38 results on '"Galvin, M."'
Search Results
2. Theme 01 - Epidemiology and Informatics.
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Opie-Martin, S., Bredin, A., Grey, E., Talbot, K., Al-Chalabi, A., McFarlane, R., Caravaca Puchades, A., Chio, A., Corcia, P., Galvin, M., Heverin, M., Hobin, F., Holmdahl, O., Ingre, C., Lamaire, N., Mac Domhnaill, É., McDonough, H., Manera, U., McDermott, C., and Mouzouri, M.
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AMYOTROPHIC lateral sclerosis ,EPIDEMIOLOGY ,LIBRARY users ,NEURODEGENERATION - Abstract
The document titled "Theme 01 - Epidemiology and Informatics" provides a comprehensive overview of research conducted by multiple authors on the topics of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The authors explore various aspects of these neurodegenerative diseases, including epidemiology, informatics, and clinical characteristics. The document features a wide range of contributors from different countries, highlighting the global nature of ALS and FTD research. This resource would be valuable for library patrons interested in studying the epidemiology and informatics of ALS and FTD. [Extracted from the article]
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- 2023
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3. Theme 12 - Clinical Management and Support.
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Conroy, E., Heverin, M., O'Brien, D., Hardiman, O., McDermott, C., Galvin, M., Howard, J., Locock, L., Turner, M., Musson, L., Stavroulakis, T., Bailey, M., Pierce, J., Byrd, K., Hoover, S., Lee, A., Ward, M., Ball, L., Geske, J., and Burton, E.
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AMYOTROPHIC lateral sclerosis ,MOTOR neuron diseases ,NEUROMUSCULAR diseases - Abstract
Power wheelchair prescription, utilization, satisfaction, and cost for patients with amyotrophic lateral sclerosis: preliminary data for evidence-based guidelines. Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: a retrospective analysis of data from a dose-ranging study. Support needs and interventions for family caregivers of patients with amyotrophic lateral sclerosis (ALS): a narrative review with report of telemedicine experiences at the time of COVID-19 pandemic. [Extracted from the article]
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- 2022
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4. Theme 11 - COGNITIVE AND PSYCHOLOGICAL ASSESSMENT AND SUPPORT.
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Costello, E., Ryan, M., Doherty, M., McHutchinson, C., Heverin, M., Abrahams, S., Hardiman, O., Pender, N., Kennedy, P., Conroy, É., Leroi, I., Beelen, A., van den Berg, L., Galvin, M., Palumbo, F., Canosa, A., Iazzolino, B., Peotta, L., Vasta, R., and Manera, U.
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PSYCHOLOGICAL tests ,MOTOR neuron diseases ,AMYOTROPHIC lateral sclerosis - Abstract
2018; 32 (1): 231 - 45. 15 A Programme for Amyotrophic Lateral Sclerosis Care in Europe (ALS-CarE). https://clinicaltrials.gov/ct2/show/NCT03081338. 2010; 9 (3): 327 - 53. 5 A Programme for Amyotrophic Lateral Sclerosis Care in Europe (ALS-CarE). https://clinicaltrials.gov/ct2/show/NCT03081338. ALS Focus-a new survey program for people with ALS and caregivers: results from Survey 1 on insurance needs and financial burdens. [Extracted from the article]
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- 2021
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5. A Model-Based Economic Evaluation of Hypothetical Treatments for Amyotrophic Lateral Sclerosis in the UK: Implications for Pricing of New and Emerging Health Technologies.
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Tappenden P, Hardiman O, Kwon SH, Mon-Yee M, Galvin M, and McDermott C
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Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease which leads to loss of muscle function and paralysis. Historically, clinical drug development has been unsuccessful, but promising disease-modifying therapies (DMTs) may be on the horizon., Objectives: The aims of this study were to estimate survival, quality-adjusted life-years (QALYs) and costs under current care, and to explore the conditions under which new therapies might be considered cost effective., Methods: We developed a health economic model to evaluate the cost effectiveness of future ALS treatments from a UK National Health Service and Personal Social Services perspective over a lifetime horizon using data from the ALS-CarE study. Costs were valued at 2021/22 prices. Two hypothetical interventions were evaluated: a DMT which delays progression and mortality, and a symptomatic therapy which improves utility only. Sensitivity analysis was conducted to identify key drivers of cost effectiveness., Results: Starting from King's stage 2, patients receiving current care accrue an estimated 2.27 life-years, 0.75 QALYs and lifetime costs of £68,047. Assuming a 50% reduction in progression rates and a UK-converted estimate of the price of edaravone, the incremental cost-effectiveness ratio for a new DMT versus current care is likely to exceed £735,000 per QALY gained. Symptomatic therapies may be more likely to achieve acceptable levels of cost effectiveness., Conclusions: Regardless of efficacy, DMTs may struggle to demonstrate cost effectiveness, even at a low price. The cost effectiveness of DMTs is likely to be strongly influenced by drug price, the magnitude and durability of relative treatment effects, treatment starting/stopping rules and any additional utility benefits over current care., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2024
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6. Religious and Medical Pluralism Among Traditional Healers in Johannesburg, South Africa.
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Galvin M, Chiwaye L, and Moolla A
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- Humans, South Africa, Health Behavior, Cultural Diversity, Traditional Medicine Practitioners, Medicine, Traditional
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Religion and spirituality are powerful social forces in contemporary South Africa. Traditional Health Practitioners (THPs) are commonly consulted for both spiritual and medical ailments as a first line of care. Many studies have assessed African traditional health seeking behaviors but few have examined beliefs, practices, and behaviors of THPs themselves. This study sought to explore spiritual worldviews among South African THPs. Semi-structured in-depth interviews were conducted with 18 THPs in Johannesburg, South Africa between January and May, 2022. Interviews were transcribed and translated into English. Data were managed using NVivo 12 software and thematically analyzed. The majority of THPs interviewed indicated that initiation as a THP was almost always preceded by a sickness accompanied by dreams/visions that represented an "ancestral calling" to become a healer. Most THPs also trained as both sangomas-who healed according to traditional beliefs-and prophets-who healed according to Christian beliefs. This reflects a syncretic relationship between traditional African beliefs and Christianity. However, not all churches are accepting of traditional beliefs and subsequently these THPs are members only at non-Pentecostal AIC churches who blend both African and Christian practices. Similar to these forms of religious pluralism melding Christianity and traditional beliefs, many THPs also often practice medical pluralism, mixing Western treatments with traditional practices/medicines. THPs are able to adapt elements of Western and African beliefs into healing practices that span multiple religious and medical fields. Thus, collaborative and decentralized healthcare services may be highly acceptable among such a pluralistic community., (© 2023. The Author(s).)
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- 2024
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7. Functional Characterisation of the ATOH1 Molecular Subtype Indicates a Pro-Metastatic Role in Small Cell Lung Cancer.
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Catozzi A, Peiris-Pagès M, Humphrey S, Revill M, Morgan D, Roebuck J, Chen Y, Davies-Williams B, Lallo A, Galvin M, Pearce SP, Kerr A, Priest L, Foy V, Carter M, Caeser R, Chan J, Rudin CM, Blackhall F, Frese KK, Dive C, and Simpson KL
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Molecular subtypes of Small Cell Lung Cancer (SCLC) have been described based on differential expression of transcription factors (TFs) ASCL1, NEUROD1 , POU2F3 and immune-related genes. We previously reported an additional subtype based on expression of the neurogenic TF ATOH1 within our SCLC Circulating tumour cell-Derived eXplant (CDX) model biobank. Here we show that ATOH1 protein was detected in 7/81 preclinical models and 16/102 clinical samples of SCLC. In CDX models, ATOH1 directly regulated neurogenesis and differentiation programs consistent with roles in normal tissues. In ex vivo cultures of ATOH1-positive CDX, ATOH1 was required for cell survival. In vivo , ATOH1 depletion slowed tumour growth and suppressed liver metastasis. Our data validate ATOH1 as a bona fide oncogenic driver of SCLC with tumour cell survival and pro-metastatic functions. Further investigation to explore ATOH1 driven vulnerabilities for targeted treatment with predictive biomarkers is warranted.
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- 2024
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8. Maladi Nanm, Maladi Zonbi, & Maladi Lalin : A qualitative study of cultural concepts of distress in northern Haiti.
