Search

Postpartum depression (PPD) poses significant challenges, affecting both mothers and children, with substantial societal and economic implications. Internet-based cognitive behavioral therapy interventions (iCBT) offer promise in addressing PPD, but their economic impact remains unexplored. This study aimed to evaluate the cost-utility of Be a Mom, a self-guided iCBT intervention, compared with a waiting-list control among postpartum women at high risk of PPD. This economic evaluation was conducted alongside a 14-month randomized controlled trial adopting a societal perspective. Participants were randomized to Be a Mom (n = 542) or a waitlisted control group (n = 511). Self-report data on healthcare utilization, productivity losses, and quality-adjusted life years (QALYs) were collected at baseline, post-intervention, and 4 and 12 months post-intervention. Incremental cost-effectiveness ratios (ICERs) were calculated, and cost-effectiveness acceptability curves were generated using nonparametric bootstrapping. Sensitivity analyses were conducted to assess result robustness. Over 14 months, Be a Mom generated a QALY gain of 0.0184 (0.0022, 0.0346), and cost savings of EUR 34.06 (−176.16, 108.04) compared to the control group. At a willingness to pay of EUR 20,000, Be a Mom had a 97.6 % probability of cost-effectiveness. Results have limitations due to self-selected sample, potential recall bias in self-reporting, missing data, limited follow-up, and the use of a waiting-list control group. This study addresses a critical gap by providing evidence on the cost-utility of an iCBT intervention tailored for PPD prevention. Further research is essential to identify scalable and cost-effective interventions for reducing the burden of PPD. • First randomized trial on cost-utility of iCBT for prevention of PPD • Compared to the control group, the intervention yielded more QALYs and less costs over 14 months. • The intervention had a 97.6 % probability of cost-effectiveness at a WTP of EUR 20,000. • iCBT has the potential to be adopted as a cost-effective preventive strategy for PPD. [ABSTRACT FROM AUTHOR]

In an inpatient treatment center for pediatric obesity, the effectiveness of an emotion regulation (ER) training on top of the multidisciplinary obesity treatment (MOT) was tested by means of an RCT. The ER training was evaluated on primary outcomes: ER and emotional eating, and secondary outcomes: well-being and weight loss, taking into account pre, post, and follow-up measurements. Of the 115 10- to-14-year old adolescents with obesity (52.2% girls), 65 were allocated to the ER training. Physicians measured their height and weight objectively (4 times). Participants also filled out questionnaires on ER competencies (ER abilities and ER strategies), emotional eating and well-being (3 times). Significant pre-post interactions were found for "emotional awareness," "problem solving," and "evoking a positive mood." Moreover, the positive effects of the ER training on emotion regulation strategies were maintained at follow-up. Concerning well-being, no significant pre-post interaction effects were found but a significant interaction effect was found when comparing pre with follow-up. Analyses show a significant main effect of time on weight loss, but this was not qualified by a Time × Condition interaction effect. The current RCT study shows limited but promising effects of adding an ER training to the MOT. Further research should investigate whether the positive short-term effects will be maintained. [ABSTRACT FROM AUTHOR]

Preclinical studies support a protective role for aspirin in early diabetic retinopathy (DR), but the findings from randomized trials are limited. We present randomized evidence for the efficacy and safety of aspirin on DR outcomes. A substudy of the A Study of Cardiovascular Events in Diabetes (ASCEND) double-masked, randomized, placebo-controlled trial of 100 mg aspirin daily for the primary prevention of serious cardiovascular events in people with diabetes. Fifteen thousand four hundred eighty United Kingdom adults at least 40 years of age with diabetes. Linkage to electronic National Health Service Diabetic Eye Screening Programme records in England and Wales and confirmation of participant-reported eye events via medical record review were carried out. Log-rank methods were used for intention-to-treat analyses of time until the first primary efficacy and safety outcomes. The primary efficacy end point was the first record of referable disease after randomization, a composite of referable retinopathy or referable maculopathy based on the grading criteria defined by the United Kingdom National Screening Committee. The primary safety outcome was the first sight-threatening eye bleed, defined as clinically significant bleeding in the eye that resulted in unresolved visual loss or required an urgent intervention such as laser photocoagulation, vitreoretinal surgery, intraocular injection, or a combination thereof. Linkage data were obtained for 7360 participants (48% of those randomized in ASCEND). During the mean follow-up of 6.5 years, 539 participants (14.6%) experienced a referable disease event in the aspirin group, compared with 522 participants (14.2%) in the placebo group (rate ratio, 1.03; 95% confidence interval [CI], 0.91–1.16; P = 0.64). No statistically significant between-group difference was found in the proportions of sight-threatening eye bleed events (57 participants [0.7%] and 64 participants [0.8%], respectively; rate ratio, 0.89; 95% CI, 0.62–1.27). These data exclude any clinically meaningful benefits of aspirin for DR, but give reassurance regarding the ophthalmologic safety of aspirin. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

To determine whether primary trabeculectomy or medical treatment produces better outcomes in terms of quality of life (QoL), clinical effectiveness, and safety in patients with advanced glaucoma. Multicenter randomized controlled trial. Between June 3, 2014, and May 31, 2017, 453 adults with newly diagnosed advanced open-angle glaucoma in at least 1 eye (Hodapp classification) were recruited from 27 secondary care glaucoma departments in the United Kingdom. Two hundred twenty-seven were allocated to trabeculectomy, and 226 were allocated medical management. Participants were randomized on a 1:1 basis to have either mitomycin C-augmented trabeculectomy or escalating medical management with intraocular pressure (IOP)-reducing drops as the primary intervention and were followed up for 5 years. The primary outcome was vision-specific QoL measured with the 25-item Visual Function Questionnaire (VFQ-25) at 5 years. Secondary outcomes were general health status, glaucoma-related QoL, clinical effectiveness (IOP, visual field, and visual acuity), and safety. At 5 years, the mean ± standard deviation VFQ-25 scores in the trabeculectomy and medication arms were 83.3 ± 15.5 and 81.3 ± 17.5, respectively, and the mean difference was 1.01 (95% confidence interval [CI], –1.99 to 4.00; P = 0.51). The mean IOPs were 12.07 ± 5.18 mmHg and 14.76 ± 4.14 mmHg, respectively, and the mean difference was –2.56 (95% CI, –3.80 to –1.32; P < 0.001). Glaucoma severity measured with visual field mean deviation were –14.30 ± 7.14 dB and –16.74 ± 6.78 dB, respectively, with a mean difference of 1.87 (95% CI, 0.87–2.87 dB; P < 0.001). Safety events occurred in 115 (52.2%) of patients in the trabeculectomy arm and 124 (57.9%) of patients in the medication arm (relative risk, 0.92; 95% CI, 0.72–1.19; P = 0.54). Serious adverse events were rare. At 5 years, the Treatment of Advanced Glaucoma Study demonstrated that primary trabeculectomy surgery is more effective in lowering IOP and preventing disease progression than primary medical treatment in patients with advanced disease and has a similar safety profile. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Pregnant women often experience anxiety due to pregnancy, negatively impacting their and their fetus' health. Non-pharmacological interventions, such as virtual reality (VR), could reduce anxiety levels, potentially impacting non-stress tests or the physiological responses of the pregnant woman and the fetus. A randomized clinical trial conducted between February and December 2022 involved 286 term pregnant women. They were divided into a VR intervention group (146 women) and a control group (140 women). The intervention consisted of 20 min of 3D glasses with images and sounds during a third-trimester nonstress test. Anxiety was measured using the Spielberg State-Trait Anxiety Inventory (STAI), alongside physiological parameters. The VR group exhibited lower anxiety levels compared to controls (STAI score: Rosenthal's r: −0.54, p = 0.01; state anxiety: Rosenthal's r: −0.40, p = 0.001; trait anxiety: Rosenthal's r: −0.41, p = 0.001). Within the VR group, there was a significant reduction in trait anxiety (Rosenthal's r, 1.27; p < 0.001) and total anxiety (Rosenthal's r, 1.63; p < 0.001) post-intervention, along with decreased systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), and maternal heart rate (p = 0.02). Future research could explore additional pregnancy-related variables, such as postpartum anxiety. The results confirm that the use of VR is beneficial for pregnant women and their fetuses, as it decreases anxiety levels, and improves physiological parameters such as blood pressure and maternal heart rate during the nonstress test. VR is a technique that is easy to integrate into the healthcare system due to its non-invasive and non-pharmacological nature. • Virtual reality has proven to be an effective technique in reducing anxiety of pregnant women during NST. • Anxiety is related to higher blood pressure and heart rate values in pregnant women during NST. • Blood pressure and heart rate in pregnant women improved when virtual reality was used as a therapy. [ABSTRACT FROM AUTHOR]

Depressed patients who have become victim of violence are prone to revictimization. However, no evidence-based interventions aimed at reducing revictimization in this group exist. This multicenter randomized controlled trial evaluated the effectiveness of an internet-based emotion regulation training (iERT) added to TAU in reducing revictimization, emotion dysregulation, and depressive symptoms in recently victimized, depressed patients compared to TAU alone. Adult outpatients (N = 153) with a depressive disorder who had experienced threat, physical assault, or sexual assault within the previous three years were randomly allocated to TAU+iERT (n = 74) or TAU (n = 79). TAU involved psychotherapy (mainly cognitive behavioral therapy [77.8 %]). iERT comprised six guided online sessions focused on the acquisition of adaptive emotion regulation skills. The primary outcome measure was the number of revictimization incidents at 12 months after baseline, measured with the Safety Monitor. Analyses were performed according to the intention-to-treat principle. Both groups showed a large decrease in victimization incidents. Mixed-model negative binomial regression analyses showed that TAU+iERT was not effective in reducing revictimization compared to TAU (IRR = 0.97; 95%CI = 0.64,1.46; p =.886). Linear mixed-model analyses demonstrated that TAU+iERT yielded a larger reduction of emotion dysregulation (B = −7.217; p =.046; Cohens d = 0.33), but not depressive symptoms (B = −1.041; p =.607) than TAU. The study was underpowered to detect small treatment effects. Additionally, uptake of iERT was quite low. Although TAU+iERT resulted in a larger decrease of emotion dysregulation than TAU alone, it was not effective in reducing revictimization and depressive symptoms. Patients' revictimization risk substantially decreased during psychotherapy. • Online emotion regulation training improved emotion regulation in depressed patients. • iERT did not reduce revictimization rates or depressive symptoms compared to TAU. • Violent victimization rates decreased substantially during psychotherapy. [ABSTRACT FROM AUTHOR]

