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What works for whom and why? Treatment effects and their moderators among forcibly displaced people receiving psychological and psychosocial interventions: study protocol for an individual patient data meta-analysis

Por: Kurath · J. · Akhtar · A. · Karyotaki · E. · Sijbrandij · M. · Cuijpers · P. · Bryant · R. · Morina · N.
Introduction

Forcibly displaced people (FDP) have a high risk of developing mental disorders such as post-traumatic stress (PTS) disorder. Providing adequate mental healthcare for FDP is crucial but despite overall efficacy of many existing interventions, a large proportion of FDP does not benefit from treatment, highlighting the necessity of further investigating factors contributing to individual differences in treatment outcome. Yet, the few studies that have explored moderators of treatment effects are often insufficiently powered. Therefore, the present Individual Patient Data meta-analysis (IPD-MA) will investigate treatment effects and their moderators—variables related to beneficiaries, providers, intervention and study characteristics in relation to PTS outcomes.

Methods and analysis

A systematic literature search will be conducted from database inception in the databases PsycINFO, Cochrane, Embase, PTSDpubs and Web of Science. Only studies published in English, German, French, Spanish, Portuguese, and Dutch will be considered. Retrieved records will be screened for eligibility. Randomised controlled trials on adult FDP receiving psychological and psychosocial interventions aimed at alleviating symptoms such as PTS compared with a control condition without intervention will be included in this IPD-MA. Subsequently, authors of eligible studies will be contacted to request individual patient data (IPD). All datasets obtained will be synthesised into one large dataset which will be analysed using a one-stage approach by conducting mixed-effects linear regression models (ie, primary analysis). Additionally, aggregate data meta-analyes will be run using a two-stage approach by conducting multivariate regression models including all IPD (transformed) and available meta-data from study reports (ie, secondary analysis). PTS will serve as primary outcome measure, while mental health outcomes other than PTS, attendance, attrition, treatment non-response and adverse outcomes will be examined as secondary outcomes.

Ethics and dissemination

This IPD-MA does not require ethical approval. The results will be published in international peer-reviewed journals.

PROSPERO registration number

CRD42022299510.

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.

Dexamethasone restores TNFα-induced epithelial barrier dysfunction in primary rat alveolar epithelial cells

by Naokata Kutsuzawa, Yoko Ito, Shizuko Kagawa, Chinatsu Kohno, Hiroto Takiguchi, Koichiro Asano

Alveolar barrier dysfunction is one of the major pathophysiological changes in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). In ALI/ARDS, tumor necrosis factor-alpha (TNFα) disrupts the barriers of alveolar epithelium and endothelium. Glucocorticoids (GCs) exert anti-inflammatory effects and ameliorate pulmonary edema in ALI/ARDS. However, the involvement of GCs in the restoration of alveolar epithelial barrier dysfunction has not been extensively studied. Here, we elucidated that dexamethasone (Dex) restored TNFα-induced alveolar epithelial barrier dysfunction in vitro using primary rat alveolar epithelial cells isolated from Sprague–Dawley rats. Moreover, Dex promoted the alveolar epithelial cell barrier integrity by initiating GC receptor-mediated signaling via the downregulation of myosin light chain kinase (MLCK) expression and the dephosphorylation of myosin light chain (MLC) 2. Further investigation revealed that Dex enhanced the expression of zonula occludens-1 (ZO-1), a tight junction-related protein, at intercellular junction sites. These findings suggest that GCs strengthen the integrity of the alveolar epithelial barrier in ALI/ARDS via the GR-MLCK-pMLC2 axis.

