Role of manganese in the pathogenesis of portal-systemic encephalopathy

Amongst the potential neurotoxins implicated in the pathogenesis of hepatic encephalopathy, manganese emerges as a new candidate. In patients with chronic liver diseases, manganese accumulates in blood and brain leading to pallidal signal hyperintensity on T1-weighted Magnetic Resonance (MR) Imaging. Direct measurements in globus pallidus obtained at autopsy from cirrhotic patients who died in hepatic coma reveal 2 to 7-fold increases of manganese concentration. The intensity of pallidal MR images correlates with blood manganese and with the presence of extrapyramidal symptoms occurring in a majority of cirrhotic patients. Liver transplantation results in normalization of pallidal MR signals and disappearance of extrapyramidal symptoms whereas transjugular intrahepatic portosystemic shunting induces an increase in pallidal hyperintensity with a concomitant deterioration of neurological dysfunction. These findings suggest that the toxic effects of manganese contribute to extrapyramidal symptoms in patients with chronic liver disease. The mechanisms of manganese neurotoxicity are still speculative, but there is evidence to suggest that manganese deposition in the pallidum may lead to dopaminergic dysfunction. Future studies should be aimed at evaluating the effects of manganese chelation and/or of treatment of the dopaminergic deficit on neurological symptomatology in these patients

Manganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunction

BACKGROUND & AIMS: Manganese (Mn) deposition could be responsible for the T(1)-weighted magnetic resonance signal hyperintensities observed in cirrhotic patients. These experiments were designed to assess the regional specificity of the Mn increases as well as their relationship to portal-systemic shunting or hepatobiliary dysfunction. METHODS: Mn concentrations were measured in (1) brain samples from basal ganglia structures (pallidum, putamen, caudate nucleus) and cerebral cortical structures (frontal, occipital cortex) obtained at autopsy from 12 cirrhotic patients who died in hepatic coma and from 12 matched controls; and from (2) brain samples (caudate/putamen, globus pallidus, frontal cortex) from groups (n = 8) of rats either with end-to-side portacaval anastomosis, with biliary cirrhosis, or with fulminant hepatic failure as well as from sham-operated and normal rats. RESULTS: Mn content was significantly increased in frontal cortex (by 38\%), occipital cortex (by 55\%), pallidum (by 186\%), putamen (by 66\%), and caudate (by 54\%) of cirrhotic patients compared with controls. Brain Mn content did not correlate with patient age, etiology of cirrhosis, or history of chronic hepatic encephalopathy. In cirrhotic and portacaval-shunted rats, Mn content was increased in pallidum (by 27\% and 57\%, respectively) and in caudate/putamen (by 57\% and 67\%, respectively) compared with control groups. Mn concentration in pallidum was significantly higher in portacaval-shunted rats than in cirrhotic rats. No significant changes in brain Mn concentrations were observed in rats with acute liver failure. CONCLUSIONS: These findings suggest that brain Mn deposition results both from portal-systemic shunting and from liver dysfunction

Care and services partnership in Quebec birthing centres: myth or reality?

Abstract Context Working with women to best meet their needs has always been central to midwifery in Quebec, Canada. The creation of birthing centres at the end of the 1990s consolidated this desire to prioritize women’s involvement in perinatal care and was intended to encourage the establishment of a care and services partnership between care providers and users. The aim of this pilot study is to evaluate the perceptions of clients, midwives and birth assistants of the way in which women are involved in partnership working in Quebec birthing centres. Methods A single qualitative case and pilot study was conducted with midwives (n = 5), birth assistants (n = 4), a manager (n = 1), clients (n = 5) and members of the users’ committee (n = 2) at a birthing centre in Quebec, Canada in July and August 2023. The partnership was evaluated using the dimensions of a validated CADICEE questionnaire. Results The women and professionals stressed that the relationship was established in a climate of trust. The caregivers also attached importance to autonomy, information sharing and decision-making, adaptation to context, empathy and recognition of the couple’s expertise. The women confirmed that they establish a relationship of trust with the professionals when the latter show empathy and that they adapt the follow-up to their knowledge and life context. Key factors in establishing this kind of care relationship are the time given, a de-medicalized environment, the comprehensive care received, and professionals who are well-informed about the partnership. In addition, the birthing centre has a users’ committee that can put forward ideas but has no decision-making powers. Conclusions Both the women and the professionals at the birthing centre appear to be working in partnership. However, at the organizational level, the women are not involved in decision-making. A study of all birthing centres in Quebec would provide a more comprehensive picture of the situation