Ivermectin is an antiparasitic drug administered to hundreds of millions of people worldwide. Fundamental research suggests that ivermectin is effective against coronavirus disease 2019 (COVID-19); therefore, we investigated the efficacy and safety of ivermectin as a COVID-19 treatment option. This multi-regional (Japan and Thailand), multicenter, placebo-controlled, randomized, double-blind, parallel-group, Phase III study evaluated the efficacy and safety of ivermectin in patients with mild COVID-19 (IVERMILCO Study). The participants took a specified number of the investigational product (ivermectin or placebo) tablets of, adjusted to a dose of 0.3–0.4 mg/kg, orally on an empty stomach once daily for three days. The primary efficacy endpoint was the time at which clinical symptoms first showed an improving trend by 168 h after investigational product administration. A total of 1030 eligible participants were assigned to receive the investigational product; 502 participants received ivermectin and 527 participants received a placebo. The primary efficacy endpoint was approximately 96 h (approximately four days) for both ivermectin and placebo groups, which did not show statistically significant difference (stratified log-rank test, p = 0.61). The incidence of adverse events and adverse drug reactions did not show statistically significant differences between the ivermectin and placebo groups (chi-square test, p = 0.97, p = 0.59). The results show that ivermectin (0.3–0.4 mg/kg), as a treatment for patients with mild COVID-19, is ineffective; however, its safety has been confirmed for participants, including minor participants of 12 years or older (IVERMILCO Study ClinicalTrials.gov number, NCT05056883.). [ABSTRACT FROM AUTHOR]

Our aim is to investigate the effects of the submucoperichondrial application of Platelet Rich Plasma (PRP) on nasal mucosal healing after septoplasty surgery. This prospective randomized observational study was conducted between July 2019 and February 2021, with 40 patients aged 18–60 years who underwent closed the only septoplasty operation for similar septal deviations. Patient divided into two group; 21 patients were placed in PRP group to which PRP was applied on all mucosal surface and submucoperichondrial area of septum and 19 patients were placed in control group to which saline solution was applied on same regions. Nasal obstruction score, mucociliary clearance time, presence of nasal crusting, and bleeding time were evaluated on 5th, 10th, 15th day after surgery and compared between groups. Intranasal crusting on day 10 was found to be lower in the PRP group (n :13 68.4 %) than control group (n :7 33.3 %) with a statistically significant difference (p = 0.028). The nasal obstruction score on day 10 and 15 were found to be lower in the PRP group (3,33 ± 2,75, 2,07 ± 2,20) (than the control group (5,44 ± 2,26, 3,37 ± 1,92) with a statistically significant difference (p = 0,003, p = 0,009). The mucociliary clearance rate was found to be higher and the bleeding time was found to be lower in the PRP group, but a statistically significant difference was not observed. Application of submucoperichondrial PRP could have beneficial effects on nasal mucosal repair, nasal crusting, and congestion after septoplasty surgery. [ABSTRACT FROM AUTHOR]

[Display omitted] • First trial using tDCS for Parkinsońs disease-related pain has been performed. • tDCS alleviates perceived pain and increases descending inhibitory systems in Parkinsońs disease patients. • Conditioned Pain Modulation could mediate pain relief in Parkinsońs disease. To evaluate the effects of transcranial direct current stimulation (tDCS) on Parkinson's disease (PD)-related pain. This triple-blind randomized controlled trial included twenty-two patients (age range 38–85, 10 male) with PD-related pain. Eleven subjects received ten sessions of 20 minutes tDCS over the primary motor cortex contralateral to pain at 2 mA intensity. Eleven subjects received sham stimulation. Outcome measures included changes in the Kinǵs Parkinsońs Pain Scale (KPPS), Brief Pain Inventory (BPI), widespread mechanical hyperalgesia (WMH), temporal summation of pain (TS), and conditioned pain modulation (CPM). Significant differences were found in KPPS between groups favoring the active-tDCS group compared to the sham-tDCS group at 15-days follow-up (p = 0.014) but not at 2 days post-intervention (p = 0.059). The active-group showed significant improvements over the sham-group after 15 days (p = 0.017). Significant changes were found in CPM between groups in favor of active-tDCS group at 2 days post-intervention (p = 0.002) and at 15 days (p = 0.017). No meaningful differences were observed in BPI or TS. tDCS of the primary motor cortex alleviates perceived PD-related pain, reduces pain sensitization, and enhances descending pain inhibition. This is the first study to test and demonstrate the use of tDCS for improving PD-related pain. [ABSTRACT FROM AUTHOR]

Preclinical studies support a protective role for omega-3 fatty acids (FAs) on diabetic retinopathy (DR), but these observations have not been confirmed in randomized trials. We present randomized evidence for the effects of omega-3 FAs on DR outcomes. A substudy of the A Study of Cardiovascular Events iN Diabetes (ASCEND) double-blind, randomized, placebo-controlled trial of 1 g omega-3 fatty acids (containing 460 mg eicosapentaenoic acid and 380 mg docosahexaenoic acid) daily for the primary prevention of serious cardiovascular events, in 15 480 UK adults at least 40 years of age, with diabetes. Fifteen thousand four hundred eighty adults at least 40 years of age from the United Kingdom with diabetes from the ASCEND cohort. Linkage to electronic National Health Service Diabetic Eye Screening Programme records in England and Wales and confirmation of participant-reported eye events via medical record review. Log-rank and stratified log-rank methods were used for intention-to-treat analyses of time until the main outcomes of interest. The primary efficacy endpoint was time to the first postrandomization recording of referable disease, a composite of referable retinopathy (R 2 or R 3a/s) or referable maculopathy (M 1) based on the grading criteria defined by the United Kingdom National Screening Committee. Secondary and tertiary outcomes included the referable disease outcome stratified by the severity of DR at baseline, any progression in retinopathy grade, and incident diabetic maculopathy. Linkage data were obtained for 7360 participants (48% of those who were randomized in ASCEND). During their mean follow-up of 6.5 years, 548 participants (14.8%) had a referable disease event in the omega-3 FAs group, compared with 513 participants (13.9%) in the placebo group (rate ratio, 1.07; 95% confidence interval, 0.95–1.20; P = 0.29). There were no statistically significant between-group differences in the proportion of events for either of the secondary or tertiary outcomes. Representing the largest prospective test of its kind to date, these data exclude any clinically meaningful benefits of 1 g daily omega-3 FAs on DR. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

The pathophysiology and the potential risks of placental transfusion (PT) differ substantially in preterm infants, necessitating specific studies in this population. This study aimed to evaluate the safety and efficacy of PT in preterm infants from the perspective of long-term neurodevelopmental outcomes. We conducted a systematic literature search using placental transfusion, preterm infant, and its synonyms as search terms. Cochrane Central Register of Controlled Trials, Medline, and Embase were searched until March 07, 2023. Two reviewers independently identified, extracted relevant randomized controlled trials, and appraised the risk of bias. The extracted studies were included in the meta-analysis of long-term neurodevelopmental clinical outcomes using fixed-effects models. A total of 5612 articles were identified, and seven randomized controlled trials involving 2551 infants were included in our meta-analysis. Compared with immediate cord clamping (ICC), PT may not impact adverse neurodevelopment events. No clear evidence was found of a difference in the risk of neurodevelopmental impairment (risk ratio [RR]: 0.89, 95% confidence interval [CI]: 0.76 to 1.03, P = 0.13, I2 = 0). PT was not associated with the incidence of cerebral palsy (RR: 1.23, 95% CI: 0.59 to 2.57, P = 0.79, I2 = 0). Analyses showed no differences between the two interventions in cognitive, language, and motor domains of neurodevelopment. From the perspective of long-term neurodevelopment, PT at preterm birth may be as safe as ICC. Future studies should focus on standardized, high-quality clinical trials and individual participant data to optimize cord management strategies for preterm infants after birth. [ABSTRACT FROM AUTHOR]

Social disconnection is common and causes significant impairment in anxiety and depressive disorders, and it does not respond sufficiently to available treatments. The positive valence system supports social bond formation and maintenance but is often hyporesponsive in people with anxiety or depression. We conducted an experimental therapeutics trial to test the hypothesis that targeting positive valence processes through cognitive and behavioral strategies would enhance responsivity to social rewards, a core mechanism underlying social connectedness. Sixty-eight adults who endorsed clinically elevated anxiety and/or depression with social impairment were randomized 1:1:1 to 5 (n = 23) or 10 (n = 22) sessions of amplification of positivity (AMP) treatment or waitlist (n = 23). Pre- to posttreatment change in striatal activity (primary outcome) during social reward anticipation was measured using functional magnetic resonance imaging, and reactivity to a social affiliation task (secondary) and self-reported social connectedness (exploratory) were examined. Primary analyses compared AMP (doses combined) versus waitlist. A second aim was to compare the effects of different doses. AMP engaged the hypothesized treatment target, leading to greater striatal activation during anticipation of social rewards versus waitlist (d = 1.01 [95% CI = 0.42–1.61]; largest striatal volume). AMP yielded larger improvements in positive affect and approach behavior during the affiliation task (but not other outcomes) and social connectedness. Larger striatal and social connectedness increases were observed for 5-session versus 10-session AMP (d range = 0.08–1.03). Teaching people with anxiety or depression strategies to increase positive thoughts, behaviors, and emotions enhances activity in brain regions that govern social reward processing and promotes social connectedness. Social reward sensitivity may be a transdiagnostic target for remediating social disconnection. [ABSTRACT FROM AUTHOR]

