Adaptation of the Tumor Antigen Presentation Machinery to Ionizing Radiation.

Ionizing radiation (IR) can reprogram proteasome structure and function in cells and tissues. In this article, we show that IR can promote immunoproteasome synthesis with important implications for Ag processing and presentation and tumor immunity. Irradiation of a murine fibrosarcoma (FSA) induced dose-dependent de novo biosynthesis of the immunoproteasome subunits LMP7, LMP2, and Mecl-1, in concert with other changes in the Ag-presentation machinery (APM) essential for CD8+ T cell-mediated immunity, including enhanced expression of MHC class I (MHC-I), ß2-microglobulin, transporters associated with Ag processing molecules, and their key transcriptional activator NOD-like receptor family CARD domain containing 5. In contrast, in another less immunogenic, murine fibrosarcoma (NFSA), LMP7 transcripts and expression of components of the immunoproteasome and the APM were muted after IR, which affected MHC-I expression and CD8+ T lymphocyte infiltration into NFSA tumors in vivo. Introduction of LMP7 into NFSA largely corrected these deficiencies, enhancing MHC-I expression and in vivo tumor immunogenicity. The immune adaptation in response to IR mirrored many aspects of the response to IFN-γ in coordinating the transcriptional MHC-I program, albeit with notable differences. Further investigations showed divergent upstream pathways in that, unlike IFN-γ, IR failed to activate STAT-1 in either FSA or NFSA cells while heavily relying on NF-κB activation. The IR-induced shift toward immunoproteasome production within a tumor indicates that proteasomal reprogramming is part of an integrated and dynamic tumor-host response that is specific to the stressor and the tumor and therefore is of clinical relevance for radiation oncology.

Development of a Machine Learning Modelling Tool for Predicting HIV Incidence Using Public Health Data from a County in the Southern United States.

BACKGROUND: Recent advancements in Machine Learning (ML) have significantly improved the accuracy of models predicting HIV incidence. These models typically utilize electronic medical records and patient registries. This study aims to broaden the application of these tools by utilizing de-identified public health datasets for notifiable sexually transmitted infections (STIs) from a southern U.S. County known for high HIV incidence rates. The goal is to assess the feasibility and accuracy of ML in predicting HIV incidence, which could potentially inform and enhance public health interventions. METHODS: We analyzed two de-identified public health datasets, spanning January 2010 to December 2021, focusing on notifiable STIs. Our process involved data processing and feature extraction, including sociodemographic factors, STI cases, and social vulnerability index (SVI) metrics. Various ML algorithms were trained and evaluated for predicting HIV incidence, using metrics such as accuracy, precision, recall, and F1 score. RESULTS: The study included 85,224 individuals, with 2,027 (2.37%) newly diagnosed with HIV during the study period. The ML models demonstrated high performance in predicting HIV incidence among males and females. Influential predictive features for males included age at STI diagnosis, previous STI information, provider type, and SVI. For females, they included age, ethnicity, previous STIs information, overall SVI, and race. CONCLUSIONS: The high accuracy of our ML models in predicting HIV incidence highlights the potential of using public health datasets for public health interventions such as tailored HIV testing and prevention. While these findings are promising, further research is needed to translate these models into practical public health applications.

Neurocognitive and psychiatric outcomes associated with postacute COVID-19 infection without severe medical complication: a meta-analysis.

