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Introduction: and objective: Tremor is a disabling symptom of PD that usually responds poorly to available standard pharmacological agents. This study aimed to assess the effect of Zonisamide 25 mg on tremor in tremor-dominant PD patients as compared to placebo.Methods: This was a randomized, placebo-controlled, double-blind study. Parkinson's disease patients were allocated either to the intervention group (standard treatment along with Zonisamide 25 mg add-on) or the placebo group (standard treatment along with placebo). Baseline Unified Parkinson's Disease Rating Scale (UPDRS) and Tremor Research Group Essential Tremor Rating Scale (TETRAS) scores, as well as accelerometric tremor analysis were done and follow-up assessments of the same were done after 12 weeks of intervention. Percentage change from baseline in the UPDRS tremor score was the primary outcome whereas percentage change from baseline of total UPDRS score, UPDRS rigidity and bradykinesia scores, TETRAS score, and accelerometric tremor analysis values were the secondary outcomes.Results: There was no significant difference in the percentage change from baseline UPDRS tremor scores between the two groups (placebo: 8.33 [-19.89-23.86] vs drug: 26.14 [-35.58 to -16.07], p-value: 0.164, CI: 0.157-0.171). Best-case analysis for missing values showed a significant improvement in the drug group, compared to the placebo group (p-value: < 0.001, CI: <0.001 - <0.001).Conclusion: Zonisamide at a dose of 25 mg per day did not improve tremor in tremor-dominant PD patients, however, a positive trend was seen as compared to Placebo in the UPDRS tremor score. Larger studies are required to confirm this finding. [ABSTRACT FROM AUTHOR]

Objective: Computer-assisted child-focused interventions are expected to improve efficiency and personalization of therapist-led treatments for children and adolescents. However, therapist-led, outpatient interventions using computer assistance are lacking for children with oppositional defiant disorder (ODD) or conduct disorder (CD). The present randomized controlled trial examined the efficacy of individualized computer-assisted social skills training for children with aggressive behavior compared to a resource activation intervention.Method: A total of 100 children aged 6-12 years with a diagnosis of ODD/CD and peer-related aggression were randomly (1:1) assigned to either individually delivered computer-assisted social skills training (ScouT) or an individually delivered supportive resource activation treatment (STARK). The primary outcome was parent-rated peer-related aggression, assessed with the respective scale of the Questionnaire for Aggressive Behavior of Children (FAVK) and measured at pre-assessment and after the 16-week intervention (post-assessment). Further parent-, self-, teacher- and/or clinician-rated outcomes included ODD and CD symptoms, a wide range of behavioral and emotional symptoms, callous-unemotional traits, functional impairment, and quality of life.Results: After correcting for multiple testing, analyses of covariance comparing the efficacy of ScouT to the efficacy of STARK yielded small to moderate treatment effects in favor of the ScouT condition regarding parent-rated peer-related aggression (primary outcome; d = -0.64, 95% CI = -1.05, -0.24), parent-rated callous and uncaring traits, and parent-rated quality of life. However, the analyses did not reveal any significant effects for self- or teacher-rated peer-related aggression assessed with the respective scale of the FAVK (self-report: d = -0.21, 95% CI = -0.69, 0.29; teacher rating: d = -0.17, 95% CI = -0.56, 0.22). Moreover, after controlling for multiple comparisons, no significant effects emerged for the following: parent-, self-, and teacher-rated adult-related aggression; parent-, self-, teacher-, and clinician-rated ODD and CD symptoms; parent-, self-, and teacher-rated emotional and behavioral symptoms; and parent-rated functional impairment.Conclusion: According to parent ratings, school-age children with disruptive behavior disorders and peer-related aggression seem to benefit more from individualized, computer-assisted social skills training than from resource activation treatment. However, this conclusion is limited by the missing effects on the clinician-, self-, and teacher-rated measures.Clinical Trial Registration Information: Treatment of Children With Peer Related Aggressive Behavior (ScouT); https://clinicaltrials.gov/; NCT02143427. [ABSTRACT FROM AUTHOR]

Few clinical trials have evaluated the efficacy of psychotherapy for Intermittent Explosive Disorder (IED). The present study tested the efficacy of a cognitive behavioral intervention (versus supportive psychotherapy) among adults with IED. In this randomized clinical trial, 44 participants with IED (22 men and 22 women) aged 20-55 years completed twelve 50-minute individual sessions of either a multi-component cognitive behavioral intervention for IED (n = 19) or a time equated supportive psychotherapy (n = 25). At baseline, posttreatment, and 3-month follow-up, all participants received the Overt Aggression Scale-Modified, which was conducted by an interviewer who was blind to the participant's study condition. During these visits, participants also completed self-report measures of relational aggression (Self-Report of Relational Aggression and Social Behavior), anger (State-Trait Anger Expression Inventory-2), cognitive biases (e.g., Social Information Processing Questionnaire Attribution and Emotional Response Questionnaire), and associated symptoms (e.g., Beck Depression Inventory). Primary study outcomes were aggressive behavior and anger. Though participants in both treatments tended to improve over time, the cognitive behavioral intervention was superior to supportive psychotherapy in decreasing aggressive behavior and relational aggression. These findings support the efficacy of a multicomponent cognitive behavioral intervention in treating aggression in IED. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effectiveness of a question prompt list (QPL) in decision self-efficacy, decision-making participation, patient-physician communication, decisional conflict or regret, and health status in patients with breast cancer.Methods: A total of 240 patients with breast cancer were randomly assigned to a QPL group or control group (n = 120 each). The intervention and control groups received an additional educational QPL booklet and routine care, respectively.Results: The intervention group exhibited significant improvements in decision self-efficacy, perceived patient-physician interactions, and patient-physician communication compared with the control group. Multilevel modeling analyses revealed significant group-time interaction effects on decision self-efficacy (β = 9.99, P < 0.01), perceived patient-physician interactions (β = 8.10, P < 0.01), patient-physician communication (β = 5.02, P < 0.01), and anxiety status (β = -3.78, P < 0.05). The QPL intervention exerted more favorable effects than routine care, with repeated measurements of the same patients and the data of patients under the care of the same surgeons accounted for.Conclusions: The QPL intervention exerted multidimensional effects on decision-making outcomes among patients with breast cancer.Practical Implications: Clinicians can integrate a QPL into routine care for patients with breast cancer. [ABSTRACT FROM AUTHOR]

• MND-2119 is a self-emulsifying eicosapentaenoic acid ethyl ester. • MND-2119 was tested in hypertriglyceridemia patients. • MND-2119 2 g/day was non-inferior to Epadel 1.8 g/day in lowering TG levels. • MND-2119 4 g/day was superior to MND-2119 2 g/day in lowering TG levels. • MND-2119 appeared safe and well tolerated. In Japan, eicosapentaenoic acid ethyl ester (EPA-E) is administered twice-daily or three-times-daily for dyslipidemia. We have developed MND-2119, a novel self-emulsifying formulation of highly purified EPA-E, which can be administered once-daily. The objective of this study was to assess non-inferiority in the efficacy of MND-2119 in patients with hypertriglyceridemia compared with highly purified EPA-E. In this multicenter, 12-week, double-blind study, patients with high triglyceride (TG levels between ≥ 150 and < 500 mg/dL) undergoing lifestyle modification were randomized to MND-2119 2 g/day (n=145), MND-2119 4 g/day (n=145), EPA-E 1.8 g/day (n=145) or EPA-E 2.7 g/day (n=145). The primary endpoint was percentage change in TG levels from baseline to end of treatment. MND-2119 2, 4 g/day and EPA-E 1.8, 2.7 g/day reduced TG levels from baseline by −10.09%, −15.51%, −9.30%, and −8.80%, respectively. The TG reduction rate of MND-2119 2 g/day was non-inferior to that of EPA-E 1.8 g/day (LS mean difference: -0.42, 95%CI: -5.76 to 4.91). Moreover, the TG reduction rate of MND-2119 4 g/day was superior to that of MND-2119 2 g/day (LS mean difference: -5.74, 95%CI: -10.59 to -0.89). There were no remarkable safety differences between MND-2119 2 g/day and EPA-E 1.8 g/day and between MND-2119 4 g/day and EPA-E 2.7 g/day. Non-inferiority of MND-2119 2 g/day to EPA-E 1.8 g/day for efficacy, and superiority of MND-2119 4 g/day over MND-2119 2 g/day for efficacy were verified. MND-2119 was safe and well tolerated. [ABSTRACT FROM AUTHOR]