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Galvin M, Michel G, Pierre E, Manguira E, and Cénat JM
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- Humans, Haiti, Anxiety Disorders, Anxiety, Mental Health, Bipolar Disorder therapy
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Cultural Concepts of Distress (CCDs) are culturally constructed diagnostic categories that exist within a specific society or culture. While several studies have assessed CCDs around the world, few studies have examined them in Haiti. This qualitative study examines manifestations of anxiety and depression via "sent spirits" in the form of maladi nanm ("Soul disorder") and maladi zonbi ("Zombie disorder"), and bipolar disorder in the form of maladi lalin ("Moon disorder"). Examples of CCDs were recorded as part of a study which interviewed 96 outpatients at the first mental health center in northern Haiti. Using qualitative methods, the authors identified three specific CCDs as reported by mental health patients. Maladi nanm and maladi zonbi represent alternative explanatory models of anxiety and depression in which the sufferer views mental illness as stemming from a sent spirit, or spirit which is intentionally sent supernaturally with the intent to cause harm. Maladi lalin is experienced by patients with bipolar disorder who associate cycles of mania and depression as in-sync with the phases of the moon. Understanding culture-bound forms of mental distress in settings such as Haiti is essential to developing accurate psychometrics for measuring mental health, as well as ensuring culturally appropriate and effective diagnosis and treatment., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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9. Pathways to care among patients with mental illness at two psychiatric facilities in Johannesburg, South Africa.
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Galvin M, Byansi W, Chiwaye L, Luvuno Z, and Moolla A
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- Humans, South Africa, Delivery of Health Care, Medicine, Traditional, Traditional Medicine Practitioners, Medicine, African Traditional, Mental Disorders therapy, Mental Disorders diagnosis
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Background: A patient's pathway to care is often characterized by a sequence of actions taken to remedy ill-health. Research exploring the help-seeking behavior of individuals with mental health problems in sub-Saharan Africa is relatively limited. This study assessed the perceptions and experiences of mental illness and treatment among patients with mental illness at two psychiatric facilities in Johannesburg, South Africa., Methods: 309 interviewer administered surveys were conducted between January and July 2022. We used a logistic regression model to examine factors associated with receiving treatment for mental illnesses from traditional healers. Semi-structured interviews were conducted with 18 participants during the same period. Interviews were transcribed and translated into English. Data were managed using NVivo 11 software and thematically analyzed., Findings: Results showed that 144 (47%) patients sought mental health care from traditional healers. Higher anxiety symptoms, number of people in the household, believing that traditional medicine can cure mental illnesses, and township living were associated with seeking mental healthcare from traditional healers. Qualitative analysis indicated that participants often believed that mental illness was due to bewitchment and consulted with multiple traditional healers, thus spending large amounts of money for treatment and ultimately delaying access to biomedical care., Conclusion: Collaborative approaches between traditional healers and biomedical professionals show promise in terms of allowing for improved identification and treatment of individuals with mental disorders.
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- 2023
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10. Epidemiologic Trends of Amyotrophic Lateral Sclerosis in Ireland, 1996-2021.
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McFarlane R, Peelo C, Galvin M, Heverin M, and Hardiman O
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- Male, Humans, Female, Middle Aged, Aged, Ireland epidemiology, Delayed Diagnosis, Riluzole, Proportional Hazards Models, Amyotrophic Lateral Sclerosis diagnosis
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Background and Objectives: The objective of this study was to examine changes to the incidence, prevalence, age at onset, and survival of patients diagnosed with amyotrophic lateral sclerosis (ALS) in the Republic of Ireland over 25 years., Methods: Incident and prevalent cases of ALS were estimated using the Irish population-based ALS Register, which has been in continuous operation since 1994. Incident cases were age standardized using the direct method and applied to 3 standard populations (Irish, European, and American). Survival was determined using Kaplan-Meier curves and Cox regression models. Non-normally distributed groups were compared using the Kruskal-Wallis test with a Bonferroni correction., Results: A total of 2,771 patients with ALS were identified in the Republic of Ireland over 25 years. Incidence per 100,000 was determined for the population older than 15 years. Crude incidence increased from 2.64 to 5.46 per 100,000. Standardized incidence increased from 2.64 to 3.1 per 100,000. Prevalence increased from 5.83 to 8.10 per 100,000. The median age at onset increased from 64 to 67 years. The peak age of incidence increased from those between 70 and 74 years to those between 75 and 79 years. Overall, women had a consistently later median age at onset of 67 years compared with men at 65 years ( p < 0.001). No significant difference in survival was noted between those captured across 3 different epochs (1996-2003, 2004-2012, 2013-2021). Older age at onset (hazard ratio [HR] 1.03, CI 1.02-1.04, p < 0.001) was a negative predictive factor of survival in multivariate Cox regression analysis. Riluzole use (HR 0.67, CI 0.50-0.90, p = 0.033) and diagnostic delay (HR 0.98, CI 0.98-0.99, p < 0.001) were positive predictive factors., Discussion: Within the Republic of Ireland, the age-standardized overall incidence, peak incidence, prevalence, and age at onset of ALS have all increased over 25 years. Despite the widespread use of noninvasive ventilation, aggressive secretion management, and changes in ALS care, the mean survival within the Irish population has not changed., (© 2023 American Academy of Neurology.)
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- 2023
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11. Lineage Plasticity in SCLC Generates Non-Neuroendocrine Cells Primed for Vasculogenic Mimicry.
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Pearsall SM, Williamson SC, Humphrey S, Hughes E, Morgan D, García Marqués FJ, Awanis G, Carroll R, Burks L, Shue YT, Bermudez A, Frese KK, Galvin M, Carter M, Priest L, Kerr A, Zhou C, Oliver TG, Humphries JD, Humphries MJ, Blackhall F, Cannell IG, Pitteri SJ, Hannon GJ, Sage J, Dive C, and Simpson KL
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- Animals, Mice, Humans, Neovascularization, Pathologic genetics, Cell Transdifferentiation, Cell Line, Tumor, Lung Neoplasms pathology
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Introduction: Vasculogenic mimicry (VM), the process of tumor cell transdifferentiation to endow endothelial-like characteristics supporting de novo vessel formation, is associated with poor prognosis in several tumor types, including SCLC. In genetically engineered mouse models (GEMMs) of SCLC, NOTCH, and MYC co-operate to drive a neuroendocrine (NE) to non-NE phenotypic switch, and co-operation between NE and non-NE cells is required for metastasis. Here, we define the phenotype of VM-competent cells and molecular mechanisms underpinning SCLC VM using circulating tumor cell-derived explant (CDX) models and GEMMs., Methods: We analyzed perfusion within VM vessels and their association with NE and non-NE phenotypes using multiplex immunohistochemistry in CDX, GEMMs, and patient biopsies. We evaluated their three-dimensional structure and defined collagen-integrin interactions., Results: We found that VM vessels are present in 23/25 CDX models, 2 GEMMs, and in 20 patient biopsies of SCLC. Perfused VM vessels support tumor growth and only NOTCH-active non-NE cells are VM-competent in vivo and ex vivo, expressing pseudohypoxia, blood vessel development, and extracellular matrix organization signatures. On Matrigel, VM-primed non-NE cells remodel extracellular matrix into hollow tubules in an integrin β1-dependent process., Conclusions: We identified VM as an exemplar of functional heterogeneity and plasticity in SCLC and these findings take considerable steps toward understanding the molecular events that enable VM. These results support therapeutic co-targeting of both NE and non-NE cells to curtail SCLC progression and to improve the outcomes of patients with SCLC in the future., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
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- 2023
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12. IMPACT-ALS: summary of results from a European survey of people living with ALS.
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Conroy E, Vélez-Gómez B, O'Brien D, Heverin M, Hardiman O, Mcdermott C, and Galvin M
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Objective: The IMPACT-ALS survey collected the experiences of people living with ALS (plwALS) across nine European countries. We aimed to better understand the functional burden of ALS to ensure the experiences of plwALS inform the development of person-centered therapies., Methods: The content was informed by the US IMPACT-ALS survey, with adjustments relevant to the European population. Questionnaires consisted of four modules, each of which was pilot tested in advance of distribution. Data were captured using the Qualtrics software and were analyzed in SPSS., Results: 857 respondents completed the survey, with a participation rate ranging from 0.2% to 6.3% across the nine participating countries. The majority were male and aged 55-74 years old. In the previous 2 weeks, symptoms experienced included weakness (81%), fatigue (61%), speech impairment (38%), pain (27%), and depression and other mood changes (23%). Eighty-two percent of respondents reported fears, of which the most common were leaving family too soon (68%) and death from respiratory failure (50%). Lifestyle changes since diagnosis were reported by 89% of respondents, with less time spent doing most daily activities but more time on the internet (81%), reading (56%) and communicating with family and friends (55%). Stopping progression of ALS was the most desired impact for a new therapy for 68% respondents., Conclusions: The European IMPACT-ALS survey has generated insights into the complex experiences of plwALS. The data provide unique patient perspectives on common symptoms, fears, functional limitations, lifestyle changes, and wishes for future therapies that will enhance patient-centric care in ALS.
