Protocol for scoping review study to map out the existing research in relation to post-traumatic stress symptoms among caregivers of individuals with neurodevelopmental, psychiatric and neurocognitive disorders

Introduction
The challenges of providing caregiving that impacts the caregiver have been attributed to high levels of intensity and physical strain, burden and distress. This is likely to include emotional and psychological distress as manifested in post-traumatic stress symptoms (PTSS). As this is a new area of investigation among caregivers of individuals with neurodevelopmental, neurocognitive and psychiatric disorders, the extent of the literature for PTSS in these groups of caregivers is limited and unclear. This scoping review aims to map the existing research focusing on key concepts and identifying gaps in relation to PTSS among these caregivers.

Methods and analysis
The scoping review will be guided by Arksey and O’Malley’s proposed 5-stage framework. A search for published and unpublished grey literature between years 2005 to 2020 in the electronic databases of CINAHL, SCOPUS, PsychInfo, OVID PubMed and ProQuest Dissertation, and Thesis Global electronic databases was conducted using keywords to identify relevant studies. Articles will be limited to the English language. Endnote 20 software will be used to eliminate duplicates, and results will be exported into Abstrackr for the review screening process consisting of two stages: title and abstract reviews and full-text reviews. Selection process of eligible studies will follow the recommendations in the Preferred Reporting Items of Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist. A data chart will be used to capture relevant information from all included studies, and results will be presented in tabular form and in a narrative report.

Ethics and dissemination
This scoping review consists of reviewing and collecting data from publicly available materials and hence does not require ethics approval. The scoping review results will be disseminated via publications in peer-reviewed journals and conference presentations. The results will also guide the design of a mixed method research study to examine the extent of trauma symptomatology and potentially traumatising experiences, and how they relate to the mental health of caregivers of adults with intellectual and developmental disability from different cultural backgrounds.

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Novembre 2022

Perceived job demands: a qualitative study of workplace stress in the Iranian healthcare workers (HCWs)

Objectives
Work-related stress is a common risk factor among healthcare workers (HCWs). In Iran, the healthcare system has undergone extensive changes to develop services. Organisational change has led to the creation of new working conditions for HCWs. The purpose of this study is to identify job demands that health workers perceive as stressors.

Design
As a qualitative study, semistructured interviews, a focus group, and related data were analysed both inductively and deductively with reference to the job demand component based on the job demands–resources model and MAXQDA.

Setting
This investigation was conducted in 18 primary healthcare centres in Qazvin, Iran.

Participant
Twenty-one female HCWs with at least 6 months of work experience and an average age of 34.4 years.

Results
The participants identified six key elements as the stressful job demands including organisation’s supervisory function, role characteristics, workload, job insecurity, client service challenges and perceived job content.

Conclusions
After organisational changes and development, HCWs were faced with role changes and increased workload. In addition, organisational supervision in terms of quantity and quality and lack of job security intensified the pressures. These factors led to the high level of stress among employees who dealt with people and those who perceived their job content as unfavourable. Perhaps teaching stress control skills and organisational support interventions can be useful to reduce and control stress among HCWs.

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Novembre 2022

Trends of blood pressure, raised blood pressure, hypertension and its control among Italian adults: CUORE Project cross-sectional health examination surveys 1998/2008/2018

Objectives
To assess in the Italian general adult population the trends of blood pressure (BP) and prevalence of raised BP (RBP), hypertension and its control in order to evaluate population health and care, and the achievement of an RBP 25% relative reduction as recommended by the WHO at population level.

Design
Results comparison of health examination surveys, cross-sectional observational studies based on health examination of randomly selected age and sex stratified samples including residents aged 35–74 years. Data of the 2018/2019 survey were compared with the previous ones collected in 1998/2002 and 2008/2012.

Setting
Health examination surveys conducted in Italy within the CUORE Project following standardised methodologies.

Participants
2985 men and 2955 women examined in 1998/2002, 2218 men and 2204 women examined in 2008/2012 and 1031 men and 1066 women examined in 2018/2019.

Primary and secondary outcome measures
Age-standardised mean of BP, prevalence of RBP (systolic BP and/or diastolic BP ≥140/90 mm Hg), hypertension (presenting or being treated for RBP) and its awareness and control, according to sex, age class and educational level.

