trial was carried out to compare the impact of testing for leaks under high versus low pressure and harvesting the vein with versus without the pedicle in patients undergoing CABG. The primary outcomes were graft wall thickness, as indicator of medial-intimal hyperplasia, and lumen diameter assessed using intravascular ultrasound after 12 months.Results: Ninety-six eligible participants were recruited. With conventional harvest, low-pressure testing tended to yield a thinner vessel wall compared with high-pressure (mean difference [MD; low minus high] -0.059 mm, 95% confidence interval (CI) -0.12, +0.0039, p = .066). With high pressure testing, veins harvested with the pedicle fat tended to have a thinner vessel wall than those harvested conventionally (MD [pedicle minus conventional] -0.057 mm, 95% CI: -0.12, +0.0037, p = .066, test for interaction p = .07). Lumen diameter was similar across groups (harvest comparison p = .81; pressure comparison p = .24). Low-pressure testing was associated with fewer hospital admissions in the 12 months following surgery (p = .0008). Harvesting the vein with the pedicle fat was associated with more complications during the index admission (p = .0041).Conclusions: Conventional saphenous vein graft preparation with low-pressure distension and harvesting the vein with a surrounding pedicle yielded similar graft wall thickness after 12 months, but low pressure was associated with fewer adverse events. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the feasibility of a multi-centre randomised controlled trial to compare the clinical and cost-effectiveness of early patient-directed rehabilitation versus standard rehabilitation following surgical repair of the rotator cuff of the shoulder. Design: Two-arm, multi-centre pilot and feasibility randomised controlled trial. Setting: Five National Health Service hospitals in England. Participants: Adults (n = 73) with non-traumatic rotator cuff tears scheduled for repair were recruited and randomly allocated remotely prior to surgery. Interventions: Early patient-directed rehabilitation (n = 37); advised to remove their sling as soon as able and move as symptoms allow. Standard rehabilitation (n = 36); sling immobilisation for four weeks. Measures: (1) Randomisation of 20% or more eligible patients. (2) Difference in time out of sling of 40% or more between groups. (3) Follow-up greater than 70%. Results: 73/185 (39%) potentially eligible patients were randomised. Twenty participants were withdrawn, 11 due to not receiving rotator cuff repair. The between-group difference in proportions of participants who exceeded the cut-off of 222.6 hours out of the sling was 50% (80% CI = 29%, 72%), with the early patient-directed rehabilitation group reporting greater time out of sling. 52/73 (71%) and 52/53 (98%) participants were followed-up at 12 weeks when withdrawals were included and excluded respectively. Eighteen full-thickness re-tears were reported (early patient-directed rehabilitation = 7, standard rehabilitation = 11). Five serious adverse events were reported. Conclusion: A main randomised controlled trial is feasible but would require allocation of participants following surgery to counter the issue of withdrawal due to not receiving surgery. [ABSTRACT FROM AUTHOR]

Purpose The aim of this research was to study the effectiveness on return to work (RTW) of an early tailored work-related support intervention in patients diagnosed with curative gastrointestinal cancer. Methods A multicenter randomized controlled trial was undertaken, in which patients were assigned randomly to the intervention or the control group (usual care). The intervention encompassed three psychosocial work-related support meetings, starting before treatment. Five self-reported questionnaires were sent over twelve months of follow-up. Primary outcome was days until RTW (fulltime or partial) and secondary outcomes included work status, quality of life, work ability, and work limitations. Descriptive analysis, Kaplan–Meier analysis, relative risk ratio and linear mixed models were applied. Results Participants (N = 88) had a mean age of 55 years; 67% were male and the most common cancer type was colon cancer (66%). Of the participants, 42 were randomized to the intervention group. The median time from sick leave until RTW was 233 days (range 187–279 days) for the control group, versus 190 days (range 139–240 days) for the intervention group (log-rank p = 0.37). The RTW rate at twelve months after baseline was 83.3% for the intervention group and 73.5% for the control group. Work limitations did statistically differ between the groups over time (p = 0.01), but quality of life and work ability did not. Conclusion Patients in the intervention group seem to take fewer days to RTW, albeit not to a statistically significant extent. Trial registration Trial NL4920 (NTR5022) (Dutch Trial Register https://www.trialregister.nl) [ABSTRACT FROM AUTHOR]