Subjective support could ameliorate the adverse effect of (pre)frailty on depressive symptoms. However, there is scarce evidence regarding subjective support-focused intervention in preventing depression among (pre)frail community-dwelling older adults. This study aims to explore the effectiveness of subjective support-focused cognitive behavioral therapy (SS-CBT) in preventing depression among this group of population. A total of 100 community-dwelling (pre)frail older adults were recruited from six communities in a Chinese city and were randomized to an 8-week SS-CBT group or a wait-list control group. Depressive symptoms and subjective support were assessed at baseline (T0), and at 8 week (T1), 12 week (T2), 16 week (T3) after randomization. Generalized estimating equation was used to examine the effectiveness of SS-CBT on depressive symptoms and subjective support. Hierarchical linear regression models and Bootstrapping method were used to examine whether subjective support mediated the effectiveness of SS-CBT on depressive symptoms. Participants in SS-CBT group reported significant reduction in depressive symptoms (Wald χ 2 = 20.800, p < 0.001) and improvement in subjective support (Wald χ 2 = 92.855, p < 0.001) compared to those in wait-list control group. Changes in subjective support mediated the effectiveness of SS-CBT on changes in depressive symptoms. Restricted regions to recruit participants, inclusion of the most motivated participants, lack of diagnosis of depression, potential experimenter bias and contamination, short follow-up period, and lack of an active control group. The findings support the benefits of SS-CBT in preventing depression among (pre)frail community-dwelling older adults, and provide insight into possible mechanisms. • (Pre)frail older adults are more likely to experience depression. • Subjective support is effective in protecting depression. • Cognitive behavioral therapy has the potential to improve subjective support. [ABSTRACT FROM AUTHOR]

• ECT is effective but has cognitive side-effects; add-on treatments are needed. • No change was seen in complex cognitive processing with ECT or EPO. • EPO infusions during ECT led to faster autobiographical memory recall. • EPO reduced memory-related parietal cortex activity compared to saline. • Autobiographical memory may be a sensitive measure for ECT side-effects. Electroconvulsive therapy (ECT) is one of the most effective and rapid-acting treatment for severe depression but is associated with cognitive side-effects. Identification of add-on treatments that counteract these side-effects would be very helpful. This randomized, double-blinded, placebo-controlled, parallel-group study investigated the effects of four add-on erythropoietin (EPO; 40,000 IU/ml) or saline (placebo) infusions over 2.5 weeks of ECT (eight ECT sessions) in severely depressed patients with unipolar or bipolar depression. Neuropsychological assessments were conducted pre-ECT, three days after the eighth ECT (week 4), and at a 3-month follow-up. Further, functional magnetic resonance imaging (fMRI) was conducted after the eighth ECT. The primary outcome was change from pre- to post-ECT in a 'speed of complex cognitive processing' composite. Secondary outcomes were verbal and autobiographical memory. Of sixty randomized patients, one dropped out before baseline. Data were thus analysed for 59 patients (EPO, n = 33; saline, n = 26), of whom 28 had fMRI data. No ECT-related decline occurred in the primary global cognition measure (p s≥0.1), and no effect of EPO versus saline was observed on this outcome (p s≥0.3). However post-ECT, EPO-treated patients exhibited faster autobiographical memory recall than saline-treated patients (p = 0.02), which was accompanied by lower memory-related parietal cortex activity. The absence of global cognition changes with ECT and EPO, coupled with the specific impact of EPO on autobiographical memory recall speed and memory-related parietal cortex activity, suggests that assessing autobiographical memory may provide increased sensitivity in evaluating and potentially preventing cognitive side-effects of ECT. ClinicalTrials.gov: NCT03339596, EudraCT no.: 2016-002326-36. [ABSTRACT FROM AUTHOR]

Discrepancies between sleep diaries and actigraphy occur among individuals with insomnia. Cognitive behavioural therapy for insomnia (CBT-I) improves insomnia but the impact on discrepancy is unclear. This study examined CBT-I's effects on actigraphy-diary discrepancy and explored sleep-related beliefs and attitudes as a mediator. Participants were 108 (age M ± SD = 47.23 ± 12.42, 67.60 % female) adults with insomnia and major depressive disorder from the Treatment of Insomnia and Depression study. They were randomized to 7 sessions of CBT-I or sham Quasi-Desensitization Therapy for Insomnia (DTI), plus 16 weeks of antidepressants. Two weeks of actigraphy and sleep diary were collected at baseline, mid-treatment, end-treatment. Differences between sleep diary and actigraphy total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency (SE) were calculated. Participants completed Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS) at baseline and mid-treatment. At baseline, diary (versus actigraphy) TST was shorter (1.1 ± 1.41h), whilst SOL (21.64 ± 41.25min) and WASO (17.45 ± 61.99min) were longer. Mixed effects models using daily data showed that after adjusting for age and sex, participants in the CBT-I group (versus DTI) showed greater reduction in all actigraphy-diary discrepancy domains (all p-values <.01), reductions evident from mid-treatment. Group differences on actigraphy-diary discrepancy reductions in TST, SOL, and SE (not WASO) were mediated by changes in DBAS from baseline to mid-treatment (all p-values <.05). Changes in discrepancy did not mediate insomnia symptom changes (p-values >.39). CBT-I reduced actigraphy-diary discrepancy in individuals with comorbid insomnia and depression; this reduction was associated with improved sleep-related attitudes, a therapeutic target of CBT-I. TRIAD (Treatment of Insomnia and Depression): Improving Depression Outcome by Adding Insomnia Therapy to Antidepressants. Prospectively registered with Clinical Trials (NCT00767624). MH078924, MH078961, MH079256. • Individuals with insomnia and depression reported shorter and worse sleep compared to actigraphy measures. • CBT-I reduced actigraphy-diary discrepancy in these individuals. • Discrepancy reduction was associated with improved sleep-related attitudes and beliefs. [ABSTRACT FROM AUTHOR]

We evaluated if Insulin-like Factor 3, basal and human chorionic gonadotropin (hCG)-stimulated testosterone could predict beneficial effects of testosterone replacement among 69 testicular cancer survivors with mild Leydig cell insufficiency randomly assigned to testosterone replacement therapy or placebo. Although the patients with Insulin-like Factor 3 and hCG-stimulated testosterone below median at baseline had less fat mass after 12 months of testosterone replacement therapy compared with placebo, we cannot recommend testosterone replacement therapy in specific subgroups of men with mild Leydig cell insufficiency. Introduction: Mild Leydig cell insufficiency affects a substantial proportion of testicular cancer survivors. Previous studies have not shown a beneficial effect of testosterone replacement therapy, however, with a pronounced interindividual effect. Thus, biomarkers identifying the subgroups that might benefit are wanted. We aimed to determine if insulinlike factor 3 (INSL3), basal and human chorionic gonadotropin (hCG)-stimulated testosterone can predict the effect of testosterone replacement therapy in testicular cancer survivors with mild Leydig cell insufficiency. Patients and Methods: We randomized adult testicular cancer survivors with mild Leydig cell insufficiency 1:1 to 12 months of transdermal testosterone replacement therapy (Tostran gel 2%) or placebo. INSL3, basal, and hCG-stimulated testosterone were measured at baseline. Outcomes (glucose, insulin, HbA1C, lipids, blood pressure, and body composition) were measured at baseline, 6 and 12 months. We applied a linear mixed-effect model comparing patients receiving testosterone with placebo in subgroups by biomarker. Results: We included and randomized 69 patients between October 2016 and February 2018. Patients with INSL3 and hCG-stimulated testosterone concentrations below the median had a -1.7 kg (95% CI: -3.1, -0.4) and -2.0 kg (95% CI: -3.5, -0.6) change in fat mass after 12 months of testosterone replacement therapy compared with placebo. This was not the case in patients with INSL3 and hCG-stimulated testosterone above the median. We did not find any effect of these biomarkers on glucose, insulin, HbA1c, or lipids. Conclusion: Patients with INSL3 and hCG-stimulated testosterone concentrations below the median had decreased fat mass after 1 12 months of testosterone replacement therapy compared with placebo. It should be evaluated in larger trials if these biomarkers can be used as predictive markers identifying testicular cancer patients with mild Leydig cell insufficiency who might benefit from testosterone substitution. [ABSTRACT FROM AUTHOR]

Insomnia is a significant health issue associated with various systemic diseases. Transcranial alternating current stimulation (tACS) has been proposed as a potential intervention for insomnia. However, the efficacy and mechanisms of tACS in chronic insomnia remain unclear. Accordingly, this study aimed to investigate the efficacy of tACS in treating chronic insomnia in adults and assess the impact of age on its effectiveness using a large sample from two centers. A total of 120 participants with chronic insomnia underwent 20 daily sessions of tACS (duration: 40 min, frequency: 77.5 Hz, and intensity: 15 mA) or sham tACS targeting the forehead and both mastoid areas over 4 weeks. Assessments were conducted at baseline, post-treatment, and 4-week follow-up. Primary outcomes included sleep quality and efficiency, onset latency, total sleep time, and daily disturbances. Secondary outcomes included depression, anxiety, and clinical impression. Compared with the control group, the tACS group demonstrated improved sleep quality and efficiency, increased total sleep time, and reduced daily disturbance (all ps < 0.01). Moreover, tACS had a significant effect on clinical impression (p < 0.001), but not depression and anxiety scores. Subgroup analyses revealed that older participants experienced significant benefits from tACS in sleep quality, efficiency, and overall insomnia reduction at post-treatment and follow-up (p < 0.001). Notably, improved insomnia correlated with attenuated depressive and anxiety symptoms. These findings suggest that tACS may be an effective intervention for chronic insomnia within an eight-week timeframe, and age affects the response to tACS in terms of insomnia improvement. • tACS improved sleep quality and efficiency. • tACS had a significant effect on clinical impression. • Older participants experienced significant benefits from tACS. • Improved insomnia correlated with attenuated depressive symptoms, anxiety symptoms and clinical impression. • tACS may be an effective intervention for chronic insomnia. [ABSTRACT FROM AUTHOR]

This paper summarizes the results of the Improving Mood with Psychoanalytic and Cognitive Therapies (IMPACT) study and its implications for psychological treatment of adolescents with moderate to severe unipolar major depression. IMPACT was a pragmatic, superiority, randomized controlled trial conducted in the United Kingdom, which compared the clinical and cost-effectiveness of short-term psychoanalytic therapy (STPP), cognitive−behavioral therapy (CBT), and a brief psychosocial intervention (BPI) in reducing depression symptoms in 465 adolescents with unipolar major depression, aged 11 to 17 years. Although this was a clinically heterogeneous group of adolescents, some symptoms (eg, sleep and concentration difficulties, irritability/anger) were common and disabling. The trial reported no significant difference among the 3 treatments in reducing depression symptoms. One year after treatment, 84% of participants showed improvement in depressive symptoms (<50% of baseline symptoms) and improved psychosocial functioning, achieving this through different symptom reduction trajectories. Although participants attended fewer treatment sessions than planned, the 3 treatments were delivered with fidelity to their respective models. Ending treatment without therapist agreement occurred in 37% of cases. This was not associated with outcomes by treatment group. Adolescents emphasized the importance of the therapeutic relationship in all 3 treatments. Results suggest that although most adolescents respond to time-limited, structured psychological therapy, subgroups of depressed adolescents are likely to need additional treatment or support. These include adolescents who live in complex circumstances and/or who believe that their needs are not met in therapy, some who stop treatment early, and the 16% to 18% of adolescents who do not respond to treatment. Improving Mood and Preventing Relapse With Psychoanalytic Psychotherapy and Cognitive Behaviour Therapy; https://www.isrctn.com ; ISRCTN83033550. [ABSTRACT FROM AUTHOR]