Results
In 2018/2019, a significant reduction was observed in systolic BP and diastolic BP in men (1998/2002: 136/86 mm Hg; 2008/2012: 132/84 mm Hg; and 2018/2019: 132/78 mm Hg) and women (132/82 mm Hg, 126/78 mm Hg and 122/73 mm Hg), and in the prevalence of RBP (50%, 40% and 30% in men and 39%, 25% and 16% in women) and of hypertension (54%, 49% and 44% in men and 45%, 35% and 32% in women). Trends were consistent by age and education attainment. In 2018/2019, hypertensive men and women with controlled BP were only 27% and 41%, but a significant favourable trend was observed.

Conclusions
Data from 2018/2019 underlined that RBP is still commonly observed in the Italian population aged 35–74 years, however, the WHO RBP target at that time may be considered met.

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Novembre 2022

NFATc1 signaling drives chronic ER stress responses to promote NAFLD progression

Objectives
Non-alcoholic fatty liver disease (NAFLD) can persist in the stage of simple hepatic steatosis or progress to steatohepatitis (NASH) with an increased risk for cirrhosis and cancer. We examined the mechanisms controlling the progression to severe NASH in order to develop future treatment strategies for this disease.

Design
NFATc1 activation and regulation was examined in livers from patients with NAFLD, cultured and primary hepatocytes and in transgenic mice with differential hepatocyte-specific expression of the transcription factor (Alb-cre, NFATc1c.a . and NFATc1/ ). Animals were fed with high-fat western diet (WD) alone or in combination with tauroursodeoxycholic acid (TUDCA), a candidate drug for NAFLD treatment. NFATc1-dependent ER stress-responses, NLRP3 inflammasome activation and disease progression were assessed both in vitro and in vivo.

Results
NFATc1 expression was weak in healthy livers but strongly induced in advanced NAFLD stages, where it correlates with liver enzyme values as well as hepatic inflammation and fibrosis. Moreover, high-fat WD increased NFATc1 expression, nuclear localisation and activation to promote NAFLD progression, whereas hepatocyte-specific depletion of the transcription factor can prevent mice from disease acceleration. Mechanistically, NFATc1 drives liver cell damage and inflammation through ER stress sensing and activation of the PERK-CHOP unfolded protein response (UPR). Finally, NFATc1-induced disease progression towards NASH can be blocked by TUDCA administration.

Conclusion
NFATc1 stimulates NAFLD progression through chronic ER stress sensing and subsequent activation of terminal UPR signalling in hepatocytes. Interfering with ER stress-responses, for example, by TUDCA, protects fatty livers from progression towards manifest NASH.

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Novembre 2022

Traumatic stress symptoms in family caregivers of patients with acute leukaemia: protocol for a multisite mixed methods, longitudinal, observational study

Introduction
The diagnosis, progression or recurrence of cancer is often highly traumatic for family caregivers (FCs), but systematic assessments of distress and approaches for its prevention and treatment are lacking. Acute leukaemia (AL) is a life-threatening cancer of the blood, which most often presents acutely, requires intensive treatment and is associated with severe physical symptoms. Consequently, traumatic stress may be common in the FCs of patients with AL. We aim to determine the prevalence, severity, longitudinal course and predictors of traumatic stress symptoms in FCs of patients with AL in the first year after diagnosis, and to understand their lived experience of traumatic stress and perceived support needs.

Methods and analysis
This two-site longitudinal, observational, mixed methods study will recruit 223 adult FCs of paediatric or adult patients newly diagnosed with AL from two tertiary care centres. Quantitative data will be collected from self-report questionnaires at enrolment, and 1, 3, 6, 9 and 12 months after admission to hospital for initial treatment. Quantitative data will be analysed using descriptive and machine learning approaches and a multilevel modelling (MLM) approach will be used to confirm machine learning findings. Semi-structured qualitative interviews will be conducted at 3, 6 and 12 months and analysed using a grounded theory approach.

Ethics and dissemination
This study is funded by the Canadian Institutes of Health Research (CIHR number PJT 173255) and has received ethical approval from the Ontario Cancer Research Ethics Board (CTO Project ID: 2104). The data generated have the potential to inform the development of targeted psychosocial interventions for traumatic stress, which is a public health priority for high-risk populations such as FCs of patients with haematological malignancies. An integrated and end-of-study knowledge translation strategy that involves FCs and other stakeholders will be used to interpret and disseminate study results.