Background: This split-mouth randomized clinical trial compared two different types of subepithelial connective tissue grafts (SCTG) considering clinical parameters and patient-centered outcomes in patients with bilateral recession type 1 multiple gingival recessions after 6 months postoperatively.Methods: A total of 21 patients were surgically treated with coronally advanced flap (CAF) associated with SCTG harvested by: double blade scalpel (DBS) and de-epithelialized (DE) SCTG. Periodontal clinical parameters and esthetics were evaluated by a calibrated periodontist at baseline and after 6 months. Patient-centered outcomes related to pain/discomfort and esthetics were assessed with visual analogue scale after 7 days and 6 months, respectively.Results: All clinical parameters, with the exception of probing depth, demonstrated differences in intragroup evaluation, comparing baseline to 6-month evaluation (P <0.05). Both groups presented reduction of recession depth and recession width and gain of keratinized tissue thickness, keratinized tissue width, and clinical attachment level (P <0.05). Intergroup comparison (DBS × DE) demonstrated no significant differences considering clinical parameters and periods. Both techniques improved esthetics evaluated by patients, without a difference between groups in patients and professional analysis. However, DBS group presented inferior pain/discomfort compared with DE (P <0.05).Conclusion: DBS and DE associated with CAF presented satisfactory clinical outcomes. However, DBS presented inferior morbidity, an important fact for decision-making process. [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: Increasing evidence has shown benefits of spinal manipulations in patients with patellofemoral pain syndrome (PFPS). There is scarcity regarding medium term effects of spinal manual therapy on outcome measures in PFPS patients. Therefore, the aim of the present study was to compare the effectiveness of local exercise therapy and spinal manual therapy for knee pain, function and maximum voluntary peak force (MVPF) velocity of the quadriceps in PFPS patients.Methods: Forty-three patients with PFPS were randomly assigned to a local exercise or spinal manual therapy group. The local exercise group received six sessions (one session per week) of supervised training of the knee-and hip muscles with mobilization of the patellofemoral joint. The spinal manual therapy group received six interventions (one intervention per week) of high velocity low thrust manipulations at the thoracolumbar region, sacroiliac joint, and/or hip. All patients were also asked to do home exercises. Maximum, minimum and current pain were measured using the visual analogue scale. Function was assessed with the anterior knee pain scale (AKPS) and MPFV was recorded using a Biodex System 3 dynamometer. Patients were assessed before intervention, after 6 weeks of intervention and after 6 weeks of follow-up. Between-group differences at assessments were analysed by way of analysis of covariance with Bonferroni correction.Results: Pain and functionality improved more following spinal manipulative therapy than local exercise therapy. After 6 weeks of intervention the between-group difference (local versus spinal) for maximal pain was 23.4 mm [95% CI: 9.3, 37.6; effect size (ES): 1.04] and - 12.4 [95% CI: - 20.2, - 4.7; ES: 1.00] for the AKPS. At 6 weeks of follow-up the between-group difference for maximal pain was 18.7 mm [95% CI: 1.4, 36.0; ES: 0.68] and - 11.5 [95% CI: - 19.9, - 3.3; ES: - 0.87] for the AKPS.Conclusions: This study suggests that spinal manual therapy is more effective than local exercise therapy in improving pain and function in patients with PFPS in the medium term. We suggest for future research to investigate whether combining local exercise therapy and spinal manual therapy is more effective than either single intervention on its own. This clinical trial study was approved by the Medical Ethics Committee METC Z under registration number NL57207.096. and registered retrospectively in ClinicalTrials.gov PRS with registration ID number NCT04748692 on the 10th of February 2021. [ABSTRACT FROM AUTHOR]

