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• Treatment with camostat did not affect the cycle threshold change in the early phase of COVID-19 disease. • Clinical improvement was similar in patients with COVID-19 treated with camostat or a placebo. • Treatment with camostat did not affect the SARS-CoV-2 neutralizing antibody response. • This randomized controlled trial showed the safe use of 300 mg camostat three times daily in patients with COVID-19. • Camostat mesylate is not effective as an antiviral drug for ambulatory patients with COVID-19. This study aimed to assess the efficacy and safety of 300 mg camostat mesylate three times daily in a fasted state to treat early phase COVID-19 in an ambulatory setting. We conducted a phase II randomized controlled trial in symptomatic (maximum 5 days) and asymptomatic patients with confirmed COVID-19 infection. Patients were randomly assigned in a 2:1 ratio to receive either camostat mesylate or a placebo. Outcomes included change in nasopharyngeal viral load, time to clinical improvement, the presence of neutralizing antibodies, and safety. Of 96 participants randomized between November 2020 and June 2021, analyses were performed on the data of 90 participants who completed treatment (N = 61 camostat mesylate, N = 29 placebo). The estimated mean change in cycle threshold between day 1 and day 5 between the camostat and placebo group was 1.183 (P = 0.511). The unadjusted hazard ratio for clinical improvement in the camostat group was 0.965 (95% confidence interval, 0.480-1.942, P = 0.921 by Cox regression). The percentage distribution of the 50% neutralizing antibody titer at day 28 visit and frequency of adverse events were similar between the two groups. Under this protocol, camostat mesylate was not found to be effective as an antiviral drug against SARS-CoV-2. Trial registration: ClinicalTrials.gov NCT04625114 ; November 12, 2020. [ABSTRACT FROM AUTHOR]

• Objective response rate (ORR) was statistically associated with overall survival (OS) in a trial-level meta-analysis. • The trial-level relationship between OS and ORR was stronger in immunotherapy-based compared to chemotherapy-only trials. • For a given ORR benefit, OS gains were significantly larger with immunotherapy-based compared to chemotherapy-only trials. The study objective was to estimate the relationship between objective response and survival-based endpoints by drug class, in first-line advanced non-small cell lung cancer (aNSCLC). A systematic literature review identified randomized controlled trials (RCTs) of first-line aNSCLC therapies reporting overall survival (OS), progression-free survival (PFS), and/or objective response rate (ORR). Trial-level and arm-level linear regression models were fit, accounting for inclusion of immunotherapy (IO)-based or chemotherapy-only RCT arms. Weighted least squares-based R2 were calculated along with 95% confidence intervals (CIs). For the main trial-level analysis of OS vs. ORR, the surrogate threshold effect was estimated. Exploratory analyses involved further stratification by: IO monotherapy vs. chemotherapy, dual-IO therapy vs. chemotherapy, and IO + chemotherapy vs. chemotherapy. From 17,040 records, 57 RCTs were included. In the main analysis, trial-level associations between OS and ORR were statistically significant in both the IO-based and chemotherapy-only strata, with R2 estimates of 0.54 (95% CI: 0.26–0.81) and 0.34 (0.05–0.63), respectively. OS gains associated with a given ORR benefit were statistically significantly larger within IO vs. chemotherapy comparisons compared to chemotherapy vs. chemotherapy comparisons (p < 0.001). Exploratory analysis suggested a trend by IO type: for a given change in ORR, 'pure' IO (IO monotherapy and dual-IO) vs. chemotherapy RCTs tended to have a larger OS benefit than IO + chemotherapy vs. chemotherapy RCTs. For ORR vs. PFS, trial-level correlations were strong in the IO-based vs. chemotherapy (R2 = 0.84; 0.72–0.95), and chemotherapy vs. chemotherapy strata (R2 = 0.69; 0.49–0.88). For OS vs. PFS, correlations were moderate in both strata (R2 = 0.49; 0.20–0.78 and R2 = 0.49; 0.23–0.76). The larger OS benefit per unit of ORR benefit in IO-based RCTs compared to chemotherapy-only RCTs provides an important addition to the established knowledge regarding the durability and depth of response in IO-based treatments. [ABSTRACT FROM AUTHOR]

Background: Lifestyle medicine (LM) is gaining increasing attention as a treatment option for anxiety, but the current state of evidence has not yet been systematically examined.Methods: Six electronic databases were systematically searched from inception to February 2022. Randomized controlled trials (RCTs) comparing the effects of multicomponent LM interventions on anxiety symptoms with either care-as-usual, waitlist, no intervention, or attention control group on anxiety symptoms were identified.Results: A total of 53 RCTs with 18,894 participants were included for qualitative synthesis, in which 45 RCTs with data available were included for meta-analysis. Multicomponent LM intervention was significantly more effective than the control groups in reducing anxiety symptoms at immediate posttreatment (d = 0.19, p < .001) and at short-term follow-up (d = 0.29, p < .001). However, no significant difference at medium-term was found (p = .14), whereas more studies are needed to study the long-term effects. The subgroup analyses suggested that baseline anxiety symptoms was a significant moderator, suggesting that those with moderate level of baseline anxiety symptoms appeared to have greater improvements (d = 0.66, p < .05).Limitations: Minimal anxiety symptoms at baseline contributed to the floor effect and influenced the degree of improvement. The included RCTs had a high risk of bias in general with potential publication bias detected.Conclusion: The findings of this meta-analysis provided support for the positive effects of multicomponent LM interventions for anxiety symptoms. Future research is needed to determine the long-term effects of multicimponent LM and the optimal baseline anxiety severity. [ABSTRACT FROM AUTHOR]

The excess neonatal adiposity is considered a risk factor for the development of childhood obesity and the birth weight is a marker of health throughout life. To evaluate the effect of a lifestyle intervention conducted among pregnant women with overweight on neonatal adiposity and birth weight. A total of 350 pregnant women were recruited and randomly allocated into the control (CG) and intervention (IG) groups. Pregnant women in the IG were invited to participate in three nutritional counselling sessions based on encouraging the consumption of unprocessed and minimally processed foods, rather than ultra-processed foods, following the NOVA food classification system, which categorizes foods according to the extent and purpose of industrial processing, and the regular practice of physical activity. Neonatal adiposity was estimated using a previously validated anthropometric model. Adjusted linear regression models were used to measure the effect. Adopting the modified intention-to-treat principle, data from 256 neonates were analyzed for birth weight, and data from 163 for body composition estimation. The treatment had no effect on the proportion of fat mass [β 0.52 (95 % CI −1.03, 2.06); p =.51], fat-free mass [β −0.50 (95 % CI −2.45, 1.45); p =.61] or birth weight [β 53.23 (95 % CI −87.19, 193.64); p =.46]. In the present study, the lifestyle counselling used had no effect on neonatal adiposity or birth weight. Future studies should investigate the effect of more intensive interventions. • The intervention based on NOVA did not cause an undesirable effect on foetal development. • The nutritional intervention based on NOVA did not impair neonatal anthropometry. • Future research is needed to elucidate whether maternal lifestyle intervention can influence neonatal body composition. [ABSTRACT FROM AUTHOR]

This analysis of secondary outcomes investigated the applicability of supramaximal high-intensity interval training (HIT) with individually prescribed external intensity performed on stationary bicycles. Sixty-eight participants with a median (min; max) age of 69 (66; 79), at the time not engaged in regular exercise were randomized to 25 twice-weekly sessions of supramaximal HIT (20-min session with 10 × 6-s intervals) or moderate-intensity training (MIT, 40-min session with 3 × 8-min intervals). The primary aim was outcomes on applicability regarding; adherence to prescribed external interval intensity, participant reported positive and negative events, ratings of perceived exertion (RPE 6–20), and affective state (Feeling Scale, FS -5–5). A secondary aim was to investigate change in exercise-related self-efficacy (Exercise Self-Efficacy Scale) and motivation (Behavioural Regulations in Exercise Questionnaire-2). Total adherence to the prescribed external interval intensity was [median (min; max)] 89 % (56; 100 %) in supramaximal HIT, and 100 % (95; 100 %) in MIT. The supramaximal HIT group reported 60 % of the positive (112 of 186) and 36 % of the negative (52 of 146) events. At the end of the training period, the median (min; max) session RPE was 15 (12; 17) for supramaximal HIT and 14 (9; 15) for MIT. As for FS, the median last within-session rating was 3 (−1; 5) for supramaximal HIT and 3 (1; 5) for MIT. Exercise-related motivation increased (mean difference in Relative Autonomy Index score = 1.54, 95 % CI [0.69; 2.40]), while self-efficacy did not change (mean difference = 0.55, 95 % CI [-0.75; 1.82]), regardless of group. This study provide support for supramaximal HIT in supervised group settings for older adults. • Supramaximal HIT was well-tolerated by non-exercising older adults. • Supramaximal HIT participants reported more positive than negative events. • The findings provide support for the applicability of supramaximal HIT. [ABSTRACT FROM AUTHOR]

