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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 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]

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

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

Objective: To evaluate the efficacy and safety of a Chinese medicine (CM) Modified Qufeng Runmian Powder (加减祛风润面散, MQFRMP) for the treatment of acne vulgaris with CM syndromes of dampness and blood stasis. Methods: In this multicenter, randomized, double-blind, placebo-controlled clinical trial, 220 acne vulgaris patients with CM syndrome of dampness and blood stasis were included and randomly assigned using a central area group random design to receive either MQFRMP or the placebo, with 110 cases in each group. MQFRMP or a placebo at 145 g/bag were administered once daily for 4 weeks, respectively. The primary index of efficacy was the effective rate according to the acne severity score (ASS). The secondary indices of efficacy included the changes in the dermatology life quality index (DLQI) score, VISIA scores (spots, pores, brown spots, porphyrins and red areas) and skin assessment (skin pH, sebum amount and hydration) according to a SOFT skin multianalyzer. Results: (1) Follow-up: a total of 204 patients completed the follow-up, with 103 in the treatment group and 101 in the control group. (2) Effective rate: the total effective rate of the treatment group was significantly higher than the control group [83.5% (86/103) vs. 31.7% (32/101), P<0.01)] with 95% confidence interval of 39.3%–66.4%. (3) DLQI: DLQI scores were significantly decreased the treatment and control groups (both P<0.01), but the treatment group was more obvious than the placebo group (P<0.01). (4) VISIA scores: the scores of spots, brown spots and red areas in the treatment group decreased compared with baseline (P<0.05). In the control group, the scores of brown spots and pores decreased compared with baseline (P<0.05). The improvement was more obvious in the treatment group than in the control group for all items (P<0.05). (5) Skin assessment: the pH and sebum score in the both groups decreased drastically compared with the baseline (all P<0.01), however, the improvement was more obvious in the treatment group than in the control group (P<0.01). The hydration amount in the two groups showed no statistically significant difference compared with the baseline (both P>0.05). (6) Safety: two cases of mild drug allergy were observed in the treatment group. Conclusion: MQFRMP was effective and safe for the treatment of acne vulgaris with syndromes of dampness and blood stasis. (No. ChiCTR1900020479). [ABSTRACT FROM AUTHOR]

Objective: To assess the effect and safety of Hydroxysafflor Yellow A for Injection (HSYAI) in treating patients with acute ischemic stroke (AIS) and blood stasis syndrome (BSS). Methods: A multicenter, randomized, double-blind, multiple-dose, active-controlled phase II trial was conducted at 9 centers in China from July 2013 to September 2015. Patients with moderate or severe AIS and BSS were randomly assigned to low-, medium-, high-dose HSYAI groups (25, 50 and 70 mg/d HSYAI by intravenous infusion, respectively), and a control group (Dengzhan Xixin Injection (灯盏细辛注射液, DZXXI) 30 mL/d by intravenous infusion), for 14 consecutive days. The primary outcome was the Modified Rankin Scale (mRS) score ⩽1 at days 90 after treatment. The secondary outcomes included the National Institute of Health Stroke Scale (NIHSS) score ⩽1, Barthel Index (BI) score ⩾95, and BSS score reduced ⩾30% from baseline at days 14, 30, 60, and 90 after treatment. The safety outcomes included any adverse events during 90 days after treatment. Results: Of the 266 patients included in the effectiveness analysis, 66, 67, 65 and 68 cases were in the low-, medium-, and high-dose HSYAI and control groups, respectively. The proportions of patients in the medium- and high-dose HSYAI groups with mRS score ⩽1 at days 90 after treatment were significantly larger than the control group (P<0.05). The incidences of favorable outcomes of NIHSS and BI at days 90 after treatment as well as satisfactory improvement of BSS at days 30 and 60 after treatment in the medium- and high-dose HSYAI groups were all significantly higher than the control group (P<0.05). No significant difference was reported among the 4 groups in any specific adverse events (P>0.05). Conclusions: HSYAI was safe and well-tolerated at all doses for treating AIS patients with BSS. The medium (50 mg/d) or high dose (75 mg/d) might be the optimal dose for a phase III trial. (Registration No. ChiCTR-2000029608) [ABSTRACT FROM AUTHOR]

Background: Tianshu capsule (TSC), a formula of traditional Chinese medicine, has been widely used in clinical practice for prophylactic treatment of headaches in China. However, former clinical trials of TSC were small, and lack of a standard set of diagnostic criteria to enroll patients. The study was conducted to re-evaluate the efficacy and safety of TSC post-marketing in an extending number of migraineurs who have diagnosed migraine with the International Classification of Headache Disorders, 3rd edition (beta version, ICHD-3β). Methods: The study was a double-blind, randomized, placebo-controlled clinical trial that conducted at 20 clinical centers in China. At enrollment, patients between 18 and 65 years of age diagnosed with migraine were assigned to receive either TSC (4.08 g, three times daily) or a matched placebo according to a randomization protocol. The primary endpoint was a relative reduction of 50% or more in the frequency of headache attacks. The secondary outcomes included a reduction in the incidence of headache, the visual analogue scale of headache attacks, days of acute analgesic usage, and percentage of patients with a decrease of 50% or more in headache severity. Accompanying symptoms were also assessed. Results: One thousand migraine patients were initially enrolled in the study, and 919 of them completed the trial. Following the 12-week treatment, significant improvement was observed in the TSC group concerning both primary and secondary outcomes. After therapy discontinuation, the gap between the TSC group and the placebo group in efficacy outcomes continued to increase. There were no severe adverse effects. Conclusions: TSC is an effective, well-tolerated medicine for prophylactic treatment of migraine, and still have prophylactic effect after medicine discontinuation. Trial registration: ClinicalTrials.gov Identifier: NCT02035111; Data of registration: 2014-01-10. [ABSTRACT FROM AUTHOR]

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

Objective: To evaluate the efficacy and safety of Tongxiening Granules (痛泻宁颗粒, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D). Methods: A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated. Results: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05). Conclusion: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415) [ABSTRACT FROM AUTHOR]

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

Background: Persistent proteinuria seems to be a risk factor for progression of renal disease. Its reduction by angiotensin-converting inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) is renoprotective. Our previous pilot study showed that 2-year lisinopril therapy is effective and safe for children with mild IgA nephropathy. When combined with ACEI and ARB, reported results are of greater decrease in proteinuria than monotherapy in chronic glomerulonephritis, including IgA nephropathy. To date, however, there have been no randomized controlled trials in children.Methods: This is an open-label, multicenter, prospective, and randomized phase II controlled trial of 63 children with biopsy-proven proteinuric mild IgA nephropathy. We compared efficacy and safety between patients undergoing lisinopril monotherapy and patients undergoing combination therapy of lisinopril and losartan to determine better treatment for childhood proteinuric mild IgA nephropathy.Results: There was no difference in proteinuria disappearance rate (primary endpoint) between the two groups (cumulative disappearance rate of proteinuria at 24 months: 89.3% vs 89% [combination vs monotherapy]). Moreover, there were no significant differences in side effects between the two groups.Conclusions: We propose lisinopril monotherapy as treatment for childhood proteinuric mild IgA nephropathy as there are no advantages of combination therapy.Clinical trial registration: Clinical trial registry, UMIN ID C000000006, https://www.umin.ac.jp. [ABSTRACT FROM AUTHOR]

Purpose: Chronic pain, depression, and fatigue are common effects resulting from the cancer experience; new interventions are needed. This study examined the effect of Reimagine, an online symptom self-management curriculum that teaches coping skills, on key outcomes.Methods: Adult breast cancer survivors with chronic pain were recruited from the Army of Women volunteer registry for this randomized controlled trial and randomized 1:1 to Reimagine or usual care conditions. Electronic surveys collected demographic, clinical, and outcome data at baseline and 18 weeks post-intervention.Results: Participants (N = 89) were mean age 56.7 ± 8.7 years; 67% married; 58% employed; mean years since diagnosis 8.2 ± 6.6; and 89% were in remission or cured of their breast cancer. There was a significant difference in the change in depression scores for treatment (M = - 1.7, SD = 4.5) and usual care (M = 0.3, SD = 3.8) conditions; t(85) = - 2.3, p = .03. Difference in the change in fatigue scores was significant for treatment (M = 4.8, SD = 9.0) and usual care (M = 1.2, SD = 6.6) conditions; t(87) = 2.2, p = .03. Most Reimagine users (94%) would recommend the curriculum to others.Conclusions: These results suggest that Reimagine has an effect on depression and fatigue symptoms for breast cancer survivors. Online programs can be a feasible and effective alternative to in-person support. Additional research is recommended with larger and more diverse samples. [ABSTRACT FROM AUTHOR]