Objectives: (1) To create a short motion graphic video to debias women, using evidence from cognitive psychology, of 2 common myths about safety of intrauterine devices (IUDs) and implants in Jamaica; and (2) to conduct a pilot study to evaluate video effectiveness.Study Design: We conducted a series of 3 focus group discussions among target users to inform the development process of the script, story, character, and look of the intervention video. We randomized young, female nonusers of long-acting contraception at risk of pregnancy at a public clinic in Kingston in 2018-2019 to watch either the intervention (n = 113) or control video (n = 112). We used logistical regression to evaluate perceptions of method safety, naturalness, and uptake after 3 months of follow up.Results: Almost all (n = 220; 97.8%) participants completed the 3-month interview. More women in the intervention arm perceived IUDs to be safe (59.1%) compared to the control arm (43.6%; p = 0.02). Perceived implant safety increased from enrollment to follow up in the intervention and control arms (10.9 and 2.7 percentage-point increases, respectively); however, the difference between arms at follow up was not statistically significant (p = 0.57). This appeared to be due to arm imbalances at enrollment. Study arms did not differ at follow up in perceived IUD naturalness (p = 0.36) or implant naturalness (p = 0.68).Conclusions: Findings from a pilot study of a video intervention suggest that using debiasing strategies from cognitive psychology has the potential to address misconceptions about contraceptive safety. A larger trial with adequate power is warranted.Implications: Evidence from a pilot randomized controlled trial suggested that use of debiasing strategies from cognitive psychology could be effective in correcting women's misconceptions about contraception safety and thus show promise for the design of future contraceptive promotion videos to increase uptake. [ABSTRACT FROM AUTHOR]

Objective: The aim of this work was to assess the cost-effectiveness of induction of labor with outpatient balloon catheter cervical priming versus inpatient prostaglandin vaginal gel or tape.Study Design: Economic evaluation alongside a multi-centre, randomized controlled trial at eight Australian maternity hospitals. The trial reported on 448 women with live singleton term pregnancies, undergoing induction of labor for low-risk indications between September 2015 and October 2018. An economic decision tree model was designed from a health services perspective from time of induction of labor to hospital discharge. Sensitivity and subgroup analyses were performed to test the robustness of model outcomes. We estimated resource use, collected data on health outcomes (using EQ-5D-3 L questionnaire) and reported cost (Australian Dollars) per quality-adjusted life year gained, incremental cost-effect ratio and net monetary benefit.Results: Deterministic analysis showed lower mean costs ($7294 versus $7585) in the outpatient-balloon (n = 205) compared to the inpatient-prostaglandin group (n = 243), with similar health outcomes (0.75 vs 0.74 quality-adjusted life years gained) and overall higher net monetary benefit ($30,054 vs $29,338). In probabilistic analyses outpatient-balloon induction of labor was cost-effective in 55.3 % of all simulations and 59.1 % for women with favourable cervix (modified Bishop score >3) and 64.5 % for nulliparous women.Conclusions: Outpatient-balloon induction of labor may be cost-saving compared to inpatient induction of labor with prostaglandin and is most likely to be cost-effective for nulliparous women, but more research is warranted in other settings to explore the generalisability of results. [ABSTRACT FROM AUTHOR]

Objective: ADHD has been associated with persistent problems of working memory. This study investigated the efficacy of an intensive and adaptive computerized working memory treatment (CWMT) at behavioral and neural levels. Method: College students (n = 89; 40 females) with ADHD were randomized into a standard-length CWMT (45 min/session, 25 sessions, n = 29), shortened-length CWMT (15 min/session, 25 sessions, n = 32), and a waitlist group (n = 28). Both CWMT groups received treatment for 5 days a week for 5 weeks. Lab sessions before and after CWMT assessed electroencephalography (EEG) indicators of working memory, behavioral indicators of working memory performance, and ADHD symptomatology. Results: No evidence was found for neural or any other behavioral transfer effects of improvement for the CWMT treatment groups over the active control or waitlist group. Conclusion: Our study does not provide evidence for the benefits of CWMT at neural or behavioral levels. [ABSTRACT FROM AUTHOR]

Background: For some common cancers, survival is lower in the UK than in comparable high-income countries.Aim: To assess the effectiveness of a targeted postal intervention (to promote awareness of cancer symptoms and earlier help seeking) on patient consultation rates.Design and Setting: A two-arm randomised controlled trial was carried out on patients aged 50-84 years registered at 23 general practices in rural and urban areas of Greater London, Greater Manchester, and the North East of England.Method: Patients who had not had a consultation at their general practice in the previous 12 months and had at least two other risk factors for late presentation with cancer were randomised to intervention and control arms. The intervention consisted of a posted letter and leaflet. Primary outcome was the number of consultations at the practice with patients randomised to each arm in the 6 months subsequent to posting the intervention. All patients with outcome data were included in the intention-to-treat analyses.Results: In total, 1513 patients were individually randomised to the intervention (n = 783) and control (n = 730) arms between Nov 2016 - May 2017; outcome data were available for 749 and 705 patients, respectively, with a statistically significantly higher rate of consultation in the intervention arm compared with the control arm: 436 versus 335 consultations (relative risk 1.40, 95% confidence interval = 1.11 to 1.77, P = 0.004). There was, however, no difference in the numbers of patients consulting.Conclusion: Targeted interventions of this nature can change behaviour; there is a need to develop interventions that can be more effective at engaging patients with primary care. This study demonstrates that targeted interventions promoting both awareness of possible cancer symptoms and earlier health seeking, can change behaviour. There is a need to develop and test interventions that can be more effective at engaging the most at-risk patients. [ABSTRACT FROM AUTHOR]