• Home-visiting interventions have positive effects on child cognitive development, parenting beliefs and parenting practices of caregivers in rural China. • Home-visiting interventions have null effects on child social-emotional development in rural China. • Three mechanisms are identified through which interventions are able to raise child cognitive development. • Shifting parenting beliefs; increasing parenting practices; and shifting parenting beliefs thus fostering better parenting practices of primary caregivers are the three mechanisms that are driving our overall results of the impact of home-visiting interventions on early child development. To better understand the impacts of parenting interventions (e.g., parental training of psychosocial stimulating activities) on child developmental outcomes and design effective policies to benefit young children, it is essential to identify the mechanisms through which the interventions work. To this end, this paper presents the results of two randomized controlled trials that offered home visitation, parenting trainings to 435 households (with 527 households as the control group) in 174 villages across three provinces in China. The findings from the randomized controlled trials showed that the interventions significantly improved child cognitive development and had a positive effect on the primary caregivers' parenting practices and their parenting beliefs. The analysis suggests three possible mechanisms through which the parenting interventions affected child cognitive development: changing the parenting beliefs of the primary caregivers, shifting the parenting practices of the primary caregivers, and improving the primary caregivers' parenting beliefs, thus fostering better parenting practices. [ABSTRACT FROM AUTHOR]

Despite their proliferation, limited knowledge exists regarding possible benefits of brief mindfulness ecological momentary interventions (MEMIs) for social anxiety disorder (SAD). Propositions that MEMIs could alleviate SAD symptoms and related clinical outcomes remain untested. This trial evaluated a 14-day MEMI for SAD. Participants with self-reported SAD were randomized to MEMI (n = 96) or self-monitoring app (SM; n = 95). Whereas MEMI instructed mindfulness exercises, SM prompted only self-monitoring five times daily for 14 days. Participants completed state-level self-reports of depression, anxiety, and mindfulness pre-post-mindfulness practice and SAD symptoms, worry, depression severity, repetitive negative thinking, and trait mindfulness at pre-randomization, post-intervention, and 1-month follow-up (1MFU). Hierarchical linear modeling was conducted. The MEMI yielded statistically significantly larger improvements in momentary depression, anxiety, and mindfulness (Cohen's d = −0.10–0.11). Although no between-group effects emerged in alleviating SAD fear and avoidance, excessive worry, depression severity, repetitive negative thinking, and trait mindfulness (−0.13–0.15), within-group effects were significantly small-to-large from pre-post and pre-1MFU (−4.62–0.67). A significant reduction in depression severity occurred in MEMI (−0.63–−0.60) but not SM (−0.31–−0.29). Brief MEMI and SM yielded nondifferent sustained effects on SAD, comorbid symptoms, and risk factors, highlighting its potential value within stepped-care delivery settings. • MEMI (vs. SM) notably improved state depression, anxiety, and mindfulness. • MEMI and SM enhanced SAD, worry, repetitive thinking, and trait mindfulness. • Depression severity was reduced in the MEMI but not the SM arm. • Brief MEMI might be efficacious for targeting pathological worry but not SAD. • MEMIs for SAD must be high-intensity and have exposure therapy to be efficacious. [ABSTRACT FROM AUTHOR]

Evaluate and compare the efficacy and safety of molnupiravir and favipiravir in outpatients with mild to moderate COVID-19 and at risk of severe COVID-19. In an open-label, parallel-group, multicenter trial in Thailand, participants with moderate COVID-19 and at least one factor associated with severe COVID-19 were randomly assigned 1:1 to receive oral molnupiravir or oral favipiravir (standard of care). Phone calls for remote symptom assessment were made on Days 6, 15, and 29. Participants with worsening symptoms were instructed to return to the hospital. The primary endpoint was pulmonary involvement by Day 29, as evidenced by ≥2 of the following: dyspnea, oxygen saturation <92% or imaging. Nine hundred seventy-seven participants (487 molnupiravir, 490 favipiravir) were enrolled from 8 July 2022 to 19 January 2023. 98% had received ≥1 dose of COVID-19 vaccine and 83% ≥3 doses. By Day 29, pulmonary involvement occurred in 0% (0/483) in molnupiravir arm versus 1% (5/482) in favipiravir arm (−1.0%; Newcombe 95.2% CI: −2.4% to −0.0%; P = 0.021); all-cause death in 0% (0/483) and <1% (1/482); COVID-19 related hospitalization in <1% (1/483) and 1% (3/482); treatment-related adverse event in 1% (5/483) and 1% (4/486); and serious adverse event in 1% (4/483) and 1% (4/486). Favipiravir and molnupiravir had a similar efficacy and safety profile. Whether either of the two reduced the risk of complications during the omicron era in this population with a low risk of pulmonary involvement and a high vaccine coverage remains unclear. There were no differences in any of the safety endpoints. TCTR20230111009. [ABSTRACT FROM AUTHOR]

Chinese herbal medicine is increasingly used as complementary therapy to manage nausea and vomiting in different cultures. One such herbal recipe is the Hezhong granules, which contain classical antiemetic formulations, and are commonly used to prevent chemotherapy-induced nausea and vomiting (CINV). Modern pharmacological studies have shown that the key components of Hezhong granules, including Pinellia ternata (Thunb.), Evodia rutaecarpa (Juss.), and Zingiber officinale exhibit significant antiemetic and antitumor properties. Despite this promising evidence, controlling CINV remains a significant challenge in cancer treatment. Moreover, there is a lack of scientifically designed clinical trials to validate the efficacy and safety of classical antiemetic formulas for CINV interventions. To investigate the efficacy and safety of Hezhong granules in preventing CINV in patients with advanced colorectal cancer (CRC). This study was conducted between October 2020 and February 2022 in 12 hospital wards in Southwest China. In this multicenter, randomized controlled trial, we enrolled patients with advanced CRC who received fluorouracil-based chemotherapy. The patients were randomly assigned in a 1:1 ratio to either the Hezhong granule group (receiving a 5-HT3-receptor antagonist, dexamethasone, and Hezhong granules) or the placebo group (receiving a 5-HT3-receptor antagonist, dexamethasone, and placebo) during the first and second courses of chemotherapy. A 5-day diary was provided to all patients. Acute and delayed CINV were defined as CINV occurring within 24 h or between 24 and 120 h after the start of treatment. The primary endpoints were complete response rate (CRR, defined as the proportion of patients without nausea/vomiting) and objective response rate (ORR, defined as the proportion of patients without nausea/vomiting plus mild nausea/vomiting) for both acute and delayed CINV. Secondary endpoints were the daily rates of CINV events and Functional Living Index-Emesis (FLIE). To identify the predictors of CINV, we conducted multivariate ordered logistic regression analysis. This study was registered with the Chinese Clinical Trial, number ChiCTR2100041643. A total of 120 participants were randomly assigned, of whom 112 (56/56) completed two cycles and were included in the full analysis. In the acute phase, there were minor improvements in the Hezhong granule group, but there were no significant differences in the CRRs for nausea and vomiting (mean difference:10.7 %, P = 0.318, 0.324), while the ORRs increased by approximately 17.5 % (mean difference:16.1 %, P = 0.051; 17.9 %, P = 0.037, respectively). In the delayed phase, significant improvements of approximately 20 % were observed in both the CRRs (mean difference:19.6 %, P = 0.053; 21.4 %, P = 0.035) and ORRs (mean difference:17.9 %, P = 0.037, 0.043) for nausea and vomiting. Additionally, the daily rate of CINV events showed a mean difference of 19 % (P < 0.05). According to FLIE scores, approximately 70 % of patients who received Hezhong granules reported an improvement in their quality of life, with CINV symptoms having"no impact on daily life (NIDL)". No serious adverse events were attributed to herbal medicine. Hezhong granules proved to be both effective and well-tolerated in preventing CINV in patients with advanced CRC, with notable benefits in preventing delayed CINV. These promising results set the stage for subsequent phase III clinical trials and experimental research on Hezhong Granules. [Display omitted] • Hezhong granule can increase the complete response rate of CINV by about 10 %–20 %. • Hezhong granule can increase the objective response rate of CINV by about 16 %–18 %. • Hezhong granule show better efficacy in preventing delayed CINV. • Hezhong granule is well tolerated and can significantly improve the quality of life of patients. [ABSTRACT FROM AUTHOR]