Background: Despite the potential for benefit, resilience remains an emergent area in late-life mental health care, and evidence of resilience intervention for suicide among nursing home residents is especially limited. This study aims to evaluate the effects of a resilience-targeted program based on the "I have, I am, and I can" strategy on suicidal ideation and related problems.Methods: From the 562 nursing home residents who were contacted, 68 with suicidal ideation were recruited and then randomly assigned to a resilience intervention group (eight-week resilience training; n = 34) or a wait-list control group (eight-week health education; n = 34). Self-reported suicidal ideation, and depression and anxiety symptoms as outcomes, and resilience as potential mediators were assessed at baseline, postintervention, and one-month follow-up.Results: Resilience training participants reported significant improvement in suicidal ideation (group × time interaction x2=12.564, p = 0.002) and depression symptoms (x2=9.441, p = 0.009) compared to wait-list control group participants. Changes in resilience mediated the intervention's effects on changes in suicidal ideation and depression symptoms. Limitations The observed effects must be considered preliminary due to the small sample size.Conclusions: The findings support the benefits of resilience training based on the "I have, I am, and I can" strategy in reducing suicidal ideation and suicide-related symptoms in nursing home older adults, and provide insight into possible mechanisms. [ABSTRACT FROM AUTHOR]

Background: The use of guideline-directed medical therapy (GDMT) is underprescribed in patients with heart failure with reduced ejection fraction (HFrEF).Objectives: This study sought to examine whether targeted and tailored electronic health record (EHR) alerts recommending GDMT in eligible patients with HFrEF improves GDMT use.Methods: PROMPT-HF (PRagmatic trial Of Messaging to Providers about Treatment of Heart Failure) was a pragmatic, EHR-based, cluster-randomized comparative effectiveness trial. A total of 100 providers caring for patients with HFrEF were randomized to either an alert or usual care. The alert notified providers of individualized GDMT recommendations along with patient characteristics. The primary outcome was an increase in the number of GDMT classes prescribed at 30 days postrandomization. Providers were surveyed on knowledge of guidelines and user experience.Results: The study enrolled 1,310 ambulatory patients with HFrEF from April to October 2021. Median age was 72 years; 31% were female; 18% were Black; and median left ventricular ejection fraction was 32%. At baseline, 84% of participants were receiving β-blockers, 71% received a renin-angiotensin-aldosterone system inhibitor, 29% received a mineralocorticoid receptor antagonist, and 11% received a sodium-glucose cotransporter-2 inhibitor. The primary outcome occurred in 176 of 685 (26%) participants in the alert arm vs 117 of 625 (19%) in the usual care arm, thus increasing GDMT class prescription by >40% after alert exposure (adjusted relative risk: 1.41; 95% CI: 1.03-1.93; P = 0.03). The number of patients needed to alert to result in an increase in addition of GDMT classes was 14. A total of 79% of alerted providers agreed that the alert was effective at enabling improved prescription of medical therapy for HF.Conclusions: A real-time, targeted, and tailored EHR-based alerting system for outpatients with HFrEF led to significantly higher rates of GDMT at 30 days when compared with usual care. This low-cost intervention can be rapidly integrated into clinical care and accelerate adoption of high-value therapies in heart failure. (PRagmatic trial Of Messaging to Providers about Treatment of Heart Failure [PROMPT-HF; NCT04514458]). [ABSTRACT FROM AUTHOR]

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is frequently defined as one with an estimated fetal weight of <10th percentile. This condition has been considered syndromic and has been frequently attributed to fetal growth restriction, a constitutionally small fetus, congenital infections, chromosomal abnormalities, or genetic conditions. Small for gestational age is not synonymous with fetal growth restriction, which is defined by deceleration of fetal growth determined by a change in fetal growth velocity. An abnormal umbilical artery Doppler pulsatility index reflects an increased impedance to flow in the umbilical circulation and is considered to be an indicator of placental disease. The combined finding of an estimated fetal weight of <10th percentile and abnormal umbilical artery Doppler velocimetry has been widely accepted as indicative of fetal growth restriction. Clinical studies have shown that the gestational age at diagnosis can be used to subclassify suspected fetal growth restriction into early and late, depending on whether the condition is diagnosed before or after 32 weeks of gestation. The early type is associated with umbilical artery Doppler abnormalities, whereas the late type is often associated with a low pulsatility index in the middle cerebral artery. A large randomized clinical trial indicated that in the context of early suspected fetal growth restriction, the combination of computerized cardiotocography and fetal ductus venosus Doppler improves outcomes, such that 95% of surviving infants have a normal neurodevelopmental outcome at 2 years of age. A low middle cerebral artery pulsatility index is associated with an adverse perinatal outcome in late fetal growth restriction; however, there is no evidence supporting its use to determine the time of delivery. Nonetheless, an abnormality in middle cerebral artery Doppler could be valuable to increase the surveillance of the fetus at risk. We propose that fetal size, growth rate, uteroplacental Doppler indices, cardiotocography, and maternal conditions (ie, hypertension) according to gestational age are important factors in optimizing the outcome of suspected fetal growth restriction. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is frequent among patients undergoing bariatric surgery. Beyond weight reduction, dietary supplements like micronutrients or probiotics that modify insulin resistance and lipotoxicity can be used to prevent or delay the progression of liver disease.Objectives: We evaluated the effect of a dietary approach with a specifically tailored multistrain probiotic and micronutrient mixture compared with a basic care micronutrient supplement on serum alanine aminotransferase (ALAT) in obese patients after mini gastric bypass (MGB) surgery.Methods: This randomized, double-blind, controlled trial included 60 obese patients (age: 40 ± 10 y; BMI: 44 ± 3 kg/m²). Patients received a combination of specifically tailored multistrain probiotic powder and a specific micronutrient mixture (Pro+SM) or a control treatment consisting of a placebo and a basic care micronutrient mixture (Con+BM), with some micronutrients in lower doses than SM, for 12 wk after hospital discharge. Primary (serum ALAT) and secondary outcomes [serum aspartate aminotransferase (ASAT), fatty liver index, NAFLD fibrosis score, glucose metabolism, blood pressure (BP), heart rate] were assessed at week 0 and week 12. Data were analyzed using unpaired Student's t-tests or Mann-Whitney U tests to compare the changes due to each treatment to one another.Results: A total of 48 patients were included in the analyses. Changes in serum ALAT concentrations did not differ between groups. Compared with Con+BM, Pro+SM improved serum ASAT (difference: -8.0 U/L, 95% CI: -17.0, -4.0; P = 0.043), NAFLD fibrosis score (difference: -0.39; 95% CI: -0.78, 0; P = 0.048), serum triglycerides (difference: -22.8 mg/dL; 95% CI: -45.6, -0.1; P = 0.049) and the visceral adiposity index (difference: -0.70; 95% CI: -1.31, -0.08; P = 0.027).Conclusion: Supplementation with a specifically tailored probiotic and micronutrient mixture improved NAFLD-related markers more than a basic micronutrient mixture in obese patients following MGB surgery. The trial was registered under clinicaltrials.gov as NCT03585413. [ABSTRACT FROM AUTHOR]