BACKGROUND: Cognitive symptoms are often reported by those with a history of COVID-19 infection. No comprehensive meta-analysis of neurocognitive outcomes related to COVID-19 exists despite the influx of studies after the COVID-19 pandemic. This study meta-analysed observational research comparing cross-sectional neurocognitive outcomes in adults with COVID-19 (without severe medical/psychiatric comorbidity) to healthy controls (HCs) or norm-referenced data. METHODS: Data were extracted from 54 studies published between January 2020 and June 2023. Hedges' g was used to index effect sizes, which were pooled using random-effects modelling. Moderating variables were investigated using meta-regression and subgroup analyses. RESULTS: Omnibus meta-analysis of 696 effect sizes extracted across 54 studies (COVID-19 n=6676, HC/norm-reference n=12 986; average time since infection=~6 months) yielded a small but significant effect indicating patients with COVID-19 performed slightly worse than HCs on cognitive measures (g=-0.36; 95% CI=-0.45 to -0.28), with high heterogeneity (Q=242.30, p<0.001, τ=0.26). Significant within-domain effects was yielded by cognitive screener (g=-0.55; 95% CI=-0.75 to -0.36), processing speed (g=-0.44; 95% CI=-0.57 to -0.32), global cognition (g=-0.40; 95% CI=-0.71 to -0.09), simple/complex attention (g=-0.38; 95% CI=-0.46 to -0.29), learning/memory (g=-0.34; 95% CI=-0.46 to -0.22), language (g=-0.34; 95% CI=-0.45 to -0.24) and executive function (g=-0.32; 95% CI=-0.43 to -0.21); but not motor (g=-0.40; 95% CI=-0.89 to 0.10), visuospatial/construction (g=-0.09; 95% CI=-0.23 to 0.05) and orientation (g=-0.02; 95% CI=-0.17 to 0.14). COVID-19 samples with elevated depression, anxiety, fatigue and disease severity yielded larger effects. CONCLUSION: Mild cognitive deficits are associated with COVID-19 infection, especially as detected by cognitive screeners and processing speed tasks. We failed to observe clinically meaningful cognitive impairments (as measured by standard neuropsychological instruments) in people with COVID-19 without severe medical or psychiatric comorbidities.

Guided recall of positive autobiographical memories increases anticipated pleasure and psychological resources, and reduces depressive symptoms: a replication and extension of a randomised controlled trial of brief positive cognitive-reminiscence therapy.

Reminiscence-based interventions focus on recalling autobiographical memories and reflective reasoning to develop a healthy and adaptive view of oneself and one's life. This study aimed to replicate the effects of a three-session, group-based, positive-memory version of cognitive-reminiscence therapy (CRT) on psychological resources and mental well-being and extend the findings to anticipated pleasure. The participants (N = 75, Mage = 43.7 (SD = 16.7), 60% females) were randomised to CRT or control group. Anticipated pleasure, psychological resources (schemas of positive self-esteem, self-efficacy, meaning in life, optimism), mental well-being (depression, anxiety, and stress symptoms) and theorised change processes (automatic negative thoughts, awareness of narrative identity) were assessed. Relative to the control group, the CRT group reported significantly higher anticipated pleasure (d = 0.76-0.93) and psychological resources of self-esteem, self-efficacy, and optimism (d's = 0.58-0.99) at post-CRT and follow-up, and lower depressive symptoms post-CRT and at follow-up (d = 0.56-0.67). Findings on meaning in life and negative automatic thinking were partially replicated. This study replicates findings of the effectiveness of this intervention for improving psychological resources such as self-worth, confidence and optimism and depressive symptoms, and indicates additional effects on anticipated pleasure. CRT may serve as a standalone intervention, or as an adjunct "memory booster" for interventions focused on future thinking and related anticipated reward.

Correction: Hamilton et al. Receptors for Insulin-Like Growth Factor-2 and Androgens as Therapeutic Targets in Triple-Negative Breast Cancer. Int. J. Mol. Sci. 2017, 18, 2305.

In the original publication [...].

ERK mediates interferon gamma-induced melanoma cell death.

BACKGROUND: Interferon-gamma (IFNγ) exerts potent growth inhibitory effects on a wide range of cancer cells through unknown signaling pathways. We pursued complementary screening approaches to characterize the growth inhibition pathway. METHODS: We performed chemical genomics and whole genome targeting CRISPR/Cas9 screens using patient-derived melanoma lines to uncover essential nodes in the IFNγ-mediated growth inhibition pathway. We used transcriptomic profiling to identify cell death pathways activated upon IFNγ exposure. Live imaging experiments coupled with apoptosis assays confirmed the involvement of these pathways in IFNγ-mediated cell death. RESULTS: We show that IFNγ signaling activated ERK. Blocking ERK activation rescued IFNγ-mediated apoptosis in 17 of 23 (~ 74%) cell lines representing BRAF, NRAS, NF1 mutant, and triple wild type subtypes of cutaneous melanoma. ERK signaling induced a stress response, ultimately leading to apoptosis through the activity of DR5 and NOXA proteins. CONCLUSIONS: Our results provide a new understanding of the IFNγ growth inhibition pathway, which will be crucial in defining mechanisms of immunotherapy response and resistance.

Severe Maternal Morbidity in Georgia, 2009-2020.