"I thought I was going to die": Experiences of COVID-19 patients managed at home in Uganda

by Susan Nakireka, David Mukunya, Crescent Tumuhaise, Ronald Olum, Edith Namulema, Agnes Napyo, Quraish Serwanja, Prossie Merab Ingabire, Asad Muyinda, Felix Bongomin, Milton Musaba, Vivian Mutaki, Ritah Nantale, Phillip Akunguru, Rozen Ainembabazi, Derrick Nomujuni, William Olwit, Aisha Nakawunde, Specioza Nyiramugisha, Pamela Mwa Aol, Joseph Rujumba, Ian Munabi, Sarah Kiguli

Background

In Uganda, approximately 170,000 confirmed COVID-19 cases and 3,630 deaths have been reported as of January 2023. At the start of the second COVID-19 wave, the Ugandan health system was overwhelmed with a sudden increase in the number of COVID-19 patients who needed care, and the Ministry of Health resorted to home-based isolation and care for patients with mild to moderate disease. Before its rollout, the COVID-19 home-based care strategy had neither been piloted nor tested in Uganda.

Objective

To explore the experiences of COVID-19 patients managed at home in Uganda.

Methods

This was a qualitative study that was conducted to explore the lived experiences of COVID-19 patients managed at home. The study was carried out among patients who presented to three hospitals that were designated for treating COVID-19 patients in Uganda. COVID-19 patients diagnosed at these hospitals and managed at home were followed up and contacted for in-depth telephone interviews. The data were analysed using thematic content analysis with the aid of NVIVO 12.0.0 (QRS International, Cambridge, MA).

Results

Participants experienced feelings of fear and anxiety: fear of death, fear of losing jobs, fear of infecting loved ones and fear of adverse events such as loss of libido. Participants also reported feelings of loneliness, hopelessness and depression on top of the debilitating and sometimes worsening symptoms. In addition to conventional medicines, participants took various kinds of home remedies and herbal concoctions to alleviate their symptoms. Furthermore, COVID-19 care resulted in a high economic burden, which persisted after the COVID-19 illness. Stigma was a major theme reported by participants. Participants recommended that COVID-19 care should include counselling before testing and during and after the illness to combat the fear and stigma associated with the diagnosis. Another recommendation was that health workers should carry out home visits to patients undergoing home-based care and that COVID-19 treatment should be free of charge.

Conclusion

COVID-19 home-based care was associated with fear, anxiety, loneliness, depression, economic loss and stigma. Policymakers should consider various home-based follow-up strategies and strengthen counselling of COVID-19 patients at all stages of care.

Dismantling and personalising task-sharing psychosocial interventions for common mental disorders: a study protocol for an individual participant data component network meta-analysis

Por: Papola · D. · Karyotaki · E. · Purgato · M. · Sijbrandij · M. · Tedeschi · F. · Cuijpers · P. · Orestis · E. · Furukawa · T. A. · Patel · V. · Barbui · C.
Introduction

Common mental disorders, including depression, anxiety and related somatic health symptoms, are leading causes of disability worldwide. Especially in low-resource settings, psychosocial interventions delivered by non-specialist providers through task-sharing modalities proved to be valid options to expand access to mental healthcare. However, such interventions are usually eclectic multicomponent interventions consisting of different combinations of evidence-based therapeutic strategies. Which of these various components (or combinations thereof) are more efficacious (and for whom) to reduce common mental disorder symptomatology is yet to be substantiated by evidence.

Methods and analysis

Comprehensive search was performed in electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Register of Controlled Trials—CENTRAL from database inception to 15 March 2023 to systematically identify all randomised controlled trials that compared any single component or multicomponent psychosocial intervention delivered through the task-sharing modality against any active or inactive control condition in the treatment of adults suffering from common mental disorders. From these trials, individual participant data (IPD) of all measured outcomes and covariates will be collected. We will dismantle psychosocial interventions creating a taxonomy of components and then apply the IPD component network meta-analysis (IPD-cNMA) methodology to assess the efficacy of individual components (or combinations thereof) according to participant-level prognostic factors and effect modifiers.

Ethics and dissemination

Ethics approval is not applicable for this study since no original data will be collected. Results from this study will be published in peer-reviewed journals and presented at relevant conferences.

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