Recovery-oriented practice has been advocated in mental health services in Hong Kong since 2009. Well-being has become an important area of focus for mental health services. Positive Psychotherapy for Psychosis (PPP) is a well-being-focused intervention for use in psychosis, with preliminary evidence from a randomized controlled trial in the United Kingdom of impact on well-being and symptomatology. The aim of this study was to test the effectiveness of PPP on the well-being of people with psychosis in Hong Kong. The study was a randomized controlled trial with two-arm parallel groups. Both groups received treatments as usual, and in addition the intervention group received a 13-session intervention based on a Cantonese Chinese translation of the PPP manual. Intention-to-treat analysis was used. The trial was registered (ANZCTR: ACTRN12620000464965). A total of 154 participants (78 intervention, 76 control) were recruited. As compared to control group, intervention group participants showed significant changes over time on the primary outcome of well-being assessed using the Chinese Short Warwick-Edinburgh Mental Well-being Scale (p = 0.001) and on secondary outcomes of hope (Agency subscale: p = 0.029) and self-efficacy (p = 0.001). Positive Psychotherapy for Psychosis was found to be an effective treatment in improving the well-being and other mental health outcomes for people with psychosis. It can be recommended for use in mental health services to promote recovery. [ABSTRACT FROM AUTHOR]

Objectives: Use of Motivational Interviewing (MI) in education may improve medication-overuse headache (MOH) patients' ability to cope with pain. In a randomised controlled trial, we evaluated the effect of education focusing on behavioural change among MOH patients.Methods: Ninety-eight MOH patients were randomized (1:1) to standard treatment and 12-weeks of MI-based education versus standard treatment alone after detoxification. Outcome of interest was changes in coping strategies measured by the Coping Strategy Questionnaire at four- and nine months.Results: The educational program improved patients' perceived efficacy in the use of their coping strategies to control pain, both at four-and nine months follow-up (mean±SE): ∆:0.84 ± 0.35, 95% CI:0.16;1.52, p = 0.02 and: ∆: 0.90 ± 0.39, 95% CI:0.14;1.66, p = 0.02, respectively. No between-group differences were detected in the other coping subscales. Within the intervention group, the coping strategy subscales Catastrophizing, and Reinterpretation of pain sensation were significantly improved at nine months follow-up (p = 0.003 vs. p = 0.012, respectively). No changes were found in the control group.Conclusion: MI-based education focused on behavioural changes improved MOH patients' perceived efficacy in the use of their coping strategies to control pain.Practice Implications: Education based on MI could be valuable for MOH patients with respect to behavioural changes and perceived headache control. [ABSTRACT FROM AUTHOR]

Background: There is a need for high-quality research regarding exercise interventions for persons with anxiety disorders. We investigate whether a 12-week exercise intervention, with different intensities, could reduce anxiety symptoms in patients with anxiety disorders.Methods: 286 patients were recruited from primary care in Sweden. Severity of symptoms was self-assessed using the Beck Anxiety Inventory (BAI) and the Montgomery Åsberg Depression Rating Scale (MADRS-S). Participants were randomly assigned to one of two group exercise programs with cardiorespiratory and resistance training and one control/standard treatment non-exercise group, with 1:1:1 allocation.Results: Patients in both exercise groups showed larger improvements in both anxiety and depressive symptoms compared to the control group. No differences in effect sizes were found between the two groups. To study a clinically relevant improvement, BAI and MADRS-S were dichotomized with the mean change in the control group as reference. In adjusted models the odds ratio for improved symptoms of anxiety after low-intensity training was 3.62 (CI 1.34-9.76) and after moderate/high intensity 4.88 (CI 1.66-14.39), for depressive symptoms 4.96 (CI 1.81-13.6) and 4.36 (CI 1.57-12.08) respectively. There was a significant intensity trend for improvement in anxiety symptoms.Limitations: The use of self-rating measures which bears the risk of an under- or overestimation of symptoms.Conclusions: A 12-week group exercise program proved effective for patients with anxiety syndromes in primary care. These findings strengthen the view of physical exercise as an effective treatment and could be more frequently made available in clinical practice for persons with anxiety issues. [ABSTRACT FROM AUTHOR]

Background: The glycemic effects of peanuts are not well studied and no trials have been conducted in adults with elevated fasting plasma glucose (FPG). Furthermore, intake of peanuts as a nighttime snack, an eating occasion affecting FPG, has not been examined.Objectives: The aim was to determine the effect of consuming 28 g/d of peanuts as a nighttime snack for 6 wk on glycemic control and cardiovascular disease risk factors, compared with an isocaloric lower fat, higher carbohydrate (LFHC) snack (whole grain crackers and low-fat cheese), in adults with elevated FPG.Methods: In a randomized crossover trial, 50 adults (FPG 100 ± 8 mg/dL) consumed dry roasted, unsalted peanuts [164 kcal; 11% energy (E) carbohydrate, 17% E protein, and 73% E fat] or a LFHC snack (164 kcal; 54% E carbohydrate, 17% E protein, and 33% E fat) in the evening (after dinner and before bedtime) for 6 wk with a 4-wk washout period. Primary (FPG) and secondary end points [Healthy Eating Index-2015 (HEI-2015), weight, insulin, fructosamine, lipids/lipoproteins, central and peripheral blood pressure, and pulse wave velocity] were evaluated at the beginning and end of each condition. Linear mixed models were used for data analysis.Results: FPG was not different between the peanut and LFHC conditions (end point mean difference: -0.6 mg/dL; 95% CI: -2.7, 1.6; P = 0.67). There were no between-condition effects for secondary cardiometabolic endpoints. The HEI-2015 score was not different between the conditions (3.6 points; P = 0.19), although the seafood/plant protein (2.0 points; P < 0.01) and added sugar (0.8 points; P = 0.04) components were improved following peanut intake. The whole grain component was lower with peanuts compared with LFHC (-2.6 points; P < 0.01).Conclusions: In adults with elevated FPG, peanuts as a nighttime snack (28 g/d) did not affect FPG compared with an isocaloric LFHC snack after 6 wk.This trial was registered at clinicaltrials.gov as NCT03654651. [ABSTRACT FROM AUTHOR]

Objective: Negative symptoms of schizophrenia are substantially disabling and treatment resistant. Novel treatments like repetitive transcranial magnetic stimulation (TMS) need to be examined for the same using the experimental medicine approach that incorporates tests of mechanism of action in addition to clinical efficacy in trials.Methods: Study was a double-blind, parallel, randomized, sham-controlled trial recruiting schizophrenia with at least a moderate severity of negative symptoms. Participants were randomized to real or sham intermittent theta burst stimulation (iTBS) under MRI-guided neuro-navigation, targeting the cerebellar vermis area VII-B, at a stimulus intensity of 100% active motor threshold, two sessions/day for five days (total = 6000 pulses). Assessments were conducted at baseline (T0), day-6 (T1) and week-6 (T2) after initiation of intervention. Main outcomes were, a) Scale for the Assessment of Negative Symptoms (SANS) score (T0, T1, T2), b) fronto-cerebellar resting state functional connectivity (RSFC) (T0, T1).Results: Thirty participants were recruited in each arm. Negative symptoms improved in both arms (p < 0.001) but was not significantly different between the two arms (p = 0.602). RSFC significantly increased between the cerebellar vermis and the right inferior frontal gyrus (pcluster-FWER = 0.033), right pallidum (pcluster-FWER = 0.042) and right frontal pole (pcluster-FWER = 0.047) in the real arm with no change in the sham arm.Conclusion: Cerebellar vermal iTBS engaged a target belonging to the class of cerebello-subcortical-cortical networks, implicated in negative symptoms of schizophrenia. However, this did not translate to a superior clinical efficacy. Future trials should employ enhanced midline cerebellar TMS stimulation parameters for longer durations that can potentiate and translate biological changes into clinical effects. [ABSTRACT FROM AUTHOR]

