Search

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

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

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

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

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

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

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

Background: This study examined whether mobile phone-based support improve the rates, duration of exclusive breastfeeding (EBF) as well as infant growth patterns in Nigeria.Methods: A 6-month prospective randomized controlled trial with 75 participants assigned to receive 'usual care' or 'mobile phone-based support in addition to usual care' EBF rates and duration as well as anthropometric measurements of infants before and after intervention were compared using proportions and mean differences.Results: Attrition rates of 10.7% and 14.7% were observed in the intervention and control groups, respectively. Treatment groups were identical in all baseline characteristics and participants in the intervention group showed a slower rate of decline in the practice of EBF. The mean difference of 0.6 months (95% confidence interval: -0.22, 1.42) in EBF duration between intervention and control groups was not statistically significant (t = 1.45; p = 0.149). Similarly, the difference in the EBF rates at the 6th month for the intervention (55.2%) and control (46.8%) groups was not statistically significant (χ2 = 0.623; p = 0.430). Although the intervention group had significantly higher mean weight (p = 0.030) and length (p = 0.044) at the 6th month, the difference in the gain in weight and length of these infants over the period was only significant for the weight (p = 0.044). Although the incidence of adverse clinical nutritional status was more in the control group, these differences were not statistically significant.Conclusion: Mobile phone-based intervention has positive effects on the rate and duration of EBF as well as the growth of young infants. Sustaining this simple and cheap technology will improve infant wellbeing especially in resource-constrained settings. [ABSTRACT FROM AUTHOR]

Poor mental health is a pressing global health problem, with high prevalence among poor populations from low-income countries. Existing studies of conditional cash transfer (CCT) effects on mental health have found positive effects. However, there is a gap in the literature on population-wide effects of cash transfers on mental health and if and how these vary by the severity of mental illness. We use the Malawian Longitudinal Study of Family and Health containing 790 adult participants in the Malawi Incentive Programme, a year-long randomized controlled trial. We estimate average and distributional quantile treatment effects and we examine how these effects vary by gender, HIV status and usage of the cash transfer. We find that the cash transfer improves mental health on average by 0.1 of a standard deviation. The effect varies strongly along the mental health distribution, with a positive effect for individuals with worst mental health of about four times the size of the average effect. These improvements in mental health are associated with increases in consumption expenditures and expenditures related to economic productivity. Our results show that CCTs can improve adult mental health for the poor living in low-income countries, particularly those with the worst mental health. [ABSTRACT FROM AUTHOR]

Study Question: Does an artificially induced FSH surge at the time of hCG trigger improve IVF/ICSI outcomes?Summary Answer: An additional FSH bolus administered at the time of hCG trigger has no effect on clinical pregnancy rate, embryo quality, fertilization rate, implantation rate and live birth rate in women undergoing the long GnRH agonist (GnRHa) protocol for IVF/ICSI.What Is Known Already: Normal ovulation is preceded by a surge in both LH and FSH. Few randomized clinical trials have specifically investigated the role of the FSH surge. Some studies indicated that FSH given at hCG ovulation trigger boosts fertilization rate and even prevents ovarian hyperstimulation syndrome (OHSS).Study Design, Size, Duration: This was a randomized, double-blinded, placebo-controlled trial conducted at a single IVF center, from June 2012 to November 2013. A sample size calculation indicated that 347 women per group would be adequate. A total of 732 women undergoing IVF/ICSI were randomized, using electronically randomized tables, to the intervention or placebo groups. Participants and clinical doctors were blinded to the treatment allocation.Participants/materials, Setting, Methods: Patients aged ≤42 years who were treated with IVF/ICSI owing to tubal factor, male factor, unexplained, endometriosis and multiple factors were enrolled in this trial. Subjects all received a standard long GnRHa protocol for IVF/ICSI and hCG 6000-10 000 IU to trigger oocyte maturation. A total of 364 and 368 patients were randomized to receive a urinary FSH (uFSH) bolus (6 ampules, 450 IU) and placebo, respectively, at the time of the hCG trigger. The primary outcome measure was clinical pregnancy rate. The secondary outcome measures were FSH level on the day of oocyte retrieval, number of oocytes retrieved, good-quality embryo rate, live birth rate and rate of OHSS.Main Results and the Role Of Chance: There were no significant differences in the baseline demographic characteristics between the two study groups. There were also no significant differences between groups in cycle characteristics, such as the mean number of stimulation days, total gonadotrophin dose and peak estradiol. The clinical pregnancy rate was 51.6% in the placebo group and 52.7% in the FSH co-trigger group, with an absolute rate difference of 1.1% (95% CI -6.1% to 8.3%). The number of oocytes retrieved was 10.47 ± 4.52 and 10.74 ± 5.01 (P = 0.44), the rate of good-quality embryos was 37% and 33.9% (P = 0.093) and the implantation rate was 35% and 36% (P = 0.7) in the placebo group and the FSH co-trigger group, respectively.Limitations, Reasons For Caution: This was a single-center study, which may limit its effectiveness. The use of uFSH is a limitation, as this is not the same as the natural FSH. We did not collect follicular fluid for further study of molecular changes after the use of uFSH as a co-trigger.Wider Implications Of the Findings: Based on previous data and our results, an additional FSH bolus administered at the time of hCG trigger has no benefit on clinical pregnancy rates in women undergoing the long GnRHa protocol in IVF/ICSI: a single hCG trigger is sufficient.Study Funding/competing Interest(s): This study was supported by the National Key Research and Development Program of China (2016YFC1000205); Sun Yat-Sen University Clinical Research 5010 Program (2016004); the Science and Technology Project of Guangdong Province (2016A020216011 and 2017A020213028); and Science Technology Research Project of Guangdong Province (S2011010004662). There are no conflicts of interest to declare.Trial Registration Number: The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-12002246).Trial Registration Date: 20 May 2012.Date Of First Patient’s Enrolment: 10 June 2012. [ABSTRACT FROM AUTHOR]

