Search

Abstract Background Peer support workers provide support for people experiencing mental health conditions based on their own lived experience of mental health problems. Assessing fidelity to core ingredients of peer support is vital for successful implementation and intervention delivery. Modifications to its implementation are needed when scaling up to different socio-economic settings, raising further uncertainty about fidelity. As part of a large multi-centre study on peer support called Using Peer Support In Developing Empowering Mental Health Services (UPSIDES), we developed and evaluated the psychometric properties of the UPSIDES Fidelity Scale. Methods We constructed the fidelity scale based on an initial item pool developed through international expert consultation and iterative feedback. Scale refinement involved site-level expert consultation and translation, resulting in a service user-rated 28-item version and a peer support worker-rated 21-item version assessing receipt, engagement, enactment, competence, communication and peer support-specific components. Both versions are available in six languages: English, German, Luganda, Kiswahili, Hebrew and Gujarati. The scale was then evaluated at six study sites across five countries, with peer support workers and their clients completing their respective ratings four and eight months after initial peer support worker contact. Psychometric evaluation included analysis of internal consistency, construct validity and criterion validity. Results For the 315 participants, item statistics showed a skewed distribution of fidelity values but no restriction of range. Internal consistency was adequate (range α = 0.675 to 0.969) for total scores and all subscales in both versions. Confirmatory factor analysis indicated acceptable fit of the proposed factor structure for the service user version (χ2/df = 2.746; RMSEA = 0.084) and moderate fit for the peer support worker version (χ2/df = 3.087; RMSEA = 0.093). Both versions showed significant correlations with external criteria: number of peer support sessions; perceived recovery orientation of the intervention; and severity of illness. Conclusions The scale demonstrates good reliability, construct and criterion validity, making it a pragmatic and psychometrically acceptable measure for assessing fidelity to a manualised peer support worker intervention. Recommendations for use, along with research and practical implications, are addressed. As validated, multi-lingual tool that adapts to diverse settings this scale is uniquely positioned for global application. Trial registration ISRCTN, ISRCTN26008944. Registered on 30 October 2019.

It has been demonstrated previously that human leukocyte antigen class I (HLA-I) and class II (HLA-II) alleles may modulate JAK2 V617F and CALR mutation (CALRmut)-associated oncogenesis in myeloproliferative neoplasms (MPNs). However, the role of immunogenetic factors in MPNs remains underexplored. We aimed to investigate the potential involvement of HLA genes in CALRmut+ MPNs. High-resolution genotyping of HLA-I and -II loci was conducted in 42 CALRmut+ and 158 JAK2 V617F+ MPN patients and 1,083 healthy controls. A global analysis of the diversity of HLA-I genotypes revealed no significant differences between CALRmut+ patients and controls. However, one HLA-I allele (C*06:02) showed an inverse correlation with presence of CALR mutation. A meta-analysis across independent cohorts and healthy individuals from the 1000 Genomes Project confirmed an inverse correlation between the presentation capabilities of the HLA-I loci for JAK2 V617F and CALRmut-derived peptides in both patients and healthy individuals. scRNA-Seq analysis revealed low expression of TAP1 and CIITA genes in CALRmut+ hematopoietic stem and progenitor cells. In conclusion, the HLA-I genotype differentially restricts JAK2 V617F and CALRmut-driven oncogenesis potentially explaining the mutual exclusivity of the two mutations and differences in their presentation latency. These findings have practical implications for the development of neoantigen-based vaccines in MPNs.

Abstract Background Stakeholder engagement is essential to the design, implementation and evaluation of complex mental health interventions like peer support. Theory of Change (ToC) is commonly used in global health research to help structure and promote stakeholder engagement throughout the project cycle. Stakeholder insights are especially important in the context of a multi-site trial, in which an intervention may need to be adapted for implementation across very different settings while maintaining fidelity to a core model. This paper describes the development of a ToC for a peer support intervention to be delivered to people with severe mental health conditions in five countries as part of the UPSIDES trial. Methods One hundred thirty-four stakeholders from diverse backgrounds participated in a total of 17 workshops carried out at six UPSIDES implementing sites across high-, middle- and low-income settings (one site each in India, Israel, Uganda and Tanzania; two sites in Germany). The initial ToC maps created by stakeholders at each site were integrated into a cross-site ToC map, which was then revised to incorporate additional insights from the academic literature and updated iteratively through multiple rounds of feedback provided by the implementers. Results The final ToC map divides the implementation of the UPSIDES peer support intervention into three main stages: preparation, implementation, and sustainability. The map also identifies three levels of actors involved in peer support: individuals (service users and peer support workers), organisations (and their staff members), and the public. In the UPSIDES trial, the ToC map proved especially helpful in characterising and distinguishing between (a) common features of peer support, (b) shared approaches to implementation and (c) informing adaptations to peer support or implementation to account for contextual differences. Conclusions UPSIDES is the first project to develop a multi-national ToC for a mental health peer support intervention. Stakeholder engagement in the ToC process helped to improve the cultural and contextual appropriateness of a complex intervention and ensure equivalence across sites for the purposes of a multi-site trial. It may serve as a blueprint for implementing similar interventions with a focus on recovery and social inclusion among people with mental ill-health across diverse settings. Trial registration ISRCTN26008944 (Registration Date: 30/10/2019).