People engaged in treatment for opioid use disorder (OUD) report struggling with whether and how to disclose, or share information about their OUD history and/or treatment with others. Yet, disclosure can act as a gateway to re-establishing social connection and support during recovery. The current study describes a pilot randomized controlled trial of Disclosing Recovery: A Decision Aid and Toolkit, a patient decision aid designed to facilitate disclosure decisions and build disclosure skills. Participants (n = 50) were recruited from a community-based behavioral health organization in 2021–2022 and randomized to receive the Disclosing Recovery intervention versus an attention-control comparator. They responded to surveys immediately after receiving the intervention as well as one month following the intervention at a follow-up appointment. Primary outcome analyses examined indicators of implementation of the intervention to inform a future efficacy trial. Secondary outcome analyses explored impacts of the intervention on the decision-making process, disclosure rates, and relationships. Participants were successfully recruited, randomized, and retained, increasing confidence in the feasibility of future efficacy trials to test the Disclosing Recovery intervention. Moreover, participants in the Disclosing Recovery intervention agreed that the intervention is acceptable, feasible, and appropriate. They additionally reported a higher quality of their decision-making process and decisions than participants in the comparator condition. At their follow-up appointment, participants with illicit opioid use who received the Disclosing Recovery intervention were less likely to disclose than those who received the comparator condition. Moreover, significant interactions between illicit opioid use and the intervention condition indicated that participants without illicit opioid use who received the Disclosing Recovery intervention reported greater closeness to and social support from their planned disclosure recipient than those who received the comparator condition. The Disclosing Recovery intervention appears to be an acceptable, feasible, and appropriate patient decision aid for addressing disclosure processes among people in treatment for OUD. Moreover, preliminary results suggest that it shows promise in improving relationship closeness and social support in patients without illicit opioid use. More testing is merited to determine the intervention's efficacy and effectiveness in improving relationship and treatment outcomes for people in treatment for OUD. • People in opioid use disorder (OUD) treatment struggle with disclosure decisions. • Disclosing Recovery is a patient decision aid for disclosure decisions and skills. • It appears to be acceptable, appropriate, and feasible. • Future trials should examine its impacts on relationship and treatment outcomes. [ABSTRACT FROM AUTHOR]

Randomized controlled trials include interim monitoring guidelines to stop early for safety, efficacy, or futility. Futility monitoring facilitates re-allocation of limited resources. However, conventional methods for interim futility monitoring require a trial to accrue nearly half of the outcome data to make a reliable early stopping decision, limiting its benefit. As early stopping for futility will not inflate type-I error, these analyses are an appealing venue for incorporating external data to improve efficiency. We propose a Bayesian approach to futility monitoring leveraging real world data using Semi-Supervised MIXture Multi-source Exchangeability Models, which accounts for both measured and unmeasured differences between data sources. We implement futility monitoring using predictive probabilities and investigate the optimal timing with respect to the expected sample size under the null hypothesis. Because we only incorporate external data during the interim futility analysis the proposed design is not limited by type-I error inflation. When the external and trial data are exchangeable, the proposed method provides a roughly 70 person reduction in expected sample size under the null. Under scenarios where exchangeability does not hold, our approach still provides a 10–20 person reduction in expected sample size under the null with about 80% power. External data borrowing in interim futility monitoring is a promising venue to improve trial efficiency without type-I error inflation. Approaches that are acceptable to regulatory authorities and leverage the complementary strengths of real world and trial data are vital to more efficiently allocate limited resources amongst clinical trials. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the clinical efficacy and safety of administering intermittent theta burst stimulation (iTBS) to the medial prefrontal cortex for tobacco use disorder. A randomized sham-controlled trial was conducted, with 38 participants receiving 28 sessions of active (n=25) or sham (n=13) iTBS (2 sessions/day, 600 pulses/session, 110% resting motor threshold, AFz target) along with smoking cessation education (Forever Free © booklets) over 14 visits. Primary outcomes included self-reported cigarette consumption and abstinence, verified by urinary cotinine tests. Secondary outcomes included symptoms of tobacco use disorder, negative mood, and safety/tolerability. Both active and sham groups reported reduced cigarette consumption (β = −0.12, p = 0.015), cigarette craving (β = −0.16, p = 0.002), and tobacco withdrawal symptoms (β = −0.05, p < 0.001). However, there were no significant time x group interaction effects for any measure. Similarly, the two groups had no significant differences in urinary cotinine-verified abstinence. Adverse events occurred with similar frequency in both groups. There were no differences in cigarette consumption between the active and sham iTBS groups, both groups decreased cigarette consumption similarly. Further research is needed to compare iTBS to standard high-frequency rTMS and explore the potential differences in efficacy. Despite limitations, this study contributes to experimental design considerations for TMS as a novel intervention for tobacco and other substance use disorders, emphasizing the need for a more comprehensive understanding of the stimulation parameters and target sites. • Intermittent theta burst stimulation (iTBS) was tested for tobacco use disorder. • iTBS was administered on the medial prefrontal cortex for 14 visits. • Both active and sham iTBS reduced the number of cigarettes per day. [ABSTRACT FROM AUTHOR]

High prevalence and harmful consequences of hazardous drinking among medical-surgical patients underscore the importance of intervening with drinking to improve patients' health. This study evaluated a novel intervention, "Drinking Options - Motivate, Shared Decisions, Telemonitor" (DO-MoST). In a randomized design, 155 medical-surgical patients with untreated hazardous drinking were assigned to enhanced usual care or DO-MoST, and followed 3, 6, and 12 months later. We conducted intent-to-treat and per-protocol analyses. For the primary outcome, percent days of alcohol abstinence in the past 30 days, intent-to-treat analyses did not find superior effectiveness of DO-MoST. However, per-protocol analyses found abstinence increased between 3 and 12 months among participants assigned to DO-MoST who engaged with the intervention (n=46). Among DO-MoST-assigned participants who did not engage (n=27), abstinence stayed stable during follow-up. Group comparisons showed an advantage on abstinence for Engaged compared to Non-Engaged participants on change over time. Intent-to-treat analyses found that DO-MoST was superior to usual care on the secondary outcome of physical health at 12 months; per-protocol analyses found that Engaged DO-MoST-assignees had better physical health at 12 months than Non-Engaged DO-MoST-assignees. DO-MoST-assignees had lower odds of receiving substance use care during follow-up than usual care-assignees. Patients engaged in DO-MoST showed a greater degree of abstinence and better physical health relative to the non-engaged or usual care group. DO-MoST may be a source of alcohol help in itself rather than only a linkage intervention. Work is needed to increase DO-MoST engagement among medical-surgical patients with untreated hazardous drinking. • Untreated hazardous drinking harms medical-surgical patients and needs intervention. • RCT studied Drinking Options - Motivate, Shared Decisions, Telemonitor (DO-MoST). • Patients engaged in DO-MoST had better abstinence and physical health than others. • DO-MoST may be a source of alcohol help in itself, not only a linkage intervention. [ABSTRACT FROM AUTHOR]