Background: Training in interoceptive awareness is a promising behavioral approach for improving substance use disorder (SUD) treatment. This study examined the longitudinal effects of Mindful Awareness in Body-oriented Therapy (MABT) as an adjunct to women's SUD treatment. MABT teaches interoceptive awareness skills to promote self-care and emotion regulation.Methods: Women in intensive outpatient treatment for SUD at three community clinics were recruited and randomly assigned to one of three study conditions Treatment as Usual (TAU) + MABT, TAU + Women's Health Education (WHE), and TAU only. Four assessments were delivered over one year (N = 187) baseline, 3, 6 and 12 months to examine primary outcome of percent days abstinent from substance use, and secondary outcomes of emotion dysregulation, craving, psychological distress, mindfulness and interoceptive awareness. Changes in outcomes across time were assessed using multilevel mixed effects linear regression.Results: Substance use improved significantly for MABT vs. TAU at 6 months and 12 months. Positive longitudinal effects on secondary outcomes for MABT were evident on respiratory sinus arrhythmia (RSA), a physiological index of emotion regulation; on craving; and on interoceptive awareness skills. Analyses based on participants who completed >75% of the intervention sessions revealed additional immediate significant improvements for MABT vs. TAU and WHE on depressive symptoms and emotion regulation difficulties and longitudinal improvement on mindfulness skills.Conclusions: Results show MABT to be efficacious for longitudinal health outcomes to support women's recovery as an adjunct to community-based SUD treatment. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of acupuncture in patients with vascular cognitive impairment no dementia (VCIND) in comparison with citicoline, an agent for cognitive disturbances associated with chronic cerebral disorders. Design: A randomized controlled multicenter trial. Setting: In three hospitals in Beijing, China. Subjects: A total of 216 patients with VCIND were recruited. Interventions: Patients with VCIND (mean age of 65.4 years) were randomized to receive acupuncture (two sessions per week) or oral citicoline (100 mg three times daily) over three months. Main measures: The primary outcome was the change from baseline to three months in cognitive symptom, measured by Alzheimer's disease Assessment Scale, cognitive subscale (ADAS-cog). Secondary outcomes included changes from baseline to six months in ADAS-cog, executive function measured by the Clock Drawing Test (CDT), and functional disability measured by the Ability of Daily Living (ADL) scale at three and six months. Results: At three months, the acupuncture group had a greater decrease in mean ADAS-cog score (−2.33 ± 0.31) than the citicoline group (−1.38 ± 0.34) with a mean difference of −0.95 (95% CI, −1.84 to −0.07, P = 0.035). The mean change from baseline to six months in ADAS-cog also significantly favored acupuncture treatments (acupuncture change −2.61 vs citicoline −1.25, difference: −1.36 points; 95% CI, −2.20 to −0.51; P = 0.002). There was no difference between the two groups on CDT and ADL scores at either time point. Conclusion: Compared with citicoline, acupuncture has comparable and even superior efficacy with improved cognitive and daily living performance as a complementary and alternative medicine treatment for VCIND. [ABSTRACT FROM AUTHOR]

Purpose: Vena cava syndrome (VCS) from stenosis of the superior vena cava or inferior vena cava caused by compression from a malignant tumor is one of the typical clinical conditions in patients with advanced stage malignant disease. VCS is difficult to manage and painful, reducing patients' quality of life. Although several reports have investigated stent placement for VCS, this treatment has never been established as the standard because of the lack of evidence of the safety and efficacy. We conducted a phase II trial and a phase III randomized controlled trial to clarify the role of stent placement in managing patients with VCS.Methods: In the phase II trial, 28 eligible patients were treated with stent placement. The efficacy of stent placement for VCS was evaluated based on the reduction of patients' symptom scores during 14 days following treatment. Technical success, technical feasibility, overall survival, recurrence of symptoms, and adverse events were evaluated. In the phase III trial, 32 patients were enrolled and randomly assigned to the test (n = 16) and control groups (n = 16). The area under the symptom score curve was compared between the groups. The EQ-5D, SF-8, and adverse events were evaluated until discontinuation of the protocol treatment or 28 days after enrollment.Results: In the phase II trial, the median patients' symptom scores significantly decreased from 10.50 before the procedure to 3.00 after the procedure. Technical success and technical feasibility rates were 96.4% and 100%, respectively. The incidence of treatment-related grade 3 or higher adverse events was 14.3%. In the phase III trial, significant superiority of stent placement was observed in the test, compared to that in the control, group. There was no significant difference in most other evaluations between the groups.Conclusions: Stent placement significantly improved the symptoms of VCS; thus, it might be accepted as the standard treatment to manage the symptoms of VCS.Trial Registration: JIVROSG-0402, JIVROSG-0807. [ABSTRACT FROM AUTHOR]

Introduction: The role of the radioprotector amifostine in ameliorating radiotherapy side effects in head and neck squamous cell carcinoma (HNSCC) is controversial. This trial aimed to determine whether pretreatment with amifostine reduced the incidence of Radiation Therapy Oncology Group grade ≥2 acute and late xerostomia in patients receiving definitive or adjuvant radiotherapy for HNSCC, without reducing tumour control or survival.Methods: Between 14 September 2001 and 8 November 2004, 44 Royal Adelaide Hospital patients were randomized double-blind to receive amifostine (200 mg/m2 IV) or placebo (normal saline IV) 5 days/week, prior to standard radiotherapy (60-70 Gy), each having ≥75% of the parotids treated to ≥40 Gy. Side effects were assessed weekly during treatment, at 3 and 5 months after radiotherapy, then every 6 months until disease progression or death.Results: The accrual target was 200 patients over 4-5 years, but the trial closed prematurely when only 44 patients had been randomized after 3 years. Of 41 evaluable patients, 80% (16/20) in the amifostine arm had grade ≥2 acute radiation salivary toxicity versus 76% (16/21) in the placebo arm (P = 1.00). The rate of grade ≥2 late radiation salivary toxicity at 12 months was 66% in the amifostine arm and 82% in the placebo arm (estimated hazard ratio 1.61, 95% confidence interval 0.74-3.49, P = 0.22). Other toxicities tended to be worse in the amifostine arm: acute grade 3-4 skin 35% vs 5% and mucous membrane 40% vs 5%; grade ≥2 vomiting 35% vs 5%, hypocalcaemia 25% vs 5% and fatigue 85% vs 33%, with only the latter retaining statistical significance after adjusting for multiple comparisons. There were no significant differences in failure-free (P = 0.70) or overall survival (P = 0.86), with estimated 4-year rates of 48% vs 54% and 49% vs 59% for the amifostine vs placebo arms respectively.Conclusion: There was no clear evidence that pretreatment with amifostine made any difference to the incidence of grade ≥2 acute or late xerostomia. Other toxicity tended to be more severe with amifostine. There was no effect on failure-free or overall survival. Acknowledging the low statistical power, these results do not support the use of IV amifostine pre-radiotherapy in HNSCC. [ABSTRACT FROM AUTHOR]

Objective: To systematically review the effect and safety of irinotecan plus cisplatin (IP) compared with etoposide plus cisplatin (EP) in patients with previously untreated extensive-stage small cell lung cancer (E-SCLC).Materials and Methods: Databases including PubMed, The Cochrane Library, EMBASE, China National Knowledge Infrastructure, VIP, and WanFang Data were searched for the randomized controlled trials (RCTs) about IP compared with EP in patients with previously untreated E-SCLC from the establishment to June 2016. Two reviewers independently screened literature, extracted data and assessed the methodological quality of included studies. Then meta-analysis was performed using RevMan 5.3 software (Cochrane Collaboration, Oxford, UK).Results: A total of 12 RCTs involving 2030 patients were finally included. Meta-analysis showed that compared with EP regimen, IP regimen significantly improved the 1- and 2-year survival rates of the patients with previously untreated E-SCLC (risk ratio [RR] = 1.16, 95% confidence interval [CI] [1.03-1.31], P = 0.02; RR = 1.79, 95% CI [1.22-2.61], P = 0.003, respectively). However, there was no significant difference between IP regimen and EP regimen in the objective response rate (ORR) (RR = 1.07, 95% CI [0.99-1.15], P = 0.10) and disease control rate (DCR) (RR = 1.03, 95% CI [0.96-1.10], P = 0.38). The incidence of Grade 3/4 leukopenia, neutropenia, anemia, and thrombocytopenia of IP regimen was sigificantly lower than EP regimen (all P < 0.05), the incidence of Grade 3/4 nausea/vomiting and diarrhea of IP regimen was sigificantly higher than EP regimen (all P < 0.05).Conclusion: IP regimen significantly improves the 1- and 2-year survival rates, but not significantly improves the ORR and DCR, compared with EP regimen in patients with previously untreated E-SCLC. IP regimen has less Grade 3 or 4 hematological adverse events. IP regimen is an alternative of EP regimen in patients with previously untreated E-SCLC. [ABSTRACT FROM AUTHOR]