As the prevalence of tramadol toxicity is increasing, managing these patients with the aim of treatment and complete recovery has become a major challenge for health care professionals. This study evaluated the short-term effects of IV lipid emulsion (ILE) administration in cases of tramadol poisoning. In this double-blind, randomized controlled trial, 120 patients with pure tramadol poisoning and a Glasgow Coma (GCS) score ≤ 12 referred to a poisoning center in Tehran, Iran were selected and randomly assigned 1:1 to receive ILE 20% (intervention) or 0.9% saline (control) after admission and primary stabilization. The patient's vital signs, GCS score, hospitalization duration, and rate of seizure occurrence were recorded and compared between the two groups. Mean (SD) age of participants was 25.3 (5.4) years and 84 (70%) were male. Mean (SD) ingested dose of tramadol was 3118 (244) mg, which was not different between the groups. Compared with controls, the ILE group had a higher level of consciousness after treatment (median [interquartile range] GCS score 12 [10–13] vs. 10 [8–12]; p = 0.03). In addition, length of hospitalization (median [interquartile range] (2 [1–3] days vs. 4 [4–6] days; p < 0.01) and rate of seizure occurrence were lower in the intervention group (16/60 vs. 30/60; p < 0.01). In the setting of tramadol poisoning with a decreased level of consciousness and based on our study's findings, administration of ILE is suggested to help manage patients in hospital emergency departments. However, larger trials might be needed to confirm these findings before entering the guidelines. [ABSTRACT FROM AUTHOR]

Peripheral venous cannulation is one of the most common procedures in medicine. A larger cannula allows higher rates of fluid to be provided if needed in a deteriorating patient; however, it is also perceived that larger-gauge cannula placement is associated with increased pain and procedural difficulty. This study aimed to compare the pain and procedural difficulty experienced during insertion between 18-gauge (18G) and 20-gauge (20G) cannulas. We conducted a single-blinded, randomized controlled trial on adult patients who required peripheral IV cannulation within a tertiary hospital emergency department between April and October 2018. Patients were randomized to either the 18G or 20G cannula group. The primary outcomes of the study—pain experienced by patients and procedural difficulties experienced by clinical staff—were recorded on two separate 10-cm visual analog scales. Other outcomes include first-attempt success rate, operator designation, complications, and the intent and actual use of the IV cannula were documented on preformatted questionnaires. Data from 178 patients were included in the analysis. Eighty-nine patients were allocated to each cannula group. There were no statistically or clinically significant differences between mean pain score (0.23; 95% CI 0.56–1.02; p = 0.5662) and mean procedural difficulty score (0.12; 95% CI 0.66–0.93; p = 0.7396). between the two groups. There was no difference in first-attempt success rate (73 of 89 vs. 75 of 89; p = 0.1288), complications (2 of 89 vs. 1 of 89) between the 20G group and 18G group, respectively. There was no significant difference between the 18G or 20G cannula for either pain experienced by patients or procedural difficulty experienced by clinicians. [ABSTRACT FROM AUTHOR]

Endothelin receptor antagonist (ERA) and phosphodiesterase 5 inhibitor (PDE5i) combination therapy is recommended for low-/intermediate-risk pulmonary arterial hypertension (PAH) patients. A fixed-dose combination of the ERA macitentan and PDE5i tadalafil (M/T FDC) in a once-daily, single tablet would simplify treatment. The multicenter, double-blind, adaptive phase 3 A DUE study investigated the efficacy and safety of M/T FDC vs macitentan 10 mg and vs tadalafil 40 mg monotherapies in PAH patients, including treatment-naïve and prior ERA or PDE5i monotherapy-treated patients. World Health Organization functional class II-III patients were randomized to M/T FDC, macitentan, or tadalafil depending on their PAH treatment (treatment-naïve, ERA, or PDE5i monotherapy) at baseline. The primary endpoint was change in pulmonary vascular resistance (PVR) at week 16. In total, 187 patients were randomized to single-tablet M/T FDC (n = 108), macitentan (n = 35), or tadalafil (n = 44). PVR reduction with M/T FDC was significantly greater vs macitentan (29%; geometric mean ratio 0.71; 95% CL: 0.61-0.82; P < 0.0001) and vs tadalafil (28%; geometric mean ratio 0.72; 95% CL: 0.64-0.80; P < 0.0001). Three patients died in the M/T FDC arm (judged unrelated to treatment). Adverse events (AEs) leading to discontinuation, serious AEs, and those of special interest (anemia, hypotension, and edema) were more frequent with M/T FDC. Macitentan and tadalafil FDC significantly improved PVR vs monotherapies in PAH patients, with a safety and tolerability profile consistent with the individual components. The A DUE study supports M/T FDC as a once-daily, single-tablet combination for initial therapy and escalation to double combination therapy in patients with PAH. (Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension [PAH]) [A DUE]; NCT03904693) [Display omitted] [ABSTRACT FROM AUTHOR]

For most patients, direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prevention in atrial fibrillation and for venous thromboembolism treatment. However, randomized controlled trials suggest that DOACs may not be as efficacious or as safe as the current standard of care in conditions such as mechanical heart valves, thrombotic antiphospholipid syndrome, and atrial fibrillation associated with rheumatic heart disease. DOACs do not provide a net benefit in conditions such as embolic stroke of undetermined source. Their efficacy is uncertain for conditions such as left ventricular thrombus, catheter-associated deep vein thrombosis, cerebral venous sinus thrombosis, and for patients with atrial fibrillation or venous thrombosis who have end-stage renal disease. This paper provides an evidence-based review of randomized controlled trials on DOACs, detailing when they have demonstrated efficacy and safety, when DOACs should not be the standard of care, where their safety and efficacy are uncertain, and areas requiring further research. [Display omitted] • Target-specific (or direct) oral anticoagulants are preferred for prevention or treatment of thromboembolism in most patients with atrial fibrillation or venous thromboembolism. • DOACs should not be the standard treatment for patients with mechanical heart valves, atrial fibrillation with rheumatic mitral stenosis, or antiphospholipid syndrome. • The efficacy and safety of DOACs remain uncertain for several other clinical conditions and subgroups, and future studies should address those situations. [ABSTRACT FROM AUTHOR]

Up to 79 % of older adults with depression do not receive treatments commensurate with guideline recommendations. Metacognitive Training-Silver (MCT-Silver) is a low-intensity group training, which aims to reduce depressive symptoms by targeting (meta)cognitive beliefs. A randomized controlled trial comparing MCT-Silver (n = 41) to cognitive remediation (n = 39) was conducted with older adults with major depressive disorder and/or dysthymia. Clinician-rated depression (Hamilton Depression Rating Scale [HDRS, primary outcome]), self-reported depression (Beck Depression Inventory-II [BDI-II]), negative cognitive beliefs, positive metacognitive beliefs, rumination, health status, quality of life, and neurocognitive functioning were assessed at baseline, eight weeks (post) and three months (follow-up). Both groups demonstrated moderate to large reductions in depression. No superior effects of MCT-Silver on clinician-rated depression (HDRS) were detected. MCT-Silver led to greater reductions in self-reported depression and rumination at post- and follow-up. Despite this, scores at post- and follow-up assessments were similar for both groups. MCT-Silver's effect on depressive symptoms was moderated by baseline rumination, positive metacognitive beliefs and previous treatment experience. MCT-Silver was evaluated as superior according to patient appraisals. Conclusions are limited by divergent findings on measures of depression and that the study was conducted during the COVID-19 pandemic. Whereas no superior effect of MCT-Silver was found for the primary outcome, there was a significant effect of MCT-Silver for self-reported depression and rumination. Patients endorsing rumination and positive metacognitive beliefs as well as those without previous psychological treatment may benefit more from MCT-Silver. • We evaluated the efficacy of metacognitive training for depression in later life (MCT-Silver). • 80 patients were randomized to MCT-Silver or a cognitive remediation (CR) group. • MCT-Silver demonstrated statistically significant effects beyond CR on self-reported depression and rumination. • Despite statistically significant effects, total scores at post- and follow-up were similar between groups. [ABSTRACT FROM AUTHOR]

• We developed meaning-centered psychotherapy for eating disorders (MCP-ED). • The efficacy of MCP-ED was tested in women with high weight and shape concerns. • After MCP-ED and at follow-up, participants reported higher levels of life meaning. • MCP-ED also resulted in lower levels of eating disorder symptoms. • Future studies should test the effectiveness of MCP-ED in a clinical sample. Low meaning in life has been proposed as an important factor in the maintenance of eating disorders and previous findings suggest that targeting meaning might optimize treatment effectiveness. The current randomized controlled trial aimed to investigate the efficacy of meaning-centered psychotherapy adjusted for eating disorders (MCP-ED) to improve meaning in women with high weight and shape concerns. Female students with high weight and shape concerns (N = 134) were randomly assigned to the waiting-list control condition or the experimental condition, in which they followed six weekly individual sessions of MCP-ED. Self-report measures of meaning, eating disorder symptoms, general distress, psychological well-being, and satisfaction with meaningful life domains were completed at baseline, after the final session of MCP-ED or a 7-week waiting period, and at 4-week follow-up. Participants in the experimental condition showed a stronger increase in meaning than participants in the waiting-list condition after the intervention and at follow-up. The intervention also resulted in lower eating disorder symptoms and general distress, and higher psychological well-being and satisfaction with meaningful life domains. Findings support the efficacy of MCP-ED as an intervention to increase meaning and point to the relevance of examining whether adding MCP-ED to regular treatment might increase treatment effectiveness in individuals with eating disorders. [ABSTRACT FROM AUTHOR]