BACKGROUND: The increasing focus of population surveillance and research on maternal-and not only fetal and infant-health outcomes is long overdue. The United States maternal mortality rate is higher than any other high-income country, and Georgia is among the highest rates in the country. Severe maternal morbidity (SMM) is conceived of as a "near miss" for maternal mortality, is 50 times more common than maternal death, and efforts to systematically monitor SMM rates in populations have increased in recent years. Much of the current population-based research on SMM has occurred in coastal states or large cities, despite substantial geographical variation with higher maternal and infant health burdens in the Southeast and rural regions. METHODS: This population-based study uses hospital discharge records linked to vital statistics to describe the epidemiology of SMM in Georgia between 2009 and 2020. RESULTS: Georgia had a higher SMM rate than the United States overall (189.2 vs. 144 per 10,000 deliveries in Georgia in 2014, the most recent year with US estimates). SMM was higher among racially minoritized pregnant persons and those at the extremes of age, of lower socioeconomic status, and with comorbid chronic conditions. SMM rates were 5 to 6 times greater for pregnant people delivering infants <1500 grams or <32 weeks' gestation as compared with those delivering normal weight or term infants. Since 2015, SMM has increased in Georgia. CONCLUSION: SMM represents a collection of life-threatening emergencies that are unevenly distributed in the population and require increased attention. This descriptive analysis provides initial guidance for programmatic interventions intending to reduce the burden of SMM and, subsequently, maternal mortality in the US South.

Analysis of Adsorbed Polyphosphate Changes on Milled Titanium Dioxide, Using Low-Field Relaxation NMR and Photoelectron Spectroscopy.

In this study, changes in the adsorbed amount and surface structure of sodium hexametaphosphate (SHMP) were investigated for aluminum-doped TiO2 pigment undergoing milling. Relaxation NMR was utilized as a potential at-line technique to monitor the effect of milling on surface area and surface chemistry, while XPS was used primarily to consider the dispersant structure. Results showed that considerable amounts of weakly adsorbed SHMP could be removed with washing, and the level of dispersant removal increased with time, highlighting destructive effects of sustained high-energy milling. Nonetheless, there were no significant chemical changes to the dispersant, although increases to the bridging oxygen (BO) peak full width at half-maximum (FWHM) suggested some chemical degradation was occurring with excess milling. Relaxation NMR revealed a number of important features. Results with unmilled material indicated that dispersant adsorption could be tracked with pseudo-isotherms using the relative enhancement rate (Rsp), where the Rsp decreased with dispersant coverage, owing to partial blocking of the quadrupolar surface aluminum. Milled samples were also tracked, with very accurate calibrations of surface area possible from either T1 or T2 relaxation data for systems without dispersant. Behavior was considerably more complicated with SHMP, as there appeared to be an interplay between the dispersant surface coverage and relaxation enhancement from the surface aluminum. Nevertheless, findings highlight that relaxation NMR could be used as a real-time technique to monitor the extent of milling processes, so long as appropriate industrial calibrations can be achieved.

The incidence and characteristics of ventilator-associated pneumonia in a regional nontertiary Australian intensive care unit: A retrospective clinical audit study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a common complication of mechanical ventilation in the intensive care unit. The incidence, patient characteristics, and outcomes have not been described in a regional Australian setting. OBJECTIVES: Τhe primary objective was to establish the incidence of VAP in a regional intensive care unit using predetermined diagnostic criteria. The secondary objective was to compare the agreement between criteria-based and physician-based diagnostic processes. The tertiary objectives were to compare patient characteristics and clinical outcomes of cases with and without VAP. METHODS: A retrospective clinical audit was performed of adult patients admitted to Rockhampton Intensive Care Unit, Australia, between 2013 and 2016. We included all patients ventilated for ≥72 h and not diagnosed with a pneumonia before or during the first 72 h of ventilation. RESULTS: A total of 170 cases met the inclusion criteria. The incidence of VAP as per the criteria-based diagnosis was 27.3 cases per 1000 ventilator days (95% confidence interval [CI]: 18.4-36.2) and as per the physician-based diagnosis was 25.8 cases per 1000 ventilator days (95% CI: 17.1-34.4). There was a moderate chance-corrected agreement between the criteria- and physician-based diagnosis. Very obese cases (body mass index [BMI] ≥40) were nearly four times more likely to develop VAP than cases with normal BMI (BMI <30) (odds ratio: 3.664; 95% CI: 1.394-9.634; p = 0.008). After controlling for sex, BMI category, comorbidities, and Acute Physiology and Chronic Health Evaluation II scores, there was a trend (p = 0.283) for higher adjusted mortality rate for cases with VAP (10.1%, 95% CI: 4.8-21.5) than for those without VAP (6.1%, 95% CI: 3.0-12.4). Cases with VAP had a higher total hospital cost ($123,223 AUD vs $66,425 AUD, p < 0.001), than cases without VAP. CONCLUSIONS: This is the first study reporting incidence of VAP in an Australian regional intensive care unit setting. An increased length of stay and significantly higher hospital costs warrant research investigating reliable and valid clinical prediction rules to forecast those at risk of VAP.

