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1.
Int J Drug Policy ; 131: 104547, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39159532

RESUMO

BACKGROUND: The ongoing overdose crisis in Canada has prompted efforts to increase access to a "safer supply" of prescribed alternatives to the unregulated drug supply. While safer supply programs predominantly distribute hydromorphone tablets, the Safer Alternatives for Emergency Response (SAFER) program in Vancouver, Canada offers a range of prescribed alternatives, including fentanyl patches. However, little is known about the effectiveness of fentanyl patches as safer supply. Drawing on the perspectives and experiences of program participants, we sought to qualitatively evaluate the effectiveness of the SAFER fentanyl patch program in meeting its intended aims, including reducing risk of overdose by decreasing reliance on the unregulated drug supply. METHODS: As part of a larger mixed-methods evaluation of SAFER, semi-structured qualitative interviews were conducted with 17 fentanyl patch program participants between February 2022 and April 2023. Thematic analysis of interview data focused on program engagement, experiences, impacts, and challenges. RESULTS: The flexible program structure, including lack of need for daily dispensation, the extended missed dose protocol, and community pharmacy patch distribution fostered engagement and enhanced autonomy. Improved management of withdrawal symptoms and cravings due to steady transdermal dosing led to reduced unregulated drug use and overdose risk. Participants also experienced economic benefits and improvements in overall health and quality of life. However, skin irritation and patch adhesion issues were key barriers to program retention. CONCLUSION: Our findings demonstrate the value of including fentanyl patch safer supply in the substance use continuum of care and offer insights for innovations in delivery of this intervention.

2.
Cancer Med ; 13(14): e70004, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39046221

RESUMO

INTRODUCTION: Integration of exercise into standard oncology care requires a highly skilled workforce of exercise professionals; however, competency requirements have not kept pace with advancements in the field. Therefore, the aim of this study was to obtain consensus on core competencies required for an exercise professional to be qualified to work with adults undergoing active cancer treatment. MATERIALS AND METHODS: A three-round modified electronic Delphi process was used. In Round 1, an international group of 64 exercise oncology stakeholders (i.e., exercise oncology professionals (n = 29), clinical referrers (n = 21), and people with lived experience (n = 14)) responded to open-ended prompts eliciting perspectives regarding competencies needed for an exercise oncology professional to work with adults receiving active cancer treatment. Subsequently, only exercise oncology professionals participated, ranking the importance of competencies. In Round 2, professionals received summary feedback, ranked new competencies generated from open-ended responses, and reranked competencies not reaching consensus. In the final round, professionals finalized consensus ranking and rated frequency and mastery level for each. RESULTS: Consensus was reached on 103 core competencies required for exercise professionals to be qualified to deliver care to adults undergoing active cancer treatment. The core competencies represent 10 content areas and reflect the needs of clinical referrers and people with lived experience of receiving cancer treatment. CONCLUSIONS: The core competencies identified reflect significant advancements in the field of exercise oncology. Results will underpin the development of education, certification, and employment requirements for exercise oncology professionals, providing a critical step toward achieving routine integration of exercise into standard oncology care.


Assuntos
Competência Clínica , Técnica Delphi , Neoplasias , Humanos , Austrália , Estados Unidos , Feminino , Masculino , Neoplasias/terapia , Terapia por Exercício/normas , Oncologia/normas , Adulto , Consenso , Pessoa de Meia-Idade
3.
Support Care Cancer ; 32(7): 440, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888665