The safety of BCG revaccination is uncertain and there is no data on its use in patients with COVID-19. COVID-19 convalescent adults confirmed by SARS-CoV-2 RT-PCR in South-America were 1:1 randomized in the first 14 days of symptoms to BCG intradermal vaccine or placebo and evaluated for adverse events on days 7, 14, 21, and beyond 40 days. Clinical Trial Registration: NCT04369794. 151 placebo and 148 BCG patients were included in the final analysis, with an average age of 40.7 years. No severe adverse event to BCG was reported. On day 7, 130 (87.8%) of the BCG recipients had local reaction, average size of 10.6 ± 6.4 mm, compared to only 2 (1.3%) placebos. Lesions gradually shrunk in size (mean 10.5 mm, 9.7 mm, and 6.8 mm at 14, 21, and beyond 40 days, respectively. The number of symptoms in any of the visits was not different between groups, and anosmia resolved earlier (25.7% vs. 37.1% at 7 days, OR = 1.70, 1.01–2.89, p = 0.035) in the BCG recipients. The BCG revaccination is safe in convalescent COVID-19 adults of a tuberculosis endemic region, regardless of tuberculin or IGRA test results. Local adverse events were similar though occurred earlier to that previously reported in children. [ABSTRACT FROM AUTHOR]

To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness. COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here. The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59–68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3–5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%–18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4–21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms. Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19. [ABSTRACT FROM AUTHOR]

COVID-19 triggered an unprecedented crisis affecting society at every level. Research in pediatric and congenital cardiology is currently in full development and may have been disrupted. The aim of the study was to determine the impact of COVID-19 on pediatric and congenital cardiology clinical research and to analyze decision-making and adaptation processes, from a panel of ongoing academic and industry-sponsored research at the time of the pandemic. This observational study was carried out in April 2020, from a CHD clinical research network involving five tertiary care pediatric and congenital cardiology centers. Investigators and clinical research assistants from each participating research center completed an online survey questionnaire, and each principal investigator underwent a 1-h web-based videoconference interview. A total of 34 study questionnaires were collected, reporting that 18 studies were totally suspended. Upon the investigator's decision, after discussion on ethical issues and with facilitating support from health authorities, 16 studies were resumed. The rate of study suspension in interventional research (53%) was similar to that in non-interventional research (56%). Logistical problems were predominantly reported in both continued and suspended trials. Research protocols were adapted, largely thanks to telemedicine, which in some cases even improved the course of the study. The impact of the COVID-19 pandemic on clinical research in pediatric and congenital cardiology has been limited by a rapid adaptation of all research structures and an extensive use of telemedicine at all stages of the studies. [ABSTRACT FROM AUTHOR]

Background: The purpose of this meta-analysis is to compare the merits and drawbacks between reamed intramedullary nailing (RIN) and unreamed intramedullary nailing (URIN) among adults.Methods: We comprehensively searched PubMed, MEDLINE database through the PubMed search engine, Google Scholar, Cochrane Library, Embase, VIPI (Database for Chinese Technical Periodicals), and CNKI (China National Knowledge Infrastructure) from inception to March 2020. Outcomes of interest included nonunion rates, implant failure rates, secondary procedure rates, blood loss, acute respiratory distress syndrome (ARDS) rates, and pulmonary complications rates.Results: Eight randomized controlled trials were included. The result of nonunion rates shows that the nonunion rate is significantly lower in the RIN group (RR = 0.20, 95% CI = 0.09-0.48, Z = 3.63, P = 0.0003). There were no significant differences for the risk of implant failure rates (RR = 0.55, 95% CI = 0.18-1.69, Z = 1.04, P = 0.30). The secondary procedure rates were significantly lower in the RIN group (RR = 0.28, 95% CI = 0.12-0.66, Z = 2.91, P = 0.004). The result shows that the blood loss of URIN group is significantly lower (RR = 145.52, 95% CI = 39.68-251.36, Z = 2.69, P = 0.007). The result shows that there was no significant difference in the ARDS rates (RR = 1.53, 95% CI = 0.37-6.29, Z = 0.59, P = 0.55) and the pulmonary complications rates between RIN group and URIN group (RR = 1.59, 95% CI = 0.61-4.17, Z = 0.94, P = 0.35).Conclusions: Reamed intramedullary nailing would lead to lower nonunion rate, secondary procedure rate and more blood loss. Unreamed intramedullary nailing is related to a higher nonunion rate, secondary procedure rate and less blood loss. No significant difference is found in implant failure rate, ARDS rate and pulmonary complication rate between the two groups. [ABSTRACT FROM AUTHOR]

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

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

We conducted two large-scale, highly powered randomized controlled trials intended to encourage consumer debt repayments. In Study 1, we implemented five treatments varying the design of envelopes sent to debtors. We did not find any treatment effects on response and repayment rates compared to the control condition. In Study 2, we varied the letters' contents in nine treatments, implementing factorial combinations of social norm and (non-)deterrence nudges, which were either framed emotively or non-emotively. We find that all nudges are ineffective compared to the control condition and even tend to induce backfiring effects compared to the agency's original letter. The results of this study contrast with the findings of other studies, which indicate that comparable nudges are highly effective. Thus, our results are more consistent with the literature suggesting that the success of nudging interventions is limited to certain conditions. [ABSTRACT FROM AUTHOR]

A growing body of research documents the positive impacts of teacher coaching, but research contrasting the effectiveness of different coaching approaches is limited. This study contrasted paired coaching – delivered to two teachers simultaneously – with traditional coaching for individual in-service teachers. We examined the effects of these two approaches on observations of teachers' classroom management practices and student behavioral outcomes, relative to non-coached conditions, over the course of a single school year and at a 1-year follow-up. We also explored the relative time and cost efficiency of the two approaches. Two hundred fifty-two teachers from 18 elementary and middle schools participated in the randomized controlled trial. Hierarchical linear modeling was used to account for repeated measures nested within teachers and teachers within schools. Combined effects indicated improved global ratings by observers of teacher behavior management (∆ = 0.29) after a multiple comparison adjustment. Paired coaching was less effective than individual coaching at improving some observed student behaviors, although these did not remain significant after multiple comparison adjustments. Neither model demonstrated sustained effects after one year. Although the paired coaching was significantly more efficient for coach time, it represented just a modest overall cost savings per school. Results indicate a need for more research to identify feasible coaching approaches yielding sustainable effects. [ABSTRACT FROM AUTHOR]

Classic randomized controlled trials (RCTs) form the cornerstone for medical guidelines and protocols. However, in neurosurgery, RCTs are not always applicable to everyday clinical practice. Pragmatic controlled trials aim to incorporate real-life data with the preservation of the methodologic quality. This study is a systematic literature review of all pediatric neurosurgical RCTs published between 2000 and 2020 and an analysis of their pragmatism. An electronic database search was performed in PubMed, EMBASE, and the Cochrane Library to identify all relevant trials. Pragmatism was evaluated retrospectively on 9 domains: eligibility, recruitment, setting, organization, flexibility (delivery and adherence), follow-up, primary outcome, and primary analysis. Of the 1862 studies included, 15 met the inclusion criteria. On average, studies scored between equally pragmatic/explanatory and rather pragmatic (M = 3.59, standard deviation [SD] = 0.56). Lowest ratings were seen for setting (M = 2.80, SD = 1.66) and eligibility (M = 3.20, SD = 1.66). Highest scores of pragmatism were given to analysis (M = 4.67, SD = 0.82) and intervention organization (M = 4.60, SD = 1.06). There was no significant difference between studies based on number of patients included, main subject, or publication year. Pediatric neurosurgical RCTs scored reasonably well on overall pragmatism. In the future, there will be a greater need for pragmatic controlled trials in pediatric neurosurgery to bridge the divide between real-life data and reliable methodological quality. There is an opportunity to develop further applications of pragmatism tailored to surgical interventions. [ABSTRACT FROM AUTHOR]