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- 2023
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13. Examining the Etiology and Treatment of Mental Illness Among Vodou Priests in Northern Haiti.
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Galvin M, Michel G, Manguira E, Pierre E, Lesorogol C, Trani JF, Lester R, and Iannotti L
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- Humans, Haiti, Health Knowledge, Attitudes, Practice, Clergy, Mental Disorders therapy
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This study assesses the perspectives and experiences of Vodou priests (ougan) in the treatment of mental illness in northern Haiti. Our goal is to explore the etiology and popular nosologies of mental illness in the context of Haitian Vodou, through understandings of illness and misfortune which are often viewed as a result of sent spirits-or spirits sent supernaturally by others with the intent to cause harm. Using a qualitative approach, this study conducted semi-structured in-depth interviews with 20 ougan living near the city of Cap-Haïtien. Interviews highlight a sample of healers with little formal training who maintain beliefs and practices that differ significantly from current biomedical models. Ougan treat mental illness through a variety of means including prayer and conjuring of spirits, leaves for teas and baths, as well as combinations of perfumes, rum, human remains, and other powdered concoctions that are either imbibed or rubbed on the skin. The primary purpose of these treatments is to expel the spirit causing harm, yet they can often result in additional harm to the patient. Findings suggest that while ougan are willing to collaborate with biomedical practitioners, significant barriers remain preventing cooperation between these two groups., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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14. Perceptions of causes and treatment of mental illness among traditional health practitioners in Johannesburg, South Africa.
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Galvin M, Chiwaye L, and Moolla A
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Mental disorders are among the most poorly treated illnesses in sub-Saharan Africa. It is estimated that 70%-80% of South Africans consult traditional health practitioners for the treatment of psychological ailments. As traditional health practitioners maintain a strong role in assessing and treating patients with mental illness in this context, this study contributes to the burgeoning research literature on the topic. Semi-structured in-depth interviews were conducted with 18 traditional health practitioners in Johannesburg, South Africa, between January and May 2022. Interviews were transcribed and translated into English. The data were managed using NVivo 12 software and thematically analysed. Traditional health practitioners interviewed generally perceived mental illness to be of supernatural causation, either as a result of bewitchment, a calling for patients to become THPs themselves, due to displeased ancestors, or due to natural causes. Traditional health practitioners identified eight primary treatments that they use for treating mental illness. Among these were throwing of bones ( tinhlolo ) to start communicating with ancestors, steaming ( ukufutha ) to start a cleansing process, sneezing ( umbhemiso ) to forcefully dispel the spirit causing the illness, induced vomiting ( phalaza ), and the administration of laxatives ( mahlabekufeni ) to remove the spirits poisoning the body as well as animal sacrifice to purge spirits and communicate with ancestors. This is all followed by cutting ( ukucaba ), which is the final part of the treatment and ensures that the evil spirit cannot return. Due to the ubiquity of traditional health practitioner usage for mental illness in sub-Saharan Africa, it is essential to understand what conceptions traditional health practitioners have of the aetiology of these disorders as well as their modalities for administering treatment., Competing Interests: Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2023
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15. Adverse childhood experiences, traumatic events, and mental health among adults at two outpatient psychiatric facilities in Johannesburg, South Africa: a cross-sectional analysis.
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Byansi W, Galvin M, Chiwaye L, Luvuno Z, Kim AW, Sundararajan R, Tsai AC, and Moolla A
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- Female, Adult, Humans, Male, Cross-Sectional Studies, Depression epidemiology, Depression etiology, Depression psychology, South Africa epidemiology, Outpatients, Mental Health, Adverse Childhood Experiences
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Background: Adverse childhood experiences and adult trauma, including sexual abuse, physical abuse, neglect, and interpersonal violence, are highly prevalent in low-resource settings and associated with adverse psychological outcomes. However, there is limited focus on the impact of ACEs and trauma on mental health in sub-Saharan Africa. Therefore, this study examines the impact of traumatic events and ACEs on depression, anxiety, and stress scores among outpatients receiving psychiatric care at two public mental health treatment facilities in Johannesburg, South Africa., Methods: A sample of 309 participants were recruited between January and June 2022 at Helen Joseph Hospital and Alexandra 18th Avenue Clinic. Participants completed screening measures for mental health outcomes, including the 9-item Patient Health Questionnaire (PHQ-9), the 7-item General Anxiety Disorder scale (GAD-7) and the 10-item Perceived Stress Scale. We fitted modified Poisson and linear regression models to estimate the impact of ACEs and adult experiences of trauma on depression, anxiety, and stress scale scores., Results: 47.57% (n = 147) of participants screened positive for anxiety, 44.66% (n = 138) for depression, and 17% (n = 54) for severe stress. More females screened positive for anxiety (65.31%), depression (65.94%), and stress (77.78%). Each ACE was associated with a 12% increased risk of depression, a 10% increased risk of anxiety, and a 17% increased risk of stress. In separately estimated models, each additional traumatic event during adulthood was associated with a 16% increased risk for depression, an 8% increased risk of anxiety, and a 26% increased risk of stress. Across all models, being male and self-reported physical health were consistently associated with a reduced risk for depression, anxiety, and stress., Conclusions: ACEs and experiences of traumatic events as adults were associated with significantly increased risks of anxiety, depression, and severe stress. Given high exposure to ACEs and trauma and the associated impact on the mental health of individuals, families, and communities, there is a need to strengthen and scale innovative combination interventions that address multiple stressors impacting people in low-resource settings., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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16. PRECISION ALS-an integrated pan European patient data platform for ALS.
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McFarlane R, Galvin M, Heverin M, Mac Domhnaill É, Murray D, Meldrum D, Bede P, Bolger A, Hederman L, Impey S, Stephens G, O'Meara C, Wade V, Al-Chalabi A, Chiò A, Corcia P, van Damme P, Ingre C, McDermott C, Povedanos M, van den Berg L, and Hardiman O
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- Humans, Artificial Intelligence, Biomarkers, Machine Learning, Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis epidemiology, Amyotrophic Lateral Sclerosis genetics
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Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative condition. Despite significant advances in pre-clinical models that enhance understanding of disease pathobiology, translation of candidate drugs to effective human therapies has been disappointing. There is increasing recognition of the need for a precision medicine approach toward drug development, as many failures in translation can be attributed in part to disease heterogeneity in humans. PRECISION-ALS is an academic industry collaboration between clinicians, Computer Scientists, Information engineers, technologists, data scientists and industry partners that will address the key clinical, computational, data science and technology associated research questions to generate a sustainable precision medicine based approach toward new drug development. Using extant and prospectively collected population based clinical data across nine European sites, PRECISION-ALS provides a General Data Protection Regulation (GDPR) compliant framework that seamlessly collects, processes and analyses research-quality multimodal and multi-sourced clinical, patient and caregiver journey, digitally acquired data through remote monitoring, imaging, neuro-electric-signaling, genomic and biomarker datasets using machine learning and artificial intelligence. PRECISION-ALS represents a first-in-kind modular transferable pan-European ICT framework for ALS that can be easily adapted to other regions that face similar precision medicine related challenges in multimodal data collection and analysis.
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- 2023
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17. Perceptions of HIV and Mental Illness as "Western" or "Traditional" Illnesses: A Cross-Sectional Study from Limpopo Province, South Africa.
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Galvin M, Coetzee L, Leshabana P, Masebe N, Lebepe S, Moolla A, Tarullo AR, Rockers PC, and Evans D
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Although Western biomedical treatment has dramatically increased across sub-Saharan African health systems, traditional medicine as a form of healing and beliefs in supernatural powers as explanations for disease remain prevalent. Research in this region has identified HIV in particular as a disease located within both the traditional African and Western medical paradigms, whilst mental illness is ascribed to primarily supernatural causes. Within this context, this study sought to understand and explore the perceptions of HIV and mental illness among a population of rural women in Limpopo, South Africa. 82 in-depth interviews were conducted between January and December, 2022. Interviews were transcribed and translated into English. Data were managed using NVivo 11 software and thematically analyzed. The majority of participants identified HIV as a Western illness requiring biomedical treatment with causation largely attributed to biological mechanisms. A traditional form of HIV only cured using traditional treatments was also denoted. Unlike for HIV, the majority of respondents felt that there was no biological or behavioral cause for mental illness but rather the illness was conceptualized supernaturally thus likely impacting patient care pathways. Further research to study HIV and mental health perceptions among a larger sample in different regions of sub-Saharan Africa is warranted.