Background: Short-term (48-week) results of the OPTIONS trial showed that nucleoside reverse transcriptase inhibitors (NRTIs) can be safely omitted from salvage therapy as long as the regimen has a cumulative activity of >2 active antiretroviral medications. The long-term durability of this approach and outcomes in persons who have more-extensive HIV-1 drug resistance are uncertain.Methods: Participants with virologic failure and anticipated antiretroviral susceptibility received an optimized regimen and were randomized to omit or add NRTIs. A separate group with more resistance (cumulative activity ≤2 active agents) received an optimized regimen including NRTIs.Results: At week 96, among 360 participants randomized to omit or add NRTIs, 70% and 65% had HIV-1 RNA <200 copies/mL, respectively. Virologic failure was uncommon after week 48. Younger age and starting fewer new antiretroviral medications were associated with higher odds of virologic failure. In the highly resistant group, 53% had HIV-1 RNA <200 copies/mL at week 96.Conclusions: HIV-1 salvage therapy can safely omit NRTIs without compromising efficacy or durability of response as long as the new regimen has a cumulative activity of >2 active drugs. Younger people and those receiving fewer new antiretrovirals require careful monitoring. Even among individuals with more-extensive resistance, most achieve virologic suppression.Clinical Trials Registration: NCT00537394. [ABSTRACT FROM AUTHOR]

To address the rise in mental health conditions in Tunisia, a training based on the Mental Health Gap Action Programme (mhGAP) Intervention Guide (IG) was offered to primary care physicians (PCPs) working in the Greater Tunis area. Non-specialists (such as PCPs)' training is an internationally supported way to target untreated mental health symptoms. We aimed to evaluate the programme's impact on PCPs' mental health knowledge, attitudes, self-efficacy and self-reported practice, immediately following and 18 months after training. We conducted an exploratory trial with a combination of designs: a pretest-posttest control group design and a one-group pretest-posttest design were used to assess the training's short-term impact; and a repeated measures design was used to assess the training's long-term impact. The former relied on a delayed-intervention strategy: participants assigned to the control group (Group 2) received the training after the intervention group (Group 1). The intervention consisted of a weekly mhGAP-based training session (totalling 6 weeks), comprising lectures, discussions, role plays and a support session offered by trainers. Data were collected at baseline, following Group 1's training, following Group 2's training and 18 months after training. Descriptive, bivariate and ANOVA analyses were conducted. Overall, 112 PCPs were randomized to either Group 1 (n = 52) or Group 2 (n = 60). The training had a statistically significant short-term impact on mental health knowledge, attitudes and self-efficacy scores but not on self-reported practice. When comparing pre-training results and results 18 months after training, these changes were maintained. PCPs reported a decrease in referral rates to specialized services 18 months after training in comparison to pre-training. The mhGAP-based training might be useful to increase mental health knowledge and self-efficacy, and decrease reported referral rates and negative mental health attitudes among PCPs in Tunisia and other low- and middle-income countries. Future studies should examine relationships among these outcome variables. [ABSTRACT FROM AUTHOR]

Objectives Existing treatments for fibromyalgia have limited efficacy, and only a minority of individuals clinically respond to any single intervention. This study was a prospective, multicenter, randomized, double-blind, controlled clinical trial to evaluate the feasibility of alternating magnetic field therapy in fibromyalgia patients by comparing the Angel Touch device (AT-02) with a sham control (S-01). Methods Two sites enrolled 44 subjects with diagnosed fibromyalgia. After informed consent, subjects taking prohibited concomitant drugs underwent a washout period of two or more weeks. All subjects then began a one-week run-in period. Numerical rating scale (NRS) pain scores were collected without device intervention for one day, followed by S-01 application to four or more painful sites for 10 minutes at each site, twice daily for six days. Subjects were then randomized to AT-02 or S-01, applied to four or more painful sites for 10 minutes at each site, twice daily for eight weeks. NRS scores were obtained twice daily during the entire treatment period. Results The primary end point (change in NRS ± SD at week 8 vs baseline) was –0.94 ± 1.33 in the AT-02 group and –0.22 ± 1.38 in the S-01 group. A trend toward a between-group difference in eight-week NRS scores favored the AT-02 group (–0.73, 95% confidence interval = –1.56 to 0.11, P  = 0.086). An adjusted repeated measure analysis detected a significant difference in NRS scores (P  = 0.039). Conclusions The reduction in NRS scores for AT-02 relative to sham was comparable to reductions observed in meta-analyses of fibromyalgia drug therapy. The unadjusted results and the persistence of the pain score reductions remain encouraging. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the efficacy and safety of electroacupuncture in reducing opioid consumption in patients with chronic musculoskeletal pain. Design A randomized, participant-assessor-blinded, three-arm trial. Setting Participants from three pain clinics and from the public. Subjects One hundred and eight adults with chronic pain who were taking opioids. Methods All participants received pain and medication management education. Participants were randomly allocated to electroacupuncture (N = 48), sham electroacupuncture (N = 29), or education alone (N = 31) to receive relevant treatment for 12 weeks. The last group received electroacupuncture during the three-month follow-up. Analysis of covariance and paired t tested were used. Results Opioid dosage, that is, the primary outcome measure, was reduced by 20.5% (P < 0.05) and 13.7% (P < 0.01) in the two acupuncture groups and by 4.5% in the education group at the end of the treatment phase, but without any group difference. Intensity of pain of all three groups did not change over time. No group differences were found in dosage of nonopioid analgesics, pain intensity, function, and opioid-related adverse events. During follow-up, the education group had a 47% reduction of opioids after a course of electroacupuncture. Adverse events to electroacupuncture were minor. Conclusion It is safe to reduce opioid medication use in patients with chronic pain. Due to the small sample size, we could not confirm if electroacupuncture offers extra benefit in addition to education. This nondrug therapy could be a promising adjunct to facilitate opioid tapering in patients who are willing to reduce opioids. [ABSTRACT FROM AUTHOR]