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Novembre 2022

Effects of mindfulness-based stress reduction on adults with sleep disturbance: an updated systematic review and meta-analysis

Objective
Mindfulness-based stress reduction (MBSR) is a meditation-based therapy originally recommended for stress management. However, it is currently used to alleviate sleep disturbances. Therefore, this contemporary systematic review aimed to elucidate the clinical effects of MBSR on sleep quality and sleep-related daytime impairment in adults with sleep disturbances, including chronic insomnia disorders.

Design
Systematic review and meta-analysis of randomised controlled trials (RCTs).

Methods
A comprehensive search was conducted using the following databases: Ovid MEDLINE, AMED, Ovidembase, PsycINFO, Cochrane Library, CINAHL, and four domestic databases: KoreaMed, KISS, KMbase and NDSL. The final search update was performed in June 2022. Two researchers independently selected relevant studies, assessed the risk of bias and extracted the data.

Results
Of the 7516 records searched, 20 RCTs and 21 reports were included. In the subgroup analysis, MBSR did not improve objective or subjective sleep quality in chronic insomnia and cancers. However, MBSR versus waitlist control might have been effective in improving subjective sleep quality, but with substantial heterogeneity (standardised mean difference=–0.32; 95% CI: –0.56 to –0.08; I2=71%). In addition, MBSR compared with active control did not improve the sleep-related daytime impairments including depression, anxiety, stress, fatigue and quality of life. The overall risk of bias included in this review was a concern because of performance and detection bias.

Conclusions
MBSR might be ineffective for improving sleep quality in patients with chronic insomnia and cancers. In addition, more than half of the RCTs included in this review had small sample sizes and were vulnerable to performance and detection biases. Therefore, well-designed RCTs with larger sample sizes are required to confirm the clinical effects of MBSR in adults with sleep disturbances.

PROSPERO registration number
CRD42015027963.

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Novembre 2022

Abstract 14496: NOX2 Inhibition Reverses Atrial Remodeling Caused by Increased Oxidative Stress and Reduces AF in Diet Induced Obese Mice

Circulation, Volume 146, Issue Suppl_1, Page A14496-A14496, November 8, 2022. Introduction:Diet induced obese (DIO) mice display increased inducible atrial fibrillation (AF) and an overall increase in reactive oxygen species (ROS) production. NADPH oxidase 2 (NOX2), a major source of cytosolic ROS production in human atria, has been implicated in AF independent of obesity and is significantly increased in the atria of DIO mice. Although treatment with MitoTEMPO, a mitochondrial specific antioxidant reduced AF burden in DIO mice, the actual role of NOX2 in increasing ROS production and atrial remodeling in the context of obesity-induced AF remains unclear.Hypothesis:To test the hypothesis that increased NOX2 modulates atrial remodeling in obesity-induced AF, we used control mice, DIO andNox2-KO mice fed with a 60% HFD for 10 weeks (DIO-KO) and DIO mice treated with a NOX2 blocker, apocynin (DIO-Apocynin).Methods:Trans-esophageal rapid (TE) pacing was used to look at the AF phenotype. Cellular electrophysiology (EP), Western blotting, whole-cell patch clamping were performed to study ion channel remodeling and ROS production.Results:All three DIO mouse groups displayed significantly greater body weight compared to their respective controls (Figure A) After TE pacing, DIO-Apocynin mice displayed 28.26 ± 25.40 s and DIO-KO mice displayed 17.43 ± 31.80 s compared to 167.3 ± 168.9 s in DIO mice (Figure B). NOX2 inhibition reversed obesity-induced ion channel remodeling of potassium channels such asKCNQ1andKCNE1encoding for the IKs current andKCNA5encoding for the IKur current and also reduced mediators of oxidative stress. (Figure C-M) Lastly, voltage clamp in DIO-KO mice showed that NOX2 inhibition reverses obesity-induced IK current increase. (Figure N-O)Conclusions:Thus, these results prove that antioxidant therapy targeting Nox2 abrogated ion channel remodeling and reversed the obesity-induced AF burden. Our findings show the importance of targeting specific antioxidant pathways to manage the AF in patients with obesity.

