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1.
PLoS One ; 19(4): e0301117, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38568987

RESUMO

Suicide is a complex, multidimensional event, and a significant challenge for prevention globally. Artificial intelligence (AI) and machine learning (ML) have emerged to harness large-scale datasets to enhance risk detection. In order to trust and act upon the predictions made with ML, more intuitive user interfaces must be validated. Thus, Interpretable AI is one of the crucial directions which could allow policy and decision makers to make reasonable and data-driven decisions that can ultimately lead to better mental health services planning and suicide prevention. This research aimed to develop sex-specific ML models for predicting the population risk of suicide and to interpret the models. Data were from the Quebec Integrated Chronic Disease Surveillance System (QICDSS), covering up to 98% of the population in the province of Quebec and containing data for over 20,000 suicides between 2002 and 2019. We employed a case-control study design. Individuals were considered cases if they were aged 15+ and had died from suicide between January 1st, 2002, and December 31st, 2019 (n = 18339). Controls were a random sample of 1% of the Quebec population aged 15+ of each year, who were alive on December 31st of each year, from 2002 to 2019 (n = 1,307,370). We included 103 features, including individual, programmatic, systemic, and community factors, measured up to five years prior to the suicide events. We trained and then validated the sex-specific predictive risk model using supervised ML algorithms, including Logistic Regression (LR), Random Forest (RF), Extreme Gradient Boosting (XGBoost) and Multilayer perceptron (MLP). We computed operating characteristics, including sensitivity, specificity, and Positive Predictive Value (PPV). We then generated receiver operating characteristic (ROC) curves to predict suicides and calibration measures. For interpretability, Shapley Additive Explanations (SHAP) was used with the global explanation to determine how much the input features contribute to the models' output and the largest absolute coefficients. The best sensitivity was 0.38 with logistic regression for males and 0.47 with MLP for females; the XGBoost Classifier with 0.25 for males and 0.19 for females had the best precision (PPV). This study demonstrated the useful potential of explainable AI models as tools for decision-making and population-level suicide prevention actions. The ML models included individual, programmatic, systemic, and community levels variables available routinely to decision makers and planners in a public managed care system. Caution shall be exercised in the interpretation of variables associated in a predictive model since they are not causal, and other designs are required to establish the value of individual treatments. The next steps are to produce an intuitive user interface for decision makers, planners and other stakeholders like clinicians or representatives of families and people with live experience of suicidal behaviors or death by suicide. For example, how variations in the quality of local area primary care programs for depression or substance use disorders or increased in regional mental health and addiction budgets would lower suicide rates.


Assuntos
Inteligência Artificial , Suicídio , Feminino , Masculino , Humanos , Estudos de Casos e Controles , Quebeque/epidemiologia , Dados de Saúde Coletados Rotineiramente
2.
Nat Commun ; 15(1): 3431, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654015

RESUMO

The gut microbiota modulates response to hormonal treatments in prostate cancer (PCa) patients, but whether it influences PCa progression remains unknown. Here, we show a reduction in fecal microbiota alpha-diversity correlating with increase tumour burden in two distinct groups of hormonotherapy naïve PCa patients and three murine PCa models. Fecal microbiota transplantation (FMT) from patients with high PCa volume is sufficient to stimulate the growth of mouse PCa revealing the existence of a gut microbiome-cancer crosstalk. Analysis of gut microbial-related pathways in mice with aggressive PCa identifies three enzymes responsible for the metabolism of long-chain fatty acids (LCFA). Supplementation with LCFA omega-3 MAG-EPA is sufficient to reduce PCa growth in mice and cancer up-grading in pre-prostatectomy PCa patients correlating with a reduction of gut Ruminococcaceae in both and fecal butyrate levels in PCa patients. This suggests that the beneficial effect of omega-3 rich diet is mediated in part by modulating the crosstalk between gut microbes and their metabolites in men with PCa.