Study Objective: To analyze the effect of enteral nutrition compared with parenteral nutrition in critically ill patients.Design: Systematic review and meta-analysis of randomized controlled trials.Setting: Intensive care unit.Patients: 23 trials containing 6478 patients met our inclusion criteria.Intervention: A systematical literature search was conducted to identify eligible trials in electronic databases including PubMed, Embase, Scopus, EBSCO and Cochrane Library. The primary outcome was mortality, the secondary outcomes were gastrointestinal complications, bloodstream infections, organ failures, length of stay in ICU and hospital. We performed a predefined subgroup analyses to explore the treatment effect by mean age, publication date and disease types.Main Results: The result showed no significant effect on overall mortality rate (OR 0.98, 95%CI 0.81 to 1.18, P = 0.83, I2 = 19%) and organ failure rate (OR 0.87, 95%CI 0.75 to 1.01, P = 0.06, I2 = 16%). The use of EN had more beneficial effects with fewer bloodstream infections when compared to PN (OR 0.59, 95%CI 0.43 to 0.82, P = 0.001, I2 = 27%) and this was more noteworthy in the subgroup analysis for critical surgical patients (OR 0.36, 95%CI 0.22 to 0.59, P < 0.0001, I2 = 0%). EN was associated with reduction in hospital LOS (MD -0.90, 95%CI -1.63 to -0.17, P = 0.21, I2 = 0%) but had an increase incidence of gastrointestinal complications (OR 2.00, 95%CI 1.76 to 2.27, P < 0.00001, I2 = 0%).Conclusion: For critically ill patients, the two routes of nutrition support had no different effect on mortality rate. The use of EN could decrease the incidence of bloodstream infections and reduce hospital LOS but was associated with increased risk of gastrointestinal complications. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of an innovative strategy to improve implementation of evidence-based guidelines on the management of hypertension in pregnancy compared to a common strategy of professional audit and feedback.Design: Cluster randomized controlled trial (c-RCT).Setting: Sixteen Dutch hospitals.Population: All patients with a hypertensive disorder during pregnancy who were admitted to one of the participating hospitals between April 1st 2010 and May 1st 2011, were suitable for inclusion; the only exclusion criterion was the presence of lethal fetal abnormalities.Methods: Hospitals were randomly assigned to either an innovative implementation strategy including a computerized decision support system (DSS) and professional audit and feedback or a minimal implementation strategy of audit and feedback only.Main Outcome Measures: Primary outcome measure was a combined rate of major maternal complications. Secondary outcome measures included process-related measures on guideline adherence, and patient-related outcomes. A process evaluation was performed alongside.Results: No statistically significant difference was found in both the occurrence of major complications and most secondary outcome measures between the two groups. Process evaluation showed limited use of the computerized DSS, with a large variation between hospitals (0-49,5% of the eligible patients), but positive experiences of actual users.Conclusion: Using a computerized DSS for implementation of the clinical guidelines for the management of hypertension in pregnancy did not result in fewer major maternal and fetal complications. Limited use of the DSS in the innovative strategy group could be an explanation for the lack of effect. [ABSTRACT FROM AUTHOR]

Background: Cancer related fatigue (CRF) is one of the most prevalent and distressing long-term complaints reported by (non-) Hodgkin survivors. To date there has been no standard treatment for CRF in this population. A novel and promising approach to treat CRF is exposure to bright white light therapy. Yet, large scale randomized controlled trials testing its efficacy in these patients and research on potential mechanisms is lacking. The objective of the current study is to investigate the efficacy of light therapy as a treatment for CRF and to explore potential mechanisms.Methods/design: In a multicenter, randomized controlled trial we are evaluating the efficacy of two intensities of light therapy in reducing CRF complaints and restrictions caused by CRF in survivors of Hodgkin lymphoma or diffuse large B-cell lymphoma. Secondary outcomes include sleep quality, depression, anxiety, quality of life, cognitive complaints, cancer worries, fatigue catastrophizing, self-efficacy to handle fatigue, biological circadian rhythms of melatonin, cortisol and activity, and biomarkers of inflammation. We will recruit 128 survivors, with fatigue complaints, from academic and general hospitals. Survivors are randomized to either an intervention (exposure to bright white light) or a comparison group (exposure to dim white light). The longitudinal design includes four measurement points at baseline (T0), post-intervention at 3.5 weeks (T1), 3 months post-intervention (T2) and 9 months post-intervention (T3). Each measurement point includes self-reported questionnaires and actigraphy (10 days). T0 and T1 measurements also include collection of blood and saliva samples.Discussion: Light therapy has the potential to be an effective treatment for CRF in cancer survivors. This study will provide insights on its efficacy and potential mechanisms. If proven to be effective, light therapy will provide an easy to deliver, low-cost and low-burden intervention, introducing a new era in the treatment of CRF.Trial Registration: The study is registered at ClinicalTrials.gov on August 8th 2017( NCT03242902 ). [ABSTRACT FROM AUTHOR]

Background: Prolonged exposure to stress can lead to substantial suffering, impairment and societal costs. However, access to psychological treatment is limited. Internet-based cognitive behavioral therapy (ICBT) can be effective in reducing symptoms of stress, but little is known of its effects in clinical samples. The aim of this study was to investigate the efficacy of ICBT for patients suffering from chronic stress, operationalized as adjustment disorder (AD) and exhaustion disorder (ED).Methods: A total of 100 adults diagnosed with AD or ED were randomly assigned to a 12-week ICBT (n = 50) or waitlist control condition (n = 50). Primary outcome was the level of perceived stress (PSS). Secondary outcomes included several mental health symptom domains as well as functional impairment and work ability. All outcomes were assessed at baseline, after treatment and at the 6-month follow-up. The study was preregistered at Clinicaltrials.gov: NCT02540317.Results: Compared to the control condition, patients in the ICBT group made large and significant improvements on the PSS (d = 1.09) and moderate to large improvements in secondary symptom domains. Effects were maintained at the 6-month follow-up. There was no significant between-group effect on functional impairment or work ability.Conclusions: A relatively short ICBT is indicated to be effective in reducing stress-related symptoms in a clinical sample of patients with AD and ED, and has the potential to substantially increase treatment accessibility. Results must be replicated, and further research is needed to understand the relationship between symptom reduction, functional impairment and work ability. [ABSTRACT FROM AUTHOR]

We report the rationale and design of a community PHARMacy-based prospective randomized controlled interdisciplinary study for ambulatory patients with Chronic Heart Failure (PHARM-CHF) and results of its pilot study. The pilot study randomized 50 patients to a pharmacy-based intervention or usual care for 12 months. It demonstrated the feasibility of the design and showed reduced systolic blood pressure in the intervention group as indicator for improved medication adherence. The main study will randomize patients ≥60 years on stable pharmacotherapy including at least one diuretic and a history of heart failure hospitalization within 12 months. The intervention group will receive a medication review at baseline followed by regular dose dispensing of the medication, counselling regarding medication use and symptoms of heart failure. The control patients are unknown to the pharmacy and receive usual care. The primary efficacy endpoint is medication adherence, pre-specified as a significant difference of the proportion of days covered between the intervention and control group within 365 days following randomization using pharmacy claims data for three CHF medications (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists). The primary composite safety endpoint is days lost due to blindly adjudicated unplanned cardiovascular hospitalizations or death. Overall, 248 patients shall be randomized. The minimum follow-up is 12 months with an expected mean of 24 months. Based on the feasibility demonstrated in the pilot study, the randomized PHARM-CHF trial will test whether an interdisciplinary pharmacy-based intervention can safely improve medication adherence and will estimate the potential impact on clinical endpoints. ClinicalTrials.gov Identifier: NCT01692119. [ABSTRACT FROM AUTHOR]

Background: Inulin-type fructans used in formula have been shown to promote microbiota composition and stool consistency closer to those of breastfed infants and to have beneficial effects on fever occurrence, diarrhea, and incidence of infections requiring antibiotic treatment in infants.Objectives: The primary study aim was to explore whether prophylactic supplementation with prebiotic fructans is able to influence the frequency of infectious diseases in kindergarten children during a winter period. A secondary objective was to ascertain the effect on the intestinal microbiota.Methods: 142 boys and 128 girls aged 3-6 y were randomly allocated to consume 6 g/d fructans or maltodextrin for 24 wk. At baseline, stool samples were collected for microbiota analysis and anthropometric measurements were made. During the intervention period diagnoses were recorded by physicians, whereas disease symptoms, kindergarten absenteeism, dietary habits, and stool consistency were recorded by parents. Baseline measurements were repeated at wk 24.Results: In total 219 children finished the study. Both the relative abundance of Bifidobacterium (P < 0.001) and that of Lactobacillus (P = 0.014) were 19.9% and 7.8% higher, respectively, post data normalization, in stool samples of children receiving fructans as compared with those of controls at wk 24. This was accompanied by significantly softer stools within the normal range in the prebiotic group from wk 12 onwards. The incidence of febrile episodes requiring medical attention [0.65 ± 1.09 compared with 0.9 ± 1.11 infections/(24 wk × child), P = 0.04] and that of sinusitis (0.01 ± 0.1 compared with 0.06 ± 0.25, P = 0.03) were significantly lower in the prebiotic group. The number of infectious episodes and their duration reported by parents did not differ significantly between the 2 intervention groups.Conclusions: Prebiotic supplementation modified the composition of the intestinal microbiota and resulted in softer stools in kindergarten-aged children. The reduction in febrile episodes requiring medical attention supports the concept of further studies on prebiotics in young children. This trial was registered at clinicaltrials.gov as NCT03241355. [ABSTRACT FROM AUTHOR]