Spastic paraplegia type 5 (SPG5) is a rare subtype of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative disorders defined by progressive neurodegeneration of the corticospinal tract motor neurons. SPG5 is caused by recessive mutations in the gene CYP7B1 encoding oxysterol-7α-hydroxylase. This enzyme is involved in the degradation of cholesterol into primary bile acids. CYP7B1 deficiency has been shown to lead to accumulation of neurotoxic oxysterols. In this multicentre study, we have performed detailed clinical and biochemical analysis in 34 genetically confirmed SPG5 cases from 28 families, studied dose-dependent neurotoxicity of oxysterols in human cortical neurons and performed a randomized placebo-controlled double blind interventional trial targeting oxysterol accumulation in serum of SPG5 patients. Clinically, SPG5 manifested in childhood or adolescence (median 13 years). Gait ataxia was a common feature. SPG5 patients lost the ability to walk independently after a median disease duration of 23 years and became wheelchair dependent after a median 33 years. The overall cross-sectional progression rate of 0.56 points on the Spastic Paraplegia Rating Scale per year was slightly lower than the longitudinal progression rate of 0.80 points per year. Biochemically, marked accumulation of CYP7B1 substrates including 27-hydroxycholesterol was confirmed in serum (n = 19) and cerebrospinal fluid (n = 17) of SPG5 patients. Moreover, 27-hydroxycholesterol levels in serum correlated with disease severity and disease duration. Oxysterols were found to impair metabolic activity and viability of human cortical neurons at concentrations found in SPG5 patients, indicating that elevated levels of oxysterols might be key pathogenic factors in SPG5. We thus performed a randomized placebo-controlled trial (EudraCT 2015-000978-35) with atorvastatin 40 mg/day for 9 weeks in 14 SPG5 patients with 27-hydroxycholesterol levels in serum as the primary outcome measure. Atorvastatin, but not placebo, reduced serum 27-hydroxycholesterol from 853 ng/ml [interquartile range (IQR) 683-1113] to 641 (IQR 507-694) (-31.5%, P = 0.001, Mann-Whitney U-test). Similarly, 25-hydroxycholesterol levels in serum were reduced. In cerebrospinal fluid 27-hydroxycholesterol was reduced by 8.4% but this did not significantly differ from placebo. As expected, no effects were seen on clinical outcome parameters in this short-term trial. In this study, we define the mutational and phenotypic spectrum of SPG5, examine the correlation of disease severity and progression with oxysterol concentrations, and demonstrate in a randomized controlled trial that atorvastatin treatment can effectively lower 27-hydroxycholesterol levels in serum of SPG5 patients. We thus demonstrate the first causal treatment strategy in hereditary spastic paraplegia. [ABSTRACT FROM AUTHOR]

Background: Research is yet to investigate whether psychological interventions delivered early after diagnosis can benefit patients with head and neck cancer (HNC).Purpose: The aim of this study was to investigate the effectiveness of a brief self-regulatory intervention (targeting illness perceptions and coping) at improving HNC patient health-related quality of life (HRQL).Methods: A pilot randomized controlled trial was conducted, in which 64 patients were assigned to receive three sessions with a health psychologist in addition to standard care or standard care alone. Participants completed questionnaires assessing HRQL, general distress, and illness perceptions at baseline and again 3 and 6 months later.Results: Compared to the control group, patients who received the intervention had increased treatment control perceptions at 3 months (p = .01), and increased social quality of life at 6 months (p = .01). The intervention was particularly helpful for patients exhibiting distress at baseline.Conclusion: A brief psychological intervention following HNC diagnosis can improve patient perceptions of treatment and social quality of life over time. Such interventions could be targeted to patients who are distressed in order to confer the greatest benefit.Trial Registration Number: 12614000813684. [ABSTRACT FROM AUTHOR]