The aim of this randomized controlled clinical trial was to evaluate the clinical survival and quality parameters of class-II restorations using a bulk-fill composite resin compared to a conventional nanohybrid composite resin in a split-mouth design. One hundred and twenty direct restorations were placed in stress bearing class II cavities (n = 60 test group: Filtek™ Bulk Fill Posterior and n = 60 control group: Filtek™ Supreme XTE) in adult permanent teeth. Survival and clinical quality were evaluated at baseline and after 3 years using modified World Dental Federation (FDI) criteria. Participants and clinical evaluators were blinded relating to the group assignment of the restorations. Seventeen restorations (14.2%) were lost to follow-up, leading to 51 restorations available for survival analysis in the test group and 52 restorations in the control group. Seven restorations showed unfavorable events and were classified as failure. Four bulk-fill restorations failed due to tooth infracture (n = 1), chipping fractures (n = 2) and recurrent decay (n = 1), whereas three conventional nanohybrid composite restorations failed due to adhesive failure (n = 1), tooth infracture (n = 1) and chipping as well as recurrent decay (n = 1). The mean annual failure rate was 2.4% and 1.8%, respectively. The difference between test and control group was not significant (p = 0.7). Data on the detailed assessment of FDI criteria were available for n = 48 and n = 49 restorations, respectively. No significant differences between the two groups could be found regarding the assessment of esthetic, functional and biological properties. Both materials showed similar clinical performance and survival. The use of bulk-fill composite proved to be an esthetically, functionally and biologically satisfactory alternative in the posterior dentition during the 3-year follow-up. [ABSTRACT FROM AUTHOR]

Background: The generalizability of outcomes from randomized controlled trials (RCTs) in oncology is a frequent concern. Given the prevalence and multidisciplinary management of rectal cancer, understanding the generalizability of rectal cancer RCTs is critical to surgical oncologists. Methods: An exhaustive literature review identified 100 non-metastatic rectal cancer RCTs published in English over the past 10 years investigating surgery, chemotherapy, or radiotherapy. In order to evaluate the representativeness of these RCTs compared to the USA and each continent's rectal cancer populations, demographic characteristics were stratified by surgical versus chemoradiotherapy (CRT) trial and by continent then compared with the National Cancer Database and CANCER TODAY using chi-squared and Welch's t-tests. Results: Of the 100 trials identified, 65% enrolled significantly younger patients, and 38% enrolled a significantly greater proportion of males than the US rectal cancer population. These demographic differences were more prominent among CRT trials than surgical trials. Half of all trials enrolled patients who were on average more than 7 years younger and enrolled a 5% greater proportion of males than their respective continental rectal cancer populations. Patients enrolled in trials had more advanced cancers than their corresponding continental populations. Sociodemographic data was rarely reported. Conclusion: Patients enrolled in trials were younger, predominantly male, and had advanced stage cancer when compared to the rectal cancer population. Sociodemographic variables are underreported, further limiting equal participation in clinical trials. Future rectal cancer RCTs should strive to recruit representative samples. To enhance recruitment of women and underrepresented minorities, tailored recruitment strategies must be implemented. [ABSTRACT FROM AUTHOR]

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

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

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

• A randomized controlled trial to examine the effects of a nutrition education and a precise information (awareness-raising) intervention on dietary quality. • A significant and positive association between intervention and dietary quality is found. • The intervention effects are stronger for households with more than 25% and 50% of overweight people. Nutrition education interventions are widely used globally but with mixed results. We conducted a randomized controlled trial to examine the effects of a nutrition education and a precise message (awareness-raising) intervention on nutrition knowledge and dietary quality of households in rural China. Treatment groups first received a lecture on the Chinese Food Guide Pagoda, and then all family members were measured for height and weight and informed of household overweight status. We analyzed 358 households before and after this intervention. Participants in the treatment group increased their dietary knowledge by 6% and improved their dietary quality by 8% after the intervention. The intervention effects were stronger for households with more than 25% and 50% of overweight people. Our study provides evidence that an intervention based on general nutrition information and delivery of a precise message to households can effectively improve dietary quality. Our findings inform the food policy debate on whether nutrition information interventions are effective. Furthermore, to the best of our knowledge, this is the first study to evaluate the effectiveness of a nutrition information intervention to improve dietary quality in rural China. [ABSTRACT FROM AUTHOR]

• Upper-extremity musculoskeletal disorders are a prevalent public health issue. • A short spa therapy intervention did not improve function more than self-management. • Adherence to home exercise was greater for self-management than spa therapy. • Self-management interventions may reduce disability and pain. Musculoskeletal disorders (MSDs) are common in the workplace and are a public health issue. Persistent pain despite conservative treatment or surgery may lead to poor long-term outcomes. To compare the effect of a combined 6-day program of exercise, self-management workshops and spa therapy with self-management on functional capacity in personal and professional daily life at 3 months in people with musculoskeletal disorders. We conducted a prospective, randomized controlled trial. Participants were employed (any type of work) and aged between 18 and 65 years, with latent or symptomatic upper extremity MSDs, with or without a history of sick leave. They were randomized to participate in 6 days (2 h per day) of spa therapy, exercise, and self-management workshops immediately (intervention) or at 3 months (control). The control group performed self-management until 3 months. The primary outcome was the score on the self-reported Quick Disability of Arm-Shoulder-Hand (QuickDASH) at 3 months. The primary analysis was conducted using analysis of covariance with baseline QuickDASH score as the covariate. In total, 150 participants were randomized (85 % women): 78 to the control group and 72 to the intervention group. At 3 months, the QuickDASH total and work scores did not differ between groups (effect-size [ES] = -0.15, 95 %CI, -0.38 to 0.09, p = 0.215, and ES = -0.11, 95 % CI, -0.35 to 0.12, p = 0.343). However, QuickDASH sport/performing arts score was significantly different between randomization groups at 3 months (ES =-0.25, 95 % CI, -0.48 to -0.02, p = 0.035). This study provided no evidence in favor of a short-course, personalized self-management, intensive spa therapy intervention over self-management alone for the management of upper-extremity MSDs. Trial registration: ClinicalTrials.gov (NCT02702466) retrospectively registered. [ABSTRACT FROM AUTHOR]

A novel antibody–drug conjugate, trastuzumab deruxtecan is a combination of a human epidermal growth factor receptor 2 (HER2)-targeting antibody and DNA topoisomerase I inhibitor used to treat HER2-low/positive advanced breast cancer. To determine its safety and efficacy in treating HER2-low/positive advanced breast cancer, we performed a meta-analysis of several randomized clinical trials (RCTs) including DESTINY-Breast02 (NCT03523585), DESTINY-Breast03 (NCT03529110), and DESTINY-Breast04 (NCT03734029). We searched PubMed, Embase, and the Cochrane Library for RCTs on the efficacy and safety of trastuzumab deruxtecan that were published before May 2023. The efficacy endpoints included median progressive-free survival (PFS), overall survival (OS), duration of response (DOR), overall response rate (ORR), and clinical benefit rate (CBR). The safety endpoints included treatment-related adverse events. Statistical analyses were performed using RevMan 5.4 software. To ensure transparency, this study was registered on the International Prospective Register of Systematic Reviews website (CRD42023414170). Three RCTs involving 1689 patients were included. Compared with physician-recommended and conventional treatments, trastuzumab deruxtecan exhibited statistically significant improvements in PFS, ORR, and CBR. The median OS and DOR failed to be combined; however, the analyzed studies showed that they were longer. The incidence of adverse events was generally higher with trastuzumab deruxtecan than with physician-recommended or conventional treatments. The results of this study suggest that trastuzumab deruxtecan is more effective in treating HER2-low/positive advanced breast cancer than physician-recommended or conventional treatments. However, trastuzumab deruxtecan-related adverse drug reactions should be closely monitored because of its higher incidence of adverse events. • HER2-targeted therapy is ineffective in locally advanced or metastatic disease. • Trastuzumab deruxtecan may improve function compared to traditional treatments. • We included 1689 breast cancer patients from three randomized clinical studies. • Verification of trastuzumab deruxtecan's efficacy and safety is needed. [ABSTRACT FROM AUTHOR]