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- 2023
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18. Doctors' strikes show that it's time to introduce true democracy throughout the NHS.
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Galvin M
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- Humans, State Medicine, Democracy, Physician-Patient Relations, Physicians, Strikes, Employee
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Competing Interests: Competing interests: None declared.
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- 2023
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19. Uterine Inflammatory Myofibroblastic Tumors: Proposed Risk Stratification Model Using Integrated Clinicopathologic and Molecular Analysis.
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Ladwig NR, Bean GR, Pekmezci M, Boscardin J, Joseph NM, Therrien N, Sangoi AR, Piening B, Rajamanickam V, Galvin M, Bernard B, Zaloudek C, Rabban JT, Garg K, and Umetsu SE
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- Female, Humans, Middle Aged, Anaplastic Lymphoma Kinase genetics, Receptor Protein-Tyrosine Kinases genetics, Uterus pathology, Risk Assessment, Neoplasms, Connective and Soft Tissue, Granuloma, Plasma Cell pathology
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Inflammatory myofibroblastic tumor (IMT) of the uterus is a rare mesenchymal tumor with largely benign behavior; however, a small subset demonstrate aggressive behavior. While clinicopathologic features have been previously associated with aggressive behavior, these reports are based on small series, and these features are imperfect predictors of clinical behavior. IMTs are most commonly driven by ALK fusions, with additional pathogenic molecular alterations being reported only in rare examples of extrauterine IMTs. In this study, a series of 11 uterine IMTs, 5 of which demonstrated aggressive behavior, were evaluated for clinicopathologic variables and additionally subjected to capture-based next-generation sequencing with or without whole-transcriptome RNA sequencing. In the 6 IMTs without aggressive behavior, ALK fusions were the sole pathogenic alteration. In contrast, all 5 aggressive IMTs harbored pathogenic molecular alterations and numerous copy number changes in addition to ALK fusions, with the majority of the additional alterations present in the primary tumors. We combined our series with cases previously reported in the literature and performed statistical analyses to propose a novel clinicopathologic risk stratification score assigning 1 point each for: age above 45 years, size≥5 cm,≥4 mitotic figures per 10 high-power field, and infiltrative borders. No tumors with 0 points had an aggressive outcome, while 21% of tumors with 1 to 2 points and all tumors with ≥3 points had aggressive outcomes. We propose a 2-step classification model that first uses the clinicopathologic risk stratification score to identify low-risk and high-risk tumors, and recommend molecular testing to further classify intermediate-risk tumors., Competing Interests: Conflicts of Interest and Source of Funding: This study was funded by the UCSF Department of Pathology Clinical Research Endowment awards granted to N.R.L., K.G., and S.E.U. J.T.R. reports that his spouse receives salary and stock options from Merck and Co. For the remaining authors none were declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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20. Parallel Evolution in Predatory Bdellovibrio sp. NC01 during Long-Term Coculture with a Single Prey Strain.
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Mulvey K, Brosnan K, Galvin M, Mohr S, Muldowney L, Oser M, and Williams LE
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- Animals, Coculture Techniques, Predatory Behavior, Bacterial Proteins genetics, Bacterial Proteins metabolism, Gram-Negative Bacteria metabolism, Bdellovibrio genetics
- Abstract
Experimental evolution provides a powerful tool for examining how Bdellovibrio evolves in response to unique selective pressures associated with its predatory lifestyle. We tested how Bdellovibrio sp. NC01 adapts to long-term coculture with Pseudomonas sp. NC02, which is less susceptible to predation compared to other Gram-negative bacteria. Analyzing six replicate Bdellovibrio populations across six time points spanning 40 passages and 2,880 h of coculture, we detected 30 to 40 new mutations in each population that exceeded a frequency of 5%. Nonsynonymous substitutions were the most abundant type of new mutation, followed by small indels and synonymous substitutions. After completing the final passage, we detected 20 high-frequency (>75%) mutations across all six evolved Bdellovibrio populations. Eighteen of these alter protein sequences, and most increased in frequency rapidly. Four genes acquired a high-frequency mutation in two or more evolved Bdellovibrio populations, reflecting parallel evolution and positive selection. The genes encode a sodium/phosphate cotransporter family protein (Bd2221), a metallophosphoesterase (Bd0054), a TonB family protein (Bd0396), and a hypothetical protein (Bd1601). Tested prey range and predation efficiency phenotypes did not differ significantly between evolved Bdellovibrio populations and the ancestor; however, all six evolved Bdellovibrio populations demonstrated enhanced starvation survival compared to the ancestor. These results suggest that, instead of evolving improved killing of Pseudomonas sp. NC02, Bdellovibrio evolved to better withstand nutrient limitation in the presence of this prey strain. The mutations identified here point to genes and functions that may be important for Bdellovibrio adaptation to the different selective pressures of long-term coculture with Pseudomonas. IMPORTANCE Bdellovibrio attack and kill Gram-negative bacteria, including drug-resistant pathogens of animals and plants. This lifestyle is unusual among bacteria, and it imposes unique selective pressures on Bdellovibrio . Determining how Bdellovibrio evolve in response to these pressures is valuable for understanding the mechanisms that govern predation. We applied experimental evolution to test how Bdellovibrio sp. NC01 evolved in response to long-term coculture with a single Pseudomonas strain, which NC01 can kill, but with low efficiency. Our experimental design imposed different selective pressures on the predatory bacteria and tracked the evolutionary trajectories of replicate Bdellovibrio populations. Using genome sequencing, we identified Bdellovibrio genes that acquired high-frequency mutations in two or more populations. Using phenotype assays, we determined that evolved Bdellovibrio populations did not improve their ability to kill Pseudomonas, but rather are better able to survive starvation. Overall, our results point to functions that may be important for Bdellovibrio adaptation.
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- 2023
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21. Care, burden and self-described positive aspects of caring in amyotrophic lateral sclerosis: an exploratory, longitudinal, mixed-methods study.
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Conroy É, Kennedy P, Heverin M, Hardiman O, and Galvin M
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- Humans, Female, Adult, Middle Aged, Male, Quality of Life, Personal Satisfaction, Research Design, Caregivers psychology, Amyotrophic Lateral Sclerosis therapy
- Abstract
Objectives: To explore factors associated with care burden and the self-described positive aspects of caring for a person living with amyotrophic lateral sclerosis (ALS) over time., Design: Exploratory longitudinal mixed-methods study., Setting: A national multidisciplinary tertiary clinic in Dublin, Ireland., Participants: Participants were informal caregivers of people living with ALS (plwALS) attending the national ALS/motor neuron disease Clinic Dublin. This study focuses on informal caregivers who completed five consecutive interviews ( n = 17) as part of a larger multisite study, over the course of 2.5 years. Participants were over the age of 18. Formal paid caregivers were not included., Outcome Measures: Data were collected on demographic and well-being measures and an open-ended question asked about positive aspects of caregiving. Relevant statistical analysis was carried out on quantitative data and qualitative data were analysed thematically., Results: The caregivers in this study were predominantly female and spouse/partners of the plwALS. Hours of care provided and self-assessed burden increased substantially over time, psychological distress reached clinical significance and quality of life remained relatively stable. Positive aspects identified were thematised as meaning in life and personal satisfaction and varied in relative frequency across phases of the caregiving trajectory., Conclusions: The co-occurrence of negative and positive factors influences the experiences of informal caregivers in ALS. It is important to explore and acknowledge positive aspects, how they develop and are sustained in order to inform supportive services. The cyclical adaptation identified in this study provides evidence for time sensitive targeted supports., Competing Interests: Competing interests: OH is editor-in-chief of the ALS and Frontotemporal Degeneration Journal. She has been a consultant for Cytokinetics, Alexion, AveXis, Biogen and Novartis., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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22. Determinants of mental illness and care seeking behaviours in Northern Haiti: an assessment of demographic, social, and religio-cultural factors among patients at the first mental health clinic in the region.