Current management guidelines for the treatment of carotid stenosis are controversial. We performed this meta-analysis to evaluate the perioperative safety of carotid artery stenting (CAS) and endarterectomy. We systematically searched EMBASE, PubMed, Web of Science, and the Cochrane Library from inception to November 10, 2022, for randomized controlled trials that compared CAS with carotid endarterectomy (CEA) among patients with carotid stenosis. The analyzed outcomes mainly included stroke, death, myocardial infarction (MI), cranial nerve palsy, the cumulative incidence of mortality, stroke, or MI and the cumulative incidence of death or stroke in the perioperative periods. The risk ratio (RR) and 95% confidence interval (95% CI) were calculated and pooled. Subgroup analyses were based on whether patients were symptomatic or asymptomatic. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Seventeen randomized controlled trials with 12,277 participants (6514 and 5763 in the CAS and CEA groups, respectively) were included. Pooled analysis demonstrated that compared with CEA, CAS was associated with decreased risks of perioperative MI (RR = 0.47, 95% CI = 0.29∼0.77) and perioperative cranial nerve palsy (RR = 0.02, 95% CI = 0.01∼0.06) but higher risks of perioperative stroke (RR = 1.48, 95% CI = 1.18∼1.87) and cumulative incidence of death or stroke (RR = 1.52, 95% CI = 1.20∼1.93). The perioperative safety was equivalent between CAS and CEA. However, CEA may be preferred when considering both procedural safety and long-term efficacy in preventing recurrent stroke. [ABSTRACT FROM AUTHOR]

To determine whether early switch to oral antibiotic treatment in adults with neutropenic sepsis at low risk of complications is non-inferior to switching later. This non-inferiority, parallel-group, randomized, open-label clinical trial enrolled UK adults hospitalized with neutropenic sepsis. Participants were randomly assigned to either switch to oral ciprofloxacin plus co-amoxiclav within 12–24 hours or to continue intravenous treatment for at least 48 hours. The primary outcome was a composite measure of treatment failure, 14 days after randomization. The non-inferiority margin was 15%. There were 129 participants from 16 centres and 125 were assessed for the primary outcome. Of these, 113 patients completed protocolized treatment and comprised the per-protocol population. In total, 9 (14.1%) of 64 patients in the standard care arm met the primary end point, compared with 15 (24.6%) of 61 in the early switch arm, giving a risk difference of 10.5% (1-sided 95% CI, −∞% to 22%; p 0.14). In the per-protocol population, 8 (13.3%) of the 60 patients in the standard care arm met the primary end point, compared with 9 (17%) of 53 in the intervention arm giving a risk difference of 3.7% (one-sided 95% CI, −∞% to 14.8%; p 0.59). Duration of hospital stay was shorter in the intervention arm (median 2 [inter-quartile range (IQR) 2–3] vs. 3 days [IQR 2–4]; p 0.002). Although non-inferiority of early oral switch was found in the per-protocol population, the intervention was not non-inferior in the intent-to-treat population. [ABSTRACT FROM AUTHOR]

Early adverse parenting predicts various negative outcomes, including psychopathology and altered development. Animal work suggests that adverse parenting might change amygdala–prefrontal cortex (PFC) circuitry, but work in humans remains correlational. The present study leveraged data from a randomized controlled trial examining the efficacy of an early parenting intervention targeting parental nurturance and sensitivity (Attachment and Biobehavioral Catch-up [ABC]) to test whether early parenting quality causally affects amygdala-PFC connectivity later in life. Participants (N = 60, mean age = 10.0 years) included 41 high-risk children whose parents were referred by Child Protective Services and randomly assigned to receive either ABC (n = 21) or a control intervention (n = 20) during the children's infancy and a comparison sample of low-risk children (n = 19). Amygdala-PFC connectivity was assessed via functional magnetic resonance imaging while children viewed fearful and neutral faces. Across facial expressions, ABC produced different changes than the control intervention in amygdala-PFC connectivity in response to faces. The ABC group also exhibited greater responses than the control intervention group to faces in areas classically associated with emotion regulation, including the orbitofrontal cortex and right insula. Mediation analysis suggested that the effect of ABC on PFC activation was mediated by the intervention's effect on amygdala-PFC connectivity. Results provide preliminary causal evidence for the effect of early parenting intervention on amygdala-PFC connectivity and on PFC responses to face viewing. Findings also highlight amygdala-PFC connectivity as a potential mediator of the effects of early parenting intervention on children's emotion regulation development. Intervening Early With Neglected Children; https://clinicaltrials.gov/ ; NCT02093052. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. [ABSTRACT FROM AUTHOR]

People with HIV (PHW) are at greater risk of depression than the general population. Insight into the time-to-treatment-response and predictors of response to psychotherapy may improve implementation in primary care. We assessed depression treatment response among 80 participants in a trial of cognitive-behavioral therapy for adherence and depression (CBT-AD) for PWH with MDD and suboptimal antiretroviral therapy (ART) adherence. Participants self-reported depressive symptoms (CES D) at each therapy session. Clinicians assessed participants' depression (HAM D), along with potential predictors of response, every four months for one year. Latent class analyses examined classes of responders for the active and the post-treatment phases. Regression analyses identified predictors of class membership for each phase. During the active treatment phase (CES D) we identified an early response (at session 2 and with continued trajectory of improvement) and a non-response group. There were also two classes during post-treatment (HAM-D): early responders (4-month) and late responders (12-month). Distress aversion was associated with lower likelihood of early response to CBT-AD (aOR = 0.74, 95%CI[0.56–0.90], p =.009), and social support was associated with increased likelihood of early response (aOR = 2.24, 95%CI[1.07–5.46], p =.045). Self-reported depression during the treatment phase may have resulted from social desirability bias. Most participants responded to CBT-AD early during treatment (89 %) and had sustained improvements in depression by 4 months (80 %). Distress aversion was a risk factor for late response, and social support was protective. Future research is needed to assess the optimal dose of CBT-AD in resource limited settings. • Cognitive Behavioural Therapy effectively treats depression and adherence in Persons with HIV. It therefore improves rates of viral suppression, more than treatment as usual. • Early self-reported improvements in depression most likely are the result of being in a trial. Improvement continued to occur throughout the acute treatment phase. • Clinician-rated depression over 4, 8 and 12 months also occurred, with steep improvement seen at 4 months. • Whether or not shorter durations of therapy, delivered by nurses, is effective remains to be explored. [ABSTRACT FROM AUTHOR]

• Heart failure with mildly reduced or preserved ejection fraction (HFpEF, HFmrEF) are fatal diseases. • Criteria of 6 pivotal drug trials for HFpEF/HFmrEF were applied in a real-world heart failure cohort. • Trial non-eligibility was overall common and due to selective exclusion criteria. • Non-eligibility was associated with higher mortality throughout all trials. • Pivotal trials in HFpEF/HFmrEF likely systematically excluded high-risk patients. Pivotal outcome trials targeting heart failure with preserved (HFpEF) and mildly-reduced ejection fraction (HFmrEF) may have excluded patients at highest risk of poor outcomes. We aimed to assess eligibility for HFpEF/HFmrEF outcome trials in an unselected heart failure cohort and its association with all-cause mortality. Among 32.028 patients presenting to a tertiary care center emergency unit for any reason between August 2018 and July 2019, we identified 407 admissions with evident HFpEF and HFmrEF. Eligibility criteria for pivotal trials CHARM-Preserved, I-PRESERVE, TOPCAT, PARAGON-HF, EMPEROR-Preserved and DELIVER were assessed by chart review. The proportions of admissions fulfilling HFpEF/HFmrEF trial eligibility criteria were 88% for CHARM-Preserved, 40% for I-PRESERVE, 35% for TOPCAT, 28% for PARAGON-HF, 51% for EMPEROR-Preserved, and 49% for DELIVER. During a median follow-up of 1.9 years, death-from-any-cause occurred in 121 cases (30%). Twenty-four-month overall survival estimates for non-eligible and eligible admissions were 53% vs. 76% for CHARM-Preserved (HR=2.32, 95% CI: 1.47–3.67, p <0.001), 62% vs. 87% for I-PRESERVE (HR=2.97, 1.85–4.77, p <0.001), 67% vs. 84% for TOPCAT (HR=2.04, 1.29–3.24, p = 0.002), 68% vs. 85% for PARAGON HF (HR=2.28, 1.33–3.90, p = 0.003), 64% vs. 81% for EMPEROR-Preserved (HR=1.90, 1.27–2.84, p = 0.002), and 65% vs. 80% for DELIVER (HR=1.71, 1.14–2.57, p = 0.010). Exclusion criteria independently predicting death were eGFR <20 ml/min/1.73 m2, COPD with home oxygen therapy, and severe valvular heart disease. Conclusively, in a contemporary HFpEF/HFmrEF cohort, non-eligibility for outcome trials predicted for strongly increased mortality. HFpEF/HFmrEF patients at highest mortality risk were likely underrepresented in previous outcome trials and their treatment remains an unmet medical need. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this double-blind, and randomized controlled clinical trial was to evaluate the 5-year clinical performance of posterior resin composite restorations placed with the incremental filling technique [IF] or the bulk-fill technique [BF]. Two different adhesive systems were used: etch-&-rinse (ER) or self-etch (SE). Posterior dental teeth of 72 participants (n = 236), with a cavity depth of at least 3 mm, were randomly divided into four groups. Restorations were applied with either Tetric N-Bond or Tetric N-Bond SE. The composite resin Tetric N-Ceram Bulk-Fill was placed either with IF or BF. Restorations were evaluated using FDI criteria at baseline and after 1, 2, 3, 4, and 5 years. Statistical analysis was performed using the Wilcoxon Signed rank test (a=0.05). Two hundred and four restorations were evaluated after 5 years. Eleven restorations were considered 'failed', ten due to fracture (4 IF and 6 BF) and one due to secondary caries (IF). The annual failure rate was 1.2% for BF and 1% for IF (p = 0.35). When comparing BF and IF, no significant differences were found for any of the parameters evaluated (p > 0.05). Regarding the adhesive systems, 44 and 51 restorations showed minor problems in terms of marginal adaptation and staining, with significantly more marginal discoloration when the self-etch adhesive was used (p = 0.002). The bulk-fill restorative technique showed good clinical behavior compared to the incremental filling technique, especially when using an etch-&-rinse adhesive, after 5 years of clinical evaluation. [Display omitted] • Bulk-fill technique had similar clinical behavior to incremental filling technique. • Use of etch & rinse adhesive reduced the risk of marginal staining after 5 years. • Minor not significant discrepancies in color match were shown between techniques. [ABSTRACT FROM AUTHOR]