RESUMO

PURPOSE: Cancer survival is improving, making optimal management of long-term treatment-related adverse effects increasingly important. Exercise and a healthy diet are beneficial and regularly recommended in cancer survivorship guidelines; however, few cancer survivors meet these recommendations so there is a need to explore why. This study aimed to understand experiences receiving exercise and diet support among Australian breast and prostate cancer survivors during and following treatment, and to explore what support they would like to receive. METHODS: Adults who completed active treatment for breast or prostate cancer were recruited via a private cancer care centre. Using a qualitative descriptive study design, participants attended in-person focus groups that were recorded, transcribed, then analysed using reflexive thematic analysis. RESULTS: In total, 26 cancer survivors (15 breast, 11 prostate) participated in one of seven focus groups (4 breast, 3 prostate). Two themes were developed: 1) It was just brushed over, and 2) Wanting more. Theme 1 reports that exercise, and especially diet, were rarely discussed. If they were, it was often limited to general recommendations. Theme 2 shows that participants wanted more specific and personalised support, and information about how exercise and/or diet could benefit their cancer treatment. CONCLUSION: Despite strong interest in receiving personalised exercise and diet support, neither are routinely provided to Western Australian breast and prostate cancer survivors. If support was provided, there was inconsistency in the level and type of support provided. These findings identify important gaps in exercise and diet support provision to cancer survivors and will inform future strategies aiming to improve cancer survivorship care.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Exercício Físico , Grupos Focais , Neoplasias da Próstata , Pesquisa Qualitativa , Humanos , Masculino , Sobreviventes de Câncer/psicologia , Feminino , Pessoa de Meia-Idade , Idoso , Austrália , Adulto , Apoio Social , Dieta
4.
PLoS Comput Biol ; 20(4): e1011800, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38656994

RESUMO

Biochemical signaling pathways in living cells are often highly organized into spatially segregated volumes, membranes, scaffolds, subcellular compartments, and organelles comprising small numbers of interacting molecules. At this level of granularity stochastic behavior dominates, well-mixed continuum approximations based on concentrations break down and a particle-based approach is more accurate and more efficient. We describe and validate a new version of the open-source MCell simulation program (MCell4), which supports generalized 3D Monte Carlo modeling of diffusion and chemical reaction of discrete molecules and macromolecular complexes in solution, on surfaces representing membranes, and combinations thereof. The main improvements in MCell4 compared to the previous versions, MCell3 and MCell3-R, include a Python interface and native BioNetGen reaction language (BNGL) support. MCell4's Python interface opens up completely new possibilities for interfacing with external simulators to allow creation of sophisticated event-driven multiscale/multiphysics simulations. The native BNGL support, implemented through a new open-source library libBNG (also introduced in this paper), provides the capability to run a given BNGL model spatially resolved in MCell4 and, with appropriate simplifying assumptions, also in the BioNetGen simulation environment, greatly accelerating and simplifying model validation and comparison.


Assuntos
Método de Monte Carlo , Software , Difusão , Simulação por Computador , Modelos Biológicos , Linguagens de Programação , Biologia Computacional/métodos , Transdução de Sinais/fisiologia
5.
Curr Pharm Teach Learn ; 16(5): 352-362, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38503571

RESUMO

BACKGROUND AND PURPOSE: The purpose of this study was to use the first three levels of the Kirkpatrick Model to evaluate the effectiveness of a simulation center-based escape room activity designed to positively influence student learning. EDUCATIONAL ACTIVITY AND SETTING: In this simulation, learners solve puzzles related to care of a critically ill patient. This activity was assessed via an assessment questionnaire (Kirkpatrick level 1), a pre/post learner knowledge quiz and learner self-assessment of skills and attitudes (Kirkpatrick level 2), and unstructured observation of learners upon return to the clinical environment (Kirkpatrick level 3). FINDINGS: Average learner knowledge assessment scores (Kirkpatrick level 2) improved from 80% (pre-) to 90.5% (post-) and learners identified an increased confidence in disease state diagnosis and expression of recommendations (Kirkpatrick level 2). Learner perception of the activity (Kirkpatrick level 1) was positive but also included areas for improvement. Anecdotal reporting supports learners transfer of the knowledge and skills reviewed in the session to practice (Kirkpatrick level 3), but no formal data collection or analysis was completed. SUMMARY: This study provides quantitative and qualitative evidence to support effectiveness of the activity according to Kirkpatrick's Levels 1 and 2, and anecdotal evidence to support effectiveness according to Kirkpatrick's Level 3. Learners had positive perspectives of this activity and demonstrated evidence of increased knowledge and self-reported confidence in skills and attitudes, suggesting this activity has a positive impact on learners in the short-term; however, the data is not robust enough to support conclusions that this activity influences learner practice.