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Ottobre 2022

Abstract 11330: Association of Left Ventricular Wall Stress and Incident Heart Failure in Elderly Community Dwelling Individuals

Circulation, Volume 146, Issue Suppl_1, Page A11330-A11330, November 8, 2022. Introduction:Greater left ventricular (LV) wall stress is associated with adverse outcomes among patients with prevalent heart failure (HF). Less is known about the association between LV wall stress and risk of incident HF in community dwelling individuals.Methods:Using data from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center, we studied 4,601 participants of the Atherosclerosis Risk in Communities study without prevalent HF who underwent echocardiography at visit 5 (2011-2013). LV end systolic and diastolic wall stress (LVESWS, LVEDWS) were calculated from chamber and wall thickness measures, E/e’ as a surrogate for LV end diastolic pressure, and systemic blood pressure. Incident HF was assessed by cohort surveillance for hospitalized HF through December 31, 2016. The relationship between LVESWS and LVEDWS was examined by Spearman rank correlation. The association between wall stress and risk of incident HF was tested in Cox regression adjusted for demographics, traditional CV risk factors, prevalent CAD and atrial fibrillation, as well as creatinine, NT-proBNP, troponin, triglycerides, C-reactive protein, LV ejection fraction, and LV mass.Results:The cohort was elderly (median age 75 years), predominantly female (58%), with 18% of individuals identifying as black. Median LVESWS and LVEDWS were 48.8 (IQR: 39.3, 60.1) and 18.9 (IQR: 15.8, 22.5) kdynes/cm2, respectively. LVESWS and LVEDWS were modestly correlated (rho = 0.30, p

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Ottobre 2022

Abstract 15056: Cardiac P62/sqstm1 Deficiency Exacerbates Hypoxic Stress via Impaired Hypoxia Inducible Factor 1α Signaling

Circulation, Volume 146, Issue Suppl_1, Page A15056-A15056, November 8, 2022. Ischemic heart disease (IHD), a major cause of heart failure, is characterized by metabolic dysfunction and myocardial cell death. Cellular hypoxia activates hypoxia inducible factor 1α (HIF1α) to initiate metabolic, angiogenic, and growth-factor related responses. Under normoxia, HIF1α is degraded by prolyl hydroxylase (PHD) domain-containing proteins via the proteasome. Due to the short half-life of HIF1α (

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Ottobre 2022

Abstract 10014: Work-Related Stress and Ideal Cardiovascular Health: The Multi-Ethnic Study of Atherosclerosis

Circulation, Volume 146, Issue Suppl_1, Page A10014-A10014, November 8, 2022. Background:Work-related stress is a psychosocial risk factor linked to a higher risk of adverse health outcomes, especially cardiovascular disease (CVD). However, the association between work-related stress and ideal cardiovascular health (CVH) is not well established. We examined whether work-related stress was negatively associated with favorable CVH in a multi-ethnic population of adults free of CVD at baseline.Methods:We analyzed cross-sectional data of 6,486 men and women aged 45-84 years. Work-related stress was assessed by the presence or absence of ongoing job difficulty and ongoing job difficulty for >6 months. CVH was measured by a scoring system that assigned points to 7 metrics (smoking, physical activity, body mass index, diet, total cholesterol, blood pressure and blood glucose). Each metric had 3 categories: poor (0 points), intermediate (1 point) and ideal (2 points). The total score attainable was 14 points, categorized as inadequate (0-8 points), average (9-10 points) and optimal (11-14 points). We used polytomous logistic regression to examine the association of work-related stress with the CVH score and number of ideal metrics, adjusted for sociodemographic factors.Results:The mean age (SD) was 62 (10) years and 53% were women. Ongoing job difficulty was reported by 14% of participants while 13% reported ongoing job difficulty for >6 months. Participants who reported ongoing job difficulty had 21% and 24% lower odds of having average and optimal CVH scores, respectively(Table).Additionally, the presence of ongoing job difficulty for >6 months was associated with 23% and 24% lower odds of having average and optimal CVH scores, respectively. A similar trend was observed for the association of work-related stress with the number of ideal metrics.Conclusion:Work-related stress was negatively associated with favorable CVH. Stress reduction and CVH promotion programs in the workplace may decrease the incidence of CVD.

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Ottobre 2022

Abstract 15731: Rpl13a Small Nucleolar RNAs Promote Atherosclerosis and Oxidative Stress

Circulation, Volume 146, Issue Suppl_1, Page A15731-A15731, November 8, 2022. Reactive oxygen species (ROS) exacerbate atherosclerosis (athero). ROS levels are elevated by specific non-coding, small nucleolar (sno) RNAs encoded within introns of theRpl13agene. We therefore tested the hypothesis that these snoRNAs promote athero, using “snoKO” mice deficient inRpl13asnoRNAs, but not inRpl13aitself. ROS levels assessed by CellROX Orange were 35% lower in snoKO than snoRNA+/+aorta frozen sections (p

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Ottobre 2022