To assess whether the use of rapid influenza diagnostic tests (RIDTs) for long-term care facility (LTCF) residents with acute respiratory infection is associated with increased antiviral use and decreased health care utilization. Nonblinded, pragmatic, randomized controlled trial evaluating a 2-part intervention with modified case identification criteria and nursing staff–initiated collection of nasal swab specimen for on-site RIDT. Residents of 20 LTCFs in Wisconsin matched by bed capacity and geographic location and then randomized. Primary outcome measures, expressed as events per 1000 resident-weeks, included antiviral treatment courses, antiviral prophylaxis courses, total emergency department (ED) visits, ED visits for respiratory illness, total hospitalizations, hospitalizations for respiratory illness, hospital length of stay, total deaths, and deaths due to respiratory illness over 3 influenza seasons. Oseltamivir use for prophylaxis was higher at intervention LTCFs [2.6 vs 1.9 courses per 1000 person-weeks; rate ratio (RR) 1.38, 95% CI 1.24-1.54; P <.001]; rates of oseltamivir use for influenza treatment were not different. Rates of total ED visits (7.6 vs 9.8/1000 person-weeks; RR 0.78, 95% CI 0.64-0.92; P =.004), total hospitalizations (8.6 vs 11.0/1000 person-weeks; RR 0.79, 95% CI 0.67-0.93; P =.004), and hospital length of stay (35.6 days vs 55.5 days/1000 person-weeks; RR 0.64, 95% CI 0.0.59-0.69; P <.001) were lower at intervention as compared to control LTCFs. No significant differences were noted for respiratory-related ED visits or hospitalizations or in rates for all-cause or respiratory-associated mortality. The use of low threshold criteria to trigger nursing staff–initiated testing for influenza with RIDT resulted in increased prophylactic use of oseltamivir. There were significant reductions in the rates of all-cause ED visits (22% decline), hospitalizations (21% decline), and hospital length of stay (36% decline) across 3 combined influenza seasons. No significant differences were noted in respiratory-associated and all-cause deaths between intervention and control sites. [ABSTRACT FROM AUTHOR]

• Experimental auction with RCT among groundnut consumers in Malawi. • Estimated demand for food safety in harvest and lean seasons. • People trained in food safety increased demand for unobservable quality in the lean season. • The control group did not increase demand for unobservable quality in the lean season. We implemented a clustered randomized control trial with experimental auctions among 1,098 rural households in Malawi to evaluate whether providing training about food safety increased demand for safe groundnut. We measured the impact of training on demand for observable and unobservable dimensions of quality, at harvest and in the lean season. We found that the control group who was not trained valued sorted grains (an indicator of observable quality) only. At harvest, both trained and untrained consumers placed statistically equal premiums on food safety labeling (an indicator of otherwise-unobservable quality). However, in the lean season, untrained consumers' premiums for food safety labeling disappeared, while trained consumers' premiums for food safety labeling increased. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) that conduct subgroup analyses have the potential to provide information on treatment decisions in specific groups of patients from heterogeneous populations. Although we understand several factors can modify the incidence of venous thromboembolism (VTE) and the benefit/risk ratio of anticoagulation treatments, further evidence is warranted to show the heterogeneity of treatment effects in different subgroups of patients. The primary purpose was to evaluate the appropriateness and interpretation of subgroup analysis performed on VTE RCTs reporting pharmacological interventions. A systematic review of RCTs published between January 2017 and January 2022 was conducted. Claims of subgroup effects were evaluated with predefined criteria. High-quality claims of subgroup effect were further analyzed and discussed. Overall, 28 RCTs with a generally low bias risk were included. The purposes of the treatments included pharmacologic thromboprophylaxis (17), therapeutic dose anticoagulation (9), and catheter-directed pharmacologic thrombolysis (2). The evaluated subgroup analyses generally presented: a high number of subgroup analyses reported, a lack of prespecification, and a lack of usage of statistical tests for interaction. The authors reported 13 claims of subgroup effect; only two were considered potentially reliable to represent heterogeneity in the direction or magnitude of treatment effect. Subgroup analyses of VTE RCTs reporting pharmacologic interventions are generally methodologically poor. Most claims of subgroup effect did not meet critical criteria and lacked credibility. Clinicians in this field may proceed with scepticism when assessing claims of subgroup effects due to methodological concerns and misleading interpretations. [Display omitted] [ABSTRACT FROM AUTHOR]

Excessive and protracted lipolysis in adipose tissues of dairy cows is a major risk factor for clinical ketosis (CK). This metabolic disease is common in postpartum cows when lipolysis provides fatty acids as an energy substrate to offset negative energy balance. Lipolysis in cows can be induced by the canonical (hormonally induced) and inflammatory pathways. Current treatments for CK focus on improving glucose in blood (i.e., oral propylene glycol [PG], or i.v. dextrose). However, these therapies do not inhibit the canonical and inflammatory lipolytic pathways. Niacin (NIA) can reduce activation of the canonical pathway. Blocking inflammatory responses with cyclooxygenase inhibitors such as flunixin meglumine (FM) can inhibit inflammatory lipolytic activity. The objective of this study was to determine the effects of including NIA and FM in the standard PG treatment for postpartum CK on circulating concentrations of ketone bodies. A 4-group, parallel, individually randomized trial was conducted in multiparous Jersey cows (n = 80) from a commercial dairy in Michigan during a 7-mo period. Eligible cows had CK symptoms (lethargy, depressed appetite, and milk yield) and hyperketonemia (blood β-hydroxybutyrate [BHB] ≥1.2 mmol/L). Cows with CK were randomly assigned to 1 of 3 groups where the first group received 310 g of oral PG once per day for 5 d; the second group received PG for 5 d + 24 g of oral NIA once per day for 3 d (PGNIA); and the third group received PG for 5 d + NIA for 3 d + 1.1 mg/kg i.v. FM once per day for 3 d (PGNIAFM). The control group consisted of cows that were clinically healthy (HC; untreated; BHB <1.2 mmol/L, n = 27) matching for parity and DIM with all 3 groups. Animals were sampled at enrollment (d 0), and d 3, 7, and 14 to evaluate ketone bodies and circulating metabolic and inflammatory biomarkers. Effects of treatment, sampling day, and their interactions were evaluated using mixed effects models. Logistic regression was used to calculate the odds ratio (OR) of returning to normoketonemia (BHB <1.2 mmol/L). Compared with HC, enrolled CK cows exhibited higher blood concentrations of dyslipidemia markers, including nonesterified fatty acids (NEFA) and BHB, and lower glucose and insulin levels. Cows with CK also had increased levels of biomarkers of pain (substance P), inflammation, including lipopolysaccharide-binding protein, haptoglobin, and serum amyloid A, and proinflammatory cytokines IL-4, MCP-1, MIP-1α, and TNFα. Importantly, 72.2% of CK cows presented endotoxemia and had higher circulating bacterial DNA compared with HC. By d 7, the percentage of cows with normoketonemia were higher in PGNIAFM = 87.5%, compared with PG = 58.33%, and PGNIA = 62.5%. At d 7 the OR for normoketonemia in PGNIAFM cows were 1.5 (95% CI, 1.03–2.17) and 1.4 (95% CI, 0.99–1.97) relative to PG and PGNIA, respectively. At d 3, 7, and 14, PGNIAFM cows presented the lowest values of BHB (PG = 1.36; PGNIA = 1.24; PGNIAFM = 0.89 ± 0.13 mmol/L), NEFA (PG = 0.58; PGNIA = 0.59; PGNIAFM = 0.45 ± 0.02 mmol/L), and acute phase proteins. Cows in PGNIAFM also presented the highest blood glucose increment across time points and insulin by d 7. These data provide evidence that bacteremia or endotoxemia, systemic inflammation, and pain may play a crucial role in CK pathogenesis. Additionally, targeting lipolysis and inflammation with NIA and FM during CK effectively reduces dyslipidemia biomarkers, improves glycemia, and improves overall clinical recovery. [ABSTRACT FROM AUTHOR]

The primary objective of this research was to assess the impact of a novel, peer-directed intervention (iNSPiRED) on diabetes distress (DD) among veterans with type 2 diabetes and DD. Secondary objectives were to assess iNSPiRED's impact on anxiety, depression, and diabetes self-management behaviors. A single-blinded, randomized, parallel-group trial was conducted. Participants (n = 218) were recruited through a Veterans Affairs medical center and community agencies in a major metropolitan area from September 2019 through January 2022. Certified mental health peer specialists delivered iNSPiRED, a three-month goal-setting and resource navigation intervention. Outcomes were assessed at baseline, postintervention, and month six. Multilevel random-intercept linear regression models with treatment x time interaction terms were used to assess treatment effects. Frequency of following a healthy eating plan was higher for iNSPiRED vs usual care at month three relative to baseline (B = 0.58; p = 0.03) after adjusting for race and socioeconomic status. No other treatment effects differed significantly from zero (ps ≥ 0.05). Peer-directed interventions have the potential to deliver low-cost, highly scalable care. However, based on the largely negative findings of the current study, it is likely that more intense, multimodal interventions are needed to address DD. • Diabetes distress (DD) is linked to poor diabetes outcomes and quality of life. • A peer-led intervention (iNSPiRED) targeting DD and related outcomes was tested. • iNSPiRED participants improved more in frequency of healthy eating vs usual care. • No other treatment effects differed significantly from zero (ps ≥ 0.05). • More intense, multimodal interventions may be needed to address DD. [ABSTRACT FROM AUTHOR]

To synthesize results of six controlled trials of self-care interventions for depression and/or anxiety, focusing on five trials in which lay guidance was compared to self-directed use of the same self-care tools. The trials were conducted in Canada in different target populations. Self-care tools were adapted to each population. Guidance was provided in 3–15 calls over a period of 6–26 weeks. Depression and/or anxiety were assessed at follow-up (6–26 weeks). Pooled analyses used a meta-analytic approach. Engagement with the self-care tools was compared using the standardized difference or Cohen's d effect size. In studies with homogeneous outcomes (three for depression, four for anxiety), the pooled effect sizes of guidance vs. self-directed use of the self-care tools were 0.36 (95% CI 0.10, 0.62, N = 235) for depression and 0.21 (95% CI -0.03, 0.44, N = 285) for anxiety. Guidance consistently led to greater engagement with the tools. The intervention model is a potentially sustainable and accessible alternative to professionally guided self-care for people with mild-moderate depression. Factors which may have limited implementation success include: co-interventions, reduced number of guide calls (3 vs 6 or more), and delivery to dyads (patient-caregiver). [ABSTRACT FROM AUTHOR]

