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Chloroquine decreases cardiac fibrosis and improves cardiac function in a mouse model of Duchenne muscular dystrophy

by Takuya Hirata, Shiro Baba, Kentaro Akagi, Koichi Matsuda, Katsutsugu Umeda, Souichi Adachi, Toshio Heike, Junko Takita

Background

Duchenne muscular dystrophy (DMD), a severe degenerative skeletal and cardiac muscle disease, has a poor prognosis, and no curative treatments are available. Because decreased autophagy has been reported to contribute to skeletal muscle degeneration, therapies targeting autophagy are expected to improve skeletal muscle hypofunction. However, the role of this regulatory mechanism has not been evaluated clearly in DMD cardiomyocytes.

Methods

In this present study, we evaluated myocardial fibrosis and its mechanism in mdx mice, a model of DMD, and also evaluated changes in cardiac function.

Results

As assessed by LC3 immunohistochemistry, a small number of autophagosomes were detected in cardiomyocytes of both mdx mice and control wild-type (WT) mice. The number of autophagosomes was significantly enhanced by 4 weeks of isoproterenol-induced cardiac stress in cardiomyocytes of mdx but not WT mice. Simultaneously, isoproterenol increased cardiomyocyte fibrosis in mdx but not WT mice. Administration of chloroquine significantly decreased cardiomyocyte fibrosis in mdx mice, even after isoproterenol treatment. Left ventricle size and function were evaluated by echocardiography. Left ventricular contraction was decreased in mdx mice after isoproterenol treatment compared with control mice, which was alleviated by chloroquine administration.

Conclusions

Heart failure in DMD patients is possibly treated with chloroquine, and the mechanism probably involves chloroquine’s anti-inflammatory effects.

Profiles of vulnerability for suicide and self-harm in UK prisoners: Neurodisability, mood disturbance, substance use, and bullying

by Hope Kent, Bella Magner-Parsons, George Leckie, Tuna Dulgar, Anggita Lusiandari, Lee Hogarth, Huw Williams, Amanda Kirby

Screening for vulnerability factors associated with historic suicidality and self-harm on entry to prison is critical to help prisons understand how to allocate extremely limited mental health resources. It has been established that having previous suicide attempts increases odds of future suicidality and self-harm in prison. We utilised administrative screening data from 665 adult male prisoners on entry to a category B prison in Wales, UK, collected using the Do-IT Profiler. This sample represents 16% of all prisoners who entered that prison during a 26-month period. 12% of prisoners reported a history of attempted suicide, 11% reported historic self-harm, and 8% reported a history of both. Historic traumatic brain injury and substance use problems were associated with a 3.3- and 1.9- times increased odds of a historic suicide attempt, respectively, but no significant increased risk of historic self-harm (95% CI: 1.51–6.60 and 1.02–3.50). However, those who were bullied at school had 2.7 times increased odds of reporting a history of self-harm (95% CI: 1.63–6.09). The most salient risk factors associated with both historic suicide and self-harm were higher levels of functional neurodisability (odds ratio 0.6 for a 1 standard deviation change in score, 95% CI: 0.35–0.75), and mood disturbance (odds ratio 2.1 for a 1 standard deviation change in score, 95% CI: 1.26–3.56). Therefore, it could be beneficial for prisons to screen for broader profiles of needs, to better understand how to provide appropriate services to prisoners vulnerable to suicide and self-harm. Multidisciplinary care pathways for prisoner mental health interventions are important, to account for complex multimorbidity. Adaptations may be needed for mental health interventions to be appropriate for, for example, a prisoner with a brain injury. Understanding this broad profile of vulnerability could also contribute to more compassionate responses to suicide and self-harm from prison staff.