Aims: The aim of the study was to assess the clinical efficacy of antazoline, a first-generation anti-histaminic agent, in the rapid conversion of paroxysmal non-valvular atrial fibrillation (AF) to sinus rhythm in patients without heart failure.Methods and Results: This study was a single center, randomized, double blind, placebo-controlled, superiority clinical trial. We enrolled patients with an AF episode lasting less than 43 h, in stable cardiopulmonary condition. Subjects who fulfilled the selection criteria were randomly assigned to receive intravenously either a placebo or up to 250 mg of antazoline. The primary end point was the conversion of AF to sinus rhythm confirmed in electrocardiogram (ECG). We enrolled 74 patients: 36 (48.6%) in the antazoline group and 38 (51.4%) in the control group. The mean age was 68 ± 12 years (range 31-90 years), 39 (53.3%) patients were male. The successful conversion of AF to sinus rhythm during the observation period was achieved in 26 (72.2%) patients treated with antazoline and 4 (10.5%) in the control group: RR 6.86 (95% CI: 2.66-17.72, P < 0.0001). Median time to conversion was 16.0 min in antazoline and 72.5 min in the control group (P = 0.0246). There were no cases of atrial tachycardia/flutter in the antazoline group.Conclusion: Intravenous antazoline was effective and safe in the rapid conversion of non-valvular paroxysmal atrial fibrillation to sinus rhythm in patients without heart failure. Clinical Trial Registration number: NCT01527279. [ABSTRACT FROM AUTHOR]

Aims: There is lack of conclusive evidence from randomized clinical trials on the efficacy and safety of upgrade to cardiac resynchronization therapy (CRT) in patients with implanted pacemakers (PM) or defibrillators (ICD) with reduced left ventricular ejection fraction (LVEF) and chronic heart failure (HF). The BUDAPEST-CRT Upgrade Study was designed to compare the efficacy and safety of CRT upgrade from conventional PM or ICD therapy in patients with intermittent or permanent right ventricular (RV) septal/apical pacing, reduced LVEF, and symptomatic HF.Methods and Results: The BUDAPEST-CRT study is a prospective, randomized, multicentre, investigator-sponsored clinical trial. A total of 360 subjects will be enrolled with LVEF ≤ 35%, NYHA functional classes II-IVa, paced QRS ≥ 150 ms, and a RV pacing ≥ 20%. Patients will be followed for 12 months. Randomization is performed in a 3:2 ratio (CRT-D vs. ICD). The primary composite endpoint is all-cause mortality, a first HF event, or less than 15% reduction in left ventricular (LV) end-systolic volume at 12 months. Secondary endpoints are all-cause mortality, all-cause mortality or HF event, and LV volume reduction at 12 months. Tertiary endpoints include changes in quality of life, NYHA functional class, 6 min walk test, natriuretic peptides, and safety outcomes.Conclusion: The results of our prospective, randomized, multicentre clinical trial will provide important information on the role of cardiac resynchronization therapy with defibrillator (CRT-D) upgrade in patients with symptomatic HF, reduced LVEF, and wide-paced QRS with intermittent or permanent RV pacing.Clinical Trials.gov Identifier: NCT02270840. [ABSTRACT FROM AUTHOR]

Study Question: Does repeat administration of misoprostol for early pregnancy loss increase the treatment success rate?Summary Answer: Repeat administration of misoprostol does not increase the treatment success rate, and is associated with more analgesics use.What Is Known Already: Misoprostol reduces the need for surgical evacuation and shortens the time to complete expulsion in patients with early pregnancy loss. However, the impact of repeat doses of misoprostol is not clear.Study Design, Size, Duration: A randomized clinical trial was conducted in a single tertiary hospital, recruiting women with early pregnancy loss (<12 weeks), seeking medical treatment, between August 2015 and June 2016. A sample size of 160 patients was sufficient to detect a 30% decrease in treatment success.Participants/materials, Setting, Methods: Participants received 800 μg of misoprostol vaginally on Day 1, and were then randomly assigned into two groups: Patients in the single-dose group were evaluated on Day 8. Patients in the repeat-dose group were evaluated on Day 4, when they were given a repeat dose if required, and scheduled for re-evaluation on Day 8. If complete expulsion was not achieved on Day 8 (endometrial thickness >15 mm or the presence of gestational sac on transvaginal sonography), participants underwent surgical evacuation. The primary outcome was treatment success, defined as no need for surgical intervention up to Day 8.Main Results and the Role Of Chance: Final analysis included 87 participants in the single-dose group and 84 participants in the repeat-dose group, out of whom 41 (48.8%) received a second dose. Treatment succeeded in 67 (77%) patients in the single-dose group and 64 (76%) patients in the repeat-dose group (RR 0.98; 95% CI 0.83-1.16; P = 0.89). Patients in the repeat-dose group reported more use of over the counter analgesics (82.1% versus 69.0%, P = 0.04).Limitations, Reasons For Caution: The study was not blinded and our definition of complete expulsion may be debated. Follow-up time was not equal in all participants, since some had a complete expulsion on Day 4 and some underwent emergent D&C before Day 8. This, however, should not affect the primary outcome.Wider Implications Of the Findings: Our results suggest that a single-dose protocol is superior to a repeat-dose protocol due to a comparable success rate and more favorable outcomes regarding the need for analgesic drugs.Study Funding/competing Interest(s): We did not receive funding for this study and we declare no conflict of interest.Trial Registration Number: ClinicalTrials.gov (NCT02515604).Trial Registration Date: 2 August 2015.Date Of First Patient's Enrolment: 19 August 2015. [ABSTRACT FROM AUTHOR]

