Efficacy and safety of sodium–glucose co‐transporter 2 inhibition according to left ventricular ejection fraction in DAPA‐HF

AIMS:The aim of this study was to examine whether left ventricular ejection fraction (LVEF) modified efficacy and safety of dapagliflozin 10 mg compared with placebo in the 4744 patients with LVEF ≤40% randomized in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). METHODS AND RESULTS:We examined whether LVEF, analysed categorically or continuously, modified the effect of dapagliflozin. The primary efficacy outcome was the composite of a worsening heart failure (HF) event (unplanned HF hospitalization/an urgent HF visit requiring intravenous therapy) or cardiovascular death. Mean LVEF was 31.1% and LVEF categories analysed were: <26% (n = 1143), 26-30% (n = 1018), 31-35% (n = 1187), and >35% (n = 1396). Each 5% decrease in LVEF was associated with a higher risk of the primary outcome [hazard ratio (HR) 1.18; 95% confidence interval (CI) 1.13-1.24]. The benefit of dapagliflozin was consistent across the spectrum of LVEF: the dapagliflozin vs. placebo HR was 0.75 (95% CI 0.59-0.95) for LVEF <26%, 0.75 (0.57-0.98) for LVEF 26-30%, 0.67 (0.51-0.89) for LVEF 31-35%, and 0.83 (0.63-1.09) for LVEF >35% (P for interaction = 0.762). Similarly, the effect of dapagliflozin on the components of the primary endpoint was not modified by baseline LVEF (P for interaction for cardiovascular death = 0.974, and for worsening HF = 0.161). Safety of dapagliflozin was also consistent across the range of LVEF and neither efficacy nor safety were modified by diabetes status. CONCLUSION:Left ventricular ejection fraction was a significant predictor of hospitalization and mortality in patients with HF with reduced ejection fraction but did not modify the beneficial effect of dapagliflozin, overall or separately, in patients with and without diabetes. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov Identifier NCT03036124

Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF

Background: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. Methods: We examined the effects of study treatment in the following subgroups: No diuretic and diuretic dose equivalent to furosemide 40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. Results: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on 40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: Hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. Conclusions: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF

A Case Series Study of Help-Seeking among Younger and Older Men in Suicidal Crisis

Due to the continuing high suicide rates among young men, there is a need to understand help-seeking behaviour and engagement with tailored suicide prevention interventions. The aim of this study was to compare help-seeking among younger and older men who attended a therapeutic centre for men in a suicidal crisis. In this case series study, data were collected from 546 men who were referred into a community-based therapeutic service in North West England. Of the 546 men, 337 (52%) received therapy; 161 (48%) were aged between 18 and 30 years (mean age 24 years, SD = 3.4). Analyses included baseline differences, symptom trajectories for the CORE-34 Clinical Outcome Measure (CORE-OM), and engagement with the therapy. For the CORE-OM, there was a clinically significant reduction in mean scores between assessment and discharge (p < 0.001) for both younger and older men. At initial assessment, younger men were less affected by entrapment (46% vs. 62%; p = 0.02), defeat (33% vs. 52%; p = 0.01), not engaging in new goals (38% vs. 47%; p = 0.02), and positive attitudes towards suicide (14% vs. 18%; p = 0.001) than older men. At discharge assessment, older men were significantly more likely to have an absence of positive future thinking (15% vs. 8%; p = 0.03), have less social support (45% vs. 33%; p = 0.02), and feelings of entrapment (17% vs. 14%; p = 0.02) than younger men. Future research needs to assess the long-term effects of help-seeking using a brief psychological intervention for young men in order to understand whether the effects of the therapy are sustainable over a period of time following discharge from the service

Evaluating the role and effectiveness of co‐produced community‐based mental health interventions that aim to reduce suicide among adults: A systematic review

Abstract Background Suicide is a major public health risk requiring targeted suicide prevention interventions. The principles of co‐production are compatible with tailoring suicide prevention interventions to meet an individual's needs. Aims This review aimed to evaluate the role and effectiveness of co‐produced community‐based suicide prevention interventions among adults. Methods Four electronic databases (PsycInfo, CINAHL, MEDLINE and web of science) were systematically searched. A narrative synthesis was conducted. Results From 590 papers identified through searches, 14 fulfilled the inclusion criteria. Most included studies elicited the views and perspectives of stakeholders in a process of co‐design/co‐creation of community‐based suicide prevention interventions. Conclusion Stakeholder involvement in the creation of community‐based suicide prevention interventions may improve engagement and give voice to those experiencing suicidal crisis. However, there is limited evaluation extending beyond the design of these interventions. Further research is needed to evaluate the long‐term outcomes of co‐produced community‐based suicide prevention interventions. Patient and Public Involvement This paper is a systematic review and did not directly involve patients and/or the public. However, the findings incorporate the views and perspectives of stakeholders as reported within the studies included in this review, and the findings may inform the future involvement of stakeholders in the design, development and delivery of community‐based suicide prevention interventions for adults

Ordinary magic in extraordinary circumstances:factors associated with positive mental health outcomes for early adolescents during the COVID-19 pandemic