Assuntos
Assistência Farmacêutica , Farmácia , Sepse , Humanos , Estudantes , Aprendizagem
6.
J Urban Health ; 101(2): 233-244, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38536600

RESUMO

In response to an increase in overdose deaths, there was a rapid scale-up of supervised consumption services (SCS), including federally sanctioned SCS and low-barrier SCS known as overdose prevention sites (OPS), in Vancouver, Canada, beginning in December 2016. However, little is known about the use of such services among adolescents and young adults (AYA) in this context. We therefore sought to characterize factors associated with the use of federally sanctioned SCS and OPS among street-involved AYA who inject drugs in Vancouver during an overdose crisis. From December 2016 to March 2020, data were collected from a prospective cohort of street-involved AYA aged 14 to 26 at baseline. Using multivariable generalized estimating equation analyses, we identified factors associated with recent use of federally sanctioned SCS and OPS, respectively. Among 298 AYA who inject drugs, 172 (57.8%) and 149 (50.0%) reported using federally sanctioned SCS and OPS during the study period, respectively. In multivariable analyses, public injecting, negative police interactions, and residing or spending time ≥ weekly in the Downtown Eastside neighborhood were all positively associated with the use of federally sanctioned SCS and OPS, respectively. Additionally, ≥ daily unregulated opioid use and residential eviction were positively associated with federally sanctioned SCS use, while requiring help injecting was inversely associated. Self-identified female or non-binary gender was also positively associated with OPS use (all p < 0.05). Both federally sanctioned SCS and OPS successfully engaged AYA at heightened risk of adverse health outcomes. However, the lack of accommodation of AYA who require manual assistance with injecting at federally sanctioned SCS may be inhibiting service engagement.


Assuntos
Overdose de Drogas , Abuso de Substâncias por Via Intravenosa , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Overdose de Drogas/epidemiologia , Adulto , Abuso de Substâncias por Via Intravenosa/epidemiologia , Estudos Prospectivos , Colúmbia Britânica/epidemiologia , Jovens em Situação de Rua/estatística & dados numéricos , Programas de Troca de Agulhas/estatística & dados numéricos
7.
bioRxiv ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38352446