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

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

Context: Long-term care facility (LTCF) residents have unmet needs in end-of-life and symptom care.Objectives: This study examines the effects of an end-of-life care staff training intervention on LTCF residents' pain, symptoms, and psychological well-being and their proxies' satisfaction with care.Methods: We report findings from a single-blind, cluster randomized controlled trial featuring 324 residents with end-of-life care needs in 20 LTCF wards in Helsinki. The training intervention included four 4-hour educational workshops on palliative care principles (advance care planning, adverse effects of hospitalizations, symptom management, communication, supporting proxies, challenging situations). Training was provided to all members of staff in small groups. Education was based on constructive learning methods and included participants' own resident cases, role-plays, and small-group discussions. During a 12-month follow-up we assessed residents' symptoms with the Edmonton Symptom Assessment Scale (ESAS), pain with the PAINAD instrument and psychological well-being using a PWB questionnaire. Proxies' satisfaction with care was assessed using the SWC-EOLD.Results: The change in ESAS symptom scores from baseline to 6 months favored the intervention group compared with the control group. However, the finding was diluted at 12 months. PAINAD, PWB, and SWC-EOLD scores remained unaffected by the intervention. All follow-up analyses were adjusted for age, gender, do-not-resuscitate order, need for help, and clustering.Conclusion: Our rigorous randomized controlled trial on palliative care training intervention demonstrated mild effects on residents' symptoms and no robust effects on psychological well-being or on proxies' satisfaction with care. [ABSTRACT FROM AUTHOR]

Background: Previous studies have indicated that statins can reduce the severity of depressive symptoms. However, the optimal choice of statin remains unclear. Therefore, we conducted a network meta-analysis to determine the optimal statin for treating depression.Method: We performed a pairwise and network meta-analysis by searching the PubMed, Embase, and Cochrane Library databases on October 29th, 2020. Eligible studies were randomized controlled trials that reported on changes in depressive symptoms. The Cochrane Collaboration tool was used to assess risk of bias. We tested for possible inconsistency globally by using a χ2-test and locally by calculating inconsistency factors for each comparison in closed loops. The ranking probabilities of being at each possible rank for each intervention were estimated. Comparison-adjusted funnel plots were obtained to assess publication bias. Sensitivity analysis was also performed.Results: We identified 13 studies that matched our inclusion criteria. The risks of bias were mostly low. None of the global or local tests found significance. Compared with placebo, atorvastatin significantly reduced the severity of depressive symptoms (mean difference -3.46, 95% confidence interval -5.26 to -1.67). Atorvastatin had the first and second rank with probabilities of 44.9% and 39.0%, respectively. Comparison-adjusted funnel plots revealed no significant publication bias.Limitations: Low similarity of included studies and a relative large treatment effect of a single study were observed.Conclusions: In this first network meta-analysis, atorvastatin, with high intensity and a lipophilic effect, was identified as the optimal choice of statin for treating depression. [ABSTRACT FROM AUTHOR]

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

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

Objectives: To model the cost-effectiveness of the TYRX Absorbable Antibacterial Envelope when used in patients at increased risk of cardiac implantable electronic device (CIED) infection in the context of 3 European healthcare systems: Germany, Italy, and England.Methods: A decision tree model with a lifetime horizon was populated using data from the Worldwide Randomized Antibiotic Envelope Infection Prevention Trial, a large multicenter randomized controlled trial. Use of the antibacterial envelope adjunctive to standard of care was compared to standard of care infection prevention alone. Patients in the model were divided into subgroups based on presence of factors known to increase infection risk.Results: The antibacterial envelope had the most favorable cost-effectiveness profile when patients had previously experienced CIED infection, had a history of immunosuppressive therapy, or had a Prevention of Arrhythmia Device Infection Trial (PADIT) score indicating high risk of infection (scores ≥6) at cost-effectiveness thresholds of €50 000 in Germany (assumed in the absence of an official threshold), €40 000 in Italy, and £30 000 in England. Probabilistic sensitivity analysis indicated that the antibacterial envelope was likely to be cost-effective in patients with other risk factors (including replacement of high power CIEDs, generator replacement with lead modification, and PADIT scores indicating intermediate risk of infection) when used with some device types and in some countries.Conclusions: The absorbable antibacterial envelope was associated with cost-effectiveness ratios below European benchmarks in selected patients at increased risk of infection, suggesting the envelope provides value for European healthcare systems by reducing CIED infections. [ABSTRACT FROM AUTHOR]

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

Background: Meru Health Program (MHP) is a therapist-guided, 8-week intervention for depression delivered via smartphone. The aim was to test its efficacy in patients with clinical depression in a Finnish university student health service.Methods: Patients (n=124, women 72.6%, mean age 25y) were stratified based on antidepressant status, and randomized into intervention group receiving MHP plus treatment as usual (TAU), and control group receiving TAU only. Depression, measured by the Patient Health Questionnaire-9 (PHQ-9) scale, was the primary outcome. After baseline (T0), follow-ups were at mid-intervention (T4), immediately post-intervention (T8); 3 months (T20), and 6 months (T32) post-intervention.Results: The intervention group and control group did not have significant differences in depression outcomes throughout end of treatment and follow-up. Among secondary outcomes, increase in resilience (d=0.32, p=0.03) and mindfulness (d=0.57, p=0.002), and reduction in perceived stress (d=-0.52, p=0.008) were greater in MHP+TAU versus TAU at T32; no differences were found in anxiety, sleep disturbances, and quality of life between groups. Post-hoc comparisons of patients on antidepressants showed significantly greater reduction in depression at T32 for MHP+TAU versus TAU (d=-0.73, p=0.01); patients not on antidepressants showed no between-group differences.Limitations: Limitations include unknown characteristics of TAU, potential bias from patients and providers not being blinded to treatment group, and failure to specify examination of differences by antidepressant status in the protocol.Conclusions: Most outcomes, including depression, did not significantly differ between MHP+TAU and TAU. Exploratory analysis revealed intervention effect at the end of the 6-month follow-up among patients on antidepressant medication. [ABSTRACT FROM AUTHOR]

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

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

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

Background: Few treatments are available for patients with idiopathic hypersomnia (IH). Modafinil, an established treatment for narcolepsy, was tested for efficacy and safety in Japanese patients with IH without long sleep time.Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study was conducted at 20 institutions in Japan. Patients who met the diagnostic criteria of IH in the International Classification of Sleep Disorders (second edition) were included. The study comprised a ≥17-day observation period and a 3-week treatment period during which modafinil (200 mg) or placebo was administered orally once daily (in the morning). The primary efficacy endpoint was change in mean sleep latency on the Maintenance of Wakefulness Test (MWT). Adverse events (AEs) were also recorded to evaluate safety.Results: In total, 123 patients were screened and 71 were randomized to receive modafinil (N = 34) or placebo (N = 37). Patients treated with modafinil experienced a significantly prolonged mean sleep latency on the MWT at the end of the study compared with placebo (5.02 min, 95% confidence interval: 3.26-6.77 min; p < 0.001). AEs occurred in 58.8% (20/34) and 27.0% (10/37) of patients in the modafinil and placebo groups, respectively. Frequent AEs in the modafinil group were headache (n = 6), dry mouth (n = 3), and nausea (n = 3); no clinically significant AEs occurred.Conclusion: Modafinil was shown to be an effective and safe treatment for excessive daytime sleepiness in patients with IH without long sleep time.Clinical Trial Registration: JapicCTI; 142539. [ABSTRACT FROM AUTHOR]

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

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]

Background: Patients with unipolar depressive disorder are frequently hospitalized, and the period following discharge is a high-risk-period. Smartphone-based treatments are receiving increasing attention among researchers, clinicians, and patients. We aimed to investigate whether a smartphone-based monitoring and treatment system reduces the rate and duration of readmissions, more than standard treatment, in patients with unipolar depressive disorder following hospitalization.Methods: We conducted a pragmatic, investigator-blinded, randomized controlled trial. The intervention group received a smartphone-based monitoring and treatment system in addition to standard treatment. The system allowed patients to self-monitor symptoms and access psycho-educative information and cognitive modules. The patients were allocated a study-nurse who, based on the monitoring data, guided and supported them. The control group received standard treatment. The trial lasted six months, with outcome assessments at 0, 3, and 6 months.Results: We included 120 patients with unipolar depressive disorder (ICD-10). Intention-to-treat analyses showed no statistically significant differences in time to readmission (Log-Rank p=0.9) or duration of readmissions (B=-16.41,95%CI:-47.32;25.5,p=0.3) (Primary outcomes). There were no differences in clinically rated depressive symptoms (p=0.6) or functioning (p=0.1) (secondary outcomes). The intervention group had higher levels of recovery (B=7,29, 95%CI:0.82;13,75,p=0.028) and a tendency towards higher quality of life (p=0.07), wellbeing (p=0,09) satisfaction with treatment (p=0.05) and behavioral activation (p=0.08) compared with the control group (tertiary outcomes).Limitations: Patients and study-nurses were unblinded to allocation.Conclusions: We found no effect of the intervention on primary or secondary outcomes. In tertiary outcomes, patients in the intervention group reported higher levels of recovery compared to the control group. [ABSTRACT FROM AUTHOR]