We previously reported the finding of symptom relief in a randomized controlled trial with the combined use of kakkonto and shosaikotokakikyosekko added to conventional treatment in patients with coronavirus disease 2019 (COVID-19). For further evaluation, we performed post hoc analysis focused on symptom disappearance without recurrence, to determine a clearer effect of Kampo medicine. Patients with mild and moderate COVID-19 were randomly allocated to a control group receiving symptomatic therapy or a Kampo group receiving kakkonto (2.5 g) with shosaikotokakikyosekko (2.5 g) three times daily in addition to symptomatic therapy. The data of 161 patients (Kampo group, n = 81; control group, n = 80) were analyzed post hoc for the time to symptom disappearance. Kaplan-Meier and Cox proportional hazard estimates of disappearance of symptoms showed that all and each symptom targeted in this study disappeared faster in the Kampo group than in the control group, although not statistically significant (all symptomatic cases; hazard ratio [HR] 3.73, 95% confidence interval [CI] 0.46−29.98, log-rank p = 0.1763). In a supplemental assessment using covariate adjustment and competing risk analysis, fever disappeared faster in the Kampo group than in the control group (all symptomatic cases, HR 1.62, 95% CI 0.99−2.64, p = 0.0557; unvaccinated cases, HR 1.68, 95% CI 1.00−2.83, p = 0.0498) and shortness of breath disappeared significantly faster in Kampo group than in control group (all symptomatic cases, HR 1.92, 95% CI 1.07−3.42, p = 0.0278; unvaccinated cases, HR 2.15, 95% CI 1.17−3.96, p = 0.0141). These results demonstrate the advantages of Kampo treatment for acute COVID-19. [ABSTRACT FROM AUTHOR]

Transcutaneous auricular vagus nerve stimulation (taVNS) is used for treating depression but the efficacy and safety have not been well assessed. This study was conducted to evaluate the efficacy and safety of taVNS in depression. The retrieval databases included English databases of PubMed, Web of Science, Embase, the Cochrane Library and PsycINFO, and Chinese databases of CNKI, Wanfang, VIP and Sino Med, and the retrieval period was from their inception to November 10, 2022. The clinical trial registers (ClinicalTrials.gov and Chinese Clinical Trial Registry) were also searched. Standardized mean difference and the risk ratio were used as the effect indicator and the effect size was represented by the 95 % confidence interval. Revised Cochrane risk-of-bias tool for randomized trials and the Grades of Recommendation, Assessment, Development and Evaluation system were used to assess the risk of bias and quality of evidence respectively. Totally, 12 studies of 838 participants were included. taVNS could significantly improve depression and reduce Hamilton Depression Scale scores. Low to very low evidence showed that taVNS had higher response rates than sham-taVMS and comparable response rates compared to antidepressants (ATD) and that taVNS combined with ATD had comparable efficacy to ATD with fewer side effects. The number of studies in subgroups was small and the evidence quality was low to very low. taVNS is an effective and safe method for alleviating depression scores and had a comparable response rate to ATD. • taVNS is an effective and safe method for mild to moderate depression. • taVNS has significantly higher response rate than sham-taVNS. • taVNS has comparable effect than antidepressants in reducing Hamilton Depression Scale scores with less side effects. [ABSTRACT FROM AUTHOR]

• Individuals with high body shame are at heightened risk for body dissatisfaction. • Compassion interventions reduced state body shame compared to the control group. • Self-compassion interventions reduced state shame, but not state body image. • The effectiveness of compassion interventions on state shame remained at follow-up. State body shame is a risk factor for eating disorders, and self-compassion is emerging as a potentially effective treatment option in such cases. This study tested the efficacy of a brief (15-minute) self-compassion intervention in reducing state body shame. Using dismantling trial methodology, participants were randomly allocated to an active compassion condition (n = 23), an inactive control compassion condition (n = 23), or an educational control condition (n = 23). Measures of state body image and state shame were collected pre-intervention, immediately after the intervention, and a day after the intervention. Subjective units of state body shame (SUBS) were intensively measured during each invention. Self-compassion interventions were equally efficacious at protecting against deterioration of state body shame and were effective at reducing state shame compared to the educational control condition, with medium effect sizes (respectively – n p 2 =.07 and n p 2 =.08). Reductions in state shame were retained at follow-up. None of the interventions had an effect on body image (n p 2 =.04). Findings demonstrate the clinical promise of brief self-compassion interventions, particularly as evidenced-based "homework" exercises. [ABSTRACT FROM AUTHOR]

• Community treatment for ADHD was most effective when delivered by licensed clinicians. • Behavior therapy for ADHD outperformed usual care for conduct problems and may be particularly effective for these youth. • Clinics might assign adolescent ADHD cases to licensed professionals. • All other comorbidity outcomes did not show group differences between STAND and usual care. Though behavior therapy (BT) for ADHD in adolescence is evidence-based, almost no work examines its implementation and effectiveness in community settings. A recent randomized community-based trial of an evidence-based BT for adolescent ADHD (Supporting Teens' Autonomy Daily; STAND; N = 278) reported high clinician, parent, and youth acceptability but variable implementation fidelity. Primary outcome analyses suggested no significant differences between STAND and usual care (UC) unless the clinician delivering STAND was licensed. The present study reports secondary outcomes for this trial on indices of comorbidity (anxiety, depression, oppositional defiant disorder, conduct disorder) and ADHD outcomes not targeted by the active treatment (social skills, sluggish cognitive tempo). We also examine whether therapist licensure moderated treatment effects (as in primary outcome analyses). Using intent-to-treat and per protocol linear mixed models, patients randomized to STAND were compared to those randomized to UC over approximately 10 months of follow-up. Group × Time effects revealed that, overall, STAND did not outperform usual care when implemented by community clinicians. However, a Group × Time × Licensure interaction revealed a significant effect on conduct problems when STAND was delivered by licensed clinicians (d =.19–.47). When delivered in community settings, behavior therapy for adolescent ADHD can outperform UC with respect to conduct problems reduction. Community mental health clinics should consider: (1) assigning adolescent ADHD cases to licensed professionals to maximize impact and (2) choosing psychosocial approaches when ADHD presents with comorbid conduct problems. There is also a need to reduce implementation barriers for unlicensed clinicians in community settings. [ABSTRACT FROM AUTHOR]

Mind My Mind (MMM) cognitive behavioral therapy (CBT) manualized treatment is effective in the management of common emotional and behavioral mental health problems in youth, yet not all individuals respond satisfactorily to treatment. This study explored potential effect modifiers, i.e., baseline factors associated with a differential treatment effect. We conducted secondary effect modifier analyses with MMM trial data, which involved randomization of 396 youths aged 6–16 years to either MMM CBT treatment (9–13 sessions) or management as usual in local community settings. We examined sociodemographic- (sex, age, family composition, ethnicity, parental education, and income) and clinical variables (mental disorders and duration of mental health problems) as potential effect modifiers of the a) change in parent-rated impact of mental health problems measured by the Strengths and Difficulties Questionnaire (SDQ) or b) response (reduction of ≥1 on SDQ-impact). In intention-to-treat analyses, superior treatment (net) benefits from the MMM intervention were found among youths who met criteria for any mental disorder at baseline (-1.25 [95%CI: -1.67;-0.82]) compared to youths that did not meet diagnostic criteria (-0.22 [95%CI:-1.09;0.65]). Comorbidity vs no comorbidity (-1.84 [95%CI:-2.58;-1.10] vs -0.72 [95%CI:-1.15;-0.29]) and longer duration of untreated mental health problems, i.e., more vs less than 6 months (-1.16 [95%CI:-1.55;-0.78] vs 0.43 [95%CI:-1.01;1.86]) were also associated with superior treatment benefits. The sociodemographic factors were not associated with differential treatment effects in the intention-to-treat analyses. These findings suggest that community-based programs like the MMM are well-suited for youths with substantial mental health problems. Clinical Trials Identifier: NCT03535805 [ABSTRACT FROM AUTHOR]

• We did a phase 3 randomized placebo-controlled trial of vitamin D to prevent tuberculosis (TB) infection in 1682 QuantiFERON-TB Plus-negative children in Cape Town, South Africa. • In total, 63.2% of participants had serum 25-hydroxyvitamin D (25[OH]D) concentrations <75 nmol/l at baseline. • The intervention was weekly oral administration of 10,000 IU vitamin D 3 for 3 years. • This was effective in elevating serum 25(OH)D concentrations in participants randomized to the intervention arm of the trial. • The intervention did not influence the risk of QuantiFERON-TB Plus conversion. To determine whether weekly oral supplementation with 10,000 IU vitamin D 3 for 3 years reduces the risk of sensitization to M. tuberculosis in South African schoolchildren aged 6-11 years with negative QuantiFERON-tuberculosis (TB) Gold Plus (QFT-Plus) assay results at baseline. We conducted a phase 3 randomized placebo-controlled trial in 1682 children attending 23 primary schools in Cape Town. The primary outcome was a positive end-trial QFT-Plus result, analyzed using a mixed effects logistic regression model with the school of attendance included as a random effect. 829 vs. 853 QFT-Plus-negative children were randomized to receive vitamin D 3 vs. placebo, respectively. Mean end-study 25(OH)D concentrations in participants randomized to vitamin D vs. placebo were 104.3 vs 64.7 nmol/l, respectively (95% confidence interval for difference, 37.6 to 41.9 nmol/l). A total of 76/667 (11.4%) participants allocated to vitamin D vs. 89/687 (13.0%) participants allocated to placebo tested QFT-Plus positive at 3-year follow-up (adjusted odds ratio 0.86, 95% confidence interval 0.62-1.19, P = 0.35). Weekly oral supplementation with 10,000 IU vitamin D 3 for 3 years elevated serum 25(OH)D concentrations among QFT-Plus-negative Cape Town schoolchildren but did not reduce their risk of QFT-Plus conversion. [ABSTRACT FROM AUTHOR]