Percutaneous coronary intervention for left main stem disease: Impact of diabetes mellitus on mortality.

OBJECTIVES: We assessed the impact of diabetes mellitus (DM) on mortality after percutaneous coronary intervention (PCI) for left main stem (LMS) disease. Second, we compared mortality outcomes between non-insulin treated (NITDM) and insulin treated diabetes (ITDM) in different clinical settings. BACKGROUND: There is a paucity of "real world" outcomes data in diabetic patients undergoing LMS PCI. METHODS: We undertook a retrospective analysis of consecutive patients undergoing unprotected LMS PCI at 2 high volume tertiary centers. Diabetic status and clinical setting for PCI were recorded. The primary outcome measure was all-cause 30-day and long-term mortality (up to 36 months) post index PCI. RESULTS: Between 2003 and 2017, 2,675 patients undergoing index LMS PCI were analyzed. Of those, 77.1% were non-DM, 15.8% NITDM, and 7.1% ITDM. Overall, DM status was not associated with higher 30-day mortality (OR 1.39, 95% CI 0.89-2.16, p = .15). During a median follow-up of 36 months, there was a borderline statistical association of DM with long-term mortality in all PCI settings (HR 1.31, 95% CI 1.00-1.71, p = .05). Compared to non-DM, ITDM but not NITDM was associated with short- and long-term mortality in all clinical presentations. CONCLUSIONS: Overall, DM did not impact on 30-day mortality and had only a borderline statistical association with long-term mortality. It did not have an influence on mortality in non-emergency LMS PCI. The impact of DM on mortality outcomes following LMS PCI was only significant in the insulin treated patients.

The effect of concentration, reconstitution solution and pH on the stability of a remifentanil hydrochloride and propofol admixture for simultaneous co-infusion.

BACKGROUND: There are scenarios where pre-mixing and infusing analgesic and anaesthetic agents as a single intravenous (IV) solution is highly desirable; however, it is important to ensure the agents are compatible when mixed. As such, the long-term stability of a remifentanil-propofol mixture, and means of improving this, were assessed across a range of remifentanil concentrations, diluents, and time points. METHODS: Remifentanil was reconstituted with ultrapure water, 0.9% saline, 20% saline, or 8.4% sodium bicarbonate solution (the latter two chosen for their pH characteristics, rather than their use in pharmaceutical reconstitution) and then mixed with propofol (1%) or further diluted with water to derive concentrations of 10-50 µg mL- 1. Remifentanil and propofol concentrations were determined initially and then periodically for up to 24 h using high performance liquid chromatography (HPLC). Mass spectrometry (MS) was used to detect degradation products in solutions containing 30 µg mL- 1 of remifentanil. Statistical analysis was performed using ANOVA and Student's t-test, with a significance value of 0.05. RESULTS: Isolated remifentanil (pH < 4) and propofol (pH 7.35) did not degrade significantly when reconstituted with water or saline solution over 24 h, while remifentanil reconstituted with sodium bicarbonate degraded significantly (P < 0.001, pH 8.65). Mixing with propofol substantially increased the pH of the mixture and resulted in significant remifentanil degradation for all reconstitution solutions used, while propofol remained stable (pH 6.50). The amount of degradation product detected in samples containing isolated remifentanil and a mixture of the drugs was proportional to the remifentanil degradation observed. CONCLUSIONS: Remifentanil stability is affected by both the reconstitution solution used and when mixed with propofol, with pH appearing to be a contributing factor to degradation. If the pH of the solution and concentration of remifentanil are correctly controlled, e.g. through the use of a more acidic diluent, an admixture of remifentanil and propofol may be useful clinically.