Background Context: Microendoscopic spinal surgery has demonstrated efficacy and is increasingly utilized as a minimally invasive approach to neural decompression, but there is a theoretical concern that bleeding and postoperative epidural hematoma (PEH) may occur with increased frequency in a contained small surgical field. Hemostatic agents, such as topical gelatin-thrombin matrix sealant (TGTMS), are routinely used in spine surgery procedures, yet there has been no data on whether PEH is suppressed by these agents when administered in microendoscopic spine surgery.Purpose: The purpose of this study was to investigate the effect of TGTMS on bleeding and PEH formation in lumbar micoroendoscopic surgery.Study Design: This is a randomized controlled trial (RCT) with additional prospective observational cohort.Patient Sample: Patients were registered from July 2017 to September 2018 and a hundred and three patients undergoing microendoscopic laminectomy for lumbar spinal stenosis at a single institution were enrolled in this study.Outcome Measures: The primary outcome was the drainage volume within 48 hours after surgery. Secondary outcomes were the numerical rating scale (NRS) of leg pain on the second (NRS2) and seventh day (NRS7) after surgery and the hematoma area ratio (HAR) in horizontal images on magnetic resonance image (MRI).Methods: In the RCT, 41 cases that received TGTMS (F group) were compared with 41 control group cases (C group) that did not receive TGTMS at the end of the procedure. Drainage volume, NRS2, NRS7, and HAR on MRI were evaluated. Nineteen cases were excluded from the RCT (I group) due to difficulty of hemostasis during surgery and the intentional use of TGTMS for hemostasis. I group was compared with C group in the drainage volume and NRS of leg pain as a prospective observational study.Results: The RCT demonstrated no statistically significant difference in drainage volume between those receiving TGTMS (117.0±71.7; mean±standard deviation) and controls (125.0±127.0; p=.345). The NRS2 and NRS7 was 3.5±2.6 and 2.8±2.5 in the F group, respectively, and 3.1±2.6 and 2.1±2.3 in the C group, respectively. The HAR on MRI was 0.19±0.19 in the F group and 0.17±0.13 in the C group. There was no significant difference in postoperative leg pain and HAR (p=.644 for NRS2, p=.129 for NRS7, and p=.705 for HAR). In the secondary observational cohort, the drainage volume in the I group was 118.3±151.4, and NRS2 and NRS7 was 3.5±2.0 and 2.6±2.6, respectively. There were no statistically significant differences in drainage volume (p=.386) or postoperative NRS of leg pain between these two groups (p=.981 and .477 for NRS2 and NRS7, respectively).Conclusions: The prophylactic use of TGTMS in patients undergoing microendoscopic laminotomy for lumbar spinal stenosis did not demonstrate any difference in postoperative bleeding or PEH. Nonetheless, for patients that had active bleeding that required the use of TGTMS, there was no evidence of difference in postoperative clinical outcomes relative to controls. [ABSTRACT FROM AUTHOR]

Objectives: To examine the effects of an empowerment-based intervention on health-related knowledge and resilience among patients after coronary artery stent implantation.Methods: This was a randomized controlled trial with a 4-week-long intervention. Participants were randomly allocated to an empowerment-based intervention group (n = 42) or control group (n = 43). Knowledge on CHD and resilience were evaluated and compared between groups.Results: Compared with the control group, patients in the intervention group showed higher score changes for CHD total knowledge (U = 196.500; P ＜ 0.001) and its 5 dimensions including CHD definition (U = 657.500; P = 0.022), manifestation (U = 245.000; P ＜ 0.001), examination (U = 639.000; P = 0.015), treatment (U = 475.000; P ＜ 0.001), and medication (U = 465.000; P ＜ 0.001), and higher level of resilience (t = 3.235; P = 0.002).Conclusion: The empowerment-based intervention was effective in enhancing the knowledge on CHD and improving resilience for patients with coronary artery stent implantation.Practice Implications: The structured empowerment-based intervention provides a basis for facilitating the use of this intervention in patients with coronary heart disease. [ABSTRACT FROM AUTHOR]

Background: A Growing body of literature indicates therapeutic effectiveness of mindfulness for mental disorders. Only few trials have been conducted with schizophrenia spectrum disorders (SSD), mostly in outpatient settings. Primary objective was to assess feasibility, acceptability, and preliminary outcomes of mindfulness-based group therapy (MBGT) for in-patients with SSD.Methods: A pre-registered randomized controlled trial was conducted to assess feasibility and acceptability of the MBGT. The primary outcome was mindfulness measured with the Southampton Mindfulness Questionnaire (SMQ). Secondary outcomes were rater-blinded positive- and negative symptoms, depression, social functioning, and self-reported mindfulness, depression, anxiety, psychological flexibility, quality of life, and medication regime at baseline, post-intervention, and follow-up (Clinical Trails NCT03671005).Results: 40 participants received either treatment-as-usual (TAU; n=19) or (MBGT+TAU; n = 21) for four weeks. At post-intervention, protocol adherence was 95.2%, and retention rate was 95%. ANCOVA revealed significant improvements in the MBGT+TAU for the primary outcome SMQ as well as negative symptoms at post-intervention between groups. In exploratory analyses, secondary outcomes showed medium-to-large pre-to-post-intervention effects on mindfulness, positive-, negative-, and depressive symptoms, psychological flexibility, quality of life, and social functioning for MBGT+TAU and small-to-moderate changes on positive symptoms and social functioning for TAU. No serious adverse effects were reported.Conclusions: MBGT appears feasible and acceptable for in-patient settings, with high protocol adherence and retention rates. Preliminary findings highlight a proof of concept of MBGT and various improvements in clinical- and process dimensions. A fully powered trial is warranted to determine efficacy, cost-efficiency, and longitudinal changes based on these promising outcomes. [ABSTRACT FROM AUTHOR]

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

Background: Major Depressive Disorder (MDD) has a major impact on public health. Reduction of depression burden in general population is of greatest importance and might be achieved by implementation of depression prevention measures into routine care. We evaluate an online prevention measure as part of a national project aiming to reduce depression in the occupational group of green professions.Methods: This two-armed pragmatic RCT (n = 360) evaluates the effectiveness of a tailored internet-based intervention (IMI) program compared to enhanced treatment as usual. The IMI program entailed access to one of six guided IMIs each focusing on different symptom areas (depressive mood with optional comorbid diabetes, perceived stress, insomnia, panic and agoraphobia and harmful alcohol consumption). Eligible were entrepreneurs, spouses, family members and pensioners in green professions with adequate insurance status and at least subthreshold depression (PHQ≥5). Primary outcome was depressive symptom severity (QIDS-SR16) at 9-weeks post-treatment (T1). Various secondary outcomes were assessed at T1.Results: A small effect of depression reduction (d=-0.28, 95%-CI: -0.50 to -0.07) was found at T1 favouring the IMI program (β=-0.22, 95%-CI: -0.41 to -0.02, p=.033). Categorical analysis indicated a reduced risk of potential MDD with NNTB=28.11. Adherence to the IMI program at T1 was exceptionally low.Limitations: Results are limited to green professions and representativeness might be restricted by self-selection of participants.Conclusion: Depression burden in green professions can be reduced by this online prevention measure. Yet, short-term effectiveness is restricted by low adherence rates.Trial Registration: German Clinical Trial Registration: DRKS00014000. Registered: 09 April 2018. [ABSTRACT FROM AUTHOR]