Background: Low serum 25-hydroxyvitamin D [25(OH)D] has been associated with unfavorable cardiometabolic risk profiles in many observational studies in children, but very few randomized controlled trials have investigated this.Objective: We explored the effect of winter-time cholecalciferol (vitamin D3) supplementation on cardiometabolic risk markers in young, white, 4- to 8-y-old healthy Danish children (55°N) as part of the pan-European ODIN project.Methods: In the ODIN Junior double-blind, placebo-controlled, dose-response trial, 119 children (mean ± SD age: 6.7 ± 1.5 y; 36% male; 82% normal weight) were randomly allocated to 0, 10 or 20 µg/d of vitamin D3 for 20 wk (October-March). Cardiometabolic risk markers including BMI-for-age z score (BMIz), waist circumference, systolic and diastolic blood pressure, serum triglycerides and cholesterol (total, LDL, HDL, and total:HDL), plasma glucose and insulin, and whole-blood glycated hemoglobin were measured at baseline and endpoint as secondary outcomes together with serum 25(OH)D. Intervention effects were evaluated in linear regression models as between-group differences at endpoint adjusted for baseline value of the outcome, and additionally for age, sex, baseline serum 25(OH)D, BMIz, time since breakfast, and breakfast content.Results: Mean ± SD serum 25(OH)D was 56.7 ± 12.3 nmol/L at baseline and differed between groups at endpoint with concentrations of 31.1 ± 7.5, 61.8 ± 10.6, and 75.8 ± 11.5 nmol/L in the 0-, 10-, and 20 µg/d groups, respectively (P < 0.0001). Vitamin D3 supplementation had no effect on any of the cardiometabolic risk markers in analyses adjusted for baseline value of the outcome (all P ≥ 0.05), and additional covariate adjustment did not change the results notably.Conclusions: Preventing the winter decline in serum 25(OH)D with daily vitamin D3 supplementation of 10 or 20 µg had no cardiometabolic effects in healthy 4- to 8-y-old Danish children. This trial was registered at www.clinicaltrials.gov as NCT02145195. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies have supported inverse associations between low serum 25-hydroxyvitamin D [25(OH)D] and cardiometabolic risk markers, but few randomized trials have investigated the effect of vitamin D supplementation on these markers in adolescents.Objective: The objective of this study was to investigate the effect of winter-time cholecalciferol (vitamin D3) supplementation on cardiometabolic risk markers in white, healthy 14- to 18-y-old adolescents in the UK (51°N) as part of the ODIN Project.Methods: In a dose-response trial, 110 adolescents (mean ± SD age: 15.9 ± 1.4 y; 43% male; 81% normal weight) were randomly assigned to receive 0, 10 or 20 μg/d vitamin D3 for 20 wk (October-March). Cardiometabolic risk markers including BMI-for-age z score (BMIz), waist circumference, systolic and diastolic blood pressure, fasting plasma triglycerides, cholesterol (total, HDL, LDL, and total:HDL), and glucose were measured at baseline and endpoint as secondary outcomes, together with serum 25(OH)D. Intervention effects were evaluated in linear regression models as between-group differences at endpoint, adjusted for the baseline value of the outcome variable and additionally for age, sex, Tanner stage, BMIz, and baseline serum 25(OH)D.Results: Mean ± SD baseline serum 25(OH)D was 49.1 ± 12.3 nmol/L and differed between groups at endpoint with concentrations of 30.7 ± 8.6, 56.6 ± 12.4, and 63.9 ± 10.6 nmol/L in the 0, 10, and 20 μg/d groups, respectively (P ≤ 0.001). Vitamin D3 supplementation had no effect on any of the cardiometabolic risk markers (all P > 0.05), except for lower HDL (-0.12 mmol/L; 95% CI: -0.21, 0.04 mmol/L; P = 0.003) and total cholesterol (-0.21 mmol/L; 95% CI: -0.42, 0.00 mmol/L; P = 0.05) in the 20 μg/d than in the 10 μg/d group, which disappeared in the fully adjusted analysis (P = 0.27 and P = 0.30, respectively).Conclusions: Supplementation with vitamin D3 at 10 and 20 μg/d, which increased serum 25(OH)D concentrations during the winter-time, had no effect on markers of cardiometabolic risk in healthy 14- to 18-y-old adolescents. This trial was registered at clinicaltrials.gov as NCT02150122. [ABSTRACT FROM AUTHOR]

Background: Developing effective interventions to attenuate age-related cognitive decline and prevent or delay the onset of dementia are major public health goals. Computerized cognitive training (CCT) has been marketed increasingly to older adults, but its efficacy remains unclear. Working memory (WM), a key determinant of higher order cognitive abilities, is susceptible to age-related decline and a relevant target for CCT in elders.Objective: To evaluate the efficacy of CCT focused on WM compared to an active control condition in healthy older adults.Methods: Eighty-two cognitively normal adults from two sites (USA and Sweden) were randomly assigned to Cogmed Adaptive or Non-Adaptive (active control) CCT groups. Training was performed in participants' homes, five days per week over five weeks. Changes in the performance of the Cogmed trained tasks, and in five neuropsychological tests (Trail Making Test Part A and Part B, Digit Symbol, Controlled Oral Word Association Test and Semantic Fluency) were used as outcome measures.Results: The groups were comparable at baseline. The Adaptive group showed robust gains in the trained tasks, and there was a time-by-group interaction for the Digit Symbol test, with significant improvement only after Adaptive training. In addition, the magnitude of the intervention effect was similar at both sites.Conclusion: Home-based CCT Adaptive WM training appears more effective than Non-Adaptive training in older adults from different cultural backgrounds. We present evidence of improvement in trained tasks and on a demanding untrained task dependent upon WM and processing speed. The benefits over the active control group suggest that the Adaptive CCT gains were linked to providing a continuously challenging level of WM difficulty. [ABSTRACT FROM AUTHOR]

Background: The management of suicidal crisis remains a major issue for clinicians, driving the development of new strategies to improve suicide prevention.Methods: We conducted a randomized controlled trial comparing a 7-week acceptance and commitment therapy (ACT) versus relaxation group, as adjunct to treatment as usual for adult outpatients suffering from a current suicidal behavior disorder. The primary outcome was the rate of change in the Columbia Suicide Severity Rating Scale suicidal ideation subscore (adding severity and intensity subscores). Secondary outcomes were the rates of change for depressive symptomatology, psychological pain, anxiety, hopelessness, anger, quality of life, and therapeutic processes. Assessments were performed in the 2 weeks preceding the beginning of the treatment (pretreatment assessment), and within 1 week (posttherapy assessment) and 3 months (follow-up assessment) after therapy completion.Results: Forty adults were included and randomized. The rate of change in ACT for suicidal ideation at the posttherapy assessment was higher than in the relaxation group (β [SE] = -1.88 [0.34] vs. -0.79 [0.37], respectively; p = 0.03). ACT effectiveness remained stable at the 3-month follow-up. We found a similar pattern of change for depressive symptomatology and anxiety, psychological pain, hopelessness, anger, and quality of life. Therapeutic processes improved more in the ACT group than in the relaxation group. Treatment adherence was high in the ACT group, all participants reported satisfaction with the program.Conclusions: Through its effectiveness in reducing suicidal ideation and improving the clinical dimensions associated with suicidal risk in patients suffering from a suicidal behavior disorder, ACT could be developed as an adjunctive strategy in programs for suicide prevention. [ABSTRACT FROM AUTHOR]