RESUMO

Long-term potentiation (LTP) is a biochemical process in excitatory glutamatergic synapses in the Central Nervous System (CNS). It is initiated by a bout of synaptic activation that is strong enough to contribute to production of an action potential in the axon of the postsynaptic neuron, and it results in an increase in the size of postsynaptic depolarization during subsequent activity. The first step leading to LTP is activation and autophosphorylation of an abundant postsynaptic enzyme, Ca 2+ /calmodulin-dependent protein kinase II (CaMKII). We use simulation of activation of CaMKII holoenzymes in a realistic spatial model of a spine synapse, created in MCell4, to test three hypotheses about how the autophosphorylation response of CaMKII is shaped during a repeated high-frequency stimulus. First, the simulation results indicate that autophosphorylation of CaMKII does not constitute a bistable switch under biologically realistic conditions. Instead, prolonged autophosphorylation of CaMKII may contribute to a biochemical "kinetic proof-reading" mechanism that controls induction of synaptic plasticity. Second, concentration of CaMKII near the postsynaptic membrane increases the local concentration of kinase activity. However, neither localization nor "Ca 2+ -calmodulin-trapping (CaM-trapping)" increase the proportion of autophosphorylated subunits in holoenzymes after a complex stimulus, as previously hypothesized. Finally, we show that, as hypothesized, the amplitude of autophosphorylation in the first 30 seconds after a stimulus is extremely sensitive to the level and location of PP1 activity when PP1 is present in biologically accurate amounts. We further show that prolonged steric hindrance of dephosphorylation of CaMKII, caused by CaM-trapping, can increase the amplitude of autophosphorylation after a complex stimulus. These simulation results sharpen our quantitative understanding of the early events leading to LTP at excitatory synapses. Author Summary: Neurons in the brain are interconnected in an organized fashion by synapses that transmit neuronal activity from one neuron to another. Most of the billions of neurons in the brain have about 10,000 synapses spread over the neuronal membrane. Information is stored in the brain when the ability of specific synapses to pass along neuronal activity is strengthened resulting in formation of new networks. The increase in strength of a synapse is tightly controlled by the frequency and amplitude of its activity, and by neurohormonal signals, which, in combination, can cause long-lasting biochemical changes at the synapse that underlie learning and memory. Defects in these biochemical pathways cause mental and neurological diseases. To develop treatments, we need to understand the precise choreography of these critical biochemical changes. However, the tiny size of the synaptic compartment makes precise measurements of the biochemical reactions impossible. We have used computer simulation techniques and information gathered from experiments on purified synaptic proteins to simulate, within a single synapse, the choreography of the first biochemical step in synaptic strengthening: activation of the enzyme Ca 2+ / calmodulin-dependent protein kinase II. Our results provide insights that can be used in future studies to develop treatments for neuronal diseases.

8.
Front Sports Act Living ; 6: 1338658, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38313216

RESUMO

Introduction: Growth in the field of clinical exercise science and the potential impacts on overall health and wellbeing have driven the need for qualified, clinically trained, exercise professionals. And yet, it is not well understood what specific credentials employers are seeking when hiring exercise professionals. Purpose: The purpose of the study was to examine the qualification requirements for professionals seeking employment in exercise science, exercise physiology, kinesiology or equivalent fields. Methods: Search platforms Indeed.com and USAJobs.gov were examined within a two week period in 2022. Search terms included "Exercise Physiology", "Exercise Science", "Exercise Professional", "Exercise Prescription", "Exercise Specialist", and "Kinesiology". Results: A total of n = 739 jobs were retrieved and n = 615 jobs were included: Exercise Science (n = 227), Kinesiology (n = 210), Exercise Physiology (n = 91), Exercise specialist (n = 53), and Exercise prescription (n = 32). Over 70% of the jobs analyzed required a bachelor's degree with the remainder requiring various levels of education. The primary certification required was personal trainer (n = 94), followed by strength and conditioning specialist (n = 33), clinical exercise physiologist (n = 26), group exercise (n = 17), exercise specialist (n = 10), and exercise physiologist (n = 5). Four job focus areas were determined: academic teaching and research, general fitness and worksite wellness, athletic performance and rehabilitation, clinical exercise specialist all with varying levels of degree and certification requirements. Discussion: Job postings related to exercise related professions are varied across the United States with wide-ranging education, credentialing and certification requirements. These findings indicate the timely need for outreach to employers to highlight changing credentialing requirements due to evolving accreditation standards.