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Galvin M, Michel G, Pierre E, Manguira E, Lesorogol C, Trani JF, and Iannotti L
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Populations in countries such as Haiti demonstrate a high level of need for mental health care despite a lack of services and trained professionals. In addition to the dearth of biomedical services, local belief systems and explanatory models contribute to a majority of the population relying on traditional medicine as their first option for care. Using a mixed-methods approach, we aim to characterise mental illness at the first mental health clinic in the region - Sant Sante Mantal Mòn Pele (SSMMP) - by interviewing 96 patients with a demographic questionnaire as well as Anxiety, Depression, and Functionality Scales. Multivariate logistic and linear regression models were conducted examining the impact of demographic variables on whether patients believed their illness was caused by sent spirits or previously visited a Vodou priest for treatment, as well as Depression, Anxiety, and Functionality Scale scores. Factors associated with mental illness in this sample included sex, number of traumatic events, physical health status, and number of sessions attended at SSMMP. Factors which impacted traditional beliefs or practices related to mental illness included sex, age, and income., Competing Interests: Disclosure statement No potential conflict of interest was reported by the author(s).
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- 2023
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23. The role of phone-based triage nurses in supporting older adults with multimorbidity to digitally self-manage - Findings from the ProACT proof-of-concept study.
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Doyle J, McAleer P, van Leeuwen C, Smith S, Murphy E, Sillevis Smitt M, Galvin M, Jacobs A, Tompkins L, Sheerin J, and Dinsmore J
- Abstract
Background: Achieving patient-centred care necessitates supporting individuals to have more involvement in the self-management of their care. Digital health technologies are widely recognised as a solution to empower more effective self-management. However, given the complexity of multiple chronic condition (multimorbidity) management, coupled with changes that occur as part of the normal ageing process, human support alongside digital self-management is often necessary for older people with multimorbidity (PwM) to sustain successful self-management., Methods: The aim of the study was to explore the role played by a clinical, nurse-led telephone triage service in responding to alerts generated by older adults using a digital health platform, ProACT, to self-manage multiple chronic conditions over a period of 1 year. Semi-structured interviews with participants with multimorbidity were carried out across four time points during the trial, while interviews and focus groups were conducted with triage nurses at the end of the trial. Thematic analysis was conducted on the resulting transcripts., Results: Themes found in the data include the work of triage nurses; the benefits of triage support; tensions such as anxiety due to patient monitoring; and the relationship between triage nurses and participants., Discussion: This work contributes to an understanding of how older adults with multimorbidity and triage nurses collaborate in multiple chronic disease self-management. Findings are discussed within the context of Hudon et al.'s patient-centred care framework and indicate that patient-centred care was achieved, with both PwM and triage participants reporting positive experiences, relationships and several benefits of the triage support alongside digital self-management., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)
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- 2022
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24. cfDNA methylome profiling for detection and subtyping of small cell lung cancers.
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Chemi F, Pearce SP, Clipson A, Hill SM, Conway AM, Richardson SA, Kamieniecka K, Caeser R, White DJ, Mohan S, Foy V, Simpson KL, Galvin M, Frese KK, Priest L, Egger J, Kerr A, Massion PP, Poirier JT, Brady G, Blackhall F, Rothwell DG, Rudin CM, and Dive C
- Subjects
- Animals, Mice, Epigenome genetics, DNA Methylation genetics, Transcription Factors genetics, Cell-Free Nucleic Acids genetics, Small Cell Lung Carcinoma diagnosis, Lung Neoplasms diagnosis
- Abstract
Small cell lung cancer (SCLC) is characterized by morphologic, epigenetic and transcriptomic heterogeneity. Subtypes based upon predominant transcription factor expression have been defined that, in mouse models and cell lines, exhibit potential differential therapeutic vulnerabilities, with epigenetically distinct SCLC subtypes also described. The clinical relevance of these subtypes is unclear, due in part to challenges in obtaining tumor biopsies for reliable profiling. Here we describe a robust workflow for genome-wide DNA methylation profiling applied to both patient-derived models and to patients' circulating cell-free DNA (cfDNA). Tumor-specific methylation patterns were readily detected in cfDNA samples from patients with SCLC and were correlated with survival outcomes. cfDNA methylation also discriminated between the transcription factor SCLC subtypes, a precedent for a liquid biopsy cfDNA-methylation approach to molecularly subtype SCLC. Our data reveal the potential clinical utility of cfDNA methylation profiling as a universally applicable liquid biopsy approach for the sensitive detection, monitoring and molecular subtyping of patients with SCLC., (© 2022. The Author(s).)
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- 2022
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25. AACR Project GENIE: 100,000 Cases and Beyond.
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Pugh TJ, Bell JL, Bruce JP, Doherty GJ, Galvin M, Green MF, Hunter-Zinck H, Kumari P, Lenoue-Newton ML, Li MM, Lindsay J, Mazor T, Ovalle A, Sammut SJ, Schultz N, Yu TV, Sweeney SM, and Bernard B
- Subjects
- Genomics, Humans, Mutation, Precision Medicine, United States, Cell-Free Nucleic Acids, Neoplasms genetics, Neoplasms pathology, Neoplasms therapy
- Abstract
The American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) is an international pan-cancer registry with the goal to inform cancer research and clinical care worldwide. Founded in late 2015, the milestone GENIE 9.1-public release contains data from >110,000 tumors from >100,000 people treated at 19 cancer centers from the United States, Canada, the United Kingdom, France, the Netherlands, and Spain. Here, we demonstrate the use of these real-world data, harmonized through a centralized data resource, to accurately predict enrollment on genome-guided trials, discover driver alterations in rare tumors, and identify cancer types without actionable mutations that could benefit from comprehensive genomic analysis. The extensible data infrastructure and governance framework support additional deep patient phenotyping through biopharmaceutical collaborations and expansion to include new data types such as cell-free DNA sequencing. AACR Project GENIE continues to serve a global precision medicine knowledge base of increasing impact to inform clinical decision-making and bring together cancer researchers internationally., Significance: AACR Project GENIE has now accrued data from >110,000 tumors, placing it among the largest repository of publicly available, clinically annotated genomic data in the world. GENIE has emerged as a powerful resource to evaluate genome-guided clinical trial design, uncover drivers of cancer subtypes, and inform real-world use of genomic data. This article is highlighted in the In This Issue feature, p. 2007., (©2022 The Authors; Published by the American Association for Cancer Research.)
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- 2022
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26. Care burden, loneliness, and social isolation in caregivers of people with physical and brain health conditions in English-speaking regions: Before and during the COVID-19 pandemic.
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Grycuk E, Chen Y, Almirall-Sanchez A, Higgins D, Galvin M, Kane J, Kinchin I, Lawlor B, Rogan C, Russell G, O'Sullivan R, and Leroi I
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- Brain, Caregiver Burden, Caregivers psychology, Cross-Sectional Studies, Female, Humans, Loneliness psychology, Pandemics, Social Isolation psychology, COVID-19 epidemiology
- Abstract
Background: Public health restrictions due to the COVID-19 (SARS CoV-2) pandemic have disproportionately affected informal caregivers of people living with long term health conditions. We aimed to explore levels of care burden, loneliness, and social isolation among caregivers of people with enduring physical and brain health conditions in English-speaking regions worldwide, by investigating outcomes before and during the COVID-19 pandemic., Methods: A cross-sectional anonymous online survey data from 2287 English-speaking caregivers of people with long term health conditions from four English-speaking regions (UK, Ireland, USA, New Zealand) included measures of care burden, loneliness, and social isolation, reported before and during the COVID-19 pandemic. Analyses were descriptive, followed by an ordinal regression model for predictors of burden., Results: Compared to pre-pandemic levels, all caregivers experienced a significant increase in burden, loneliness, and isolation. Caregivers of people with both brain health and physical conditions were the most burdened and had the highest levels of loneliness and isolation compared to caregivers of people with either a brain health or physical condition only. The increase in care burden among caregivers of people with brain health challenges was associated with caregiver's gender, moderate and severe emotional loneliness, magnitude and frequency of isolation during the pandemic, and care circumstances (cohabitation with the care recipient, restrictions on the ability to provide care)., Conclusions: Health and social care interventions should target caregivers' care circumstances and psychological outcomes, particularly in women, accounting for the significant additional burden of care, loneliness, and isolation resulting from pandemic-related restrictions., (© 2022 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)
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- 2022
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27. Expanding Therapeutic Opportunities for Extrapulmonary Neuroendocrine Carcinoma.