Effect of Levothyroxine on Left Ventricular Ejection Fraction in Patients With Subclinical Hypothyroidism and Acute Myocardial Infarction: A Randomized Clinical Trial.

Importance: Thyroid hormones play a key role in modulating myocardial contractility. Subclinical hypothyroidism in patients with acute myocardial infarction is associated with poor prognosis. Objective: To evaluate the effect of levothyroxine treatment on left ventricular function in patients with acute myocardial infarction and subclinical hypothyroidism. Design, Setting, and Participants: A double-blind, randomized clinical trial conducted in 6 hospitals in the United Kingdom. Patients with acute myocardial infarction including ST-segment elevation and non-ST-segment elevation were recruited between February 2015 and December 2016, with the last participant being followed up in December 2017. Interventions: Levothyroxine treatment (n = 46) commencing at 25 µg titrated to aim for serum thyrotropin levels between 0.4 and 2.5 mU/L or identical placebo (n = 49), both provided in capsule form, once daily for 52 weeks. Main Outcomes and Measures: The primary outcome measure was left ventricular ejection fraction at 52 weeks, assessed by magnetic resonance imaging, adjusted for age, sex, type of acute myocardial infarction, affected coronary artery territory, and baseline left ventricular ejection fraction. Secondary measures were left ventricular volumes, infarct size (assessed in a subgroup [n = 60]), adverse events, and patient-reported outcome measures of health status, health-related quality of life, and depression. Results: Among the 95 participants randomized, the mean (SD) age was 63.5 (9.5) years, 72 (76.6%) were men, and 65 (69.1%) had ST-segment elevation myocardial infarction. The median serum thyrotropin level was 5.7 mU/L (interquartile range, 4.8-7.3 mU/L) and the mean (SD) free thyroxine level was 1.14 (0.16) ng/dL. The primary outcome measurements at 52 weeks were available in 85 patients (89.5%). The mean left ventricular ejection fraction at baseline and at 52 weeks was 51.3% and 53.8%, respectively, in the levothyroxine group compared with 54.0% and 56.1%, respectively, in the placebo group (adjusted difference in groups, 0.76% [95% CI, -0.93% to 2.46%]; P = .37). None of the 6 secondary outcomes showed a significant difference between the levothyroxine and placebo treatment groups. There were 15 (33.3%) and 18 (36.7%) cardiovascular adverse events in the levothyroxine and placebo groups, respectively. Conclusions and Relevance: In this preliminary study involving patients with subclinical hypothyroidism and acute myocardial infarction, treatment with levothyroxine, compared with placebo, did not significantly improve left ventricular ejection fraction after 52 weeks. These findings do not support treatment of subclinical hypothyroidism in patients with acute myocardial infarction. Trial Registration: isrctn.org Identifier: http://www.isrctn.com/ISRCTN52505169.

Health-Related Quality of Life in Irritable Bowel Syndrome: A Systematic Review and Meta-analysis.

Irritable bowel syndrome (IBS) affects up to 20% of the global population and is associated with impaired health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to investigate differences in HRQoL of those with IBS compared with healthy controls and to examine whether HRQoL improves following psychological intervention. Online databases were searched for articles from 2002 to 2017. Studies were screened and data extracted according to predetermined criteria. A total of 4,154 citations were identified from which 36 were eligible for inclusion. Eight studies compared HRQoL of those with IBS (n = 822) with that of healthy individuals (n = 3,809). Those with IBS suffered significant impairment across all HRQoL domains compared with healthy individuals, with the majority of effects (Cohen's d) being moderate to large. Twenty-eight studies investigated HRQoL in IBS following psychological intervention (n = 1,308) relative to controls (n = 1,006). All HRQoL domains improved with large effects following treatment; however, maintenance of these effects was inconsistent. Those with IBS experience poorer HRQoL than the wider community; nevertheless, psychological interventions are associated with improved HRQoL across all domains. High-quality studies are needed to better inform gastroenterological nurses of which interventions are most efficacious in alleviating the burden of IBS, and which IBS subpopulations would benefit.

A pilot randomised controlled trial of an online mindfulness-based program for people diagnosed with melanoma.