Abstract Background Peer support is an essential part of recovery-oriented care worldwide. Contextual factors have an impact on the implementation of peer support work. However, research has paid little attention to similarities and differences of implementation factors in settings varying by income-level and cultural values. The aim of this study is to assess the factors influencing the implementation of a peer support intervention across study sites in low-, middle- and high-income countries in line with the Consolidation Framework for Implementation Research (CFIR). Method 6 focus groups with a total of 54 key informants with relevant contextual (organisational) knowledge regarding implementation facilitators and barriers were conducted at six study sites Ulm and Hamburg (Germany), Butabika (Uganda), Dar es Salaam (Tanzania), Be’er Sheva (Israel), and Pune (India) before and 1.5 years after the start of UPSIDES peer support. Transcripts were analysed using qualitative content analysis. Results Across study sites key informants reported benefits of peer support for service users and peer support workers as implementation facilitators. At study sites with lower resources, reduced workload for mental health workers and improved access to mental health services through peer support were perceived as implementation facilitators (CFIR Domain 1: Intervention characteristics). The degree of engagement of mental health workers (CFIR Domain 3: Inner Setting/Domain 4: Individuals involved) varied across study sites and was seen either as a barrier (low engagement) or a facilitator (high engagement). Across study sites, adequate training of peer support workers (CFIR Domain 5: Implementation process) was seen as animplementation facilitator, while COVID-19 as well as low resource availability were reported as implementation barriers (CFIR Domain 2: Outer setting). Conclusions This study highlights the importance of considering contextual factors when implementing peer support, including previous experience and perceived benefits. Particular attention should be given to organisational benefits such as workload reduction and the allocation of sufficient resources as key drivers in LMICs. In HICs, the potential of organisational benefits for successful implementation should be further investigated and promoted.

Abstract Ecological niche models (ENMs) serve as valuable tools in assessing the potential species distribution, identifying crucial habitat components for species associations, and facilitating conservation efforts. The current study aimed to investigate the gastrointestinal nematodes (GINs) infection in sheep, predict and analyze their ecological niches and ranges, and identify the key bioclimatic variables influencing their distribution across three distinct climatic regions in Iran. In a cross-sectional study, a total of 2140 fecal samples were collected from semi-arid (n = 800), arid (n = 500), and humid-subtropical (n = 840) climates in East Azerbaijan, Kerman, and Guilan provinces, respectively. The flotation method was employed to assess stool samples, whereby the fecal egg count (the number of parasite eggs per gram [EPG]) was ascertained for each individual specimen. Employing a presence-only approach, the multi-scale maximum entropy (MaxEnt) method was used to model GINs' habitat suitability using 93 selected points/locations. The findings revealed that Guilan (34.2%) and East Azerbaijan (19.62%) exhibited the utmost proportion of Strongyle-type eggs. East Azerbaijan province also displayed the highest proportion of Marshallagia and Nematodirus, respectively (approximately 40% and 27%), followed by Guilan and Kerman provinces, while Kerman province had the highest proportion of Trichuris (approximately 15%). Ecological niche modeling revealed that the precipitation of the driest quarter (Bio17) exerted the most significant influence on Marshallagia, Nematodirus, Trichuris, and ُSُُُtrongyle-type eggs' presence in East Azerbaijan and Kerman provinces. For Guilan province, the most influential factor defining habitat suitability for Strongyle-type eggs, Marshallagia, and Nematodirus was increasing slope. Additionally, the distribution of Trichuris was most affected by the variable Bio2 in Guilan province. The study highlights the response of GINs to climate drivers in highly suitable regions, providing insights into ecologically favorable areas for GINs. In conclusion, this study provides a better understanding of GINs and the environmental factors influencing their transmission dynamics.