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Frizziero M, Kilgour E, Simpson KL, Rothwell DG, Moore DA, Frese KK, Galvin M, Lamarca A, Hubner RA, Valle JW, McNamara MG, and Dive C
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- Biomarkers, Tumor therapeutic use, Humans, Infant, Newborn, Lung pathology, Carcinoma, Neuroendocrine diagnosis, Carcinoma, Neuroendocrine drug therapy, Carcinoma, Neuroendocrine genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Neuroendocrine Tumors drug therapy, Neuroendocrine Tumors pathology, Small Cell Lung Carcinoma pathology
- Abstract
Poorly differentiated neuroendocrine carcinomas (PD-NEC) are rare cancers garnering interest as they become more commonly encountered in the clinic. This is due to improved diagnostic methods and the increasingly observed phenomenon of "NE lineage plasticity," whereby nonneuroendocrine (non-NE) epithelial cancers transition to aggressive NE phenotypes after targeted treatment. Effective treatment options for patients with PD-NEC are challenging for several reasons. This includes a lack of targetable, recurrent molecular drivers, a paucity of patient-relevant preclinical models to study biology and test novel therapeutics, and the absence of validated biomarkers to guide clinical management. Although advances have been made pertaining to molecular subtyping of small cell lung cancer (SCLC), a PD-NEC of lung origin, extrapulmonary (EP)-PD-NECs remain understudied. This review will address emerging SCLC-like, same-organ non-NE cancer-like and tumor-type-agnostic biological vulnerabilities of EP-PD-NECs, with the potential for therapeutic exploitation. The hypotheses surrounding the origin of these cancers and how "NE lineage plasticity" can be leveraged for therapeutic purposes are discussed. SCLC is herein proposed as a paradigm for supporting progress toward precision medicine in EP-PD-NECs. The aim of this review is to provide a thorough portrait of the current knowledge of EP-PD-NEC biology, with a view to informing new avenues for research and future therapeutic opportunities in these cancers of unmet need., (©2022 American Association for Cancer Research.)
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- 2022
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28. Burden and benefit-A mixed methods study of informal Amyotrophic Lateral Sclerosis caregivers in Ireland and the Netherlands.
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Kennedy P, Conroy É, Heverin M, Leroi I, Beelen A, van den Berg L, Hardiman O, and Galvin M
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Objectives: Amyotrophic Lateral Sclerosis (ALS) is a systemic and terminal disorder of the central nervous system which causes paralysis of limbs, respiratory and bulbar muscles, impacting on physical, communication, cognitive and behavioural functioning. Informal caregivers play a key role in the care of people with ALS. This study aimed to explore experiences of burden along with any beneficial aspects of caregiving in ALS. An understanding of both burden and benefit is important to support the informal caregiver and the person with ALS., Methods/design: This exploratory mixed methods study characterizes two groups of informal caregivers in Ireland (n = 76) and the Netherlands (n = 58). In a semi-structured interview, quantitative data were collected in the form of standardized measures assessing psychological distress, quality of life and burden. Qualitative data were collected from an open ended question, in which caregivers identified positive aspects in their caregiving experience. These data types were purposefully mixed in the analysis and interpretation stages, to provide a greater depth of evidence through diverse research lenses., Results: The caregiver cohorts were predominantly female (69%) and spouse/partners (84%) of the person with ALS. Greater levels of self-assessed burden were found among the caregivers in the Netherlands (p < 0.05), and higher levels of quality of life among the cohort from Ireland (p < 0.05). Themes generated through qualitative analysis identified caregiver satisfaction, ability to meet the patient's needs and the (re) evaluation of meaning and existential aspects of life as positive aspects of caregiving. Existential factors were identified frequently by the caregivers in Ireland, and personal satisfaction and meeting their care recipient's needs by caregivers in the Netherlands. Three percent of all respondents reported there was nothing positive about caregiving., Conclusions: Based on our findings, we suggest that both burden and the presence of positive factors should be evaluated and monitored. The possibility of concurrent positive and challenging experiences should be considered in the design and delivery of supportive interventions for informal caregivers., (© 2022 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)
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- 2022
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29. A Clinical Decision Support System for the Prediction of Quality of Life in ALS.
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Antoniadi AM, Galvin M, Heverin M, Wei L, Hardiman O, and Mooney C
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Amyotrophic Lateral Sclerosis (ALS), also known as Motor Neuron Disease (MND), is a rare and fatal neurodegenerative disease. As ALS is currently incurable, the aim of the treatment is mainly to alleviate symptoms and improve quality of life (QoL). We designed a prototype Clinical Decision Support System (CDSS) to alert clinicians when a person with ALS is experiencing low QoL in order to inform and personalise the support they receive. Explainability is important for the success of a CDSS and its acceptance by healthcare professionals. The aim of this work isto announce our prototype (C-ALS), supported by a first short evaluation of its explainability. Given the lack of similar studies and systems, this work is a valid proof-of-concept that will lead to future work. We developed a CDSS that was evaluated by members of the team of healthcare professionals that provide care to people with ALS in the ALS/MND Multidisciplinary Clinic in Dublin, Ireland. We conducted a user study where participants were asked to review the CDSS and complete a short survey with a focus on explainability. Healthcare professionals demonstrated some uncertainty in understanding the system's output. Based on their feedback, we altered the explanation provided in the updated version of our CDSS. C-ALS provides local explanations of its predictions in a post-hoc manner, using SHAP (SHapley Additive exPlanations). The CDSS predicts the risk of low QoL in the form of a probability, a bar plot shows the feature importance for the specific prediction, along with some verbal guidelines on how to interpret the results. Additionally, we provide the option of a global explanation of the system's function in the form of a bar plot showing the average importance of each feature. C-ALS is available online for academic use.
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- 2022
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30. Risk factors of stunting and wasting in Somali pre-school age children: results from the 2019 Somalia micronutrient survey.
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Donkor WES, Mbai J, Sesay F, Ali SI, Woodruff BA, Hussein SM, Mohamud KM, Muse A, Mohamed WS, Mohamoud AM, Mohamud FM, Petry N, Galvin M, Wegmüller R, Rohner F, Katambo Y, and Wirth JP
- Subjects
- Child, Child, Preschool, Cross-Sectional Studies, Diarrhea complications, Growth Disorders prevention & control, Humans, Infant, Iron, Micronutrients, Prevalence, Risk Factors, Somalia epidemiology, Trace Elements, Wasting Syndrome etiology
- Abstract
Background: Stunting and wasting in children less than 5 years of age are two key indicators of child malnutrition. Reducing their prevalence is a priority of the global public health community and for Somalia, a country suffering complex humanitarian emergencies such as drought, flooding, conflict and large-scale displacements., Methods: Data from the nationally representative cross-sectional Somalia Micronutrient Survey (SMS 2019) on 1947 children were analyzed to assess the prevalence and potential risk factors of stunting and wasting. Bivariate and multivariable analyses were conducted separately for children 0-5 months and 6-59 months, and population attributable fractions were calculated using adjusted risk ratios produced by Poisson regression models., Results: Among the 1947 children, the prevalence of stunting and wasting were 17.2% (95% CI: 15.0, 19.6) and 11.0% (95% CI: 9.3, 12.9), respectively. Among children 6-59 months of age, those residing in severely food insecure households had a higher risk of stunting (adjusted risk ratio [aRR] 1.47; CI: 1.12, 1.93) compared to those in food secure households. This risk of stunting was also higher in children with inflammation (aRR 1.75; CI: 1.35, 2.25) and iron deficiency (ID) (aRR 2.09; CI: 1.58, 2.80). For wasting, a dose-response relationship was found with household wealth, with the risk of wasting increasing significantly as the household wealth quintile decreased. On the other hand, the risk of wasting was lower in iron-deficient children (aRR 0.69; CI: 0.49, 0.98) than in iron-replete children. Among children 0-5 months of age no variables remained statistically significantly associated with stunting in the multivariable analysis. Wasting, however, was more common in children with recent diarrhea (aRR 3.51; CI: 1.68, 7.36)., Conclusions: Nutritional status of children in Somalia may be improved by prevention of diarrhea and other infections and improvements in household food security., (© 2022. The Author(s).)
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- 2022
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31. Electronically controlled cooling pads can improve litter growth performance and indirect measures of milk production in heat-stressed lactating sows.