Background: Fermented milk products containing Bifidobacterium breve strain Yakult (BFM) may improve clinical status in ulcerative colitis (UC) patients.Aims: To assess efficacy of BFM in maintaining remission in Japanese patients with quiescent UC.Methods: This double-blind study (B-FLORA) enrolled 195 patients with quiescent UC, randomized to receive one pack of BFM fermented milk per day [Bifidobacterium breve strain Yakult (10 billion bacteria) and Lactobacillus acidophilus (1 billion bacteria)] (n = 98) or matching placebo (n = 97) for 48 weeks. The primary efficacy endpoint was relapse-free survival (relapse: rectal bleeding score ≥ 2 on Sutherland disease activity index scale for 3 consecutive days and/or initiation of remission induction therapy for worsening of UC).Results: An interim analysis was conducted after inclusion and follow-up of one-third of patients for the first phase of the study (n = 195). Relapse-free survival was not significantly different between the BFM and placebo groups (P = 0.643; hazard ratio 1.16; 95% CI 0.63-2.14, log-rank test), nor was the incidence of relapse. Therefore, the study was discontinued for lack of efficacy. An exploratory analysis of fecal samples from a subgroup of patients revealed no effects of either study beverage on intestinal microbiota, but there was a significant decrease in Bifidobacterium species before relapse, regardless of treatment group. Three mild adverse events occurred for which a causal relationship with the study beverage could not be ruled out (placebo: abdominal bloating and stress in one patient; BFM: body odor in one patient).Conclusions: BFM had no effect on time to relapse in UC patients compared with placebo.Study Registration: UMIN000007593. [ABSTRACT FROM AUTHOR]

Objectives: Occurrence of delirium in the ICU is associated with a longer stay in the ICU. To examine whether the use of ramelteon, a melatonin agonist, can prevent delirium and shorten the duration of ICU stay of critically ill patients.Design: A single-center, triple-blinded, randomized placebo-controlled trial.Setting: ICU of an academic hospital.Patients: Eligible patients were ICU patients who could take medicines orally or through a nasogastric tube during the first 48 hours of admission.Interventions: The intervention group received ramelteon (8 mg/d), and the control group received placebo (1 g/d of lactose powder) at 20:00 hours every day until discharge from the ICU.Measurements and Main Results: A total of 88 subjects were randomized to the ramelteon group (45 subjects) or the placebo group (43 subjects). As the primary endpoint, there was a trend toward decrease in the duration of ICU stay (4.56 d) in the ramelteon group compared with the placebo group (5.86 d) (p = 0.082 and p = 0.028 before and after adjustments). As the secondary endpoints, statistically significant decreases in the occurrence rate (24.4% vs 46.5%; p = 0.044) and duration (0.78 vs 1.40 d; p = 0.048) of delirium were observed in the ramelteon group. The nonintubated patients of the ramelteon group showed statistically significantly fewer awakenings per night and a higher proportion of nights without awakenings.Conclusions: Ramelteon tended to decrease the duration of ICU stay as well as decreased the occurrence rate and duration of delirium statistically significantly. [ABSTRACT FROM AUTHOR]

Background: Since current therapies for depression are effective but not for all patients alike, we need to further improve available treatments. Existing research suggests that acceptance and commitment therapy (ACT) may effectively treat major depressive disorder (MDD). We compared ACT with cognitive behavioral therapy (CBT) for depression, testing the hypothesis that CBT would outperform ACT.Methods: We conducted a randomized controlled trial with 82 patients suffering from MDD. Data were collected before and after treatment and at the 6-month follow-up, assessing diagnosis, symptom levels of depression, and quality of life.Results: After treatment, the rates of remission from depression were 75 and 80% for the ACT and CBT conditions, respectively. Patients in both conditions further reported significant and large reductions in depressive symptoms and improvement in quality of life from before to after treatment as well as at the follow-up. Our findings indicated no significant differences between the two intervention groups.Conclusion: Our results indicate that CBT is not more effective in treating depression than ACT. Further research is needed to investigate whether ACT and CBT work differently for different groups of patients with depression. [ABSTRACT FROM AUTHOR]

Objectives: We tested whether complementary use of the somatostatin analogue pasireotide would augment efficacy of aspiration sclerotherapy of hepatic cysts.Methods: We conducted a double-blind, placebo-controlled trial in patients who underwent aspiration sclerotherapy of a large (>5 cm) symptomatic hepatic cyst. Patients were randomized to either intramuscular injections of pasireotide 60 mg long-acting release (n = 17) or placebo (sodium chloride 0.9 %, n = 17). Injections were administered 2 weeks before and 2 weeks after aspiration sclerotherapy. The primary endpoint was proportional cyst diameter reduction (%) from baseline to 6 weeks. Secondary outcomes included long-term cyst reduction at 26 weeks, patient-reported outcomes including the polycystic liver disease-questionnaire (PLD-Q) and safety.Results: Thirty-four patients (32 females; 53.6 ± 7.8 years) were randomized between pasireotide or placebo. Pasireotide did not improve efficacy of aspiration sclerotherapy at 6 weeks compared to controls (23.6 % [IQR 12.6-30.0] vs. 21.8 % [9.6-31.8]; p = 0.96). Long-term cyst diameter reduction was similar in both groups (49.1 % [27.0-73.6] and 45.6 % [29.6-59.6]; p = 0.90). Mean PLD-Q scores improved significantly in both groups (p < 0.01) without differences between arms (p = 0.92).Conclusions: In patients with large symptomatic hepatic cysts, complementary pasireotide to aspiration sclerotherapy did not improve cyst reduction or clinical response.Key Points: • Complementary pasireotide treatment does not improve efficacy of aspiration sclerotherapy. • Cyst fluid reaccumulation after aspiration sclerotherapy is a transient phenomenon. • Aspiration sclerotherapy strongly reduces symptoms and normalizes quality of life. [ABSTRACT FROM AUTHOR]

Background: Most individuals with depression do not receive adequate treatment. Internet interventions may help to bridge this gap. Research on attitudes toward Internet interventions might facilitate the dissemination of such interventions by identifying factors that help or hinder uptake and implementation, and by clarifying who is likely to benefit. This study examined whether attitudes toward Internet interventions moderate the effects of a depression-focused Internet intervention, and how attitudes change over the course of treatment among those who do or do not benefit.Methods: We recruited 1,004 adults with mild-to-moderate depression symptoms and investigated how attitudes toward Internet interventions are associated with the efficacy of the program deprexis, and how attitudes in the intervention group change from pre to post over a 3 months intervention period, compared to a control group (care as usual). This study consists of a subgroup analysis of the randomized controlled EVIDENT trial.Results: Positive initial attitudes toward Internet interventions were associated with greater efficacy (η2p  = .014) independent of usage time, whereas a negative attitude (perceived lack of personal contact) was associated with reduced efficacy (η2p  = .012). Users' attitudes changed during the trial, and both the magnitude and direction of attitude change were associated with the efficacy of the program over time (η2p  = .030).Conclusions: Internet interventions may be the most beneficial for individuals with positive attitudes toward them. Informing potential users about evidence-based Internet interventions might instill positive attitudes and thereby optimize the benefits such interventions can provide. Assessing attitudes prior to treatment might help identify suitable users. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess changes in cortical thickness related to the use of n-3 polyunsaturated fatty acids (PUFA) as add-on therapy in patients with first episode schizophrenia. A double-blind randomized controlled study was conducted using a 26-week intervention composed of concentrated fish oil containing 2.2g/d of eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) or placebo (olive oil). Participants underwent MRI scanning twice to assess changes in cortical thickness: at the beginning and at the end of intervention. Data of suitable quality was obtained from 29 participants. The T1-weighted images for each participant were analyzed using FreeSurfer methodology for longitudinal pipeline. Significant differences in cortical thickness loss were observed between the groups in the parieto-occipital regions of Brodmann areas 7 and 19 of the left hemisphere, dysfunctions in which may be involved in schizophrenia symptomatology. The results of the study support the previous observations carried out in older individuals and patients with mild cognitive impairment, indicating that n-3 PUFA may have neuroprotective properties, especially at early stages of neurodegenerative diseases, such as schizophrenia. If replicated, the results of the present study may encourage clinicians to consider n-3 PUFA as a promising addition to antipsychotics for long-term treatment of schizophrenia. [ABSTRACT FROM AUTHOR]

Aims: There is a scarcity of clinical trials on psychological treatments for concurrent borderline personality disorder (BPD) and substance use disorder (SUD). Mentalization-based treatment (MBT) have shown efficacy in several trials on BPD. The aim of the present study was to examine the feasibility and effectiveness of MBT for concurrent BPD and SUD.Methods: Patients (n = 46) with concurrent BPD and SUD were randomized either to MBT in combination with SUD treatment (n = 24) or to SUD treatment alone (n = 22). Outcome was measured after 18 months using objective data, as well as interview and self-report measures.Results: There was no significant difference between the groups on any outcome variable. No suicide attempts occurred in the MBT group in contrast to 4 suicide attempts that occurred in the control group - a difference that did not reach statistical significance (p = 0.06). A majority of the therapists did not show sufficient MBT adherence and quality.Conclusion: MBT for patients with concurrent BPD and SD does not appear to be harmful; on the other hand, it is possibly helpful in reducing the risk involved in suicide attempts. [ABSTRACT FROM AUTHOR]