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

Objective: The aim of the study was to evaluate the clinical effectiveness of complementary treatment using self-applied electrotherapy treatment for pain control over the standard hormonal treatment alone for deep infiltrative endometriosis (DIE).Study Design: Multicentre randomized clinical trial. We included a hundred-one participants with DIE in electrotherapy (n = 53) (hormonal treatment + electrotherapy) or control group (n = 48) (only hormonal treatment) by 8 weeks of follow-up. The primary measurement was chronic pelvic pain (CPP) using a visual analogue scale (VAS) and deep dyspareunia. The secondary outcomes were the quality of life by endometriosis health profile (EHP-30) and sexual function by female sexual function index (FSFI).Results: CPP relief was observed only in the electrotherapy group (pre:7.11 ± 2.40, post:4.55 ± 3.08, p < 0.001). In terms of deep dyspareunia, improvements were observed for both groups (electrotherapy pre:2.02 ± 0.54-1.36 ± 0.96, p < 0.001; control pre:1.95 ± 0.86-1.68 ± 0.82, p = 0.006). Considering the secondary outcomes, a higher total score post-treatment for the EHP-30 was noted in both groups. Regarding sexual function, there was a statistically significant improvement in the FSFI score for the electrotherapy group (p < 0.001), with an increase in the scores for lubrication and pain domains (p = 0.013 and p < 0.001).Conclusions: Electrotherapy treatment using transcutaneous electrical nerve stimulation proved to be a good complementary option for pain control, showing benefits in the reduction of CPP and deep dyspareunia and improving patient's quality of life and sexual function. [ABSTRACT FROM AUTHOR]

Objectives: We applied principles for conducting economic evaluations of factorial trials to a trial-based economic evaluation of a cluster-randomized 2 × 2 × 2 factorial trial. We assessed the cost-effectiveness of atorvastatin, omega-3 fish oil, and an action-planning leaflet, alone and in combination, from a UK National Health Service perspective.Methods: The Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes (AFORRD) Trial randomized 800 patients with type 2 diabetes to atorvastatin, omega-3, or their respective placebos and randomized general practices to receive a leaflet-based action-planning intervention designed to improve compliance or standard care. The trial was conducted at 59 UK general practices. Sixteen-week outcomes for each trial participant were extrapolated for 70 years using the United Kingdom Prospective Diabetes Study Outcomes Model v2.01. We analyzed the trial as a 2 × 2 factorial trial (ignoring interactions between action-planning leaflet and medication), as a 2 × 2 × 2 factorial trial (considering all interactions), and ignoring all interactions.Results: We observed several qualitative interactions for costs and quality-adjusted life-years (QALYs) that changed treatment rankings. However, different approaches to analyzing the factorial design did not change the conclusions. There was a ≥99% chance that atorvastatin is cost-effective and omega-3 is not, at a £20 000/QALY threshold.Conclusions: Atorvastatin monotherapy was the most cost-effective combination of the 3 trial interventions at a £20 000/QALY threshold. Omega-3 fish oil was not cost-effective, while there was insufficient evidence to draw firm conclusions about action planning. Recently-developed methods for analyzing factorial trials and combining parameter and sampling uncertainty were extended to estimate cost-effectiveness acceptability curves within a 2x2x2 factorial design with model-based extrapolation. [ABSTRACT FROM AUTHOR]

Background: This report seeks to evaluate improvements in symptoms of irritability with sertraline (a selective serotonin reuptake inhibitor antidepressant) versus placebo.Methods: Participants of Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study who were randomized to 8 weeks of treatment with either sertraline or placebo and completed 5-item irritability domain of Concise Associated Symptom Tracking scale (CAST-IRR) at baseline were included (n = 292). Repeated measures mixed model analysis with CAST-IRR as the outcome variable and treatment arm-by-time interaction as the independent variable of interest evaluated whether changes in irritability with treatment differed between sertraline and placebo arms. A separate analysis controlled for levels of overall depression severity (17-item Hamilton Depression Rating Scale). Covariates included age, sex, race, ethnicity, and site.Results: There was a significant treatment arm-by-time interaction (F = 6.96, df = 6, 1418, p <0.0001) suggesting that changes in irritability with sertraline differed from placebo. The magnitude of reduction in irritability from baseline to week-8 was greater with sertraline than with placebo (Cohen's d effect size = 0.56). After controlling for levels of overall depression severity at each visit, reduction in irritability with time continued to be significant with sertraline but not with placebo.Limitations: Secondary analysis, limited generalizability, lack of non-serotonergic antidepressants.Discussion: There is greater improvement in irritability with sertraline than with placebo. Improvement in irritability with sertraline was independent of its effects on overall depression severity. CLINICALTRIALS.Gov Identifier: NCT01407094. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare the effect of ulipristal acetate (UPA) and gonadotropin-releasing hormone agonists (GnRHa) before laparoscopic myomectomy on long term secondary outcomes of the MYOMEX-trial, regarding quality of life, ultrasound characteristics, hemoglobin levels 6 weeks post-operative, sexual function and menstrual bleeding control. A cost-analysis was also performed. Short-term primary and secondary outcomes are reported elsewhere.Study Design: A double-blind, randomized, controlled, non-inferiority trial in nine hospitals in the Netherlands. Participants were randomized in a 1:1 ratio (block size of four, stratified per hospital) to either UPA or GnRHa pre-treatment. Additional placebo injections containing saline, respectively daily placebo tablets were given to both groups to ensure double-blinding. Surgery was performed within a month after the last tablet. Women were followed up until six months post-surgery.Results: A total of 55 participants were randomized: 30 to the UPA- and 25 to the GnRHa-group between May 2015 and July 2017. Uterine volume at six weeks post-operative did not differ significantly between both pre-treatment groups with 170.1 cm3 (106.8-243.5; N = 29) vs. 152.8 cm3 (92.3-205.6; N = 23) for the UPA- and GnRHa-group respectively (p = 0.423). Hemoglobin levels six weeks post-operatively recovered back to baseline and were not significantly different between groups with 7.7 mmol/L for the UPA- vs. 8.1 mmol/L for the GnRHa-group (p = 0.157; mean difference -0.4 (CI -0.9, 0.2). Menstrual bleeding pattern, quality of life, effects on general and sexual health showed a significant improvement compared to baseline in both groups without any differences between the treatment groups. Symptom severity scores also decreased significantly at 6 week post-operatively compared to baseline, but did not differ between the treatment groups. Fibroid characteristics at baseline (e.g. mean diameter of largest fibroid) appeared not to be a confounding factor. An exploratory cost analysis showed no significant differences in absenteeism costs, total healthcare and societal costs, after adjustment for confounding factors.Conclusion: Pre-treatment prior to laparoscopic myomectomy with UPA compared to GnRHa has similar effects on bleeding pattern, menopausal symptoms, sexual functioning, symptom severity and quality of life from baseline up to six months post-operative. Due to the small sample size, these findings should be interpreted with caution. Also, no firm conclusions on costs could be made. [ABSTRACT FROM AUTHOR]