Abstract Background Although GqPCR activation often leads to cell survival by activating the PI3K/AKT pathway, it was previously shown that in several cell types AKT activity is reduced and leads to JNK activation and apoptosis. The mechanism of AKT inactivation in these cells involves an IGBP1-coupled PP2Ac switch that induces the dephosphorylation and inactivation of both PI3K and AKT. However, the machinery involved in the initiation of PP2A switch is not known. Methods We used phospho-mass spectrometry to identify the phosphorylation site of PP2Ac, and raised specific antibodies to follow the regulation of this phosphorylation. Other phosphorylations were monitored by commercial antibodies. In addition, we used coimmunoprecipitation and proximity ligation assays to follow protein–protein interactions. Apoptosis was detected by a TUNEL assay as well as PARP1 cleavage using SDS-PAGE and Western blotting. Results We identified Ser24 as a phosphorylation site in PP2Ac. The phosphorylation is mediated mainly by classical PKCs (PKCα and PKCβ) but not by novel PKCs (PKCδ and PKCε). By replacing the phosphorylated residue with either unphosphorylatable or phosphomimetic residues (S24A and S24E), we found that this phosphorylation event is necessary and sufficient to mediate the PP2A switch, which ultimately induces AKT inactivation, and a robust JNK-dependent apoptosis. Conclusion Our results show that the PP2A switch is induced by PKC-mediated phosphorylation of Ser24-PP2Ac and that this phosphorylation leads to apoptosis upon GqPCR induction of various cells. We propose that this mechanism may provide an unexpected way to treat some cancer types or problems in the endocrine machinery.

Objective The introduction of peer support in mental health teams creates opportunities and challenges for both peer and non-peer staff. However, the majority of research on mental health workers’ (MHWs) experiences with peer support comes from high-income countries. Using Peer Support In Developing Empowering Mental Health Services (UPSIDES) is an international multicentre study, which aims at scaling up peer support for people with severe mental illness in Europe, Asia and Africa. This study investigates MHWs experiences with UPSIDES peer support.Design Six focus groups with MHWs were conducted approximately 18 months after the implementation of the UPSIDES peer support intervention. Transcripts were analysed with a descriptive approach using thematic content analysis.Setting Qualitative data were collected in Ulm and Hamburg (Germany), Butabika (Uganda), Dar es Salaam (Tanzania), Be’er Sheva (Israel) and Pune (India).Participants 25 MHWs (19 females and 6 males) from UPSIDES study sites in the UPSIDES Trial (ISRCTN26008944) participated.Findings Five overarching themes were identified in MHWs’ discussions: MHWs valued peer support workers (PSWs) for sharing their lived experiences with service users (theme 1), gained trust in peer support over time (theme 2) and provided support to them (theme 3). Participants from lower-resource study sites reported additional benefits, including reduced workload. PSWs extending their roles beyond what MHWs perceived as appropriate was described as a challenge (theme 4). Perceptions about PSWs varied based on previous peer support experience, ranging from considering PSWs as equal team members to viewing them as service users (theme 5).Conclusions Considering local context is essential in order to understand MHWs’ views on the cooperation with PSWs. Especially in settings with less prior experience of peer support, implementers should make extra effort to promote interaction between MHWs and PSWs. In order to better understand the determinants of successful implementation of peer support in diverse settings, further research should investigate the impact of contextual factors (eg, resource availability and cultural values).Trial registration number ISRCTN26008944.

BackgroundPeer support in mental health is a low-threshold intervention with increasing evidence for enhancing personal recovery and empowerment of persons living with severe mental health conditions. As peer support spreads globally, there is a growing need for peer support training programmes that work well in different contexts and cultures. This study evaluates the applicability and transferability of implementing a manualised multi-national training programme for mental health peer support workers called UPSIDES from the perspective of different local stakeholders in high-, middle-, and low-income countries.MethodData from seven focus groups across six study sites in Africa (Tanzania, Uganda), Asia (India, Israel), and Europe (Germany 2 sites) with 44 participants (3 service users, 7 peer support workers, 25 mental health staff members, 6 clinical directors and 3 local community stakeholders) were thematically analysed.Results397 codes were identified, which were thematically analysed. Five implementation enablers were identified: (i) Enhancing applicability through better guidance and clarity of training programme management, (ii) provision of sufficient time for training, (iii) addressing negative attitudes towards peer support workers by additional training of organisations and staff, (iv) inclusion of core components in the training manual such as communication skills, and (v) addressing cultural differences of society, mental health services and discrimination of mental health conditions.DiscussionParticipants in all focus groups discussed the implementation of the training and peer support intervention to a greater extent than the content of the training. This is in line with growing literature of difficulties in the implementation of peer support including difficulties in hiring peer support workers, lack of funding, and lack of role clarity. The results of this qualitative study with stakeholders from different mental health settings worldwide emphasises the need to further investigate the successful implementation of peer support training. All results have been incorporated into the manualisation of the UPSIDES peer support training.