Assuntos
Transplante de Microbiota Fecal , Fezes , Microbioma Gastrointestinal , Neoplasias da Próstata , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/dietoterapia , Neoplasias da Próstata/microbiologia , Animais , Humanos , Camundongos , Fezes/microbiologia , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Camundongos Endogâmicos C57BL , Ácidos Graxos Insaturados/metabolismo
3.
Commun Med (Lond) ; 4(1): 56, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519581

RESUMO

BACKGROUND: High prostate eicosapentaenoic fatty acid (EPA) levels were associated with a significant reduction of upgrading to grade group (GG) ≥ 2 prostate cancer in men under active surveillance. We aimed to evaluate the effect of MAG-EPA long-chain omega-3 fatty acid dietary supplement on prostate cancer proliferation. METHODS: A phase II double-blind randomized placebo-controlled trial was conducted in 130 men diagnosed with GG ≥ 2 prostate cancer and undergoing radical prostatectomy between 2015-2017 (Clinicaltrials.gov: NCT02333435). Participants were randomized to receive 3 g daily of either MAG-EPA (n = 65) or placebo (n = 65) for 7 weeks (range 4-10) prior to radical prostatectomy. The primary outcome was the cancer proliferation index quantified by automated image analysis of tumor nuclear Ki-67 expression using standardized prostatectomy tissue microarrays. Additional planned outcomes at surgery are reported including plasma levels of 27 inflammatory cytokines and fatty acid profiles in circulating red blood cells membranes and prostate tissue. RESULTS: Cancer proliferation index measured by Ki-67 expression was not statistically different between the intervention (3.10%) and placebo (2.85%) groups (p = 0.64). In the per protocol analyses, the adjusted estimated effect of MAG-EPA was greater but remained non-significant. Secondary outcome was the changes in plasma levels of 27 cytokines, of which only IL-7 was higher in MAG-EPA group compared to placebo (p = 0.026). Men randomized to MAG-EPA prior to surgery had four-fold higher EPA levels in prostate tissue compared to those on placebo. CONCLUSIONS: This MAG-EPA intervention did not affect the primary outcome of prostate cancer proliferation according to nuclear Ki-67 expression. More studies are needed to decipher the effects of long-chain omega-3 fatty acid dietary supplementation in men with prostate cancer.


It is thought that our diet can impact our risk of cancer and affect outcomes in patients with cancer. Omega-3 fatty acids, mostly found in fatty fish, might be beneficial by protecting against prostate cancer and its adverse outcomes. We conducted a clinical trial to test the effects of an omega-3 dietary supplement (MAG-EPA) in men with prostate cancer. We randomly allocated 130 men to receive either MAG-EPA or a placebo for 7 weeks before their prostate cancer surgery. We measured a marker of how much tumor cells were proliferating (or growing in number) at the point of surgery, which might indicate how aggressive their disease was. However, the supplement did not affect tumor cell proliferation. The supplement was therefore not beneficial in this group of patients and further studies  are needed to test and confirm the effects of MAG-EPA on prostate cancer cells.

4.
Psychiatry Res ; 332: 115718, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38198857

RESUMO

The Signature Biobank is a longitudinal repository of biospecimen, psychological, sociodemographic, and diagnostic data that was created in 2012. The Signature Consortium represents a group of approximately one hundred Quebec-based transdisciplinary clinicians and research scientists with various expertise in the field of psychiatry. The objective of the Signature Biobank is to investigate the multi-faceted underpinnings of psychiatric disorders among patients in crisis. The Signature Consortium is expanding and includes new active members that seek to highlight the contributions made by Signature Biobank since its inception. This article details our research protocol, directions, and summarizes contributions. To date, we have collected biological samples (n = 1,986), and questionnaire data (n = 2,085) from psychiatric emergency patients of the Institut universitaire en santé mentale de Montréal (Quebec, Canada), with a large proportion from whom both data types were collected (n = 1,926). In addition to this, a subsample of patients was followed-up at hospital discharge, and two additional outpatient clinic appointments (n = 958 with at least one follow-up). In addition, a socio-demographically matched comparison group of individuals who were not hospitalized for psychiatric disorders (n = 149) was recruited from the surrounding catchment area. To summarize, a systematic review of the literature shows that the Signature Biobank has contributed to better characterizing psychiatric comorbidities, biological profiles, and psychosocial functioning across some of the most common psychiatric disorders, including psychosis, mood, anxiety, and substance use disorders. The Signature Biobank is now one of the world's largest repositories of data collected from patients receiving care at a psychiatric emergency unit.