The COVID-19 pandemic and associated restrictions have had a negative impact on the mental health and wellbeing of many people worldwide, but this may have been particularly challenging for adolescents. However, there is a paucity of research examining the factors associated with good mental health during this time. The aim of the current study was to identify the protective factors amongst early adolescents in the UK that were associated with better mental health outcomes (internalising and externalising difficulties, and wellbeing) during the first national COVID-19 lockdown. Between September and December 2020, 290 11–14 year olds across North West England completed an online survey consisting of several measures pertaining to experiences of lockdown, and mental health and wellbeing. Hierarchical multiple regression was used to analyse the data. Results indicated that higher participant-rated lockdown experience (the extent to which it was fun, easy, and good) and higher levels of optimism were protective factors for all three outcomes of interest. Greater adherence to government guidance was a protective factor for internalising difficulties and wellbeing only, while family keyworker status was protective for externalising difficulties and wellbeing only. Community and school connection were protective factors for internalising difficulties; family connection and number of parents at home were protective factors for externalising difficulties; and peer support and family knowledge of COVID-19 were protective factors for wellbeing. In summary, the ‘ordinary magic’ of supportive relationships and positive experiences appear to be some of the key factors needed to maintain adolescents’ mental health and wellbeing, and to help them overcome difficulties posed by the COVID-19 pandemic

Pulmonary medication adherence and health-care use in cystic fibrosis

Poor treatment adherence is common in cystic fibrosis (CF) and may lead to worse health outcomes and greater health-care use. This study evaluated associations of adherence to pulmonary medications, age, health-care use, and cost among patients with CF. Patients with CF aged ≥ 6 years were identified in a national commercial claims database. A 12-month medication possession ratio (MPR) was computed for each pulmonary medication and then averaged for a composite MPR (CMPR) for each patient. The CMPR was categorized as low (< 0.50), moderate (0.50-0.80), or high (≥ 0.80). Annual health-care use and costs were measured during the first and second year and compared across adherence categories by multivariable modeling. Mean CMPR for the sample (N = 3,287) was 48% ± 31%. Age was inversely related to CMPR. In the concurrent year, more CF-related hospitalizations were observed among patients with low (event rate ratio [ERR], 1.35; 95% CI, 1.15-1.57) and moderate (ERR, 1.25; 95% CI, 1.05-1.48) vs high adherence; similar associations were observed for all-cause hospitalizations and CF-related and all-cause acute care use (hospitalizations + ED) in the concurrent and subsequent year. Rates of CF-related and all-cause outpatient visits did not differ by adherence. Low and moderate adherence predicted higher concurrent health-care costs by $14,211 ($5,557-$24,371) and$8,493 (-$1,691 to$19,709), respectively, compared with high adherence. Worse adherence to pulmonary medications was associated with higher acute health-care use in a national, privately insured cohort of patients with CF. Addressing adherence may reduce avoidable health-care use

Internet-Delivered Cognitive Behavioral Therapy to Treat Insomnia: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>Insomnia is of major public health importance. While cognitive behavioral therapy is beneficial, in-person treatment is often unavailable. We assessed the effectiveness of internet-delivered cognitive behavioral therapy for insomnia.</p><p>Objectives</p><p>The primary objectives were to determine whether online cognitive behavioral therapy for insomnia could improve sleep efficiency and reduce the severity of insomnia in adults. Secondary outcomes included sleep quality, total sleep time, time in bed, sleep onset latency, wake time after sleep onset, and number of nocturnal awakenings.</p><p>Data Sources</p><p>We searched PubMed/MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, PsycInfo, Cochrane Library, Embase, and the Web of Science for randomized trials.</p><p>Methods</p><p>Studies were eligible if they were randomized controlled trials in adults that reported application of cognitive behavioral therapy for insomnia via internet delivery. Mean differences in improvement in sleep measures were calculated using the Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis.</p><p>Results</p><p>We found 15 trials, all utilizing a pretest-posttest randomized control group design. Sleep efficiency was 72% at baseline and improved by 7.2% (95% CI: 5.1%, 9.3%; p<0.001) with internet-delivered cognitive behavioral therapy versus control. Internet-delivered cognitive behavioral therapy resulted in a decrease in the insomnia severity index by 4.3 points (95% CI: -7.1, -1.5; p = 0.017) compared to control. Total sleep time averaged 5.7 hours at baseline and increased by 20 minutes with internet-delivered therapy versus control (95% CI: 9, 31; p = 0.004). The severity of depression decreased by 2.3 points (95% CI: -2.9, -1.7; p = 0.013) in individuals who received internet-delivered cognitive behavioral therapy compared to control. Improvements in sleep efficiency, the insomnia severity index and depression scores with internet-delivered cognitive behavioral therapy were maintained from 4 to 48 weeks after post-treatment assessment. There were no statistically significant differences between sleep efficiency, total sleep time, and insomnia severity index for internet-delivered versus in-person therapy with a trained therapist.</p><p>Conclusion</p><p>In conclusion, internet-delivered cognitive behavioral therapy is effective in improving sleep in adults with insomnia. Efforts should be made to educate the public and expand access to this therapy. Registration Number, Prospero: CRD42015017622</p></div

Mean Differences in Insomnia Severity Index between Internet-Delivered Cognitive Behavioral Therapy for Insomnia and Wait List after Long-Term Follow-up.

<p>Mean Differences in Insomnia Severity Index between Internet-Delivered Cognitive Behavioral Therapy for Insomnia and Wait List after Long-Term Follow-up.</p

Mean Differences in Sleep Efficiency between Internet-Delivered Cognitive Behavioral Therapy for Insomnia and Wait List.

<p>Mean Differences in Sleep Efficiency between Internet-Delivered Cognitive Behavioral Therapy for Insomnia and Wait List.</p