Study Question: Does the use of hCG as luteal phase support in natural cycle frozen embryo transfer (FET) increase the ongoing pregnancy rate?Study Answer: The use of hCG in natural cycle FET did not improve the ongoing pregnancy rate.What Is Known Already: The use of luteal phase support in stimulated cycles has been associated with higher live-birth rates and the results are similar when using hCG or progesterone.Study Design Size, Duration: This is a randomized double-blinded controlled trial of 450 women recruited between August 2013 and October 2015.Participants/materials Setting Methods: Women with regular cycles undergoing natural cycle FET were recruited. Serial serum hormonal concentrations were used to time natural ovulation and at least Day 2 cleavage embryos were replaced. Patients were randomized into either: (i) the treatment group, receiving 1500 IU hCG on the day of FET and 6 days after FET, or (ii) the control group, receiving normal saline on these 2 days.Main Results and the Role Of Chance: The ongoing pregnancy rate [60/225 (26.7%) in the treatment group vs 70/225 (31.3%) in the control group, odds ratio 1.242 (95% CI 0.825-1.869)], implantation rate and miscarriage rate were comparable between the two groups. In the treatment group, there were significantly more cycles with top quality embryos transferred and a significantly higher serum oestradiol level, but a comparable serum progesterone level, 6 days after FET. However, no significant differences were observed in serum oestradiol and progesterone levels 6 days after FET between the pregnant and non-pregnant women. In the multivariate logistic regression, the number of embryos transferred was the only significant factor predictive of the ongoing pregnancy rate after natural cycle FET.Limitations Reason For Caution: This study only included FET with cleavage stage embryos and only hCG, not vaginal progesterone, was used as luteal phase support.Wider Implantations Of the Findings: The findings in this study do not support the use of hCG for luteal phase support in natural cycle FET.Study Funding/competing Interests: No external funding was used and there were no competing interests.Trial Registration Number: clinicaltrial.gov identifier: NCT01931384.Trial Registration Date: 23/8/2013.Date Of First Patient's Enrolment: 30/8/2013. [ABSTRACT FROM AUTHOR]

Background: Optimal nutritional choices are linked with better health, but many current interventions to improve diet have limited effect. We tested the hypothesis that providing personalized nutrition (PN) advice based on information on individual diet and lifestyle, phenotype and/or genotype would promote larger, more appropriate, and sustained changes in dietary behaviour.Methods: : Adults from seven European countries were recruited to an internet-delivered intervention (Food4Me) and randomized to: (i) conventional dietary advice (control) or to PN advice based on: (ii) individual baseline diet; (iii) individual baseline diet plus phenotype (anthropometry and blood biomarkers); or (iv) individual baseline diet plus phenotype plus genotype (five diet-responsive genetic variants). Outcomes were dietary intake, anthropometry and blood biomarkers measured at baseline and after 3 and 6 months' intervention.Results: At baseline, mean age of participants was 39.8 years (range 18-79), 59% of participants were female and mean body mass index (BMI) was 25.5 kg/m 2 . From the enrolled participants, 1269 completed the study. Following a 6-month intervention, participants randomized to PN consumed less red meat [-5.48 g, (95% confidence interval:-10.8,-0.09), P  = 0.046], salt [-0.65 g, (-1.1,-0.25), P  = 0.002] and saturated fat [-1.14 % of energy, (-1.6,-0.67), P  < 0.0001], increased folate [29.6 µg, (0.21,59.0), P  = 0.048] intake and had higher Healthy Eating Index scores [1.27, (0.30, 2.25), P  = 0.010) than those randomized to the control arm. There was no evidence that including phenotypic and phenotypic plus genotypic information enhanced the effectiveness of the PN advice.Conclusions: Among European adults, PN advice via internet-delivered intervention produced larger and more appropriate changes in dietary behaviour than a conventional approach. [ABSTRACT FROM AUTHOR]

Aims: To conduct a randomized trial in order to guide the optimum therapy of symptomatic atrioventricular nodal re-entrant tachycardia (AVNRT).Methods and Results: Patients with at least one symptomatic episode of tachycardia per month and an electrophysiologic diagnosis of AVNRT were randomly assigned to catheter ablation or chronic antiarrhythmic drug (AAD) therapy with bisoprolol (5 mg od) and/or diltiazem (120-300 mg od). All patients were properly educated to treat subsequent tachycardia episodes with autonomic manoeuvres or a 'pill in the pocket' approach. The primary endpoint of the study was hospital admission for persistent tachycardia cardioversion, during a follow-up period of 5 years. Sixty-one patients were included in the study. In the ablation group, 1 patient was lost to follow-up, and 29 were free of arrhythmia or conduction disturbances at a 5-year follow-up. In the AAD group, three patients were lost to follow-up. Of the remainder, 10 patients (35.7%) continued with initial therapy, 11 patients (39.2%) remained on diltiazem alone, and 7 patients (25%) interrupted their therapy within the first 3 months following randomization, and subsequently developed an episode requiring cardioversion. During a follow-up of 5 years, 21 patients in the AAD group required hospital admission for cardioversion. Survival free from the study endpoint was significantly higher in the ablation group compared with the AAD group (log-rank test, P < 0.001).Conclusions: Catheter ablation is the therapy of choice for symptomatic AVNRT. Antiarrhythmic drug therapy is ineffective and not well tolerated. [ABSTRACT FROM AUTHOR]