Assuntos
Psiquiatria , Transtornos Psicóticos , Transtornos Relacionados ao Uso de Substâncias , Humanos , Bancos de Espécimes Biológicos , Comorbidade , Transtornos Psicóticos/diagnóstico
5.
BMC Health Serv Res ; 24(1): 150, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291443

RESUMO

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.


Assuntos
Pessoal de Saúde , Neoplasias , Humanos , Grupos Focais , Pesquisa Qualitativa , Oncologia , Neoplasias/terapia
6.
Cancer Med ; 12(19): 20163-20176, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37787025

RESUMO

BACKGROUND: In the general population, a higher omega-3 polyunsaturated fatty acids intake is associated with lower levels of several psychological symptoms, especially depression. However, the existing evidence in cancer is equivocal. METHODS: This phase IIB double-blind, placebo-controlled trial was aimed at comparing the effects of eicosapentaenoic acid monoacylglyceride (MAG-EPA) supplementation and high oleic acid sunflower oil (HOSO; placebo) on depression levels (primary outcome) and other symptoms (anxiety, fear of cancer recurrence, fatigue, insomnia, perceived cognitive impairments; secondary outcomes). Participants, recruited in a prostate cancer clinic, were randomized to MAG-EPA (3.75 g daily; n = 65) or HOSO (3.75 g daily; n = 65) for 1 year post-radical prostatectomy (RP), starting 4-10 weeks before surgery. Patients completed self-report scales at baseline (before RP) and 3, 6, 9, and 12 months after: Hospital Anxiety and Depression Scale (HADS), Fear of Cancer Recurrence Inventory (FCRI), Insomnia Severity Index (ISI), Fatigue Symptom Inventory (FSI), and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). RESULTS: Analyses showed significant reductions in HADS-depression, HADS-anxiety, FCRI, ISI, FSI-number of days, and FACT-Cog-impact scores over time. A significant group-by-time interaction was obtained on FACT-Cog-Impact scores only; yet, the temporal change was significant in HOSO patients only. CONCLUSIONS: Several symptoms significantly decreased over time, mainly within the first months of the study. However, MAG-EPA did not produce greater reductions than HOSO. Omega-3 supplementation does not seem to improve psychological symptoms of men treated with RP.


Assuntos
Neoplasias da Próstata , Distúrbios do Início e da Manutenção do Sono , Humanos , Masculino , Suplementos Nutricionais , Método Duplo-Cego , Ácido Eicosapentaenoico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia
7.
BMC Cancer ; 23(1): 369, 2023 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-37087438

RESUMO

BACKGROUND: Centre hospitalier de l'Université de Montréal in Canada introduced accompanying patients (APs) into the breast cancer care trajectory. APs are patients who have been treated for breast cancer and have been integrated into the clinical team to expand the services offered to people affected by cancer. This study describes the profiles of the people who received the support and explores whether one-offs vs ongoing encounters with APs influence their experience of care, on self-efficacy in coping with cancer, and on their level of psychological distress. METHODS: An exploratory cross-sectional study was carried out among patients to compare patients who had one encounter with an AP (G1) with those who had had several encounters (G2). Five questionnaires were administered on socio-demographic characteristics, care pathway, evaluation of the support experience, self-efficacy in coping with cancer, and level of psychological distress. Logbooks, completed by the APs, determined the number of encounters. Linear regression models were used to evaluate the associations between the number of encounters, patient characteristics, care pathway, number of topics discussed, self-efficacy measures in coping with cancer, and level of psychological distress. RESULTS: Between April 2020 and December 2021, 60% of 535 patients who were offered support from an AP accepted. Of these, one hundred and twenty-four patients participated in the study. The study aimed to recruit a minimum of 70 patients with the expectation of obtaining at least 50 participants, assuming a response rate of 70%. There were no differences between G1 and G2 in terms of sociodemographic data and care pathways. Statistical differences were found between G1 and G2 for impacts on and the return to daily life (p = 0.000), the return to the work and impacts on professional life (p = 0.044), announcement of a diagnosis to family and friends (p = 0.033), and strategies for living with treatment under the best conditions (p = 0.000). Significant differences were found on the topics of cancer (p = 0.000), genetic testing (p = 0.023), therapeutic options (p = 0.000), fatigue following treatment (p = 0.005), pain and discomfort after treatment or surgery (p = 0.000), potential emotions and their management (p = 0.000) and the decision-making processes (p = 0.011). A significant relationship was found between the two groups for patients' ability to cope with cancer (p = 0.038), and their level of psychological distress at different stages of the care pathway (p = 0.024). CONCLUSIONS: This study shows differences between one-time and ongoing support for cancer patients. It highlights the potential for APs to help patients develop self-efficacy and cope with the challenges of cancer treatment.