• A home-delivered non-pharmacological intervention contributed to reducing the immediate total and social loneliness of homebound older adults. • The decrease in perceived social loneliness mediated the improvement of depressive symptom levels. • Social loneliness may be a relevant target of intervention to improve depressive symptomatology. The present study aimed to explore whether the Homebound Elderly People Psychotherapeutic Intervention (HEPPI), a home-delivered ten-week cognitive-emotional intervention, was effective in reducing self-reported loneliness among homebound older adults presenting mild cognitive impairment and psychological symptomatology. Effects of HEPPI in total, social, and emotional loneliness, compared with a treatment-as-usual group, were investigated at post-intervention and 3-month follow-up. In addition, the potential role of social and emotional loneliness as mediators of the HEPPI impact on episodic memory and symptoms of depression and anxiety was examined. This study built upon the data of a previously conducted randomized controlled trial. Participants were randomly assigned to the HEPPI group (n = 98) or the treatment-as-usual group (n = 101) and completed baseline, post-intervention, and 3-month follow-up assessments, including measures of loneliness (UCLA - Loneliness scale), episodic memory (Wechsler Memory Scale-III), depressive symptoms (Geriatric Depression Scale-30), and anxiety symptoms (Geriatric Anxiety Inventory). Data were analyzed on an intention-to-treat basis employing linear mixed models and mediation analyses for repeated measures. ClinicalTrials.gov identifier: NCT05499767. Compared with usual care controls, the HEPPI participants reported a significant immediate decrease in total and social loneliness, but these effects were not maintained at a 3-month follow-up. The reduction in immediate perceived social loneliness significantly mediated the improvement of depressive symptoms. The current findings suggest that HEPPI potentially reduced total and social loneliness of the homebound older population immediately post-intervention, and such decrease in social loneliness may be a relevant mechanism for improving their short-term depressive symptomatology. [ABSTRACT FROM AUTHOR]

To improve symptoms and reduce poor outcomes related to heart failure (HF), international guidelines recommend cardiac rehabilitation (CR), particularly for those with a reduced ejection fraction. Unfortunately, patient adherence to rehabilitation programs remains suboptimal, with dropouts ranging from 15.4 to 63.3%. An innovative and promising intervention that could improve adherence to rehabilitation is virtual reality (VR). This study aims to evaluate the effects of VR in patients with HF who undergo CR using this technology in terms of adherence (primary outcome), functional capacity, perceived exertion, angina, quality of life, heart rate, oxygen saturation, blood pressure, maximum oxygen uptake, minute ventilation/carbon dioxide production slope, oxygen pulse, blood values of NT-proBNP and HF related rehospitalization rates (secondary outcomes). A randomized controlled trial will be conducted in a sample of 80 patients referred to CR. Participants will be enrolled in a cardiological rehabilitation unit of a large university hospital in Italy and randomized (1:1) to the experimental intervention consisting of CR performed with high-quality immersive VR with PICO 4® Head Mounted Display headset and TREADMILL XR® software (Arm 1) or standard CR (Arm 2). Patients, according to guidelines, will perform 30-min of CR sessions with moderate intensity, twice a week for one month. Significant improvements in primary and secondary outcomes are expected in patients in the intervention group. If proven to be effective, VR could be an innovative, safe, and easy digital health intervention to improve adherence to CR in patients with HF, as well as important clinical outcomes. [ABSTRACT FROM AUTHOR]

Although cognitive behavioral group therapy (CBGT) is an effective treatment for social anxiety disorder, many socially anxious patients are still symptomatic after treatment. A possible improvement for CBGT could come from the more experiential group psychotherapy, psychodrama (PD). The integration of CBGT and PD (labeled CBPT) might offer an even more effective treatment than CBGT or PD alone. With the present study, we investigated first whether three kinds of group therapy (CBGT, PD, and CBPT) are superior to a waitlist (WL). Second, we investigated whether CBPT is more effective than CBGT or PD alone. One hundred and forty-four social anxiety patients were randomly assigned to three active conditions or a WL. After wait, WL-participants were randomized over the active treatment conditions. The results of a multilevel analysis showed that all treatments were superior to WL in reducing social anxiety complaints. Only CBGT and CBPT differed significantly from WL in reducing fear of negative evaluations. There were no significant differences between active conditions in any of the variables after treatment and after six-month follow up, neither were there significant differences in treatment dropout. First there is the lack of a long-term follow-up. Second, because of loss of participants, we did not reach the planned numbers in the active treatment groups in comparison to WL. Moreover, this study was not designed as a non-inferiority or equivalence trial. Although the integrative CBPT showed good results, it was not more effective than the other treatments. • All treatments were superior to the waiting list group in reducing social anxiety. • Compared to WL, CBGT and CBPT but not PD decreased fear of negative evaluation. • Comparing only active treatments, no treatment was superior to another treatment. [ABSTRACT FROM AUTHOR]

Treatments for eating disorders are moderately effective, with cognitive behavior therapy (CBT) providing the strongest evidence. However, it remains important to investigate other interventions, particularly for eating disorders with greater complexity (e.g., substantial comorbidity; trauma history) or for patients who have not responded adequately to previous treatments. This randomized controlled trial compared CBT against compassion-focused therapy for eating disorders (CFT-E), where half of the sample had a childhood trauma history. The study was pre-registered and adequately powered. A total of 130 patients were randomly assigned to CBT or CFT-E and were assessed at pre-treatment, post-treatment and one-year follow-up. The primary outcome measure was the total score on the Eating Disorder Examination-Interview (EDE), and secondary outcome measures were the Symptom Checklist-90, Inventory of Interpersonal Problems–64 and Post-Traumatic Symptom Scale. Attrition during treatment was low (13%), suggesting good acceptability. Eating pathology (EDE scores) reduced substantially overall, with large effect sizes, and there were no differences between therapies. However, at follow-up, for patients with a childhood trauma history, CFT-E maintained benefits better than CBT. Conclusion : While both CBT and CFT-E resulted in significant reductions in eating pathology, CFT-E showed superior maintenance of benefits for patients with a history of childhood trauma at one-year follow-up, underlining the necessity of tailored interventions for specific patient subgroups. • Lack of treatment studies for eating disorder patients with trauma histories. • First study comparing CFT and CBT for eating disorders. • Both treatments viable; CFT superior in long-term outcomes for patients with trauma histories. [ABSTRACT FROM AUTHOR]

Need-based care is a structured and standardized model that supports formal caregivers in nursing homes in delivering person-centered care by responding with tailored non-pharmacological interventions on residents' unmet needs as well as having positive effects on behavioral and psychological symptoms on residents with dementia. However, limited resources as well as the shortage of caregivers in nursing homes make the implementation of need-based care challenging, especially when it comes to finding ways to spend more time with residents. The aim of this study is to evaluate the impact of the implementation of need-based care in nursing homes on formal caregivers' wellbeing. A three-arm cluster randomized controlled trial was set up in 24 Belgian nursing homes: formal caregivers in the 'need-based care' group (intervention; n = 195) spent time twice a week with residents who had behavioral and psychological symptoms according to the principles of need-based care while formal caregivers in the 'time' group (n = 257) filled in the way they spent time twice a week; a third group delivered standard care (n = 299). An implementation strategy was built upon the Implementation Quality Framework and used in the 'need-based care group'. A total of 741 formal caregivers completed the digital questionnaire at one or more of the five time points (every nine weeks) between November 2021 and July 2022; they rated their sense of competence in dementia care, level of burnout, and, level of engagement. Moments of time were registered in a printed registration book. Only formal caregivers from the 'need-based care' group experienced a higher sense of competence in dementia care at time points three (p = 0.010) and four (p = 0.001) compared with baseline with an increase of respectively 1.5 (95 % confidence interval [0.25, 2.84]) and 2.4 (95 % confidence interval [0.77, 4.04]) points. No differences in scores on burnout and engagement were found. Despite challenging workforce circumstances in nursing homes, caregivers in the need-based care group as well as in the time group were able to spend time twice a week with residents with behavioral and psychological symptoms. No negative effects were found on formal caregivers' wellbeing after the implementation of need-based care in nursing homes. However, it requires strong leadership and the use of well-considered implementation strategies including reflective practice. Trial registration number ISRCTN56768265 (10/08/2023). [ABSTRACT FROM AUTHOR]