Background: Outcome data after extended long-term follow-up of patients with coronary artery disease treated with drug-eluting stents (DES) in randomized clinical trials are scant.Objectives: Performance differences among devices may be expected to emerge over time depending on whether stenting is done with polymer-free or durable polymer DES. This study assessed the 10-year outcomes of patients enrolled in the ISAR-TEST-5 (Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus-Eluting Stents) trial.Methods: A total of 3,002 patients were randomized to treatment with either polymer-free sirolimus- and probucol-eluting stents (n = 2,002) or durable polymer zotarolimus-eluting stents (n = 1,000). The primary endpoint was the composite of cardiac death, target vessel-related myocardial infarction, or target lesion revascularization (a device-oriented composite endpoint [DOCE]). Additional endpoints of interest were the patient-oriented composite endpoint (POCE), including all-cause death, any myocardial infarction, or any revascularization; individual components of the composite endpoints; and definite or probable stent thrombosis.Results: The median age of the patients at randomization was 67.8 years. At 10 years, 63.9% of patients were alive. The rates of DOCE and POCE were high in both groups with no difference in the incidence between polymer-free sirolimus- and probucol-eluting stents and durable polymer zotarolimus-eluting stents (DOCE: 43.8% vs. 43.0%, respectively; hazard ratio: 1.01; 95% confidence interval [CI]: 0.89 to 1.14; p = 0.90; POCE: 66.2% vs. 67.7%, respectively; hazard ratio: 0.94; 95% CI: 0.86 to 1.04; p = 0.22). The rates of the individual components of the composite endpoints were comparable in both groups. The incidence of definite/probable stent thrombosis over 10 years was low and comparable in both groups (1.6% vs. 1.9%; hazard ratio: 0.85; 95% CI: 0.46 to 1.54; p = 0.58).Conclusions: At 10 years, there were no measurable differences in outcomes between patients treated with polymer-free versus durable polymer DES. The incidence of stent thrombosis was low and comparable in both groups. High overall adverse clinical event rates were observed during extended follow-up. (Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus-Eluting Stents [ISAR-TEST-5]; NCT00598533). [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether online resources developed to educate people about the risks associated with experimental stem cell (SC) treatments influence stroke survivors' attitudes about the safety and effectiveness of these treatments.Methods: Adult stroke survivors who had not previously received SC treatments (N = 112) were recruited from international stroke advocacy/support groups for a prospective, parallel-group randomized controlled trial. Participants indicated whether they were considering SC treatments (yes/no) prior to, immediately following, and 30-days after reading/viewing the International Society for Stem Cell Research booklet or Stem Cell Network video. Participant attitudes regarding the safety, effectiveness, accessibility and affordability of SC treatments were examined on each occasion, and compared to those of a waitlist control group.Results: Significantly fewer participants were considering SC treatments immediately after reading the SC research booklet (p =.031), although neither intervention had any impact after 30-days (p >.05). Waitlist and intervention groups reported positive attitudes toward SC treatments at each assessment.Conclusions: Stroke survivor attitudes toward SC treatments were initially influenced by the patient booklet, however these changes were not maintained.Practical Implications: Clinicians are encouraged to initiate discussions about experimental SC treatments during inpatient rehabilitation and to reinforce the risks throughout subsequent care. [ABSTRACT FROM AUTHOR]

Background: Postprandial inflammation that occurs concurrently with hyperglycemia and hyperlipidemia after ingestion of a high-saturated-fat, high-carbohydrate meal (HFCM) is a risk factor for cardiovascular disease (CVD). Numerous preclinical and clinical studies demonstrate anti-inflammatory effects of individual spices. However, the effect of consumption of a spice blend on inflammatory mediators has not been examined in a randomized controlled trial.Objectives: The objective of this study was to investigate the postprandial effect of a blend of spices in a HFCM on inflammatory cytokine responses.Methods: Nonsmoking men (40-65 y old) with overweight/obesity (25 ≤ BMI ≤ 35 kg/m2), elevated waist circumference (≥ 94 cm), and ≥ 1 CVD risk factor were recruited for a 3-period crossover study ( n = 12). In random order, participants consumed the following: a HFCM (∼1000 kcal, 33% kcal from saturated fat and 36% kcal from carbohydrate), a HFCM containing 2 g spice blend, or an HFCM containing 6 g spice blend. The spice blend consisted of basil, bay leaf, black pepper, cinnamon, coriander, cumin, ginger, oregano, parsley, red pepper, rosemary, thyme, and turmeric. Blood was collected before, and hourly for 4 h after the HFCM. Peripheral blood mononuclear cells (PBMCs) were isolated, and the percentage of CD14 +/Human Leukocyte Antigen-DR isotype + (HLA-DR +) monocytes and proinflammatory cytokine concentrations in plasma and LPS-stimulated PBMCs were quantified as secondary outcomes.Results: There was a significant spice-by-time interaction on IL-1β (P < 0.001), IL-8 (P = 0.020), and TNF-α (P = 0.009) secretion from LPS-stimulated PBMCs. IL-1β secretion from LPS-stimulated PBMCs was significantly reduced (1314%) at 240 min after HFCM consumption containing 6 g, but not 2 g, of spice blend compared with 0 g spice blend.Conclusions: A HFCM containing 6 g spice blend attenuated HFCM-induced postprandial IL-1β secretion in men with overweight/obesity.This trial was registered at clinicaltrials.gov as NCT03064958. [ABSTRACT FROM AUTHOR]

Hangovers are associated with negative economic consequences due to decreased job performance or frequent visits to physicians. Thus, a new strategy for the alleviation of hangover-related symptoms is needed to avoid this detriment to society. The purpose of this nationwide randomized, double-blind, placebo-controlled physicians' trial was to evaluate the efficacy of loxoprofen sodium for the alleviation of fatigue, headache, and nausea after hangover. A total of 229 participants were randomized to receive loxoprofen sodium (60 mg once orally) or placebo. The study was closed when the first 150 participants (n = 74 in the loxoprofen vs. n = 76 in the placebo groups) experienced hangovers. The primary endpoint was set as the difference in severity of general fatigue before and 3 h after taking the test drugs and was evaluated using a visual analogue scale. Secondary endpoints included difference in severity of headache, nausea, and incidence of adverse events. The study participants were 34 (interquartile range; 30-39) years old, 92.0% were men, and both groups were comparable for baseline characteristics. The alleviation of general fatigue did not differ statistically between the loxoprofen and placebo groups (24 [14-49] vs. 19 [9-35], p = 0.07). However, the alleviation of headache was statistically greater in the loxoprofen group (25 [10-50] vs. 10 [2-30], adjusted difference 14, 95% confidence interval 8-21, p < 0.001), whereas, there was no difference in nausea (7 [0-27] vs. 10 [0-24], p = 0.68). The incidence of adverse symptoms such as epigastric discomfort was also comparable between groups (2.7% vs. 3.9%, p = 0.25). Loxoprofen sodium was effective for relieving headaches after hangovers but did not alleviate general fatigue or nausea. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the preventive effects of low-dose aspirin on the incidence of preeclampsia and pregnancy outcomes of women at high-risk for preeclampsia.Study Design: This prospective randomized clinical trial was conducted at the Obstetrics Department of The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, China. It analyzed data from 1105 high-risk women who were divided into the control group (placebo group) and the aspirin group (including three subgroups: 25 mg, 50 mg and 75 mg). The aspirin group in this study was instructed to take aspirin daily before bedtime beginning in the 12th week of pregnancy.Main Outcome Measures: The primary outcome is the occurrence of preeclampsia. The secondary outcomes included maternal and neonatal outcomes (such as premature delivery, FGR etc.), maternal serum biomarkers (including d-dimers, platelet aggregation rates, etc.) and uterine arterial blood flow resistance. The onset of preeclampsia and pregnancy outcomes were recorded after all participants delivered.Results: Low-dose aspirin significantly reduced the incidence of preeclampsia and early-onset preeclampsia. Aspirin also showed significant dose dependence in preeclampsia prevention. The results of Mantel-Haenszel trend test showed that there was a linear relationship between the dosage and the incidence of preeclampsia and early preeclampsia (P < 0.05). Pearson's results showed that the incidence of preeclampsia and early preeclampsia was negatively correlated with aspirin dosage. There was also a linear relationship between the dosage and the rates of postpartum hemorrhage, fetal growth restriction, premature births and cesarean section (P < 0.05). There was no evidence to suggest differences in the incidence of fetal distress, miscarriage and placental abruption among the four groups. The blood resistance S/D value of uterine artery in early pregnancy was the only independent factor affecting the efficacy of aspirin (OR = 1.405; 95 %CI,1.058-1.867; P = 0.019).Conclusion: Low-dose aspirin can prevent preeclampsia and early-preeclampsia. Its efficacy is dose-dependent. It can reduce the rates of postpartum hemorrhage, fetal growth restriction, premature births and cesarean section. The prophylactic effect of aspirin on preeclampsia seemed to be greater in patients with higher blood resistance S/D value of uterine artery during early pregnancy. [ABSTRACT FROM AUTHOR]