Assuntos
Neoplasias da Mama , Angústia Psicológica , Humanos , Feminino , Estudos Transversais , Estresse Psicológico/psicologia , Autoeficácia , Adaptação Psicológica , Neoplasias da Mama/terapia , Neoplasias da Mama/psicologia , Inquéritos e Questionários
8.
Nutrients ; 15(6)2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36986098

RESUMO

Prostate cancer (PCa) and associated treatments incur symptoms that may impact patients' quality of life. Studies have shown beneficial relationships between diet, especially omega-3 fatty acids, and these symptoms. Unfortunately, only few data describing the relationship between long-chain omega-3 fatty acids (LCn3) and PCa-related symptoms in patients are available. The purpose of this study was to evaluate the effects of LCn3 supplementation on PCa-specific quality of life in 130 men treated by radical prostatectomy. Men were randomized to receive a daily dose of either 3.75 g of fish oil or a placebo starting 7 weeks before surgery and for up to one-year post-surgery. Quality of life was assessed using the validated EPIC-26 and IPSS questionnaires at randomization, at surgery, and every 3 months following surgery. Between-group differences were assessed using linear mixed models. Intention-to-treat analyses showed no significant difference between the two groups. However, at 12-month follow-up, per-protocol analyses showed a significantly greater increase in the urinary irritation function score (better urinary function) (MD = 5.5, p = 0.03) for the LCn3 group compared to placebo. These results suggest that LCn3 supplementation may improve the urinary irritation function in men with PCa treated by radical prostatectomy and support to conduct of larger-scale studies.


Assuntos
Ácidos Graxos Ômega-3 , Qualidade de Vida , Masculino , Animais , Suplementos Nutricionais , Óleos de Peixe/uso terapêutico , Prostatectomia/efeitos adversos
9.
BMJ Open ; 13(2): e066423, 2023 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-36849211

RESUMO

INTRODUCTION: Suicide has a complex aetiology and is a result of the interaction among the risk and protective factors at the individual, healthcare system and population levels. Therefore, policy and decision makers and mental health service planners can play an important role in suicide prevention. Although a number of suicide risk predictive tools have been developed, these tools were designed to be used by clinicians for assessing individual risk of suicide. There have been no risk predictive models to be used by policy and decision makers for predicting population risk of suicide at the national, provincial and regional levels. This paper aimed to describe the rationale and methodology for developing risk predictive models for population risk of suicide. METHODS AND ANALYSIS: A case-control study design will be used to develop sex-specific risk predictive models for population risk of suicide, using statistical regression and machine learning techniques. Routinely collected health administrative data in Quebec, Canada, and community-level social deprivation and marginalisation data will be used. The developed models will be transformed into the models that can be readily used by policy and decision makers. Two rounds of qualitative interviews with end-users and other stakeholders were proposed to understand their views about the developed models and potential systematic, social and ethical issues for implementation; the first round of qualitative interviews has been completed. We included 9440 suicide cases (7234 males and 2206 females) and 661 780 controls for model development. Three hundred and forty-seven variables at individual, healthcare system and community levels have been identified and will be included in least absolute shrinkage and selection operator regression for feature selection. ETHICS AND DISSEMINATION: This study is approved by the Health Research Ethnics Committee of Dalhousie University, Canada. This study takes an integrated knowledge translation approach, involving knowledge users from the beginning of the process.