Friendship interventions for children with neurodevelopmental needs: A systematic review and meta-analysis

by Reinie Cordier, Lauren Parsons, Sarah Wilkes-Gillan, Matthew Cook, Matthew McCloskey-Martinez, Pamela Graham, David Littlefair, Cally Kent, Renée Speyer

Rationale

Children with neurodevelopmental disorders such as attention-deficit hyperactivity disorder (ADHD), autism, developmental language disorder (DLD), intellectual disability (ID), and social (pragmatic) communication disorder (SPCD) experience difficulties with social functioning due to differences in their social, emotional and cognitive skills. Previous systematic reviews have focussed on specific aspects of social functioning rather than broader peer functioning and friendships.

Objective

To systematically review and methodologically appraise the quality and effectiveness of existing intervention studies that measured friendship outcomes for children with ADHD, autism, DLD, ID, and SPCD.

Method

Following PRISMA guidelines, we searched five electronic databases: CINAHL, Embase, Eric, PsycINFO, and PubMed. Two independent researchers screened all abstracts and disagreements were discussed with a third researcher to reach consensus. The methodological quality of studies was assessed using the Cochrane Risk of Bias Tool for Randomised Trials.

Results

Twelve studies involving 15 interventions were included. Studies included 683 children with a neurodevelopmental disorder and 190 typically-developing children and diagnosed with either autism or ADHD. Within-group meta-analysis showed that the pooled intervention effects for friendship across all interventions were small to moderate (z = 2.761, p = 0.006, g = 0.485). The pooled intervention effect between intervention and comparison groups was not significant (z = 1.206, p = 0.400, g = 0.215).

Conclusion

Findings provide evidence that some individual interventions are effective in improving social functioning and fostering more meaningful friendships between children with neurodevelopmental disorders and their peers. Effective interventions involved educators, targeted child characteristics known to moderate peer functioning, actively involved peers, and incorporated techniques to facilitate positive peer perceptions and strategies to support peers. Future research should evaluate the effectiveness of friendship interventions for children with DLD, ID and SPCD, more comprehensively assess peer functioning, include child self-report measures of friendship, and longitudinally evaluate downstream effects on friendship.

Public perceptions of physician-pharmaceutical industry relationships and trust in physicians

by Sayaka Saito, Kei Mukohara, Kazuhiro Shimomura, Kenta Murotani

Background

In Japan, as elsewhere, physicians meet with and receive gifts from pharmaceutical representatives (PRs). This study aimed to clarify the Japanese public perceptions of physicians’ relationships with PRs, examine the association between these perceptions and their trust in physicians, and compare the public’s and physicians’ awareness, acceptance, and perceptions of the influence of physician-PR relationships.

Methods

A cross-sectional, self-administered, anonymous, internet-panel survey was conducted involving 1,000 participants from the general public. The survey implementation was contracted to Cross Marketing Inc.

Results

The mean age of the 1000 participants was 44.8 years (standard deviation 18.3). Forty-eight percent were female. Many of our participants were unaware of certain physician-PR relationships. The public was more acceptable with physicians’ receiving stationery and/or medical textbooks and attending promotional drug seminars at their workplaces compared with receiving meals at restaurants. Many thought that physicians’ involvement in promotional activities influenced their prescribing habits and estimated that the majority of physicians received office stationery and meals from PRs. They were divided as to whether they would like to know about their physicians’ relationships with the industry. Factors associated with higher trust in physicians included participants being 65 years or older, having a primary care physician, being in better health, the belief that physicians’ involvement in promotional activities is acceptable, and their high estimate that physicians are not receiving gifts from PRs. Compared to the physicians, the public had lower awareness of and was more accepting of physicians’ involvement in promotional activities. Meanwhile, the public believed that physician-PR relationships influenced physicians’ prescribing habits more than the physicians themselves.

Conclusion

Our survey provided insights into Japanese public perceptions of physician-pharmaceutical industry relationships and their impact on trust in physicians. Physicians should be aware of these perceptions and carefully consider how to foster appropriate relationships with the industry.