Background: Evidence for antidepressant effects of L-Carnosine was shown in some experimental studies. In this study we tried to evaluate the efficacy and tolerability of L-Carnosine combination therapy in treatment of patients with major depressive disorder (MDD).Methods: Fifty-eight patients with MDD (DSM-V) and Hamilton Depression Rating Scale (HAM-D) score ≥ 19 were randomized to receive either 400 mg twice daily L-Carnosine or placebo in addition to citalopram (maximum dosage of 40 mg/day) for six weeks in a randomized double-blind, and placebo-controlled study. Patients were assessed using the HAM-D scale at baseline and weeks 2, 4, and 6.Results: Fifty-two patients completed the trial. General linear model repeated measure showed significant difference for time × treatment on HAM-D score [F = 3.17, df = 2.39, p-value = 0.03]. Significantly greater improvement was detected in HAM-D score of the L-Carnosine group compared with the placebo group from baseline to weeks 2, 4 and 6 [Ps = 0.013, 0.028 and 0.023; respectively]. Patients in the L-Carnosine group experienced significantly greater response and remission rate than the placebo group [Ps = 0.023 and 0.012; respectively]. There was no significant difference between the two groups in baseline parameters and frequency of side effects.Limitations: Short follow-up period and small population size were two important limitations of this study.Conclusions: L-Carnosine combination therapy with citalopram can effectively improve symptoms of patients with major depressive disorder. Rapid-onset antidepressant effects of L-Carnosine were also shown which need further investigation. [ABSTRACT FROM AUTHOR]

Background: Effects of very low carbohydrate (VLC) diets on appetite response in individuals with type 2 diabetes remain unclear.Objective: A secondary analysis was conducted to determine appetite responses to an energy-restricted [30% of energy (%E) deficit] very low carbohydrate (VLC) diet compared with a higher carbohydrate (HC) diet in adults who were overweight or obese with type 2 diabetes.Methods: Forty-four men and 40 women (mean ± SD, age: 58.7 ± 6.6 y; weight: 100.4 ± 15.5 kg; BMI: 34.5 ± 4.1 kg/m2; glycated hemoglobin: 7.3 ± 1.0%; duration of diabetes: 6.7 ± 5.6 y) were randomly assigned to diets categorized as VLC [14%E carbohydrate (<50 g/d), 28%E protein, 58%E fat (<10%E saturated fat)], or energy-matched HC [53%E carbohydrate, 17%E protein, 30%E fat (<10%E saturated fat)] combined with progressive multicomponent exercise (60 min; 3 d/wk). Body weight, average weekly "daily fasting" and "daily overall" appetite perceptions (hunger, fullness, prospective consumption, and desire to eat-visual analog scales) were assessed at baseline and after 4 and 16 wk. Changes between diets over time were assessed using repeated measures ANOVA.Results: Significant decreases in body weight did not differ between groups (VLC: -11.0 ± 5.4 kg/16 wk compared with HC: -10.1 ± 4.3 kg/16 wk, P = 0.40). Compared with HC, VLC had greater decreases in "daily overall" ratings of fullness (P time × diet < 0.01), such that scores were higher in HC at Week 4 (VLC:48 ± 3 vs HC:56 ± 3 mm, P = 0.001) and 16 (VLC:51 ± 2 vs HC:57 ± 3 mm, P = 0.019). Compared with HC, VLC had greater increases in prospective consumption ratings (P time × diet = 0.03), such that scores were lower in HC at Week 4 (VLC:33 ± 2 vs HC:28 ± 2 mm, P = 0.008), but not at Week 16 (VLC:33 ± 2 vs HC 31 ± 2 mm, P = 0.289).Conclusions: In the context of energy restriction, both HC and VLC energy-matched diets promoted comparable effects on fasting perceptions of appetite, but the HC diet resulted in greater "daily overall" fullness and reduced prospective consumption. Further research is required to evaluate the effects of ad libitum diets differing in amounts of carbohydrate on appetite response in populations with type 2 diabetes. This trial was registered at www.anzctr.org.au as ACTRN12612000369820. [ABSTRACT FROM AUTHOR]

Background: Internet-based intervention could help drug users recover from drug dependence. This study evaluated the effectiveness of a newly developed web-based relapse prevention program (e-SMARPP) for people with a drug problem, including the use of methamphetamine, in Japan.Methods: The study was a pilot randomized controlled trial comprised of 48 psychiatric outpatients diagnosed with drug use disorder. The participants were randomly assigned to an eight-week, six-session web-based relapse prevention program (an intervention group) or only web-based self-monitoring (a control group). The primary outcome was the duration of abstinence from a primary drug during the intervention and relapse risk. Secondary outcomes included motivation to change, self-efficacy, and money spent on drugs. The outcomes, except for the duration of abstinence during the intervention, were assessed at baseline, 2-, 5-, and 8-months. Program completion rate was also assessed.Results: No significant difference was observed between the intervention and the control groups for the primary and the secondary outcomes. The effect size of the duration of abstinence during the intervention was d = 0.42, which was comparable to previous studies. In the intervention group, about 26% did not complete the entire intervention.Conclusions: e-SMARPP failed to demonstrate efficacy, however, is potentially helpful for enhancing abstinence. The low attrition rate may suggest the acceptance and feasibility of the program. Further improvement of the program and evaluation in a full-scale trial are needed. [ABSTRACT FROM AUTHOR]

Context: Chronic breathlessness is a clinical syndrome that results in significant distress and disability. Morphine can reduce chronic breathlessness when the contributing etiologies are optimally treated.Objectives: Does oxycodone reduce chronic breathlessness compared with placebo?Methods: A multisite, randomized, placebo-controlled, double-blind, parallel-arm, fixed-dose trial of oral controlled-release oxycodone 15 mg (5 mg, eight hourly) or placebo (ACTRN12609000806268 at www.anzctr.org.au). As-needed immediate-release morphine (2.5 mg per dose; six and less doses/day) was available for both arms as required by one ethics committee overseeing the trial. Recruitment occurred from 2010 to 2014 in 14 inpatient and outpatient respiratory, cardiology, and palliative care services across Australia. Participants were adults, with chronic breathlessness (modified Medical Research Council Scale 3 or 4), who were opioid naive. The primary end point was the proportion of people with greater than 15% reduction from baseline in the intensity of breathlessness now (0-100 mm visual analogue scale) comparing arms Days 5-7. Secondary end points were average and worst breathlessness, quality of life, function, and harms.Results: Of 157 participants randomized, 155 were included (74 oxycodone and 81 placebo), but the study did not reach target recruitment. There was difference in neither between groups for the primary outcome (P = 0.489) nor any of the prespecified secondary outcomes. Placebo participants used more as-needed morphine (mean 7.0 vs. 4.2 doses; P ≤ 0.001). Oxycodone participants reported more nausea (P < 0.001).Conclusion: There was no signal of benefit from oxycodone over placebo. Future research should focus on investigating the existence of an opioid class effect on the reduction of chronic breathlessness. [ABSTRACT FROM AUTHOR]

Background: The pain of a burn mainly results from the inflammatory cascade that is induced by the injured tissue, and is classified as background, breakthrough, procedural and postoperative pain. High doses of opioids are usually needed to treat background pain, so its management includes a combination of types of analgesia to reduce the side effects. Lidocaine given intravenously has been shown in two small, uncontrolled studies to have an appreciable effect on pain after burns.Objectives: In this prospective double-blind controlled trial we aimed to examine and quantify the opioid-sparing effect of a continuous infusion of lidocaine for the treatment of background pain during the early period after a burn.Methods: Adult patients injured with burns of >10 total body surface area burned (TBSA%) and treated with a morphine based patient-controlled analgesia device (PCA) were randomised to have either lidocaine infusion starting with a bolus dose (1 mg lidocaine/kg) followed by continuous infusion (180 mg lidocaine/hour) or a placebo infusion, for seven consecutive days. Total daily consumption of opioids (mg) and amount of pain (visual analogue score, VAS) were recorded.Results: We included 19 patients, 10 of whom were given a lidocaine infusion. There were no differences between groups in VAS, TBSA%, time of enrolment to the study since the initial burn, or duration of hospital stay. The opioid consumption in the lidocaine group declined by roughly 25% during the period of the study.Conclusion: An intravenous infusion of lidocaine was safe and had an opioid-sparing effect when treating background pain in burns. [ABSTRACT FROM AUTHOR]