Assuntos
Suicídio , Feminino , Masculino , Humanos , Estudos de Casos e Controles , Prevenção do Suicídio , Fatores de Proteção , Canadá/epidemiologia
10.
Health Expect ; 26(2): 847-857, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36704843

RESUMO

INTRODUCTION: Since 2018, four establishments in Quebec, Canada, have decided to implement the PAROLE-Onco programme, which introduced accompanying patients (APs) in healthcare teams to improve the experience of cancer patients. APs are patient advisors who have had a cancer treatment experience and who conduct consultations to complement the service offered by providing emotional, informational and educational support to patients undergoing treatments (e.g., radiotherapy, chemotherapy, surgery), mostly for breast cancer. We aimed to explore the evolution of APs' perspectives regarding their activities within the clinical oncology teams as well as the perceived effects of their intervention with patients, the clinical team and themselves. METHODS: A qualitative study based on semistructured interviews and focus groups was conducted with APs at the beginning of their intervention (T1) and 2 years afterwards (T2). The themes discussed were APs' activities and the perceived effects of their interventions on themselves, on the patients and on the clinical team. RESULTS: In total, 20 APs were interviewed. In T2, APs' activities shifted from listening and sharing experiences to empowering patients by helping them become partners in their care and felt generally more integrated into the clinical team. APs help patients feel understood and supported, alleviate stress and become partners in the care they receive. They also alleviate the clinical team's workload by offering a complementary service through emotional support, which, according to them, helps patients feel calmer and more prepared for their appointments with healthcare professionals. They communicate additional information about their patients' health journey, which makes the appointment more efficient for healthcare professionals. When APs accompany patients, they feel as if they can make a difference in patients' lives. Their activities are perceived by some as an opportunity to give back but also as a way of giving meaning to their own experience, in turn serving as a learning experience. CONCLUSION: By mobilizing their experiential knowledge, APs provide emotional, informational, cognitive and navigational support, which allows patients to be more empowered in their care and which complements professionals' scientific knowledge, thereby helping to refine their sensitivity to the patients' experiences. PATIENT OR PUBLIC CONTRIBUTION: Two patient-researchers have contributed to the study design, the conduct of the study, the data analysis and interpretation, as well as in the preparation and writing of this manuscript.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/psicologia , Oncologia , Pesquisa Qualitativa , Grupos Focais , Pacientes
12.
Mol Metab ; 62: 101516, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35598879

RESUMO

OBJECTIVE: The prostate is metabolically unique: it produces high levels of citrate for secretion via a truncated tricarboxylic acid (TCA) cycle to maintain male fertility. In prostate cancer (PCa), this phenotype is reprogrammed, making it an interesting therapeutic target. However, how the truncated prostate TCA cycle works is still not completely understood. METHODS: We optimized targeted metabolomics in mouse and human organoid models in ex vivo primary culture. We then used stable isotope tracer analyses to identify the pathways that fuel citrate synthesis. RESULTS: First, mouse and human organoids were shown to recapitulate the unique citrate-secretory program of the prostate, thus representing a novel model that reproduces this unusual metabolic profile. Using stable isotope tracer analysis, several key nutrients were shown to allow the completion of the prostate TCA cycle, revealing a much more complex metabolic profile than originally anticipated. Indeed, along with the known pathway of aspartate replenishing oxaloacetate, glutamine was shown to fuel citrate synthesis through both glutaminolysis and reductive carboxylation in a GLS1-dependent manner. In human organoids, aspartate entered the TCA cycle at the malate entry point, upstream of oxaloacetate. Our results demonstrate that the citrate-secretory phenotype of prostate organoids is supported by the known aspartate-oxaloacetate-citrate pathway, but also by at least three additional pathways: glutaminolysis, reductive carboxylation, and aspartate-malate conversion. CONCLUSIONS: Our results add a significant new dimension to the prostate citrate-secretory phenotype, with at least four distinct pathways being involved in citrate synthesis. Better understanding this distinctive citrate metabolic program will have applications in both male fertility as well as in the development of novel targeted anti-metabolic therapies for PCa.


Assuntos
Ciclo do Ácido Cítrico , Malatos , Animais , Ácido Aspártico/metabolismo , Citratos/metabolismo , Ácido Cítrico/metabolismo , Humanos , Malatos/metabolismo , Masculino , Redes e Vias Metabólicas , Camundongos , Oxaloacetatos/metabolismo , Próstata/metabolismo
14.
Clin Transl Med ; 12(1): e581, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35075795