There is an on-going debate about whether health products, such as insecticide-treated bednets (ITNs) for protection against malaria, should be distributed for free or at a positive price to maximize ownership and use. One argument in favour of free distribution is related to positive externalities. Like vaccines, individual use of ITNs provides a community-wide protective effect against malaria even for non-users. In addition, price may act as a barrier to ownership particularly among those most at-risk who are frequently poor. Alternatively, charging a positive price may reduce donor dependence, more efficiently allocate nets to those most at risk of malaria, and encourage use through a hypothesized sunk cost effect, where individuals are more likely to use goods they pay for. Using a randomized experiment in Madagascar, we evaluate the impact of price on demand for and use of ITNs. We find that price negatively affects both demand and use of ITNs. When price increases by $0.55, demand falls by 23.1% points (CI 19.6–26.6; P < 0.01) and effective coverage falls by 23.1% points (CI 19.6–26.6; P < 0.01). We fail to find evidence of a screening effect for prices greater than zero, but households eligible for free ITNs are more likely to use them if they have more self-reported fevers in the household at baseline. We also fail to find evidence of a sunk cost effect, meaning that households are not more likely to use nets that they pay for. Our results suggest that: (1) only partially subsidizing ITNs significantly limits ownership and (2) distributing ITNs for free or at a small nominal price will maximize demand and effective coverage. Alternative sources of financing should be identified to completely (or almost completely) subsidize the cost of ITNs in order to maximize coverage of ITNs among poor populations at risk of malaria. [ABSTRACT FROM AUTHOR]

Background: Prospective data suggest depressive symptoms worsen insulin resistance and accelerate type 2 diabetes (T2D) onset.Purpose: We sought to determine whether reducing depressive symptoms in overweight/obese adolescents at risk for T2D would increase insulin sensitivity and mitigate T2D risk.Method: We conducted a parallel-group, randomized controlled trial comparing a 6-week cognitive-behavioral (CB) depression prevention group with a 6-week health education (HE) control group in 119 overweight/obese adolescent girls with mild-to-moderate depressive symptoms (Center for Epidemiological Studies-Depression Scale [CES-D] ≥16) and T2D family history. Primary outcomes were baseline to post-intervention changes in CES-D and whole body insulin sensitivity index (WBISI), derived from 2-h oral glucose tolerance tests. Outcome changes were compared between groups using ANCOVA, adjusting for respective baseline outcome, puberty, race, facilitator, T2D family history degree, baseline age, adiposity, and adiposity change. Multiple imputation was used for missing data.Results: Depressive symptoms decreased (p < 0.001) in CB and HE from baseline to posttreatment, but did not differ between groups (ΔCESD = -12 vs. -11, 95 % CI difference = -4 to +1, p = 0.31). Insulin sensitivity was stable (p > 0.29) in CB and HE (ΔWBISI = 0.1 vs. 0.2, 95 % CI difference = -0.6 to +0.4, p = 0.63). Among all participants, reductions in depressive symptoms were associated with improvements in insulin sensitivity (p = 0.02).Conclusions: Girls at risk for T2D displayed reduced depressive symptoms following 6 weeks of CB or HE. Decreases in depressive symptoms related to improvements in insulin sensitivity. Longer-term follow-up is needed to determine whether either program causes sustained decreases in depressive symptoms and improvements in insulin sensitivity.Trial Registration Number: The trial was registered with clinicaltrials.gov (NCT01425905). [ABSTRACT FROM AUTHOR]

Background: This study is to examine the effects of folic acid supplementation on cognitive function in Chinese older adults with mild cognitive impairment who are unexposed to folic acid fortification and assess cognitive functioning in relation to folate, homocysteine, and vitamin B12 values at baseline.Methods: This was a single-center, randomized, controlled trial in Tianjin, China; 180 individuals aged 65 years and older who had mild cognitive impairment were assigned randomly to one of two groups: (a) those treated with oral folic acid (400 µg/day) and (b) those treated via conventional treatment. Tests of cognitive performance and biomarkers were measured at baseline, 3 months, and 6 months. Analysis was by intention-to-treat. Changes in cognitive or clinical function were analyzed by repeated-measure analysis of variance or mixed-effects models. This trial has been registered with the trial number ChiCTR-TRC-13003227.Results: Total of 159 participants (intervention group: 80; control group: 79) completed the trial. Repeated-measure analysis of variance showed significant improvements in serum folate (ηp (2) = 0.712, p = .009), homocysteine (ηp (2) = 0.119, p = .017), serum vitamin B12 (ηp (2) = 0.144, p = .022), and S-adenosylmethionine (ηp (2) = 0.117, p = .033) in the intervention group over the control group. Folic acid supplementation improved Full Scale IQ (p = .031; effect size d = 0.168), Digit Span (p = .009; d = 0.176), and Block Design (p = .036; effect size d = 0.146) scores at 6 months in comparison to the control. There were no significant findings for all other cognitive measures.Conclusion: There was a beneficial effect from relatively short-term folate supplementation on cognitive functioning in later life. Larger-scale, randomized, controlled trials of longer duration in selected age groups are needed. [ABSTRACT FROM AUTHOR]