Although swallowing exercises are a fundamental treatment for dysphagia, few studies have evaluated the effectiveness of swallowing training in patients with Alzheimer's disease. We recruited 93 patients with Alzheimer's disease from three hospitals in Guangdong, China. This was a parallel armed randomized controlled trial that randomly assigned patients to intervention (n = 48) and control (n = 45) groups. The intervention group adopted systematic stepwise swallowing training for four weeks based on routine dysphagia care. The control group implemented routine dysphagia care, including diet and posture management and health education about swallowing dysfunction. The swallowing function was the primary outcome, which was assessed using the Water Swallowing Test and Standard Swallowing Assessment. An abnormal eating behavior questionnaire was used to assess the incidence of aberrant eating behavior in patients with Alzheimer's disease. The Mini-Nutritional Assessment Short Form and Barthel index were adopted to evaluate the nutritional status and ability to carry out daily activities between groups. SPSS software was used to perform the chi-square test, t -test, and generalized estimation equation for data analysis. We analyzed the effects of the stepwise swallowing training program using the generalized estimating equation method. The intervention group exhibited greater improvements in their swallowing function (Water Swallowing Test: β = − 3.133, 95 % CI: − 4.113, − 2.154, P < 0.001; Standard Swallowing Assessment: β = − 5.813, 95 % CI: − 7.782, − 3.844, P < 0.001), abnormal eating behaviors (abnormal eating behavior questionnaire: β = − 13.324, 95 % CI: − 21.643, − 5.005, P = 0.002), daily function (Barthel index: β = 11.280, 95 % CI: 4.021, 18.540, P = 0.002), and nutritional status (Mini-Nutritional Assessment Short Form: β = 2.402, 95 % CI: 1.313, 3.490, P < 0.001) over time than the routine-care group in the fourth week. Stepwise swallowing training is a safe and effective intervention for managing dysphagia and other related symptoms in patients with Alzheimer's disease. [ABSTRACT FROM AUTHOR]

• Multi-domain cognitive improvements were found following low-intensity rTMS. • The majority of cognitive improvements sustained at 6 months. • Cognitive improvements were not correlated with psychotic improvement. Cognitive impairments are a core symptom of schizophrenia. Although low-intensity repetitive transcranial magnetic stimulation (rTMS) also has cognitive improving effect like the commonly used high-intensity rTMS, it has not been applied in schizophrenia yet. To fill this gap, inpatients with schizophrenia were randomized to receive 20 sessions of daily adjunctive active low-intensity rTMS in 4 weeks, or sham treatment. At baseline, 4 weeks, and 6 months, the Positive and Negative Syndrome Scale (PANSS) was used to assess psychotic symptom severity, while the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color and Word Test (SCWT) were used to assess cognitive functions. Compared to the sixty-nine patients receiving sham treatment, those fifty-nine patients receiving active rTMS performed better in all cognitive domains at post-treatment with small to large effect sizes. This superiority of active rTMS over sham treatment remained significant at 6-month follow-up, with small to large effect sizes, except for visuospatial function and delayed memory. The reduction in PANSS scores were not correlated with cognitive improvements. Our findings provide evidence for using low-intensity rTMS to ameliorate cognitive impairments in schizophrenia. More research are needed to determine the optimal intensity for each domain of cognitive functions. [ABSTRACT FROM AUTHOR]

Mindfulness apps have become popular tools for addressing symptoms of depression and anxiety. Since the publication of earlier meta-analyses evaluating the efficacy of mindfulness apps for depression and anxiety symptoms, over 20 randomized controlled trials (RCTs) have been conducted. There is a need for an updated meta-analysis that quantifies the effects of mindfulness apps on these symptoms and tests for potential moderators.. Random effects meta-analyses were conducted on 45 RCTs. Small, significant effect sizes were found for symptoms of depression (N comp = 46, N = 5852, g = 0.24, 95% CI = 0.17, 0.31, NNT = 13.57) and anxiety (N comp = 48, N = 6082, g = 0.28, 95% CI = 0.21, 0.35, NNT = 11.47) in favour of mindfulness apps over control groups. This effect was not explained by symptom deterioration in participants allocated to control groups. Effects remained stable when restricting analyses to lower risk of bias and larger sample trials. No significant moderators were observed, except trials that offered monetary compensation produced larger effects on depression. Non-significant effects were observed when comparing mindfulness apps to active therapeutic comparisons (g = −0.15 depression, g = 0.10 anxiety), though the number of studies was low. Growing evidence indicates that mindfulness apps can acutely reduce symptoms of depression and anxiety, although higher quality studies with longer follow-ups are needed. • Conducted a meta-analysis of 45 trials of mindfulness apps on depression and anxiety. • Mindfulness apps led to small improvements in depression and anxiety relative to controls. • Mindfulness was not significantly different to active therapeutic comparisons. • Mindfulness apps may help improve symptoms of depression and anxiety to a modest degree. [ABSTRACT FROM AUTHOR]

To investigate the effects of a temporal self-regulation theory-based intervention on self-management in hemodialysis patients. A randomized controlled trial was carried out in Lanzhou, China. Participants were randomly allocated to either the intervention group (n = 42) or control group (n = 42). The outcomes of self-management level, interdialytic weight gain, serum potassium and serum phosphorus were collected at baseline (T0), 1 month after intervention (T1), and 2 months after follow-up (T2). After intervention and follow-up, the self-management score of the intervention group was significantly higher than that of the control group, while the interdialytic weight gain, serum potassium, and serum phosphorus were significantly lower. The group and time interaction effects revealed that participants in the intervention group exhibited significantly greater improvement in self-management at T1 and T2. Interdialytic weight gain decreased significantly at T2. Serum potassium levels did not differ significantly at T1 or T2. The changes in serum phosphorus were both significant at T1 and T2. This study demonstrated that the temporal self-regulation theory-based intervention was effective in improving hemodialysis patients' self-management. The findings suggest popularizing and applying this intervention in the clinic to maintain the long-term effectiveness of the intervention effect. • The temporal self-regulation theory is effective in the education of HD patients. • The intervention promotes HD patients' self-management. • The intervention can maintain the effects in a period of time. [ABSTRACT FROM AUTHOR]

• We assessed chatbot effects on problem gambling, with or without therapist support. • Gambling problems were improved regardless of the presence or absence of therapist support. • Therapist support showed no additional effect on gambling symptoms. • Examining the appropriate intensity and modality of therapist support is needed. Internet-based interventions can be a promising option for individuals with problem gambling facing barriers to seeking help. This study aimed to directly compare the effects of therapist-guided Internet interventions with unguided ones on gambling-related behavior, cognition, and stage of change including help-seeking intention. We conducted a participant-blinded randomized controlled trial of therapist-guided versus unguided groups with a 12-week follow-up. Both groups received self-help chatbot-delivered cognitive behavioral therapy. Additionally, at baseline and weeks 1, 2, 3, and 4, the guided group received personalized feedback messages from therapists based on their gambling diary and questionnaire responses. The unguided group received reminders of assessments from research assistants. The primary outcome was the change in scores on the Gambling Symptoms Assessment Scale (G-SAS) over 12 weeks. Secondary outcomes included the stage of change including help-seeking intention, money wagered, gambling frequency, and gambling-related cognitions. We included 139 participants with a mean Problem Gambling Severity Index total score of 14.6 and a mean G-SAS total score of 27.0 who sought information about gambling problems. Both groups demonstrated substantial decreases in their G-SAS scores from baseline to week 12 (-10.2, 95% CI: −7.67 to −12.7 for the guided group, and 11.7, 95% CI: −9.05 to −14.3 for the unguided group). However, we did not find a significant between-group difference (1.49, 95% CI: −2.20 to 5.17). Regarding the stage of change including help-seeking intention, there were also no between-group differences. Minimum therapist support did not have an additive effect on the self-help chatbot intervention on gambling symptoms, behavior, and the stage of change including help-seeking intention. [ABSTRACT FROM AUTHOR]

To compare the short, medium, and long-term effects of balance exercises combined with either peroneal neuromuscular electrical stimulation (NMES) or peroneal transcutaneous electrical nerve stimulation (TENS) on dynamic postural control and patient reported outcome measures (PROMs) in patients with chronic ankle instability (CAI). Thirty-four participants with CAI were randomly assigned to a 12-session home based exercise program combined with NMES (Ex-NMES) or TENS (Ex- TENS). Baseline postural control was tested with the modified Star Excursion Balance Test (mSEBT) and time to stabilization (TTS) after a single-leg drop-jump. The self-reported function was measured using the Cumberland Ankle Instability Tool (CAIT), the Identification of Functional Ankle Instability (IdFAI), and the Sports subscale of the Foot and Ankle Ability Measure (FAAM Sport). Both groups showed significant improvements in all self-reported outcome measures at the 12-month follow-up. Subjects in the Ex-NMES group had significantly better IdFAI (-4.2 [95% CI −8.1, −0.2]) and FAAM Sport (13.7 [95% CI 2.2, 25.2]) scores at 6- and 12-month follow-up, respectively, compared to the Ex-TENS group. Medium to large between-group effect sizes were observed in self-reported functional outcomes and the mSEBT. The consistent trend of improvement in self-reported functional outcomes when training is combined with NMES compared with training with TENS may indicate a potential benefit that should be further investigated as a treatment for patients with CAI. [ABSTRACT FROM AUTHOR]

Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children's and young adults' HAI titers against the 2019–2020 LAIV4 and ccIIV4. Participants aged 4–21 years were randomized 1:1 to receive ccIIV4 (n = 100) or LAIV4 (n = 98). Blood was drawn prevaccination and on day 28 (21–35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Primary outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers. GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p < 0.05). The GMFR range was 2.4–3.0 times higher for ccIIV4 than for LAIV4 (p < 0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p < 0.05) than cell-grown GMTs [ccIIV4 day 28: egg = 205 (95% CI: 178–237); cell = 136 (95% CI:113–165); LAIV4 day 28: egg = 96 (95% CI: 83–112); cell = 63 (95% CI: 58–74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR. The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. Lower prevaccination titers were associated with greater GMFR in both vaccine groups. [ABSTRACT FROM AUTHOR]

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

Adequate patient education is essential for patients to engage in shared decision-making when deciding to stop or continue anticoagulation after 3 months for venous thromboembolism (VTE). Our objectives were to evaluate the effect of an interactive, educational app on patients' level of satisfaction with information, perceived level of knowledge, decisional conflict and extent of shared decision-making when deciding on treatment duration of VTE. This randomized controlled trial in 1 academic and 3 general Dutch hospitals included adult patients diagnosed with VTE without malignancy or prolonged anticoagulation for other indications. Patients were randomized in 1:1 ratio to receive the app (intervention group) in addition to hospital-specific standard of care. The app, created for this study, contains information on VTE and anticoagulation on an interactive timeline. In the week preceding the consultation when treatment duration is decided, patients were provided with daily videos using push notifications. Outcomes were assessed through self-reported questionnaires at baseline, 1–2 days before and 1 day after consultation. Data were analyzed using t -tests and linear mixed models for repeated measurements. Data of 56 patients were analyzed (mean age 57 ± 13; 27% female). On a numeric rating scale from 0 to 10, patients who received the app were 0.9 points (95%CI 0.0–1.7; p 0.04) more satisfied with the provided information. Patients who received the app experienced significantly less decisional conflict. No differences in other outcomes were observed. An educational app about VTE and anticoagulation increases patients' satisfaction and reduces decisional conflict when deciding on treatment duration of VTE. This study was registered in the Netherlands Trial Register (NL7037). • Patient education is essential when deciding on venous thrombosis (VTE) treatment. • Patients were randomized to receive an educational app or standard education only. • Patients who received the app were more satisfied and had less decisional conflict. • Our results underline the positive effect of adequate information. [ABSTRACT FROM AUTHOR]

Previous research has identified key factors associated with improved average daily gain (ADG) in preweaning dairy calves and these factors have been combined to create a web app–based calf health plan (www.nottingham.ac.uk/herdhealthtoolkit). A randomized controlled trial was conducted to determine the effect of implementing this evidence-based calf health plan on both productivity and health outcomes for calves reared on British dairy farms. Sixty dairy farms were randomized by location (North, South, and Midlands) to either receive the plan at the beginning (INT) or after the end of the trial (CON) and recorded birth and weaning weights by weigh tape, and cases of morbidity and mortality. Calf records were returned for 3,593 calves from 45 farms (21 CON, 24 INT), with 1,760 calves from 43 farms having 2 weights recorded >40 d apart for ADG calculations, with 1,871 calves from 43 farms born >90 d before the end of the trial for morbidity and mortality calculations. Associations between both intervention group and the number of interventions in place with ADG were analyzed using linear regression models. Morbidity and mortality rates were analyzed using beta regression models. Mean ADG was 0.78 kg/d, ranging from 0.33 to 1.13 kg/d, with mean rates of 20.12% (0–96.55%), 16.40% (0–95.24%), and 4.28% (0–18.75%) for diarrhea, pneumonia, and mortality. The INT farms were undertaking a greater number of interventions (9.9) by the end of the trial than CON farms (7.6). Mean farm ADG was higher for calves on INT farms than CON farms for both male beef (MB, +0.22 kg/d) and dairy heifer (DH, +0.03 kg/d) calves. The MB calves on INT farms had significantly increased mean ADG (0.12 kg/d, 95% confidence interval: 0.02–0.22) compared with CON farms. No significant differences were observed between intervention groups for morbidity or mortality. Implementing one additional intervention from the plan, regardless of intervention group, was associated with improvements in mean ADG for DH calves of 0.01 kg/d (0.01, 0–0.03) and MB calves of 0.02 kg/d (0.00–0.04). Model predictions suggest that a farm with the highest number of interventions in place (15) compared with farms with the lowest number of interventions in place (4) would expect an improvement in growth rates from 0.65 to 0.81 kg/d for MB, from 0.73 to 0.88 kg/d for DH, a decrease in mortality rates from 10.9% to 2.8% in MB, and a decrease in diarrhea rates from 42.1% to 15.1% in DH. The calf health plan tested in this study represents a useful tool to aid veterinarians and farmers in the implementation of effective management interventions likely to improve the growth rates, health, and welfare of preweaning calves on dairy farms. [ABSTRACT FROM AUTHOR]

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

We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir–interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support. We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely. The intention-to-treat population included 583 participants—lopinavir/ritonavir (n = 145), lopinavir/ritonavir–IFN–β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)—among whom 418 (71.7%) were male, the median age was 63 years (IQR 54–71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55–1.26, p 0.39), lopinavir/ritonavir–IFN–β-1a versus control, aOR 0.69 (95%CI 0.45–1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62–1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms. In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir–IFN–β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens. [ABSTRACT FROM AUTHOR]

Objective: Many people prefer to learn secondary or "additional" findings from genomic sequencing, including findings with limited medical actionability. Research has investigated preferences for and effects of learning such findings, but not psychosocial and behavioral effects of receiving education about them and the option to request them, which could be burdensome or beneficial (e.g., causing choice overload or satisfying strong preferences, respectively).Methods: 335 adults with suspected genetic disorders who had diagnostic exome sequencing in a research study and were randomized to receive either diagnostic findings only (DF; n = 171) or diagnostic findings plus education about additional genomic findings and the option to request them (DF + EAF; n = 164). Assessments occurred after enrollment (Time 1), after return of diagnostic results and-for DF + EAF-the education under investigation (Time 2), and three and six months later (Times 3, 4).Results: Time 2 test-related distress, test-related uncertainty, and generalized anxiety were lower in the DF + EAF group (ps = 0.025-0.043). There were no other differences.Conclusions: Findings show limited benefits and no harms of providing education about and the option to learn additional findings with limited medical actionability.Practice Implications: Findings can inform recommendations for returning additional findings from genomic sequencing (e.g., to research participants or after commercial testing). [ABSTRACT FROM AUTHOR]

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

• We explored the efficacy of ACT on functioning for chronic pain. • Twelve randomized controlled trials were retrieved. • Low to moderate evidence indicates an immediate effect of ACT on functioning. • It is uncertain whether the effect can be sustained. Chronic pain is a worldwide health problem, Acceptance and Commitment Therapy (ACT) is regarded as one of the promising interventions. ACT aims to help chronic pain patients to create space for pursuing valued life activities in spite of pain. This systematic review of randomized controlled trials (RCTs) examined the efficacy of ACT on functioning for chronic pain. Literature search was performed among seven databases, and 12 RCTs were retrieved. The revised Cochrane risk of bias tool (RoB 2.0) was employed to assess the quality of the 12 RCTs, of which 10 were rated as "low risks", and 2 as "some concerns". Effect sizes of single RCTs and the pooled effect sizes of meta analyses were all rated by Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Low to moderate evidence showed that ACT played a positive immediate role in functioning for patients with chronic pain; however, it is inconsistent whether the effect can be sustained. More RCTs are warranted within specific chronic pain conditions. [ABSTRACT FROM AUTHOR]