Background: Cachexia, described as weight loss (mainly in lean body mass [LBM]) and anorexia, is common in patients with advanced cancer. This study examined the efficacy and safety of anamorelin (ONO-7643), a novel selective ghrelin receptor agonist, in Japanese cancer patients with cachexia.Methods: This double-blind clinical trial (ONO-7643-04) enrolled 174 patients with unresectable stage III/IV non-small cell lung cancer (NSCLC) and cachexia in Japan. Patients were randomized to daily oral anamorelin (100 mg) or a placebo for 12 weeks. The primary endpoint was the change from the baseline LBM (measured with dual-energy x-ray absorptiometry) over 12 weeks. The secondary endpoints were changes in appetite, body weight, quality of life, handgrip strength (HGS), and 6-minute walk test (6MWT) results.Results: The least squares mean change (plus or minus the standard error) in LBM from the baseline over 12 weeks was 1.38 ± 0.18 and -0.17 ± 0.17 kg in the anamorelin and placebo groups, respectively (P < .0001). Changes from the baseline in LBM, body weight, and anorexia symptoms showed significant differences between the 2 treatment groups at all time points. Anamorelin increased prealbumin at weeks 3 and 9. No changes in HGS or 6MWT were detected between the groups. Twelve weeks' treatment with anamorelin was safe and well tolerated in NSCLC patients.Conclusions: Anamorelin significantly increased LBM and improved anorexia symptoms and the nutritional state, but not motor function, in Japanese patients with advanced NSCLC. Because no effective treatment for cancer cachexia is currently available, anamorelin can be a beneficial treatment option. Cancer 2018;124:606-16. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. [ABSTRACT FROM AUTHOR]

Background: A lack of objective outcome measures and overreliance on subjective pain reports in early proof-of-concept studies contribute to the high attrition of potentially effective new analgesics. We studied the utility of neuroimaging in providing objective evidence of neural activity related to drug modulation or a placebo effect in a double-blind, randomized, placebo-controlled, three-way crossover trial.Methods: We chronically administered pregabalin or tramadol (first-line and second-line analgesics, respectively), recommended for neuropathic pain, in 16 post-traumatic neuropathic pain patients. We measured subjective pain reports, allodynia-evoked neural activity, and brain resting state functional connectivity from patients during the three sessions and resting state data at baseline from patients after washout of their current medication. All data were collected using a 3 T MRI scanner.Results: When compared with placebo only, pregabalin significantly suppressed allodynia-evoked neural activity in several nociceptive and pain-processing areas of the brain, despite the absence of behavioural analgesia. Furthermore, placebo significantly increased functional connectivity between the rostral anterior cingulate and the brainstem, a core component of the placebo neural network.Conclusions: Functional neuroimaging provided objective evidence of pharmacodynamic efficacy in a proof-of-concept study setting where subjective pain outcome measures are often unreliable. Additionally, we provide evidence confirming the neural mechanism underpinning placebo analgesia as identified in acute experimental imaging studies in patients during the placebo arm of a clinical trial. We explore how brain penetrant active drugs potentially interact with this mechanism.Clinical Trial Registration: NCT0061015. [ABSTRACT FROM AUTHOR]

Background: Depressive symptoms in pregnant women, which are common and debilitating, are often co-morbid with other mental disorders (e.g. anxiety and personality disorders), and related to low socioeconomic status (SES). This situation may hamper treatment outcome, which has often been neglected in previous studies on the treatment of depression during pregnancy. We developed a new group-based multicomponent treatment (GMT) comprising cognitive behavioral therapy, psycho-education and body-oriented therapy and compared the effect on depressive symptoms with individual counseling (treatment as usual, TAU) in a heterogeneous group of pregnant women with co-morbid mental disorders and/or low SES.Methods: An outpatient sample from a university hospital of 158 pregnant women who met DSM-IV criteria for mental disorders were included and 99 participants were randomized to GMT or TAU from January 2010 until January 2013. The Edinburgh Depression Scale (EDS) was used at baseline, every 5 weeks during pregnancy and as the primary outcome measure of depressive symptoms at 6 weeks postpartum. Secondary outcome measures included the clinician-reported Hamilton Depression Rating Scale (HDRS), obstetric outcomes and a 'Patient Satisfaction' questionnaire.Results: 155 participants were included the intention-to-treat (ITT)-analysis. GMT was not superior above TAU according to estimated EDS (β = 0.13, CI = - 0.46-0.71, p = 0.67) and HDRS scores (β = - 0.39, CI = - 0.82-0.05, p = 0.08) at 6 weeks postpartum. There were no differences in secondary outcomes between the GMT and TAU, nor between the randomized condition and patient-preference condition.Limitations: The ability to detect an effect of GMT may have been limited by sample size, missing data and the ceiling effect of TAU.Conclusions: GMT is an acceptable treatment for a heterogeneous group of pregnant women with depressive symptoms and co-morbid mental disorders and/or low SES, but not superior to TAU. Further research should focus on understanding and treating co-morbid disorders and psychosocial problems during pregnancy.Clinical Trials Registration: Dutch trial registry, www.trialregister.nl under reference number: NTR3015. [ABSTRACT FROM AUTHOR]

Objective: To compare vaginal misoprostol treatment with expectant management in early non-viable pregnancy with vaginal bleeding with regard to complete evacuation of the uterine cavity within 10 days after randomization.Methods: This was a parallel randomized controlled, open-label trial conducted in Skåne University Hospital, Sweden. Patients with anembryonic pregnancy or early fetal demise (crown-rump length ≤ 33 mm) and vaginal bleeding were randomly allocated to either expectant management or treatment with a single dose of 800 μg misoprostol administered vaginally. Patients were evaluated clinically and by ultrasound until complete evacuation of the uterus was achieved (no gestational sac in the uterine cavity and maximum anteroposterior diameter of the intracavitary contents < 15 mm as measured by transvaginal ultrasound on midsagittal view). Follow-up visits were planned at 10, 17, 24 and 31 days. Dilatation and evacuation (D&E) was recommended if miscarriage was not complete within 31 days, but was performed earlier at patient's request, or if there was excessive bleeding as judged clinically. Analysis was by intention to treat. The main outcome measure was number of patients with complete miscarriage without D&E ≤ 10 days.Results: Ninety-four patients were randomized to misoprostol treatment and 95 to expectant management. After exclusion of three patients and withdrawal of consent by two patients in the expectant management group, 90 women were included in this group. Miscarriage was complete ≤ 10 days in 62/94 (66%) of the patients in the misoprostol group and in 39/90 (43%) of those in the group managed expectantly (risk difference (RD) = 23%; 95% CI, 8-37%). At 31 days, the corresponding figures were 81/94 (86%) and 55/90 (61%) (RD = 25%; 95% CI, 12-38%). Two patients from each group underwent emergency D&E because of excessive bleeding and one of these in each group received blood transfusion. The number of patients undergoing D&E at their own request was higher in the expectantly managed group, 15/90 (17%) vs 3/94 (3%) in the misoprostol group (RD = 14%; 95% CI, 4-23%), as was the number of patients making out-of-protocol visits, 50/90 (56%) vs 27/94 (29%) (RD = 27%; 95% CI, 12-40%). Compared with the expectant management group, more patients in the misoprostol group experienced pain (71/77 (92%) vs 91/91 (100%); RD = 8%; 95% CI, 1-17%) and used painkillers (59/77 (77%) vs 85/91 (93%); RD = 17%; 95% CI, 5-29%). No major side effect was reported in any group.Conclusions: In women with early non-viable pregnancy and vaginal bleeding, misoprostol treatment is more effective than is expectant management for complete evacuation of the uterus. Both methods are safe but misoprostol treatment is associated with more pain than is expectant management. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: The recommended initial treatment for multidirectional instability (MDI) of the shoulder is a rehabilitation program, yet there is very low-quality evidence to support this approach. Purpose/Hypothesis: The purpose was to compare the Watson MDI program and Rockwood Instability program among patients with nontraumatic, nonstructural MDI. The hypothesis was that the Watson MDI program would produce clinically and statistically superior outcomes over the Rockwood Instability program. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Forty-one participants with MDI were randomly allocated to the Watson MDI or Rockwood Instability program. Participants attended 12 weekly physiotherapy sessions for exercise prescription. Outcomes were assessed at baseline and 6, 12, and 24 weeks after randomization. Primary outcomes were the Melbourne Instability Shoulder Score (MISS) and the Western Ontario Shoulder Index (WOSI). Secondary outcomes included the Orebro Musculoskeletal Pain Questionnaire, pain, muscle strength, scapular upward rotation, scapular coordinates, global rating of change, satisfaction scales, limiting angle in abduction range, limiting factor in abduction range, and incidence of dislocation. Primary analysis was by intention to treat based on linear mixed models. Results: Between-group differences showed significant effects favoring the Watson program for the WOSI (effect size [ES], 11.1; 95% CI, 1.9-20.2; P = .018) and for the limiting factor in abduction (ES, 0.1; 95% CI, 0.0-1.6; P = .023) at 12 weeks, and for the WOSI (ES, 12.6; 95% CI, 3.4-21.9; P =. 008), MISS (ES, 15.4; 95% CI, 5.9-24.8; P = .002), and pain (ES, -2.0; CI: -2.3 to -0.7, P = .003) at 24 weeks. Conclusion: For people with MDI, 12 sessions of the Watson MDI program were more effective than the Rockwood program at 12- and 24-week follow-up. Registration: ACTRN12613001240730 (Australian New Zealand Clinical Trials Registry). [ABSTRACT FROM AUTHOR]