Alzheimer type II astrocytic changes following sub-acute exposure to manganese and its prevention by antioxidant treatment

Exposure to manganese in an industrial or clinical setting can lead to manganism, a neurological disorder with similarities to Parkinson's disease. Although the pathogenetic basis of this disorder is unclear, studies indicate this metal is highly accumulated in astrocytes, suggesting an involvement of these glial cells. To investigate this issue, we have used a recently characterized, sub-acute model of manganese neurotoxicity. Treatment of rats with manganese (II) chloride (50 mg/kg body weight, i.p.) once daily for 1 or 4 days led to increases in manganese levels of up to 232, 523, and 427% in the cerebral cortex, globus pallidus, and cerebellum, respectively, by instrumental neutron activation analysis. These changes were accompanied by development of pathological changes in glial morphology identified as Alzheimer type II astrocytosis in both cortical and sub-cortical structures. Co-treatment with either the antioxidant N-acetylcysteine or the manganese chelator 1,2-cyclohexylenedinitrilotetraacetic acid completely blocked this pathology, indicating the cellular transformation may be mediated by oxidative stress associated with the presence of this metal. These findings represent, to our knowledge, the first report of early induction of this pathological hallmark of manganese neurotoxicity, an event previously considered a consequence of chronic exposure to manganese in primates and in human cases of manganism. Our results also indicate that use of this rodent model may provide a novel opportunity to examine the nature and role of the Alzheimer type II astrocyte in the pathophysiology of this disorder as well as in other disease processes in which cerebral accumulation of manganese occurs

How to mobilise users' experiential knowledge in the evaluation of advanced technologies and practices in Quebec? The example of the permanent users' and relatives' panel

Abstract Introduction With the purpose of supporting scientific professionals and helping them to better integrate the expertise of users in their work, a users' and relatives' panel (URP) was set up at the National Institute for Excellence in Health and Social Services in Quebec (INESSS), Canada for the social services and mental health directorate. URPs are advisory structures that mobilise the experiential knowledge of people affected by various issues. Objectives The objective of this study is to assess from a diverse stakeholders' perceptions: (1) the experience of developing and implementing the URP within the context of an Agencies for Health Technology Assessment and Assessment of Social Services (AHTAASS), (2) the contribution of such a URP, (3) the challenges encountered and (4) the perspectives of improvement for the following years. Methodology We conducted a qualitative descriptive evaluation study. Nineteen interviews were conducted: six with URP members and 13 with staff representatives. The documents related to the creation of the panel, the URP minutes summarising the discussions and the reports published during that period were collected and analysed. Following a preliminary round of data analysis, a debriefing meeting was conducted with a few participants to validate the results. Results The panel was set up as part of the INESSS' desire to better integrate experiential knowledge into its recommendations. Twelve projects were presented to the panel on various themes. The URP enabled health professionals to consider dimensions they had not identified, to better integrate the experiential data collected from users into their work and to develop recommendations that made more sense to users. Panel members and INESSS professionals learned to work together, moving the working methods from consultation to collaboration and even coconstruction. Based on the panel's significant contribution, the INESSS decided to maintain it and to strengthen its place in its system to better integrate the experiential knowledge of users into its work. Conclusion This research illustrates how AHTAASS can set up a URP composed exclusively of users, and how it can contribute and be evaluated. It shows that URPs are structures that value the sharing of experiential knowledge of its members, humanise decision‐making and give meaning to the work done by scientific professionals. Patient or Public Contribution One patient–researcher has contributed to the preparation and writing of this manuscript

Healthcare Professional Perspectives on the Use of Remote Patient-Monitoring Platforms during the COVID-19 Pandemic: A Cross-Sectional Study

The COVID-19 pandemic created an urgent need to act to reduce the spread of the virus and alleviate congestion in healthcare services, protect health professionals, and help them maintain satisfactory quality and safety of care. Remote monitoring platforms (RPM) emerged as potential solutions. In this study, we evaluate, from health professionals’ perspectives, the capacity and contribution of two different digital platforms to maintain quality, safety, and patient engagement in care. A cross-sectional study was conducted using a survey in which a total of 491 health professionals participated. The results show that, in general, user perceptions of the quality and safety of care provided through the platforms were positive. The ease of access to health professionals’ services in general and shorter waiting times for patients were the two main features that were highly appreciated by most participants. However, some problems were encountered during the use of these two platforms, such as a lack of training and/or direct support for users. To improve the two platforms and maximize their use, the areas for improvement and the issues identified should be addressed as part of a collaborative process involving health professionals and patients as well as health system leaders, decision-makers, and digital platform providers