RESUMO

Tumor-associated macrophages (TAMs) support tumor progression within the tumor microenvironment (TME). Many questions remain as to the origin, development, and function of TAMs within the prostate TME. Evaluation of TAMs in prostate cancer (PCa) patients identified the immunosuppressive TAM marker CD163 in adjacent normal epithelium as an independent predictor of metastases or PCa death. Flow cytometry analyses identified prostate TAMs as frequently expressing both proinflammatory M1 (CCR7+) and immunosuppressive M2 (CD163+) markers. In vitro, we demonstrate PCa cells similarly subvert human M1 macrophages toward a mixed M1/M2 macrophage phenotype favoring tumor growth. Further the cytokine milieu-induced transition between immunosuppressive M2 to proinflammatory M1 (M2→M1) macrophages is abrogated by the presence of PCa cells. RNA sequencing suggests alterations in chemokine expression in prostate TAMs due to the presence of PCa cells. Together, our results suggest that prostate TAMs originate from inflammatory infiltrating macrophages, which are then reprogrammed mainly by PCa cells, but also the cytokine milieu. A better understanding of this subversion of macrophages within the prostate may lead to novel treatment strategies.


Assuntos
Hospedeiro Imunocomprometido/imunologia , Macrófagos/citologia , Próstata/citologia , Adulto , Idoso , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Próstata/microbiologia , Quebeque
15.
Clin Nutr ESPEN ; 47: 221-226, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35063205

RESUMO

BACKGROUND AND AIMS: Many dietary supplements, including omega-3 fatty acids (ω3), are suspected to affect blood coagulation and platelet function. Despite no clinical evidence, discontinuation is recommended before radical prostatectomy. However, long-chain ω3 (LCω3) appear beneficial against prostate cancer progression. Here, we aim to determine the effect of LCω3 supplements on perioperative bleeding, hemoglobin, platelets, and postoperative complications after radical prostatectomy. METHODS: This is a planned exploratory analysis of 130 patients diagnosed with prostate cancer grade group 2 or greater enrolled in a randomized controlled trial (NCT02333435) testing the effects of LCω3, on prostate cancer biological and pathological outcomes at radical prostatectomy as main outcomes. The LCω3 intervention (MAG-EPA 3 g daily) or equivalent placebo was given 4-10 weeks prior to radical prostatectomy. An intention-to-treat analysis approach was used with bi-variate statistical testing of bleeding and complications outcomes. We also estimated the difference between groups using linear regression and non-parametric quantile regression models. All models were adjusted for confounding variables selected on clinical relevance. RESULTS: We found no clinically significant effect of LCω3 versus placebo on perioperative bleeding, laboratory tests or postoperative complications. In contrast, as expected, we found a significant increase in perioperative bleeding in open retropubic radical prostatectomy compared to robot-assisted radical prostatectomy (adjusted difference 115.8 mL, p = 0.04). CONCLUSIONS: Our results suggest that ω3 supplements can be safely taken before radical prostatectomy without increasing surgical bleeding risk. These findings are relevant since ω3 may beneficially affect prostate cancer evolution.


Assuntos
Perda Sanguínea Cirúrgica , Ácidos Graxos Ômega-3 , Perda Sanguínea Cirúrgica/prevenção & controle , Suplementos Nutricionais , Humanos , Masculino , Próstata/patologia , Próstata/cirurgia , Prostatectomia/efeitos adversos , Prostatectomia/métodos
16.
Sci Rep ; 11(1): 19299, 2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588590

RESUMO

Within the prostate tumor microenvironment (TME) there are complex multi-faceted and dynamic communication occurring between cancer cells and immune cells. Macrophages are key cells which infiltrate and surround tumor cells and are recognized to significantly contribute to tumor resistance and metastases. Our understanding of their function in the TME is commonly based on in vitro and in vivo models, with limited research to confirm these model observations in human prostates. Macrophage infiltration was evaluated within the TME of human prostates after 72 h culture of fresh biopsies samples in the presence of control or enzalutamide. In addition to immunohistochemistry, an optimized protocol for multi-parametric evaluation of cellular surface markers was developed using flow cytometry. Flow cytometry parameters were compared to clinicopathological features. Immunohistochemistry staining for 19 patients with paired samples suggested enzalutamide increased the expression of CD163 relative to CD68 staining. Techniques to validate these results using flow cytometry of dissociated biopsies after 72 h of culture are described. In a second cohort of patients with Gleason grade group ≥ 3 prostate cancer, global macrophage expression of CD163 was unchanged with enzalutamide treatment. However, exploratory analyses of our results using multi-parametric flow cytometry for multiple immunosuppressive macrophage markers suggest subgroup changes as well as novel associations between circulating biomarkers like the neutrophil to lymphocyte ratio (NLR) and immune cell phenotype composition in the prostate TME. Further, we observed an association between B7-H3 expressing tumor-associated macrophages and the presence of intraductal carcinoma. The use of flow cytometry to evaluate ex vivo cultured prostate biopsies fills an important gap in our ability to understand the immune cell composition of the prostate TME. Our results highlight novel associations for further investigation.