Objective. To study for the first time in a randomized controlled trial the feasibility, safety and efficacy of an exercise training programme in children and adolescents with JDM. Methods. Patients were randomly assigned to the Intervention Group (IG; n = 14) or Waiting Control Group (WCG; n = 12). The intervention comprised an individually tailored 12-week home-based exercise programme of treadmill interval training and strength exercises. The efficacy of the IG over usual care (WCG) was examined with mixed linear regression (intention-to-treat). Effect sustainability during 12 weeks follow-up was also examined. Results. Seventy-five percent of the participants completed the intervention. Reasons for discontinuation were motivation/fatigue, recurrent infections and increasing physical complaints. No hospitalizations occurred and immune suppressive therapy remained stable or decreased in the patients who participated in the intervention. The estimated marginal means after the intervention period were significantly in favour of the IG compared with the WCG for standing long jump distance [difference between groups (95% CI): 13cm (2-23)], the 30-s number of push-ups [8 (3-13)] and sit-ups [4 (0.4-8)], and the parent Childhood Health Assessment Questionnaire 30 + 8 score [-0.13 (-0.24 to-0.01)] and effects sustained at follow-up. A trend was seen for the maximal oxygen uptake divided by body mass during maximal exercise treadmill testing; the IG scored 3.0ml/kg/min (-1.3 to 7.3) higher compared with the WCG. Other outcomes (e.g. isometric muscle strength and perception of fatigue) did not differ between IG and WCG. Conclusion. Exercise training is of value in the clinical management of JDM. [ABSTRACT FROM AUTHOR]

Background: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with diverse adverse health outcomes, making it an important therapeutic target. Measurement of the diurnal rhythm of cortisol secretion provides a window into this system. At present, no guidelines exist for the optimal use of this biomarker within randomised controlled trials (RCTs).Purpose: The aim of this study is to describe the ways in which salivary diurnal cortisol has been measured within RCTs of health or behavioural interventions in adults.Methods: Six electronic databases (up to May 21, 2015) were systematically searched for RCTs which used salivary diurnal cortisol as an outcome measure to evaluate health or behavioural interventions in adults. A narrative synthesis was undertaken of the findings in relation to salivary cortisol methodology and outcomes.Results: From 78 studies that fulfilled the inclusion criteria, 30 included healthy participants (38.5 %), 27 included patients with physical disease (34.6 %) and 21 included patients with psychiatric disease (26.9 %). Psychological therapies were most commonly evaluated (n = 33, 42.3 %). There was substantial heterogeneity across studies in relation to saliva collection protocols and reported cortisol parameters. Only 39 studies (50 %) calculated a rhythm parameter such as the diurnal slope or the cortisol awakening response (CAR). Patterns of change in cortisol parameters were inconsistent both within and across studies and there was low agreement with clinical findings.Conclusions: Salivary diurnal cortisol is measured inconsistently across RCTs, which is limiting the interpretation of findings within and across studies. This indicates a need for more validation work, along with consensus guidelines. [ABSTRACT FROM AUTHOR]

Objective: Several barriers challenge resident engagement in learning quality improvement (QI). We investigated whether the incorporation of team-based game mechanics into an evidence-based online learning platform could increase resident participation in a QI curriculum.Design: Randomized, controlled trial.Setting: Tertiary-care medical center residency training programs.Participants: Resident physicians (n = 422) from nine training programs (anesthesia, emergency medicine, family medicine, internal medicine, ophthalmology, orthopedics, pediatrics, psychiatry and general surgery) randomly allocated to a team competition environment (n = 200) or the control group (n = 222).Intervention: Specialty-based team assignment with leaderboards to foster competition, and alias assignment to de-identify individual participants.Main Outcome Measures: Participation in online learning, as measured by percentage of questions attempted (primary outcome) and additional secondary measures of engagement (i.e. response time). Changes in participation measures over time between groups were assessed with a repeated measures ANOVA framework.Results: Residents in the intervention arm demonstrated greater participation than the control group. The percentage of questions attempted at least once was greater in the competition group (79% [SD ± 32] versus control, 68% [SD ± 37], P= 0.03). Median response time was faster in the competition group (P= 0.006). Differences in participation continued to increase over the duration of the intervention, as measured by average response time and cumulative percent of questions attempted (each P< 0.001).Conclusions: Team competition increases resident participation in an online course delivering QI content. Medical educators should consider game mechanics to optimize participation when designing learning experiences. [ABSTRACT FROM AUTHOR]

Objective: To assess feasibility and estimate effect size of a self-directed online intervention designed to prevent persistent posttraumatic stress after acute trauma.Methods: Children aged 8-12 years with a recent acute medical event were randomized to the intervention (N = 36) or a 12-week wait list (N = 36). Posttraumatic stress, health-related quality of life, appraisals, and coping were assessed at baseline, 6, 12, and 18 weeks.Results: Most children used the intervention; half completed it. Medium between-group effect sizes were observed for change in posttraumatic stress severity from baseline to 6 weeks (d = -.68) or 12 weeks (d = -.55). Exploratory analyses suggest greatest impact for at-risk children, and a small effect for intervention initiated after 12 weeks. Analysis of covariance did not indicate statistically significant group differences in 12-week outcomes.Conclusions: This pilot randomized controlled trial provides preliminary evidence that a self-directed online preventive intervention is feasible to deliver, and could have an effect in preventing persistent posttraumatic stress. [ABSTRACT FROM AUTHOR]