To evaluate if an internet-delivered parent training program is noninferior to its group-delivered counterpart in reducing child disruptive behavior problems (DBP). This noninferiority randomized clinical trial enrolled families seeking treatment in primary care in Stockholm, Sweden, for DBP in a child 3-11 years of age. Participants were randomized to internet-delivered (iComet) or group-delivered (gComet) parent training. The primary outcome was parent-rated DBP. Assessments were made at baseline and 3, 6, and 12 months. Secondary outcomes included child and parent behaviors and well-being and treatment satisfaction. The noninferiority analysis was determined by a one-sided 95% CI of the mean difference between gComet and iComet using multilevel modeling. This trial included 161 children (mean age 8.0); 102 (63%) were boys. In both intention-to-treat and per-protocol analyses, iComet was noninferior to gComet. There were small differences in between-group effect sizes (d = −0.02 to 0.13) on the primary outcome with the upper limit of the one-sided 95% CI below the noninferiority margin at 3-, 6-, and 12-month follow-up. Parents were more satisfied with gComet (d = 0.49, 95% CI [0.26, 0.71]). At 3-month follow-up, there were also significant differences in treatment effect on attention-deficit/hyperactivity disorder symptoms (d = 0.34, 95% CI [0.07, 0.61]) and parenting behavior (d = 0.41, 95% CI [0.17, 0.65]) favoring gComet. At 12-month follow-up, there were no differences in any outcomes. Internet-delivered parent training was noninferior to group-delivered parent training in reducing child DBP. The results were maintained at 12-month follow-up. This study supports internet-delivered parent training being used as an alternative to group-delivered parent training in clinical settings. Randomized Controlled Trial of Comet via the Internet or in Group Format; https://www.clinicaltrials.gov/ ; NCT03465384. [ABSTRACT FROM AUTHOR]

Treatment-resistant depression (TRD) accounts for a large fraction of the burden of depression. The interventions currently used are mostly pharmacological and short-term psychotherapies, but their effectiveness is limited. The Tavistock Adult Depression Study found evidence for the effectiveness of long-term psychoanalytic psychotherapy (LTPP) plus treatment as usual (TAU), versus TAU alone, for TRD. Even after a 2-year follow-up, moderate effect sizes were sustained. This study assessed the cost-effectiveness of this LTPP + TAU. We conducted a within-trial economic evaluation using a Bayesian framework. Quality-adjusted life years (QALYs) were 0.16 higher in the LTPP + TAU group compared with TAU. The direct cost of LTPP was £5500, with no substantial compensating savings elsewhere. Overall, average health and social care costs in the LTPP + TAU group were £5000 more than in the TAU group, employment rates were unchanged, and effects on other non-healthcare costs were uncertain. Accordingly, the incremental cost-effectiveness ratio was ≈£33,000/QALY; the probability that LTPP + TAU was cost-effective at a willingness to pay of £20,000/QALY was 18 %. The sample size of this study was relatively small, and the fraction of missing service-use data was approximately 50 % at all time points. The study was conducted at a single site, potentially reducing generalizability. Although LTPP + TAU was found to be clinically effective for treating TRD, it was not found to be cost-effective compared with TAU. However, given the sustained effects over the follow-up period it is likely that the time horizon of this study was too short to capture all benefits of LTPP augmentation. • Quality-adjusted life years were 0.16 higher in the intervention group. • The direct costs of the intervention were approximately £5500. • These intervention costs were not offset by savings elsewhere. • The intervention was not cost-effective, but underestimation of benefits is likely. [ABSTRACT FROM AUTHOR]

Bedtime Procrastination (BP) is defined as the behavior of going to bed later than intended, without external reasons. This study is a randomized controlled trial aiming to establish efficacy of a behavioral intervention to decrease BP in a non-clinical sample. This was an open-label trial that was conducted in sixty participants (mean age 21.33 ± 2.35 years, 86.7% females) without insomnia or psychopathology who endorsed frequent BP. They were randomized to either the treatment group (n = 32) or wait-list control group (n = 28). Participants completed the Bedtime Procrastination Scale (BPS), the Epworth Sleepiness Scale (ESS), the Insomnia Severity Index (ISI), Center for Epidemiologic Studies Depression Scale (CES-D), Morningness-Eveningness Questionnaire (MEQ), and a weekly sleep diary. Functional analysis was conducted to investigate the function of BP. Linear mixed models were used for analyses. The treatment group showed significant improvement on the BPS (35.56% decrease, d = 2.19, bedtime procrastination duration based on the sleep diary (−46.29 min, d = 1.22), and sleep efficiency (5.70% increase, d = 1.25) compared to the wait-list control group following the intervention. There were also significant reductions in time spent from bedtime to lights out, and wake time to time out of bed, in addition to improvements in ISI and ESS scores in the treatment group compared to the control group. Functional analysis results indicated emotional regulation (31.3%), compensation (26.5%), and social interaction and belongingness (18.1%) as the most frequent functions of bedtime procrastination. This study shows promising results for a behavioral intervention targeting BP and sleep. In addition, this study demonstrated various functions of BP as a sleep-interfering behavior. We expect that these findings could be used in future studies and clinical settings to decrease BP. • This study tested the efficacy of a behavioral intervention for reducing bedtime procrastination (BP). • BP improved (35.56% reduction in questionnaire scores, −46.29 min average/daily) in the intervention group. • The main function of BP was emotion regulation.. [ABSTRACT FROM AUTHOR]

Associations between dietary factors and gestational diabetes mellitus (GDM) risk are inconsistent. We evaluated existing meta-analyses based on prospective cohort studies or randomized controlled trials till March 2022. We determined methodological quality and evidence certainty by A Measurement Tool to Assess Systematic Reviews 2 and NutriGrade, respectively. We recalculated pooled effect estimates risk ratio (RR), corresponding 95% confidence interval (CI), and between-study heterogeneity from the primary studies, except for dose-response analyses from which data were directly extracted and evaluated. We included 14 studies involving 27 dietary factors in this analysis. We did not observe high-certainty evidence. We found three pieces of moderate-certainty evidence for increased GDM risk: 80 g/d increments in potato consumption, high and 100 mg/d increments in cholesterol intake, high and 1.0 mg/d increments in heme iron intake; three pieces of moderate-certainty evidence for reduced GDM: myo-inositol supplement, vitamin D supplement >601 IU/d, probiotics intake >5 × 109 colony-forming units, compared with their corresponding control groups. In region-specific analysis, we found that western dietary pattern and animal meat consumption are associated with a high GDM risk in western countries, while vitamin D supplement >601 IU/d is associated with a low GDM risk in eastern countries. In meat-type analysis, we found that red meat and processed red meat consumptions are associated with high GDM risk, while poultry and fish consumption is not. In conclusion, due to the moderate-to-low certainty of evidence and the relatively large heterogeneity between studies, further high-quality investigations are needed. • Vitamin D supplement more than 601 IU/d, probiotics intake greater than 5 × 109 CFU, and myo-inositol supplement may reduce gestational diabetes mellitus risk. • Potato consumption with 80 g/d increments, cholesterol intake, and heme iron intake may increase gestational diabetes mellitus risk. • Although there is insufficient high-certainty evidence to determine the associations of 27 dietary factors with GDM risk, this umbrella review provides evidence-based information for women of childbearing age before or during pregnancy. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Unsatisfactory responses to major depressive disorder (MDD) therapeutics available necessitated up-to-date treatment approaches. This study sought to investigate the efficacy and tolerability of adjunctive l -theanine, a green tea constituent with neuropsychotropic effects, for MDD. Sixty MDD (DSM-5) patients were equally assigned to receive sertraline (100 mg/d) plus either l -theanine (200 mg/d) or matched placebo in a six-week randomized, parallel-group, double-blind, placebo-controlled study. The participants were assessed using the Hamilton depression rating scale (HDRS) at baseline and weeks 2, 4, and 6. Changes in scores, early improvement, response and remission rates, and adverse events were compared between the groups. Twenty-five participants in each group, a total of 50 patients, completed the study. All baseline characteristics were similar between the groups. The general linear model repeated-measures analysis demonstrated a significant time-treatment interaction effect for HDRS during the trial (p -value = 0.014), indicating more remarkable symptom improvement in the l -theanine group. A greater reduction in HDRS scores was observed in the l -theanine group from baseline to weeks 2, 4, and 6 (p -values = 0.02, 0.03, and 0.01, respectively). All patients responded to sertraline plus l -theanine until week 6. l -theanine was superior to placebo regarding response to treatment and remission rates at week 6 (p -values = 0.05 and 0.02, respectively). The frequency of side effects was comparable between the groups. The small sample size and short study period were the limitations. l -theanine adjunct to sertraline outperforms placebo in treating MDD in a safe manner. Further long-term, large-scale studies are recommended to confirm this evidence. • l -theanine is an amino acid found naturally in green tea, black tea, and mushrooms. • It is beneficial and tolerable in depression, obtained from a gold-standard design. • l -theanine has been reported to modulate GABA, serotonin, and dopamine levels. • It may also exert effects through the glutamatergic and neuroimmune mechanisms. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of oral administration of tranexamic acid (TXA) in spine surgery to achieve blood loss reduction. Sixty patients undergoing major surgery of the spine were randomly assigned into 2 groups. Group 1 was assigned as the control group and the other group comprised patients who received oral administration of TXA 2 hours before surgery. Outcome measures included intraoperative blood loss, postoperative blood loss, hematologic parameters, blood transfusion needed, and surgical complications. Sixty patients linked up with the inclusion criteria. Intraoperative blood loss was significantly lower in the TXA oral group than in the control group; total blood loss in the TXA group was 930.66 ± 614 mL, which was lower than in the control group, with 1075.66 ± 956.11 mL. The mean reduction of hemoglobin was almost the same in both groups. Similarly, the total transfusion package received was lower, and the number of complications and length of stay were akin in both groups. A logistic regression model was performed with patients who had blood loss >1000 mL and surgery time >230 minutes. This result was related to the risk of bleeding, with an odds ratio of 1.31, 95% confidence interval, 1.004–1.023, P = 0.004, independent of the group. Oral TXA is as an effective measure for reducing total blood loss among patients undergoing elective spine surgery. [ABSTRACT FROM AUTHOR]