Background: Chiropractic care is commonly used to treat infantile colic. However large trials with parental blinding are missing. Therefore, the purpose of this study is to evaluate the effect of chiropractic care on infantile colic. Method: This is a multicenter, single-blind randomized controlled trial conducted in four Danish chiropractic clinics, 2015–2019. Information was distributed in the maternity wards and by maternal and child health nurses. Children aged 2–14 weeks with unexplained excessive crying were recruited through home visits and randomized (1:1) to either chiropractic care or control group. Both groups attended the chiropractic clinic twice a week for 2 weeks. The intervention group received chiropractic care, while the control group was not treated. The parents were not present in the treatment room and unaware of their child's allocation. The primary outcome was change in daily hours of crying before and after treatment. Secondary outcomes were changes in hours of sleep, hours being awake and content, gastrointestinal symptoms, colic status and satisfaction. All outcomes were based on parental diaries and a final questionnaire. Results: Of 200 recruited children, 185 completed the trial (treatment group n = 96; control group n = 89). Duration of crying in the treatment group was reduced by 1.5 h compared with 1 h in the control group (mean difference − 0.6, 95% CI − 1.1 to − 0.1; P = 0.026), but when adjusted for baseline hours of crying, age and chiropractic clinic, the difference was not significant (P = 0.066). The proportion obtaining a clinically important reduction of 1 h of crying was 63% in the treatment group and 47% in the control group (p = 0.037), and NNT was 6.5. We found no effect on any of the secondary outcomes. Conclusion: Excessive crying was reduced by half an hour in favor of the group receiving chiropractic care compared with the control group, but not at a statistically significant level after adjustments. From a clinical perspective, the mean difference between the groups was small, but there were large individual differences, which emphasizes the need to investigate if subgroups of children, e.g. those with musculoskeletal problems, benefit more than others from chiropractic care. Trial registration: Clinical Trials NCT02595515, registered 2 November 2015 [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: Few treatments are available for patients with idiopathic hypersomnia (IH). Modafinil, an established treatment for narcolepsy, was tested for efficacy and safety in Japanese patients with IH without long sleep time.Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study was conducted at 20 institutions in Japan. Patients who met the diagnostic criteria of IH in the International Classification of Sleep Disorders (second edition) were included. The study comprised a ≥17-day observation period and a 3-week treatment period during which modafinil (200 mg) or placebo was administered orally once daily (in the morning). The primary efficacy endpoint was change in mean sleep latency on the Maintenance of Wakefulness Test (MWT). Adverse events (AEs) were also recorded to evaluate safety.Results: In total, 123 patients were screened and 71 were randomized to receive modafinil (N = 34) or placebo (N = 37). Patients treated with modafinil experienced a significantly prolonged mean sleep latency on the MWT at the end of the study compared with placebo (5.02 min, 95% confidence interval: 3.26-6.77 min; p < 0.001). AEs occurred in 58.8% (20/34) and 27.0% (10/37) of patients in the modafinil and placebo groups, respectively. Frequent AEs in the modafinil group were headache (n = 6), dry mouth (n = 3), and nausea (n = 3); no clinically significant AEs occurred.Conclusion: Modafinil was shown to be an effective and safe treatment for excessive daytime sleepiness in patients with IH without long sleep time.Clinical Trial Registration: JapicCTI; 142539. [ABSTRACT FROM AUTHOR]