Objective: Tested a family-based group problem-solving intervention, "Families Taking Control," (FTC) to improve school functioning and health-related quality of life (HRQL) for children with sickle cell disease.Method: Children and caregivers completed questionnaires assessing HRQL and school functioning and children completed performance-based measures of IQ and achievement at baseline and 6 months later. Families were randomized to the intervention (FTC, n = 42) or delayed intervention control (DIC, n = 41) group. FTC involved a full-day workshop followed by 3 booster calls.Results: There were no differences between FTC completers (n = 24) and noncompleters (n = 18). FTC group (n = 24) and DIC group (n = 38) did not differ significantly on primary outcomes at follow-up: number of formal academic and disease-related accommodations, individualized education plan/504 service plan, school absences, school HRQL, or academic skills.Conclusions: Although families found FTC to be acceptable, there were no intervention effects. Challenges of the trial and implications for future research are discussed. [ABSTRACT FROM AUTHOR]

An international double-blind randomized placebo controlled study evaluated the safety and efficacy of four doses of a new sustained release naloxone capsule to treat Opioid Induced Constipation (OIC). Methods Forty patients taking opioids for noncancer related pain, and experiencing OIC, were randomized into 4 cohorts of 10 patients. A multiple ascending dose design was used to evaluate the safety and efficacy of 2.5 mg, 5 mg, 10 mg, and 20 mg naloxone sustained release (NSR) capsules vs placebo. Drug was given once-daily for 3 weeks followed by twice daily (bid) dosing between weeks 4 and 6. Results The incidence of treatment emergent adverse events was highest in the placebo group. The incidence of adverse events among the four active treatment groups were similar. There were no serious adverse events. The number of severe events was low overall but highest in the placebo group. Significant improvements were seen in Spontaneous Bowel Movements with 5 mg, 10 mg, and 20 mg NSR capsules. Mean change in SBMs from baseline of 2.21 ( P = 0.052), 2.37 ( P = 0.032); 4.11 ( P = 0.0005); 5.19 (<0.0001) was noted with NSR 2.5 mg, 5 mg, 10 mg, and 20 mg, respectively, when taken once daily, compared with 1.38 ( P = 0.2) for patients on placebo therapy. No changes in subjective or objective measures of opioid withdrawal as measured by the Subjective Opioid Withdrawal Scale or Clinical Opioid Withdrawal Scale were observed. There was no increase in patient reported pain as measured daily using a visual analogue scale. Conclusions This Phase II study has shown that using a new sustained release formulation to deliver oral naloxone to the colon allows successful treatment of OIC without comprising the desired opioid effects. [ABSTRACT FROM AUTHOR]

Background: Ovarian hyperstimulation syndrome (OHSS) seems to be induced by the ovarian release of vascular endothelial growth factor (VEGF), which increases vascular permeability. Dopamine agonists inhibit VEGF receptor phosphorylation and thereby decrease vascular permeability.Methods: A randomized, double-blind, placebo-controlled, multicentre study assessing three oral doses (50, 100, 200 microg/day) of the non-ergot derived dopamine agonist quinagolide started on the day of human chorionic gonadotrophin (hCG) and continued for 17-21 days without dose-titration in comparison to placebo in preventing moderate/severe early OHSS (onset < or =9 days after hCG administration) in 182 IVF patients with > or =20 but less than 30 follicles > or =10 mm.Results: The incidence of moderate/severe early OHSS was 23% (12/53) in the placebo group and 12% (6/51), 13% (7/52) and 4% (1/26) in the quinagolide 50, 100 and 200 microg/day groups, respectively. The moderate/severe early OHSS rate was significantly lower with all quinagolide groups combined compared with placebo [P = 0.019; OR = 0.28 (0.09-0.81)]. The incidence of ultrasound evidence of ascites among patients with no clinical pregnancy was significantly reduced from 31% (8/26) with placebo to 11% (8/70) with all quinagolide groups combined [P = 0.033; OR = 0.29 (0.10-0.88)], although there was no difference for those with clinical pregnancy. Quinagolide did not have a detrimental effect on pregnancy or live birth rates. The incidence of gastrointestinal and central nervous system adverse events increased with increasing doses of quinagolide.Conclusions: Quinagolide appears to prevent moderate/severe early OHSS while not affecting treatment outcome. The effect is more marked in patients who did not achieve a clinical pregnancy. Quinagolide administered in high doses without dose-titration is associated with poor tolerability. ClinicalTrials.gov Identifier: NCT00329693. [ABSTRACT FROM AUTHOR]

The adverse effect of raised luteinizing hormone (LH) concentrations on reproductive outcome suggests that exogenous LH administration for ovarian stimulation may not be desirable. The aim of this study was to compare the clinical pregnancy rates between follicle stimulating hormone (FSH) and human menopausal gonadotrophin (HMG) used in in-vitro fertilization (IVF) cycles. A total of 232 infertile patients, with a mean duration of infertility of 67.1 +/- 32.9 months, were selected for IVF (female age < 38 years, FSH < 15 IU/l, and total motile sperm count > 5 x 10(6)). A short (flare-up) protocol with daily leuprolide acetate was followed randomly from day 3 with FSH (n = 115) or human menopausal gonadotrophin (HMG; n = 117), at an initial dose of two ampoules per day. A maximum of three embryos was transferred, and the luteal phase was supported with four doses of HCG (2500 IU). No differences were observed between the two groups in any of the cycle response variables except fertilization rates per oocyte and per patient, both of which were significantly higher with FSH. Clinical pregnancy rates per cycle initiated, per oocyte retrieval and per embryo transfer were 19.1, 21.0 and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectively for HMG. Whilst these differences were not statistically significant, the results of this interim analysis suggest that HMG may be associated with a lower clinical pregnancy rate than FSH. [ABSTRACT FROM AUTHOR]