Purpose: To perform an intra-individual comparison of LI-RADS category and imaging features in patients at high risk of hepatocellular carcinoma (HCC) on contrast-enhanced CT, gadoxetate disodium-enhanced MRI (EOB-MRI), and extracellular agent-enhanced MRI (ECA-MRI) and to analyze the diagnostic performance of each imaging modality., Method: This retrospective study included cirrhotic patients with at least one LR-3, LR-4, LR-5, LR-M or LR-TIV observation imaged with at least two imaging modalities among CT, EOB-MRI, or ECA-MRI. Two radiologists evaluated the observations using the LI-RADS v2018 diagnostic algorithm. Reference standard included pathologic confirmation and imaging criteria according to LI-RADS v2018. Imaging features were compared between different exams using the McNemar test. Inter-modality agreement was calculated by using the weighted Cohen's kappa (k) test., Results: A total of 144 observations (mean size 34.0 ± 32.4 mm) in 96 patients were included. There were no significant differences in the detection of major and ancillary imaging features between the three imaging modalities. When considering all the observations, inter-modality agreement for category assignment was substantial between CT and EOB-MRI (k 0.60; 95%CI 0.44, 0.75), moderate between CT and ECA-MRI (k 0.46; 95%CI 0.22, 0.69) and substantial between EOB-MRI and ECA-MRI (k 0.72; 95%CI 0.59, 0.85). In observations smaller than 20 mm, inter-modality agreement was fair between CT and EOB-MRI (k 0.26; 95%CI 0.05, 0.47), moderate between CT and ECA-MRI (k 0.42; 95%CI -0.02, 0.88), and substantial between EOB-MRI and ECA-MRI (k 0.65; 95%CI 0.47, 0.82). ECA-MRI demonstrated the highest sensitivity (70%) and specificity (100%) when considering LR-5 as predictor of HCC., Conclusions: Inter-modality agreement between CT, ECA-MRI, and EOB-MRI decreases in observations smaller than 20 mm. ECA-MRI has the provided higher sensitivity for the diagnosis of HCC., Competing Interests: Declarations Conflict of interest Francesco Agnello, Giuseppe Brancatelli and Massimo Galia declare they have no financial interests. Roberto Cannella has received travel support for attending meetings from Bracco and Bayer and co-funding by the European Union-FESR or FSE, PON Research and Innovation 2014-2020 - DM 1062/2021. Ethical Approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required. Informed Consent Institutional review board approval was obtained for this retrospective study with a waiver of the requirement for informed consent., (© 2024. Italian Society of Medical Radiology.)

The liver is the second most common solid organ injured in blunt and penetrating abdominal trauma. Non-operative management (NOM) has become the standard of care for liver injuries in stable patients, where transarterial embolization (TAE) represents the main treatment, increasing success rates and avoiding invasive surgical procedures. In hemodynamically (HD) unstable patients, operative management (OM) is the standard of care. To date, there are no consensus guidelines about the endovascular treatment of patients with HD instability or in ones that responded to initial infusion therapy. A review of the literature was performed for published papers addressing the outcome of using TAE as the primary treatment for HD unstable/transient responder trauma liver patients with hemorrhagic vascular lesions, both as a single treatment and in combination with surgical treatment, focusing additionally on the different definitions used in the literature of unstable and transient responder patients. Our review demonstrated a good outcome in HD unstable/transient responder liver trauma patients treated with TAE but there still remains much debate about the definition of unstable and transient responder patients.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic became superimposed on the pre-existing obesity and diabetes mellitus (DM) pandemics. Since COVID-19 infection alters the metabolic equilibrium, it may induce pathophysiologic mechanisms that potentiate new-onset DM, and we evaluated this issue., Method: A systematic review of the literature published from the 1 January 2020 until the 20 July 2023 was performed (PROSPERO registration number CRD42022341638). We included only full-text articles of both human clinical and randomized controlled trials published in English and enrolling adults (age > 18 years old) with ongoing or preceding COVID-19 in whom hyperglycemia was detected. The search was based on the following criteria: "(new-onset diabetes mellitus OR new-onset DM) AND (COVID-19) AND adults"., Results: Articles on MEDLINE (n = 70) and the Web of Science database (n = 16) were included and analyzed by two researchers who selected 20 relevant articles. We found evidence of a bidirectional relationship between COVID-19 and DM., Conclusions: This link operates as a pathophysiological mechanism supported by epidemiological data and also by the clinical and biological findings obtained from the affected individuals. The COVID-19 pandemic raised the incidence of DM through different pathophysiological and psychosocial factors., (© 2023. The Author(s).)