9.
J Pediatr Gastroenterol Nutr ; 78(2): 272-279, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38327225

RESUMO

AIM: To investigate whether a structured yoga program improves health-related quality of life (HRQOL) and self-efficacy in pediatric patients receiving care for inflammatory bowel disease (IBD). METHODS: IBD patients who were 10-17 years old participated in a 12 week, in-person yoga intervention at two clinical sites. Outcomes were measured at time of consent (T0), start of yoga (T1), and completion of yoga (T2) and 3 months after yoga completion (T3) using the IMPACT-III, Pediatric Quality of Life Inventory (PedsQL), and General Self Efficacy (GSE) scales. RESULTS: Seventy-eight patients were enrolled. Fifty-six patients completed nine or more classes. 73.2% had Crohn's disease and 26.8% ulcerative colitis or IBD-unclassified. A significant increase in IMPACT-III was seen from T1 to T3 (mean change of 5.22, SD = 14.33, p = 0.010), in the PedsQL (mean change = 2.3, SD = 10.24, p = 0.050), and GSE (mean change = 1, SD = 3.60, p = 0.046). 85.2% of patients reported yoga helped them to control stress. Long-term data was available for 47 subjects with 31.9% (n = 15) continuing to practice yoga one to 3 years after study completion. CONCLUSION: This structured 12-week yoga program showed significant improvements in HRQOL and general self-efficacy, particularly 3 months after classes were concluded suggesting that yoga's benefits may persist. Yoga is a safe and effective adjunct to standard medical care to improve QOL and self-efficacy in youth with IBD.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Yoga , Adolescente , Criança , Humanos , Colite Ulcerativa/terapia , Doenças Inflamatórias Intestinais/terapia , Estudos Prospectivos , Qualidade de Vida
10.
Int J Drug Policy ; : 104330, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38395656

RESUMO

OBJECTIVES: In 2022, the Drug User Liberation Front opened an unsanctioned compassion club in Vancouver where members could purchase illicit drugs that had been rigorously tested to ensure quality and a lack of potentially fatal contaminants. We sought to evaluate the impact of access to this novel safer supply intervention on non-fatal overdose. METHODS: Data were obtained from 47 club members via surveys completed at 3-month intervals between August 2022 and October 2023. We conducted multivariable generalized estimating equations (GEE) analyses to examine the association between club enrolment and the outcomes of: (1) any non-fatal overdose; and (2) any non-fatal overdose involving naloxone administration. RESULTS: The final sample, including 47 study participants, contributed a total of 225 observations and 44.4 person-years of follow-up during the study, and a median follow-up duration of 12.2 months (quartile 1 - 3: 10.4 - 14.7) per participant. In multivariable GEE analyses, enrolment in the compassion club was associated with reduced likelihood of non-fatal overdose (Adjusted Odds Ratio [AOR] = 0.51, 95% Confidence Interval (CI): 0.26 - 0.99) and non-fatal overdose involving naloxone administration (AOR = 0.37, 95% CI: 0.16 - 0.84) after adjusting for potential confounders. DISCUSSION: In this study, enrolment in an unsanctioned compassion club was found to be associated with reductions in any type of non-fatal overdose and non-fatal overdose involving naloxone administration. These findings highlight the need for ongoing research on safer supply interventions, as well as the potential of non-medicalized compassion clubs to complement existing safer supply programming and reduce overdose events.

11.
J Gen Intern Med ; 39(7): 1227-1232, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38286971

RESUMO

Physicians have traditionally asked about substance use within the Social History section of the consultation note. Drawing on social science theory and using the authors' own experiences as generalists and addiction scholars, we consider the possible unintended harms associated with this approach. The inclusion of the substance use history within the Social History reproduces the discourse of substance use disorders as "life-style choices" rather than medical conditions, and reinforces stigma among healthcare workers through the attribution of personal responsibility for complications associated with problematic substance use. The ongoing placement of the substance use history within the Social History may lead to a failure to diagnose and make appropriate management plans for clients with substance use disorders. These missed opportunities may include inadequate withdrawal management leading to discharge before medically advised, insufficient use of evidence-based pharmacotherapy and psychotherapy, polypharmacy, medical complications, and repeated admissions to hospital. We argue instead that the Substance Use History should be a stand-alone section within the consultation note. This new section would reduce the invisibility of substance use disorders within our medical systems and model that these chronic medical conditions are amenable to prevention, treatment and harm reduction through the application of evidence-based practices.