PURPOSE: This study assessed the feasibility and acceptability of an online mindfulness-based intervention (MBI) for people diagnosed with melanoma. The potential benefit of the MBI on fear of cancer recurrence (FCR), worry, rumination, perceived stress and trait mindfulness was also explored. METHODS: Participants who have completed treatment for stage 2c or 3 melanoma were recruited from an outpatient clinic and randomly allocated to either the online MBI (intervention) or usual care (control). The 6-week online MBI comprised short videos, daily guided meditations and automated email reminders. Participants were asked to complete questionnaires at baseline and at 6-week post-randomisation. Study feasibility and acceptability were assessed through recruitment rates, retention and participant feedback. Clinical and psychosocial outcomes were compared between groups using linear mixed models. RESULTS: Sixty-nine (58%) eligible participants were randomised (46 in the intervention; 23 in the control group); mean age was 53.4 (SD 13.1); 54% were female. Study completion rate across both arms was 80%. The intervention was found helpful by 72% of the 32 respondents. The intervention significantly reduced the severity of FCR compared to the control group (mean difference = - 2.55; 95% CI - 4.43, - 0.67; p = 0.008). There was no difference between the intervention and control groups on any of the outcome measures. CONCLUSIONS: This online MBI was feasible and acceptable by people at high risk of melanoma recurrence. It significantly reduced FCR severity in this sample. Patients valued accessing the program at their own pace and convenience. This self-guided intervention has the potential to help survivors cope with emotional difficulties. An adequately powered randomised controlled trial to test study findings is warranted.

The computerized scoring algorithm for the autobiographical memory test: updates and extensions for analyzing memories of English-speaking adults.

The Autobiographical Memory Test (AMT) has been central in psychopathological studies of memory dysfunctions, as reduced memory specificity or overgeneralised autobiographical memory has been recognised as a hallmark vulnerability for depression. In the AMT, participants are asked to generate specific memories in response to emotional cue words, and their responses are scored by human experts. Because the manual coding takes some time, particularly when analysing a large dataset, recent studies have proposed computerised scoring algorithms. These algorithms have been shown to reliably discriminate between specific and non-specific memories of English-speaking children and Dutch- and Japanese-speaking adults. The key limitation is that the algorithm is not developed for English-speaking adult memories, which may cover a wider range of vocabulary that the existing algorithm for English-speaking child memories cannot process correctly. In the present study, we trained a new support vector machine to score memories of English-speaking adults. In a performance test (predicting memory specificity against human expert coding), the adult-memory algorithm outperformed the child-memory variant. In another independent performance test, the adult-memory algorithm showed robust performances to score memories that were generated in response to a different set of cues. These results suggest that the adult-memory algorithm reliably scores memory specificity.

The impact of diabetes on the prognostic value of left ventricular function following percutaneous coronary intervention: Insights from the British Cardiovascular Intervention Society.

OBJECTIVES: To study the relationship between diabetes mellitus (DM) and left ventricular (LV) function on outcomes following percutaneous coronary intervention (PCI). BACKGROUND: DM is a growing public health challenge worldwide and a significant risk factor for cardiovascular disease and heart failure. METHODS: All PCI procedures performed between 2006 and 2013 with LV function and diabetic status recorded in the BCIS-NICOR database were included. Demographic, procedural, and clinical outcomes data were collected. Multivariable logistic regression was used to provide adjusted estimates of clinical outcome by LV function and DM, including DM sub-type. RESULTS: Of 260,726 patients, DM was present in 52,160 (20%); moderate LV systolic dysfunction (LVSD) was present in 51,266 (20%), and severe LVSD in 18,148 (7%). Worsening LVSD in diabetic patients was associated with poorer prognosis following PCI; moderate LVSD odds ratio (OR) 2.03 (95% CI 1.72-2.38) and severe LVSD OR 4.17 (95% CI 3.52-4.93). There was a higher crude and adjusted mortality rate for patients with DM across all grades of LVSD. However, the relative effect of DM appeared attenuated in the severe LVSD group compared with moderate or good LV function, particularly evident in patients with insulin requiring DM (good LV OR 2.09 [95% CI 1.66-2.65]; moderate LVSD OR 1.56 [95% CI 1.26-1.93], poor LV OR 1.40 [95% CI 1.13-1.74]). CONCLUSIONS: DM was associated with increased 30-day mortality for all grades of LV function. The prognostic impact of DM was strongest in patients with normal LV function and less evident in patients with severe LV systolic dysfunction.

Systematic review of meditation-based interventions for children with ADHD.