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Johnson JS, Jansen TL, Galvin M, Field TC, Graham JR, Stwalley RM, and Schinckel AP
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- Animal Feed analysis, Animals, Diet, Female, Heat-Shock Response, Lactation, Litter Size, Milk, Pregnancy, Swine, Weaning, Heat Stress Disorders veterinary, Swine Diseases
- Abstract
Heat stress (HS) decreases lactation output in sows due to an attempt to reduce metabolic heat production. However, this negatively affects litter growth performance. Therefore, the study objective was to determine whether electronically controlled cooling pads (ECP) would improve indirect measures of lactation output (e.g., total heat production [THP]) and litter growth performance in HS exposed sows. Over two repetitions, 12 multiparous (2.69 ± 0.85) lactating sows (265.4 ± 26.1 kg body weight [BW]) and litters were assigned to either an ECP (n = 3/repetition) or a non-functional ECP (NECP; n = 3/repetition) and placed into farrowing crates within indirect calorimeters from days 3.7 ± 0.5 to 18.7 ± 0.5 of lactation. Litters were standardized across all sows (11.4 ± 0.7 piglets/litter), and sows were provided ad libitum feed and water. All sows were exposed to cyclical HS (28.27 ± 0.26 °C nighttime to 33.09 ± 0.19°C daytime). On days 4, 8, 14, and 18 of lactation, indirect calorimetry was performed on each individual sow and litter to determine THP and THP/kg BW0.75. Body temperature (TB) was measured hourly using vaginal implants, and respiration rate (RR; breaths per minute [bpm]) was measured daily at 0700, 1100, 1300, 1500, and 1900 h. Sow feed intake (FI) was assessed daily. Litter weights were obtained at birth, on days 4, 8, 14, and 18 of lactation, and at weaning. Data were analyzed using PROC GLIMMIX with sow and/or litter as the experimental unit. An overall decrease (P < 0.01; 25 bpm) in RR and maximum daily TB (P = 0.02; 0.40 °C) was observed in ECP vs. NECP sows. An increase in THP (P < 0.01; 20.4%) and THP/kg BW0.75 (P < 0.01; 23.1%) was observed for ECP when compared with NECP sows and litters. Litter average daily gain and weaning weight were increased (P < 0.05; 25.0 and 19.2%, respectively) for ECP vs. NECP litters. No FI differences were observed (P = 0.40) when comparing ECP (5.66 ± 0.31 kg/d) and NECP (5.28 ± 0.31 kg/d) sows. In summary, ECPs improve litter growth, thermoregulatory measures, and bioenergetic parameters associated with greater milk production in lactating sows exposed to cyclical HS., (Published by Oxford University Press on behalf of the American Society of Animal Science 2021.)
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- 2022
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32. Localizing syndemics: A comparative study of hunger, stigma, suffering, and crime exposure in three Haitian communities.
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Brewis A, Wutich A, Galvin M, and Lachaud J
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- Crime, Food Supply, Haiti epidemiology, Humans, Social Stigma, Hunger, Syndemic
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Theoretically, disease syndemics are hyper-localized in the forms they take, but little empirical data show how localization manifests. We present a comparison across three sites in Haiti, from data collected in June-august 2017 testing for localizations of risks across three communities: rural farming, border town, and in a high gang-activity urban zone. First, we modeled survey responses collected from heads of 4055 geographically-sampled households via linear regression, considering additive and interaction effects of food insecurity, crime exposure, and discrimination on depression and anxiety levels. Exposure to food insecurity, crime exposure, and discrimination were each associated with more depression and anxiety symptoms. For those living in the urban zone, there was weak evidence of possible interactional risks between the three vulnerabilities, suggesting little meaningful localized syndemic patterning. Second, we conducted thematic and word-based semantic network analysis to identify if people themselves cognitively connected vulnerabilities of hunger/poverty, crime, and suffering/discrimination using 7321 text blocks from 95 semi-structured interviews/focus groups. Network visualization suggested people commonly connect these domains. While the patterns were localized, crime concerns were central to all networks. The domain connections expressed through people's own words were more complexly inter-related than was evident from the modeled survey data, and suggested counter-intuitive influences. The quantitative approach to modeling syndemic interactions suggests no apparent practical benefits to layering or combining local anticrime, anti-hunger, and anti-discrimination programming. However, the qualitative network analysis suggests that programming could none-the-less leverage the perceived connections across domains for more meaningful and effective interventions. For the broader study of syndemics, incorporating novel qualitative approaches clarifies that constituent processes are not just potentially localizing suffering, but are also extremely important in how people cognitively understand and organize their everyday lives., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2022
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33. Risk factors of anaemia and iron deficiency in Somali children and women: Findings from the 2019 Somalia Micronutrient Survey.
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Wirth JP, Sesay F, Mbai J, Ali SI, Donkor WES, Woodruff BA, Pilane Z, Mohamud KM, Muse A, Yussuf HO, Mohamed WS, Veraguth R, Rezzi S, Williams TN, Mohamoud AM, Mohamud FM, Galvin M, Rohner F, Katambo Y, and Petry N
- Subjects
- Adolescent, Adult, Child, Female, Humans, Micronutrients, Middle Aged, Nutritional Status, Pregnancy, Prevalence, Risk Factors, Somalia epidemiology, Young Adult, Anemia epidemiology, Anemia, Iron-Deficiency complications, Iron Deficiencies
- Abstract
There are limited data on the prevalence of anaemia and iron deficiency (ID) in Somalia. To address this data gap, Somalia's 2019 micronutrient survey assessed the prevalence of anaemia and ID in children (6-59 months) and non-pregnant women of reproductive age (15-49 years). The survey also collected data on vitamin A deficiency, inflammation, malaria and other potential risk factors for anaemia and ID. Multivariable Poisson regressions models were used to identify the risk factors for anaemia and ID in children and women. Among children, the prevalence of anaemia and ID were 43.4% and 47.2%, respectively. Approximately 36% and 6% of anaemia were attributable to iron and vitamin A deficiencies, respectively, whereas household possession of soap was associated with approximately 11% fewer cases of anaemia. ID in children was associated with vitamin A deficiency and stunting, whereas inflammation was associated with iron sufficiency. Among women, 40.3% were anaemic, and 49.7% were iron deficient. In women, ID and number of births were significantly associated with anaemia in multivariate models, and approximately 42% of anaemia in women was attributable to ID. Increased parity was associated with ID, and incubation and early convalescent inflammation was associated with ID, whereas late convalescent inflammation was associated with iron sufficiency. ID is the main risk factor of anaemia in both women and children and contributed to a substantial portion of the anaemia cases. To tackle both anaemia and ID in Somalia, food assistance and micronutrient-specific programmes (e.g. micronutrient powders and iron supplements) should be enhanced., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)
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- 2022
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34. A Digital Platform to Support Self-management of Multiple Chronic Conditions (ProACT): Findings in Relation to Engagement During a One-Year Proof-of-Concept Trial.
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Doyle J, Murphy E, Gavin S, Pascale A, Deparis S, Tommasi P, Smith S, Hannigan C, Sillevis Smitt M, van Leeuwen C, Lastra J, Galvin M, McAleer P, Tompkins L, Jacobs A, M Marques M, Medina Maestro J, Boyle G, and Dinsmore J
- Subjects
- Aged, Aged, 80 and over, Belgium, Humans, Ireland, Longitudinal Studies, Multiple Chronic Conditions, Self-Management
- Abstract
Background: Populations globally are ageing, resulting in higher incidence rates of chronic diseases. Digital health platforms, designed to support those with chronic conditions to self-manage at home, offer a promising solution to help people monitor their conditions and lifestyle, maintain good health, and reduce unscheduled clinical visits. However, despite high prevalence rates of multimorbidity or multiple chronic conditions, most platforms tend to focus on a single disease. A further challenge is that despite the importance of users actively engaging with such systems, little research has explored engagement., Objective: The objectives of this study are to design and develop a digital health platform, ProACT, for facilitating older adults self-managing multimorbidity, with support from their care network, and evaluate end user engagement and experiences with this platform through a 12-month trial., Methods: The ProACT digital health platform is presented in this paper. The platform was evaluated in a year-long proof-of-concept action research trial with 120 older persons with multimorbidity in Ireland and Belgium. Alongside the technology, participants had access to a clinical triage service responding to symptom alerts and a technical helpdesk. Interactions with the platform during the trial were logged to determine engagement. Semistructured interviews were conducted with participants and analyzed using inductive thematic analysis, whereas usability and user burden were examined using validated questionnaires., Results: This paper presents the ProACT platform and its components, along with findings on engagement with the platform and its usability. Of the 120 participants who participated, 24 (20%) withdrew before the end of the study, whereas 3 (2.5%) died. The remaining 93 participants actively used the platform until the end of the trial, on average, taking 2 or 3 health readings daily over the course of the trial in Ireland and Belgium, respectively. The participants reported ProACT to be usable and of low burden. Findings from interviews revealed that participants experienced multiple benefits as a result of using ProACT, including improved self-management, health, and well-being and support from the triage service. For those who withdrew, barriers to engagement were poor health and frustration when technology, in particular sensing devices, did not work as expected., Conclusions: This is the first study to present findings from a longitudinal study of older adults using digital health technology to self-manage multimorbidity. Our findings show that older adults sustained engagement with the technology and found it usable. Potential reasons for these results include a strong focus on user-centered design and engagement throughout the project lifecycle, resulting in a platform that meets user needs, as well as the integration of behavior change techniques and personal analytics into the platform. The provision of triage and technical support services alongside the platform during the trial were also important facilitators of engagement., International Registered Report Identifier (irrid): RR2-10.2196/22125., (©Julie Doyle, Emma Murphy, Shane Gavin, Alessandra Pascale, Stéphane Deparis, Pierpaolo Tommasi, Suzanne Smith, Caoimhe Hannigan, Myriam Sillevis Smitt, Cora van Leeuwen, Julia Lastra, Mary Galvin, Patricia McAleer, Lorraine Tompkins, An Jacobs, Marta M Marques, Jaime Medina Maestro, Gordon Boyle, John Dinsmore. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 15.12.2021.)