Evaluation of a COVID‐19 fundamental nursing care guideline versus usual care: The COVID‐NURSE cluster randomized controlled trial

Abstract

Aim

To evaluate the impact of usual care plus a fundamental nursing care guideline compared to usual care only for patients in hospital with COVID-19 on patient experience, care quality, functional ability, treatment outcomes, nurses' moral distress, patient health-related quality of life and cost-effectiveness.

Design

Parallel two-arm, cluster-level randomized controlled trial.

Methods

Between 18th January and 20th December 2021, we recruited (i) adults aged 18 years and over with COVID-19, excluding those invasively ventilated, admitted for at least three days or nights in UK Hospital Trusts; (ii) nurses caring for them. We randomly assigned hospitals to use a fundamental nursing care guideline and usual care or usual care only. Our patient-reported co-primary outcomes were the Relational Aspects of Care Questionnaire and four scales from the Quality from the Patient Perspective Questionnaire. We undertook intention-to-treat analyses.

Results

We randomized 15 clusters and recruited 581 patient and 418 nurse participants. Primary outcome data were available for 570–572 (98.1%–98.5%) patient participants in 14 clusters. We found no evidence of between-group differences on any patient, nurse or economic outcomes. We found between-group differences over time, in favour of the intervention, for three of our five co-primary outcomes, and a significant interaction on one primary patient outcome for ethnicity (white British vs. other) and allocated group in favour of the intervention for the ‘other’ ethnicity subgroup.

Conclusion

We did not detect an overall difference in patient experience for a fundamental nursing care guideline compared to usual care. We have indications the guideline may have aided sustaining good practice over time and had a more positive impact on non-white British patients' experience of care.

Implications for the Profession and/or Patient Care

We cannot recommend the wholescale implementation of our guideline into routine nursing practice. Further intervention development, feasibility, pilot and evaluation studies are required.

Impact

Fundamental nursing care drives patient experience but is severely impacted in pandemics. Our guideline was not superior to usual care, albeit it may sustain good practice and have a positive impact on non-white British patients' experience of care.

Reporting Method

CONSORT and CONSERVE.

Patient or Public Contribution

Patients with experience of hospitalization with COVID-19 were involved in guideline development and writing, trial management and interpretation of findings.

Gender and racialisation of pharmaceutical sector leaders in Canada: a cross-sectional study

Por: Satgunanathan · K. · Workentin · A. · Woods · H. · Sabir · A. · Persaud · N.
Objective/design

Lacking diversity in pharmaceutical leadership positions could contribute to inequities in medicine access. The objective of this cross-sectional study was to determine the gender and racial identities of individuals who hold leadership positions in the Canadian pharmaceutical sector.

Participants

We compiled a list of all Canadian governmental bodies, pharmaceutical companies and insurance providers. We identified individuals who were part of the leadership team, including executives and members of the board of directors.

Primary outcome measures

The main outcomes of the study were the racialisation and gender of the individuals in leadership positions. The gender and racialisation of an individual were determined by reviewing their name, pronouns and institutional profile through internet searches. Two members of the research team performed the assessment and a third reviewer resolved disagreements.

Results

We identified 957 individuals holding leadership positions within the pharmaceutical sector, including 280 drug evaluation committee members, 12 governmental executive officers, 273 insurance company executive and board members and 392 executive and board members. Reviewers identified a total of 375 (39.2% of 957) women holding leadership roles, with most of these positions being held by governmental leaders (52.4% of 292) and a minority by insurance (37.0% of 273) and pharmaceutical (30.9% of 392) leaders. There were a total of 157 (16.4% of 957) racialised leaders, with most of these positions being held by governmental (18.5% of 292) and pharmaceutical (18.1% of 392) leaders, and a minority in insurance companies (11.7% of 273). Across the pharmaceutical sector, there were a total of 48 (5.0% of 957) racialised women and 327 (34.2% of 957) white women.

Conclusions

Leaders within the Canadian pharmaceutical sector are mostly white men, and racialised women hold few leadership roles. Public policy should recognise that these institutions are mostly led by white men and reasons for this disparity could be explored.

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