Assuntos
Antagonistas de Androgênios/farmacologia , Benzamidas/farmacologia , Biomarcadores Tumorais/análise , Nitrilas/farmacologia , Feniltioidantoína/farmacologia , Neoplasias da Próstata/terapia , Macrófagos Associados a Tumor/efeitos dos fármacos , Idoso , Antagonistas de Androgênios/uso terapêutico , Benzamidas/uso terapêutico , Células Cultivadas , Quimioterapia Adjuvante/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Cultura Primária de Células , Próstata/citologia , Próstata/efeitos dos fármacos , Próstata/imunologia , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Microambiente Tumoral/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia
17.
Health Expect ; 24(4): 1230-1241, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33949739

RESUMO

CONTEXT: Partnership between patients and health-care professionals (HCPs) is a concept that needs a valid, practical measure to facilitate its use by patients and HCPs. OBJECTIVE: To co-construct a tool for measuring the degree of partnership between patients and HCPs. DESIGN: The CADICEE tool was developed in four steps: (1) generate key dimensions of patient partnership in clinical care; (2) co-construct the tool; (3) assess face and content validity from patients' and HCPs' viewpoints; and (4) assess the usability of the tool and explore its measurement performance. RESULTS: The CADICEE tool comprises 24 items under 7 dimensions: 1) relationship of Confidence or trust between the patient and the HCPs; 2) patient Autonomy; 3) patient participation in Decisions related to care; 4) shared Information on patient health status or care; 5) patient personal Context; 6) Empathy; and 7) recognition of Expertise. Assessment of the tool's usability and measurement performance showed, in a convenience sample of 246 patients and relatives, high face validity, acceptability and relevance for both patients and HCPs, as well as good construct validity. CONCLUSIONS: The CADICEE tool is developed in co-construction with patients to evaluate the degree of partnership in care desired by patients in their relationship with HCPs. The tool can be used in various clinical contexts and in different health-care settings. PATIENT OR PUBLIC CONTRIBUTION: Patients were involved in determining the importance of constructing this questionnaire. They co-constructed it, pre-tested it and were part of the entire questionnaire development process. Three patients participated in the writing of the article.


Assuntos
Pessoal de Saúde , Participação do Paciente , Humanos , Reprodutibilidade dos Testes , Projetos de Pesquisa , Inquéritos e Questionários
18.
JMIR Res Protoc ; 9(12): e22500, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33259326