Meditation-based interventions such as mindfulness and yoga are commonly practiced in the general community to improve mental and physical health. Parents, teachers and healthcare providers are also increasingly using such interventions with children. This review examines the use of meditation-based interventions in the treatment of children with Attention-Deficit Hyperactivity Disorder (ADHD). Electronic databases searched included PsycINFO, Medline, CINAHL, and AMED. Inclusion criteria involved children (aged to 18 years) diagnosed with ADHD, delivery of a meditation-based intervention to children and/or parents, and publication in a peer-reviewed journal. Studies were identified and coded using standard criteria, risk of bias was assessed using Risk of Bias in Non-randomised Studies- of interventions (ROBINS-I), and effect sizes were calculated. A total of 16 studies were identified (8 that included children in treatment, and 8 that included combined parent-child treatment). Results indicated that risk of bias was high across studies. At this stage, no definitive conclusions can be offered regarding the utility of meditation-based interventions for children with ADHD and/or their parents, since the methodological quality of the studies reviewed is low. Future well designed research is needed to establish the efficacy of meditation-based interventions, including commonly used practices such as mindfulness, before recommendations can be made for children with ADHD and their families.

Impact of irritability: a 2-year observational study of outpatients with bipolar I or schizoaffective disorder.

OBJECTIVES: Many people experience irritability when manic, hypomanic, or depressed, yet its impact on illness severity and quality of life in bipolar and schizoaffective disorders is poorly understood. This study aimed to examine the relationship between irritability and symptom burden, functioning, quality of life, social support, suicidality, and overall illness severity in a naturalistic cohort of people with bipolar I or schizoaffective disorder. METHODS: We used data from 239 adult outpatients with bipolar I or schizoaffective disorder in the Bipolar Comprehensive Outcomes Study (BCOS) - a non-interventional observational study with a 2-year follow-up period. Baseline demographic and clinical characteristics of participants with and without irritability were compared. A mixed-model repeated measures analysis was conducted to examine the longitudinal effect of irritability on clinical and quality-of-life variables over follow-up using significant baseline variables. RESULTS: At baseline, 54% of participants were irritable. Baseline irritability was associated with illness severity, mania, depression, psychotic symptoms, suicidality, poor functioning, and quality of life, but not diagnosis (schizoaffective/bipolar disorder). Participants with irritability were less likely to have a partner and perceived less adequate social support. On average, over follow-up, those with irritability reported more symptoms, functional impairment, and suicidality. Furthermore, the effects of irritability could not be fully explained by illness severity. CONCLUSIONS: Irritability was associated with more negative symptomatic, functional, and quality-of-life outcomes and suicidality. The identification, monitoring, and targeted treatment of irritability may be worth considering, to enhance health and wellbeing outcomes for adults with bipolar and schizoaffective disorders.

An online psychological intervention can improve the sexual satisfaction of men following treatment for localized prostate cancer: outcomes of a Randomised Controlled Trial evaluating My Road Ahead.

BACKGROUND: Prostate cancer treatment often results in significant psycho-sexual challenges for men following treatment; however, many men report difficulty in accessing appropriate care. METHODS: A randomized controlled trial was undertaken to assess the efficacy of a 10-week self-guided online psychological intervention called My Road Ahead (MRA) for men with localized prostate cancer in improving sexual satisfaction. Participants were randomized to 1 of 3 conditions MRA alone or MRA plus online forum, or forum access alone. Pre, post, and follow-up assessments of overall sexual satisfaction were conducted. Mixed models and structural equation modeling were used to analyze the data. RESULTS: One hundred forty-two men (mean age 61 y; SD = 7) participated. The majority of participants had undergone radical prostatectomy (88%) and all men had received treatment for localized prostate cancer. Significant differences were obtained for the 3 groups (P = .026) and a significant improvement in total sexual satisfaction was observed only for participants who were allocated to MRA + forum with a large effect size (P = .004, partial η2  = 0.256). Structural equation modeling indicated that increases in sexual function, masculine self-esteem, and sexual confidence contributed significantly to overall sexual satisfaction for the MRA + forum plus forum condition. CONCLUSIONS: This study is the first, to our knowledge, that has evaluated a self-guided online psychological intervention tailored to the specific needs of men with prostate cancer. The findings indicate the potential for MRA to deliver support that men may not otherwise receive and also highlight the importance of psychological intervention to facilitate improved sexual outcomes.