Background: Self-harm is an important risk factor for subsequent suicide and repetition of self-harm, and a common cause of emergency department presentations. However, there still remains limited evidence on intervention in emergency department settings for individuals who self-harm.Methods: This multicentre, randomised controlled trial was conducted at 17 general hospitals in Japan. In total, 914 adult patients admitted to emergency departments for a suicide attempt and had a DSM-IV-TR axis I disorder were randomly assigned to two groups, to receive either assertive case management (intervention) or enhanced usual care (control). Assertive case management was introduced by the case manager during emergency department admissions for suicide attempts, and continued after discharge. Interventions were provided until the end of the study period (for at least 18 months and up to 5 years).Results: The number of overall self-harm episodes per person-year was significantly lower in the intervention group (adjusted incidence risk ratio (IRR) 0.88, 95%CI 0.80-0.96, p=0.0031). Subgroup analysis showed a greater reduction of overall self-harm episodes among patients with no previous suicide attempt at baseline (adjusted IRR 0.73, 95% CI 0.53-0.98, p=0.037).Limitations: Patients younger than 20 years and patients who self-harmed but were not admitted to an emergency department were excluded.Conclusions: The present study showed that assertive case management following emergency admission for a suicide attempt reduced the incident rate of repeat overall self-harm. [ABSTRACT FROM AUTHOR]

Background: The number of bariatric interventions for morbid obesity is increasing worldwide. Rapid weight loss is a major risk factor for gallstone development. Approximately 11 % of patients who underwent Roux-en-Y gastric bypass develop symptomatic gallstone disease. Gallstone disease can lead to severe complications and often requires hospitalization and surgery. Ursodeoxycholic acid (UDCA) prevents the formation of gallstones after bariatric surgery. However, randomized controlled trials with symptomatic gallstone disease as primary endpoint have not been conducted. Currently, major guidelines make no definite statement about postoperative UDCA prophylaxis and most bariatric centers do not prescribe UDCA.Methods: A randomized, placebo-controlled, double-blind multicenter trial will be performed for which 980 patients will be included. The study population consists of consecutive patients scheduled to undergo Roux-en-Y gastric bypass or sleeve gastrectomy in three bariatric centers in the Netherlands. Patients will undergo a preoperative ultrasound and randomization will be stratified for pre-existing gallstones and for type of surgery. The intervention group will receive UDCA 900 mg once daily for six months. The placebo group will receive similar-looking placebo tablets. The primary endpoint is symptomatic gallstone disease after 24 months, defined as admission or hospital visit for symptomatic gallstone disease. Secondary endpoints consist of the development of gallstones on ultrasound at 24 months, number of cholecystectomies, side-effects of UDCA and quality of life. Furthermore, cost-effectiveness, cost-utility and budget impact analyses will be performed.Discussion: The UPGRADE trial will answer the question whether UDCA reduces the incidence of symptomatic gallstone disease after Roux-en-Y gastric bypass or sleeve gastrectomy. Furthermore it will determine if treatment with UDCA is cost-effective.Trial Registration: Netherlands Trial Register (trialregister.nl) 6135 . Date registered: 21-Nov-2016. [ABSTRACT FROM AUTHOR]

Background: Despite advances in the health and long-term survival of infants born preterm, they continue to face developmental challenges including higher risk for autism spectrum disorder (ASD) and atypical sensory processing patterns.Aims: This secondary analysis aimed to describe sensory profiles and explore effects of combined dietary docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and gamma-linolenic acid (GLA) supplementation on parent-reported sensory processing in toddlers born preterm who were exhibiting ASD symptoms.Study Design: 90-day randomized, double blinded, placebo-controlled trial.Subjects: 31 children aged 18-38months who were born at ≤29weeks' gestation.Outcome Measure: Mixed effects regression analyses followed intent to treat and explored effects on parent-reported sensory processing measured by the Infant/Toddler Sensory Profile (ITSP).Results: Baseline ITSP scores reflected atypical sensory processing, with the majority of atypical scores falling below the mean. Sensory processing sections: auditory (above=0%, below=65%), vestibular (above=13%, below=48%), tactile (above=3%, below=35%), oral sensory (above=10%; below=26%), visual (above=10%, below=16%); sensory processing quadrants: low registration (above=3%; below=71%), sensation avoiding (above=3%; below=39%), sensory sensitivity (above=3%; below=35%), and sensation seeking (above=10%; below=19%). Twenty-eight of 31 children randomized had complete outcome data. Although not statistically significant (p=0.13), the magnitude of the effect for reduction in behaviors associated with sensory sensitivity was medium to large (effect size=0.57). No other scales reflected a similar magnitude of effect size (range: 0.10 to 0.32).Conclusions: The findings provide support for larger randomized trials of omega fatty acid supplementation for children at risk of sensory processing difficulties, especially those born preterm. [ABSTRACT FROM AUTHOR]

Background: 13-Cis retinoic acid (13-CRA) is a synthetic vitamin A derivative. High-dose 13-CRA in patients with squamous cell cancers of the head and neck (SCCHNs) reduces the incidence of second primary tumors (SPTs). The authors report long-term results from a phase 3 randomized trial that compared treatment with low-dose 13-CRA versus placebo for patients who had early stage SCCHN, with a focus on the development of SPTs and overall survival (OS).Methods: In total, 176 patients who received treatment for stage I/II SCCHN were randomized to receive either low-dose 13-CRA (weight-based dose of 7.5 mg or 10 mg) or placebo for 2 years. A competing-risk approach and the log-rank test were used to compare the time to SPT and OS, respectively, between groups.Results: 13-CRA neither significantly reduced the cumulative incidence of SPT (P = .61) nor improved the time to SPT (hazard ratio [HR] for 13-CRA/placebo; 0.86; P = .61). Despite limited power, there was a trend toward improved OS for the 13-CRA arm (HR, 0.75; P = .14), particularly among patients whose index tumor was surgically excised (N = 26; HR, 0.50; P = .057) and among women (N = 39; HR, 0.44; P = .065) and never/former smokers (N = 129; HR, 0.61; P = .055), with a median follow-up of 16 years. The main 13-CRA related toxicities were dry skin and cheilitis.Conclusions: Treatment with low-dose 13-CRA for 2 years did not decrease the incidence of SPT; subset analysis indicates a potential survival advantage among patients who are women and never/former smokers. More targeted interventions based on clinical risk factors and molecular characterization of tumors may yield greater success in future prevention trials. Cancer 2017;123:4653-4662. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Rationale: Targeted temperature management (TTM) improves survival with good neurological outcome after out-of-hospital cardiac arrest (OHCA), but is delivered inconsistently and often with delay.Objective: To determine if prehospital cooling by paramedics leads to higher rates of 'successful TTM', defined as achieving a target temperature of 32-34°C within 6h of hospital arrival.Methods: Pragmatic RCT comparing prehospital cooling (surface ice packs, cold saline infusion, wristband reminders) initiated 5min after return of spontaneous circulation (ROSC) versus usual resuscitation and transport. The primary outcome was rate of 'successful TTM'; secondary outcomes were rates of applying TTM in hospital, survival with good neurological outcome, pulmonary edema in emergency department, and re-arrest during transport.Results: 585 patients were randomized to receive prehospital cooling (n=279) or control (n=306). Prehospital cooling did not increase rates of 'successful TTM' (30% vs 25%; RR, 1.17; 95% confidence interval [CI] 0.91-1.52; p=0.22), but increased rates of applying TTM in hospital (68% vs 56%; RR, 1.21; 95%CI 1.07-1.37; p=0.003). Survival with good neurological outcome (29% vs 26%; RR, 1.13, 95%CI 0.87-1.47; p=0.37) was similar. Prehospital cooling was not associated with re-arrest during transport (7.5% vs 8.2%; RR, 0.94; 95%CI 0.54-1.63; p=0.83) but was associated with decreased incidence of pulmonary edema in emergency department (12% vs 18%; RR, 0.66; 95%CI 0.44-0.99; p=0.04).Conclusions: Prehospital cooling initiated 5min after ROSC did not increase rates of achieving a target temperature of 32-34°C within 6h of hospital arrival but was safe and increased application of TTM in hospital. [ABSTRACT FROM AUTHOR]