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- 2021
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35. A Digital Health Platform for Integrated and Proactive Patient-Centered Multimorbidity Self-management and Care (ProACT): Protocol for an Action Research Proof-of-Concept Trial.
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Dinsmore J, Hannigan C, Smith S, Murphy E, Kuiper JML, O'Byrne E, Galvin M, Jacobs A, Sillevis Smitt M, van Leeuwen C, McAleer P, Tompkins L, Brady AM, McCarron M, and Doyle J
- Abstract
Background: Multimorbidity is defined as the presence of two or more chronic diseases and associated comorbidities. There is a need to improve best practices around the provision of well-coordinated, person-centered care for persons with multimorbidities. Present health systems across the European Union (EU) focus on supporting a single-disease framework of care; the primary challenge is to create a patient-centric, integrated care ecosystem to understand and manage multimorbidity. ProACT is a large-scale project funded by the European Commission under the Horizon 2020 programme, that involved the design, development, and evaluation of a digital health platform to improve and advance home-based integrated care, and supported self-management, for older adults (aged ≥65 years) living with multimorbidity., Objective: This paper describes the trial implementation protocol of a proof-of-concept digital health platform (ProACT) in 2 EU member states (Ireland and Belgium) to support older persons with multimorbidities self-managing at home, supported by their care network (CN)., Methods: Research was conducted across 2 EU member states, Ireland and Belgium. A 12-month action research trial design, divided into 3 evaluation cycles and lasting 3 months each, with a reflective redesign and development phase of 1 month after cycles 1 and 2 was conducted. Participants were 120 (60/120, 50% in Ireland and 60/120, 50% in Belgium) older persons with multimorbidities diagnosed with two or more of the following chronic conditions: diabetes, chronic obstructive pulmonary disease, chronic heart failure, and cardiovascular diseases. With permission from persons with multimorbidities, members of their CN were invited to participate in the study. Persons with multimorbidities were provided with ProACT technologies (tablet, devices, or sensors) to support them in self-managing their conditions. CN members also received access to an app to remotely support their persons with multimorbidity. Qualitative and quantitative feedback and evaluation data from persons with multimorbidity and CN participants were collected across four time points: baseline (T1), at the end of each 3-month action research cycle (T2 and T3), and in a final posttrial interview (T4). Thematic analysis was used to analyze the qualitative interview data. Quantitative data were analyzed via platform use statistics (to assess engagement) and standardized questionnaires (using descriptive and inferential statistics). This study is approved by the ethics committees of Ireland and Belgium., Results: The trial implementation phase for this 44-month (2016-2019) funded study was April 2018 to June 2019. The trial outcomes are at various stages of publication since 2021., Conclusions: ProACT aims to co-design and develop a digital intervention with persons with multimorbidities and their CN, incorporating clinical guidelines with the state of the art in human-computer interaction, behavioral science, health psychology, and data analytic methods to deliver a digital health platform to advance self-management of multimorbidity at home, as part of a proactive, integrated model of supported person-centered care., International Registered Report Identifier (irrid): RR1-10.2196/22125., (©John Dinsmore, Caoimhe Hannigan, Suzanne Smith, Emma Murphy, Janneke M L Kuiper, Emma O'Byrne, Mary Galvin, An Jacobs, Myriam Sillevis Smitt, Cora van Leeuwen, Patricia McAleer, Lorraine Tompkins, Anne-Marie Brady, Mary McCarron, Julie Doyle. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 15.12.2021.)
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- 2021
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36. Soluble guanylate cyclase signalling mediates etoposide resistance in progressing small cell lung cancer.
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Schenk MW, Humphrey S, Hossain ASMM, Revill M, Pearsall S, Lallo A, Brown S, Bratt S, Galvin M, Descamps T, Zhou C, Pearce SP, Priest L, Greenhalgh M, Chaturvedi A, Kerr A, Blackhall F, Dive C, and Frese KK
- Subjects
- Animals, Cyclic GMP-Dependent Protein Kinases metabolism, Disease Models, Animal, Disease Progression, Drug Resistance, Neoplasm genetics, Enzyme Inhibitors therapeutic use, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, Mice, Neoplastic Cells, Circulating metabolism, Nitric Oxide metabolism, Nitric Oxide Synthase Type II antagonists & inhibitors, Receptors, Notch metabolism, Signal Transduction genetics, Small Cell Lung Carcinoma drug therapy, Small Cell Lung Carcinoma pathology, Soluble Guanylyl Cyclase genetics, Drug Resistance, Neoplasm drug effects, Etoposide therapeutic use, Lung Neoplasms metabolism, Small Cell Lung Carcinoma metabolism, Soluble Guanylyl Cyclase metabolism
- Abstract
Small cell lung cancer (SCLC) has a 5-year survival rate of <7%. Rapid emergence of acquired resistance to standard platinum-etoposide chemotherapy is common and improved therapies are required for this recalcitrant tumour. We exploit six paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models from donors with extensive stage SCLC to investigate changes at disease progression after chemotherapy. Soluble guanylate cyclase (sGC) is recurrently upregulated in post-chemotherapy progression CDX models, which correlates with acquired chemoresistance. Expression and activation of sGC is regulated by Notch and nitric oxide (NO) signalling with downstream activation of protein kinase G. Genetic targeting of sGC or pharmacological inhibition of NO synthase re-sensitizes a chemoresistant CDX progression model in vivo, revealing this pathway as a mediator of chemoresistance and potential vulnerability of relapsed SCLC., (© 2021. The Author(s).)
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- 2021
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37. Informal Caregivers in Amyotrophic Lateral Sclerosis: A Multi-Centre, Exploratory Study of Burden and Difficulties.
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Conroy É, Kennedy P, Heverin M, Leroi I, Mayberry E, Beelen A, Stavroulakis T, van den Berg LH, McDermott CJ, Hardiman O, and Galvin M
- Abstract
Amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) is a systemic and fatal neurodegenerative condition for which there is currently no cure. Informal caregivers play a vital role in supporting the person with ALS, and it is essential to support their wellbeing. This multi-centre, mixed methods descriptive exploratory study describes the complexity of burden and self-defined difficulties as described by the caregivers themselves. Quantitative and qualitative data were collected during face-to-face interviews with informal caregivers from centres in the Netherlands, England, and Ireland. Standardised measures assessed burden, quality of life, and psychological distress; furthermore, an open-ended question was asked about difficult aspects of caregiving. Most caregivers were female, spouse/partners, and lived with the person with ALS for whom they provided care. Significant differences between national cohorts were identified for burden, quality of life, and anxiety. Among the difficulties described were the practical issues associated with the caregiver role and emotional factors such as witnessing a patient's health decline, relationship change, and their own distress. The mixed-methods approach allows for a more nuanced understanding of the burden and difficulties experienced. It is important to generate an evidence base to support the psychosocial wellbeing and brain health of informal caregivers.
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- 2021
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38. How Providers in Child Neurology Transitioned to Telehealth During COVID-19 Pandemic.
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Bain JM, Dyer CA, Galvin M, Goldman S, Selman J, Silver WG, and Tom SE
- Abstract
To understand child neurology care practices in telehealth (TH), we conducted an online survey interested in identifying which patients should be triaged for in-person evaluations in lieu of telehealth management. We also sought to identify provider and patient/parent limitations of the TH experience. One hundred fourteen clinicians completed the online survey. The majority of child neurologists transitioned within 3 weeks of the pandemic onset and found it inappropriate to evaluate a child under 1 year of age via TH. We identified specific disorders considered inappropriate for initial evaluation via TH, including neuromuscular disease, neuropathy, weakness, autoimmune disease and autism spectrum disorders. Patient and parent technical and economic issues are significant limitations of TH. We suggest quality improvement measures to provide additional training, focusing on particular disorders and increased access for those patients currently excluded from or limited in using or accessing TH., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)
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- 2021
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