Telehealth-Delivered Program and Accompanying Patients to Enhance the Clinical Condition of Patients Throughout a Liver Transplant: Protocol for a Mixed Methods Study

BackgroundLiver transplantation (LT) is indicated in patients with severe acute or chronic liver failure for which no other therapy is available. With the increasing number of LTs in recent years, liver centers worldwide must manage their patients according to their clinical situation and the expected waiting time for transplantation. The LT clinic at the Centre hospitalier de l’Université de Montréal (CHUM) is developing a new health care model across the entire continuum of pre-, peri-, and posttransplant care that features patient monitoring by an interdisciplinary team, including an accompanying patient; a digital platform to host a clinical plan; a learning program; and data collection from connected objects. ObjectiveThis study aims to (1) evaluate the outcomes following the implementation of a patient platform with connected devices and an accompanying patient, (2) identify implementation barriers and facilitators, (3) describe service outcomes in terms of health outcomes and the rates and nature of contact with the accompanying patient, (4) describe patient outcomes, and (5) assess the intervention’s cost-effectiveness. MethodsSix types of participants will be included in the study: (1) patients who received transplants and reached 1 year after transplantation before September 2023 (historical cohort or control group), (2) patients who will receive an LT between December 2023 and November 2024 (prospective cohort/intervention group), (3) relatives of those patients, (4) accompanying patients who have received an LT and are interested in supporting patients who will receive an LT, (5) health care professionals, and (6) decision makers. To describe the study sample and collect data to achieve all the objectives, a series of validated questionnaires, accompanying patient logbooks, transcripts of interviews and focus groups, and clinical indicators will be collected throughout the study. ResultsIn total, 5 (steering, education, clinical-technological, nurse prescription, and accompanying patient) working committees have been established for the study. Recruitment of patients is expected to start in November 2023. All questionnaires and technological platforms have been prepared, and the clinicians, stakeholders, and accompanying patient personnel have been recruited. ConclusionsThe implementation of this model in the trajectory of LT recipients at the CHUM may allow for better monitoring and health of patients undergoing transplantation, ultimately reducing the average length of hospital stay and promoting better use of medical resources. In the event of positive results, this model could be transposed to all transplant units at the CHUM and across Quebec (potentially affecting 888 patients per year) but could also be applied more widely to the monitoring of patients with other chronic diseases. The lessons learned from this project will be shared with decision makers and will serve as a model for other initiatives involving accompanying patients, connected objects, or digital platforms. International Registered Report Identifier (IRRID)PRR1-10.2196/5444

Integrating accompanying patients into clinical oncology teams: limiting and facilitating factors

Abstract Objectives Since 2018, four establishments in Quebec have been instrumental in implementing the PAROLE-Onco program, which introduced accompanying patients (APs) into healthcare teams to improve cancer patients’ experience. APs are patient advisors who have acquired specific experiential knowledge related to living with cancer, using services, and interacting with healthcare professionals. They are therefore in a unique and reliable position to be able to provide emotional, informational, cognitive and navigational support to patients who are dealing with cancer. We aimed to explore APs’ perspectives regarding the limiting and facilitating factors in terms of how they are integrated into the clinical oncology teams. Methods A qualitative study based on semi-structured interviews and focus groups was conducted with 20 APs at the beginning of their intervention (T1) and, two years later, during a second data collection (T2). Limiting and facilitating factors of APs’ integration into clinical teams were analyzed in terms of governance, culture, resources and tools. Results The limited factors raised by APs to be integrated into clinical teams include the following: confusion about the specific roles played by APs, lifting the egos of certain professionals who feel they are already doing what APs typically do, lack of identification of patient needs, absence of APs in project governance organizational boundaries, and team members' availability. Various communication challenges were also raised, resulting in the program being inadequately promoted among patients. Also mentioned as limiting factors were the lack of time, space and compensation. Creating opportunities for team members to meet with APs, building trust and teaching team members how APs’ activities complement theirs were enhancing factors. Other facilitators include APs being involved in decision-making committees, being leaders in promoting the PAROLE-Onco program to patients and clinical team members and creating opportunities to communicate with team members to help enhance their work and provide feedback to improve patient services. Awareness of APs’ added value for the team and patients is also a key facilitator. Regarding tools, offering accompanying services by telephone allows both patients and APs to benefit from the flexibility they need. Conclusion Over time, APs were able to identify optimal factors for successful implementation. Recommendations include APs and professionals working in co-construction on organization, leadership, resources and status factors. This could help catalyze a change in culture within health establishments and allow people dealing with cancer to benefit from the experiential knowledge of other patients within their clinical team