RESUMO

BACKGROUND: In times of pandemics, social distancing, isolation, and quarantine have precipitated depression, anxiety, and substance misuse. Scientific literature suggests that patients living with mental health problems or illnesses (MHPIs) who interact with peer support workers (PSWs) experience not only the empathy and connectedness that comes from similar life experiences but also feel hope in the possibility of recovery. So far, it is the effect of mental health teams or programs with PSWs that has been evaluated. OBJECTIVE: This paper presents the protocol for a web-based intervention facilitated by PSWs. The five principal research questions are whether this intervention will have an impact in terms of (Q1) personal-civic recovery and (Q2) clinical recovery, (Q3) how these recovery potentials can be impacted by the COVID-19 pandemic, (Q4) how the lived experience of persons in recovery can be mobilized to cope with such a situation, and (Q5) how sex and gender considerations can be taken into account for the pairing of PSWs with service users beyond considerations based solely on psychiatric diagnoses or specific MHPIs. This will help us assess the impact of PSWs in this setting. METHODS: PSWs will lead a typical informal peer support group within the larger context of online peer support groups, focusing on personal-civic recovery. They will be scripted with a fixed, predetermined duration (a series of 10 weekly 90-minute online workshops). There will be 2 experimental subgroups-patients diagnosed with (1) psychotic disorders (n=10) and (2) anxiety or mood disorders (n=10)-compared to a control group (n=10). Random assignment to the intervention and control arms will be conducted using a 2:1 ratio. Several instruments will be used to assess clinical recovery (eg, the Recovery Assessment Scale, the Citizenship Measure questionnaire). The COVID-19 Stress Scales will be used to assess effects in terms of clinical recovery and stress- or anxiety-related responses to COVID-19. Changes will be compared between groups from baseline to endpoint in the intervention and control groups using the Student paired sample t test. RESULTS: This pilot study was funded in March 2020. The protocol was approved on June 16, 2020, by the Research Ethics Committees of the Montreal Mental Health University Institute. Recruitment took place during the months of July and August, and results are expected in December 2020. CONCLUSIONS: Study results will provide reliable evidence on the effectiveness of a web-based intervention provided by PSWs. The investigators, alongside key decision makers and patient partners, will ensure knowledge translation throughout, and our massive open online course (MOOC), The Fundamentals of Recovery, will be updated with the evidence and new knowledge generated by this feasibility study. TRIAL REGISTRATION: ClinicalTrials.gov NCT04445324; https://clinicaltrials.gov/ct2/show/NCT04445324. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/22500.

19.
J Pers Med ; 10(4)2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33053639

RESUMO

Several instruments have been developed by clinicians and academics to assess clinical recovery. Based on their life narratives, measurement tools have also been developed and validated through participatory research programs by persons living with mental health problems or illnesses to assess personal recovery. The main objective of this project is to explore possible correlations between clinical recovery, personal recovery, and citizenship by using patient-reported outcome measures. All study participants are currently being treated and monitored after having been diagnosed either with (a) psychotic disorders or (b) anxiety and mood disorders. They have completed questionnaires for clinical evaluation purposes (clinical recovery) will further complete the Recovery Assessment Scale and Citizenship Measure (personal-civic recovery composite index). Descriptive and statistical analyses will be performed to determine internal consistency for each of the subscales, and assess convergent-concurrent validity between clinical recovery, citizenship and personal recovery. Recovery-oriented mental health care and services are particularly recognizable by the presence of Peer Support Workers, who are persons with lived experience of recovery. Upon training, they can personify personalized mental health care and services, that is to say services that are centered on the person's recovery project and not only on their symptoms. Data from our overall research strategy will lay the ground for the evaluation of the effects of the intervention of Peer Support Workers on clinical recovery, citizenship and personal recovery.

20.
Soc Psychiatry Psychiatr Epidemiol ; 55(9): 1201-1213, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32086537

RESUMO

BACKGROUND: For ICD-11, the WHO emphasized the clinical utility of communication and the need to involve service users and carers in the revision process. AIMS: The objective was to assess whether medical vocabulary was accessible, which kinds of feelings it activated, whether and how users and carers would like to rephrase terms, and whether they used diagnosis to talk about mental health experiences. METHOD: An innovative protocol focused on two diagnoses (depressive episode and schizophrenia) was implemented in 15 different countries. The same issues were discussed with users and carers: understanding, feelings, rephrasing, and communication. RESULTS: Most participants reported understanding the diagnoses, but associated them with negative feelings. While the negativity of "depressive episode" mostly came from the concept itself, that of "schizophrenia" was largely based on its social impact and stigmatization associated with "mental illness". When rephrasing "depressive episode", a majority kept the root "depress*", and suppressed the temporal dimension or renamed it. Almost no one suggested a reformulation based on "schizophrenia". Finally, when communicating, no one used the phrase "depressive episode". Some participants used words based on "depress", but no one mentioned "episode". Very few used "schizophrenia". CONCLUSION: Data revealed a gap between concepts and emotional and cognitive experiences. Both professional and experiential language and knowledge have to be considered as complementary. Consequently, the ICD should be co-constructed by professionals, service users, and carers. It should take the emotional component of language, and the diversity of linguistic and cultural contexts, into account.


Assuntos
Cuidadores , Esquizofrenia , Comunicação , Pesquisa Participativa Baseada na Comunidade , Humanos , Classificação Internacional de Doenças , Esquizofrenia/diagnóstico , Esquizofrenia/terapia
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