Background: Sepsis and septic shock occur commonly in severe burns. Acute kidney injury (AKI) is also common and often results as a consequence of sepsis. Mortality is unacceptably high in burn patients who develop AKI requiring renal replacement therapy and is presumed to be even higher when combined with septic shock. We hypothesized that high-volume hemofiltration (HVHF) as a blood purification technique would be beneficial in this population.Methods: We conducted a multicenter, prospective, randomized, controlled clinical trial to evaluate the impact of HVHF on the hemodynamic profile of burn patients with septic shock and AKI involving seven burn centers in the United States. Subjects randomized to the HVHF were prescribed a dose of 70 ml/kg/hour for 48 hours while control subjects were managed in standard fashion in accordance with local practices.Results: During a 4-year period, a total of nine subjects were enrolled for the intervention during the ramp-in phase and 28 subjects were randomized, 14 each into the control and HVHF arms respectively. The study was terminated due to slow enrollment. Ramp-in subjects were included along with those randomized in the final analysis. Our primary endpoint, the vasopressor dependency index, decreased significantly at 48 hours compared to baseline in the HVHF group (p = 0.007) while it remained no different in the control arm. At 14 days, the multiple organ dysfunction syndrome score decreased significantly in the HVHF group when compared to the day of treatment initiation (p = 0.02). No changes in inflammatory markers were detected during the 48-hour intervention period. No significant difference in survival was detected. No differences in adverse events were noted between the groups.Conclusions: HVHF was effective in reversing shock and improving organ function in burn patients with septic shock and AKI, and appears safe. Whether reversal of shock in these patients can improve survival is yet to be determined.Trial Registration: Clinicaltrials.gov NCT01213914 . Registered 30 September 2010. [ABSTRACT FROM AUTHOR]

Background: Effective yet practical strategies are needed to increase engagement in HIV treatment and prevention services, particularly in high-HIV-prevalence hotspots. We designed a community-based intervention called "Health Scouts" to promote uptake and adherence to HIV services in a highly HIV-prevalent fishing community in Rakai, Uganda. Using a situated Information, Motivation, and Behavioral skills theory framework, the intervention consists of community health workers, called Health Scouts, who use motivational interviewing strategies and mobile health tools to promote engagement in HIV treatment and prevention services.Methods/design: The Health Scout intervention is being evaluated through a pragmatic, parallel, cluster-randomized controlled trial with an allocation ratio of 1:1. The study setting is a single high-HIV-prevalence fishing community in Rakai, Uganda divided into 40 contiguous neighborhood clusters each containing about 65 households. Twenty clusters received the Health Scout Intervention; 20 clusters received standard of care. The Health Scout intervention is delivered within the community at the household level, targeting all residents aged 15 years or older. The primary programmatic outcomes are self-reported HIV care, antiretroviral therapy, and male circumcision coverage; the primary biologic outcome is population-level HIV viremia prevalence. Follow-up is planned for about 3 years.Discussion: HIV treatment and prevention service engagement remains suboptimal in HIV hotspots. New, community-based implementation approaches are needed. If found to be effective in this trial, the Health Scout intervention may be an important component of a comprehensive HIV response.Trial Registration: ClinicalTrials.gov, ID: NCT02556957 . Registered on 20 September 2015. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that acupuncture is beneficial for the alleviation of chemotherapy-induced nausea and vomiting. However, there is a lack of clinical evidence concerning the effects of acupoint-matching on chemotherapy-induced nausea and vomiting.Methods/design: This is a parallel randomized controlled trial to evaluate the occurrence of nausea and vomiting after chemotherapy (the incidence of nausea and vomiting, frequency, VAS score, RINVR rating) as the main outcome for cancer. Quality of life, anxiety and depression scores are the secondary outcomes. Quality of life, anxiety and depression scores are the secondary phase. Use of remedy drugs, routine blood examination, and blood biochemical tests are the safety evaluation. We also compare the different effects of ST36 (single acupoint), CV12 (single acupoint), and ST36-CV12 matching groups.Discussion: The results of this trial are expected to explore the effects of matching different acupoints and to offer biologic plausibility for the use of acupuncture in the treatment of chemotherapy-induced nausea and vomiting (CINV).Trial Registration: This trial is registered with clinicaltrials.gov NCT02195921 , The date of registration was 17 July 2014. [ABSTRACT FROM AUTHOR]

Background: Both enzalutamide and abiraterone have demonstrated improved radiographic progression-free and overall survival for castration-resistant prostate cancer (CRPC) compared with placebo controls before docetaxel treatment in phase III studies. These oral agents target androgen and androgen receptor signaling and are thought to be less toxic than chemotherapy. Cross-resistance to these agents was recently reported because of their similar mechanism of action, and it is important to assess which agent is more effective to use initially for CRPC.Methods/design: The present study is a phase III, investigator-initiated, multicenter, head-to-head, randomized controlled trial investigating enzalutamide vs. abiraterone as a first-line treatment for CRPC patients. Patients will be randomly assigned to an enzalutamide or an abiraterone treatment group. The primary endpoint is the time to prostate-specific antigen progression. The target sample size is set at 100 patients per group (total, 200 patients). The study duration is 5 years, and the duration for recruitment is 2 years and 6 months.Discussion: Thus far, there have been no prospective head-to-head studies comparing enzalutamide and abiraterone. This ENABLE study will clarify which agent should be prioritized for CRPC patients and enable clinicians to decide the appropriate treatment before chemotherapy.Trial Registration: University hospital Medical Information Network (UMIN) Center identifier UMIN000015529 . Registrated 11/1/2014. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of acupuncture for patients with chronic tension-type headache (CTTH) is controversial. In this article, we report the protocol for a randomized controlled trial aiming to evaluate the long-term effect of acupuncture for CTTH, in comparison with superficial acupuncture.Design: A two-armed, parallel-design, patient-assessor blind, randomized controlled trial is underway in China. A total of 218 participants with CTTH will be randomly assigned to the treatment group or the control group in a 1:1 ratio. Participants in the treatment group and control group will receive acupuncture or superficial acupuncture treatments in a fixed prescription of acupoints respectively, for a total of 20 sessions over 8 weeks. The posttreatment follow-up period will be 24 weeks. The primary outcome will be the proportion of responders assessed at week 16 after randomization. The secondary outcomes will include the number of headache days, the mean intensity of headache, the reduction of medication intake, results from the 36-item short form health survey, the Hamilton Depression Scale and the Hamilton Anxiety Scale, the number of participants with adverse events, the expectation value of acupuncture treatment, and the intensity of deqi sensation. The first five secondary outcomes will be assessed or calculated at baseline, and at 4, 8, 12, 16, 20, 24, 28, and 32 weeks after randomization. Moreover, the expectation value will be collected at baseline and at week 8 after randomization, the intensity of deqi sensation will be assessed at 5 minutes after each treatment and adverse events will be summarized at the end of the follow-up period.Discussion: Results from this trial will provide evidence for the long-term effect of acupuncture for CTTH with a long follow-up period.Trial Registration: ClinicalTrial.gov NCT03133884 . Registered on 25 April 2017. [ABSTRACT FROM AUTHOR]

Background: Although traditionally dosed combined oral contraceptives (COCs) (21 days of active pills, 7 days of inactive pills) have not been demonstrated as superior to placebo for the treatment of premenstrual dysphoria (PMD), some randomized controlled trials (RCTs) indicate that oral contraceptives administered with a shortened or eliminated hormone-free interval are superior to placebo. However, results of such trials are mixed, and no existing studies have directly compared continuous and intermittent dosing schedules of the same oral contraceptive. The present study compared placebo, intermittent dosing of oral contraceptives, and continuous dosing of contraceptives for the treatment of PMD.Methods: Fifty-five women with prospectively confirmed PMD completed a three-arm, RCT in which they were randomized to 3 months of placebo (n = 22), intermittent drospirenone/ethinyl estradiol dosed on a 21-7 schedule (n = 17), or continuous drospirenone/estradiol (n = 16) following a baseline assessment month.Results: All three groups demonstrated similar, robust reductions in premenstrual symptoms over time. A marked placebo response was observed.Conclusions: The study fails to replicate a uniquely beneficial effect of continuous COC on PMD. Additional work is needed to understand the psychosocial context bolstering the placebo response in women with PMD. [ABSTRACT FROM AUTHOR]