Context: Functional hyperandrogenism may be associated with a mild increase in body iron stores. Iron depletion exerts a beneficial effect on metabolic endpoints in other iron overload states.Objectives: (i) To determine the effect of iron depletion on the insulin sensitivity and frequency of abnormal glucose tolerance in patients with functional hyperandrogenism submitted to standard therapy with combined oral contraceptives (COC). ii) To assess the overall safety of this intervention.Design: Randomized, parallel, open-label, clinical trial.Setting: Academic hospital.Patients: Adult women with polycystic ovary syndrome or idiopathic hyperandrogenism.Intervention: After a 3-month run-in period of treatment with 35 μg ethinylestradiol plus 2 mg cyproterone acetate, participants were randomized (1:1) to 3 scheduled bloodlettings or observation for another 9 months.Main Outcome Measures: Changes in insulin sensitivity index and frequency of prediabetes/diabetes, and percentage of women in whom bloodletting resulted in plasma hemoglobin <120 g/L and/or hematocrit <0.36.Results: From 2015 to 2019, 33 women were included by intention-to-treat. During the follow-up, insulin sensitivity did not change in the whole group of women or between study arms [mean of the differences (MD): 0.0 (95%CI: -1.6 to 1.6)]. Women in the experimental arm showed a similar odds of having prediabetes/diabetes than women submitted to observation [odds ratio: 0.981 (95%CI: 0.712 to 1.351)]. After bloodletting, 4 (21.1%) and 2 women (10.5%) in the experimental arm had hemoglobin (Hb) levels <120 g/L and hematocrit (Hct) values <0.36, respectively, but none showed Hb <110 g/L or Hct <0.34.Conclusions: Scheduled bloodletting does not improve insulin sensitivity in women with functional hyperandrogenism on COC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether the efficacy of Getong Tongluo Capsule (葛酮通络胶囊, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. Methods: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. Results: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). Conclusion: GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667) [ABSTRACT FROM AUTHOR]

Objective: Family caregivers (FCs) of cancer patients often experience high distress. This randomized clinical trial assessed the feasibility and preliminary effects of an intervention to improve FC supportive care.Method: A pragmatic and minimal intervention to improve FC supportive care was developed and pretested with FCs, oncology team, and family physicians to assess its relevance and acceptability. Then, FCs of lung cancer patients were randomized to the intervention or the control group. The intervention included (1) systematic FC distress screening and problem assessment in the first months after their relative cancer diagnosis, and every 2 months after; (2) privileged contact with an oncology nurse to address FC problems, provide emotional support and skills to play their caregiving role; (3) liaison with the family physician of FCs reporting high distress (distress thermometer score ≥4/10) to involve them in the provision of supportive care. Distress, the primary outcome, was measured every 3 months, for 9 months. Secondary outcomes included quality of life, caregiving preparedness, and perceived burden. At the end of their participation, a purposive sample of FC from the experimental group was individually interviewed to assess the intervention usefulness. Content analysis was performed.Results: A total of 109 FCs participated in the trial. FC distress decreased over time, but this reduction was observed in both groups. Similar results were found for secondary outcomes. However, FCs who received the intervention felt better prepared in caregiving than controls (p = 0.05). All 10 interviewed FCs valued the intervention, even though they clearly underused it. Knowing they could contact the oncology nurse served as a security net.Significance Of Results: Although the intervention was not found effective, some of its aspects were positively perceived by FCs. As many of them experience high distress, an improved intervention should be developed to better support them. [ABSTRACT FROM AUTHOR]

Background: Caring for someone with dementia is associated with negative and positive experiences. There is little evidence based on large datasets.Objective: To present data around the experience of caring for someone with dementia, to identify support (emotional and practical) needs, and inform future service provision.Methods: A mixed-methods study embedded in the Promoting Activity, Independence and Stability in Early Dementia (PrAISED) Randomized Controlled Trial. We administered questionnaires on strain, quality of life (QoL), and perceived health to 301 caregivers and assessment of cognitive performance, depression, anxiety, and disability in activities of daily living to 301 participants with dementia. Data were analyzed through descriptive and modelling statistics. A subsample of 20 patient-caregiver dyads were qualitatively interviewed. Data around caregivers' experience of providing care were extrapolated and analyzed through inductive thematic analysis.Results: There were significant negative associations between caregiver strain and QoL (p < 0.01) and between caregiver age and QoL (p < 0.01), and significant positive associations between caregiver strain and disability (p < 0.01), cognitive impairment (p < 0.01), depression (p < 0.05), and anxiety of the person with dementia (p < 0.05). Older caregivers reported a lack of support, reinforced by their reluctance to seek help. All caregivers reported contradictory emotions associated with caring and accumulation of strain over time.Conclusion: While there is recognition that it is essential to support caregivers, dedicated intervention programs, and support strategies to respond to the needs of older caregivers are still needed. [ABSTRACT FROM AUTHOR]