Assuntos
Anamnese , Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtornos Relacionados ao Uso de Substâncias/terapia , Transtornos Relacionados ao Uso de Substâncias/psicologia
13.
Calcif Tissue Int ; 114(1): 38-52, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38043101

RESUMO

Sarcopenia is a skeletal muscle disease categorized by low muscle strength, muscle quantity or quality, and physical performance. Sarcopenia etiology is multifaceted, and while resistance training is widely agreed upon for prevention and treatment, disease progression is also highly related to poor diet. The incidence of sarcopenia appears sex-specific and may be increased in females, which is problematic because dietary quality is often altered later in life, particularly after menopause. Identifying effective nutrition or supplementation interventions could be an important strategy to delay sarcopenia and related comorbidities in this vulnerable population. This systematic review examined randomized controlled trials (RCTs) of nutrition strategies on muscle-related components of sarcopenia in middle-aged and older females. A protocol was registered (PROSPERO CRD42022382943) and a systematic search of MEDLINE and CINAHL was undertaken. RCTs from 2013 to 2023 that assessed nutrition-only interventions on muscle mass, muscle strength, and physical function in female participants were included. Fourteen RCTs were included based on selection criteria. Study designs and interventions were heterogeneous in supplementation type and amount, age, and duration. Six RCTs reported beneficial effects of protein, Vitamin D, Vitamin D and Magnesium (Mg), and fish oil on muscle protein synthesis, muscle strength, and/or muscle function. Eight studies that examined various protein interventions, VitD alone, Mg alone, and dairy derivatives did not demonstrate any effect. Exercise appeared to modulate results in several studies. Nutrition interventions alone are likely to have a limited but positive effect on muscle-related components of sarcopenia in females. Current evidence suggests that a combination of dietary intervention and exercise is likely to be key to preventing and treating sarcopenia in middle aged and older females and there is a need for well-designed nutrition based studies in this population.


Assuntos
Sarcopenia , Humanos , Suplementos Nutricionais , Força Muscular/fisiologia , Músculo Esquelético , Ensaios Clínicos Controlados Aleatórios como Assunto , Sarcopenia/prevenção & controle , Vitamina D
14.
Am J Prev Med ; 66(1): 10-17, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37633426

RESUMO

INTRODUCTION: The proliferation of fentanyl and its analogs in illegal, unregulated drug markets remains a major driver of the overdose crisis in North America. Drug checking services have been implemented as a harm reduction strategy to address the crisis. However, little is known about their potential utility as a mechanism for monitoring population-level risk of overdose stemming from changing fentanyl concentration in unregulated drugs over time. Therefore, this study assessed the relationship between median fentanyl concentration in expected opioid drug checking samples and the death rate due to illicit drug toxicity over time in Vancouver, Canada. METHODS: Monthly population-based rates of death due to illicit drug toxicity were drawn from provincial coroner records. Monthly median percent fentanyl concentration was calculated using a validated quantification model from point-of-care Fourier-transform infrared spectra among expected opioid samples that tested positive for fentanyl at community drug checking services. A time-series analysis using generalized additive modeling was conducted to examine the association between monthly median fentanyl concentration and monthly death rate due to illicit drug toxicity, controlling for calendar month. Analyses were conducted in 2021-2022. RESULTS: Between January 2019 and October 2020, 577 deaths due to illicit drug toxicity occurred in Vancouver, and the observed monthly rate ranged from 1.75 to 7.65 deaths per 100,000 population. A significant, positive association was observed between monthly median fentanyl concentration and monthly death rate due to illicit drug toxicity, adjusting for calendar month (chi-square=52.21, p<0.001). CONCLUSIONS: Findings suggest a role for point-of-care drug checking as a tool for monitoring evolving overdose risk at the population level.


Assuntos
Overdose de Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Drogas Ilícitas , Humanos , Fentanila , Analgésicos Opioides/efeitos adversos , Heroína , Overdose de Drogas/epidemiologia , Canadá/epidemiologia
15.
Arch Clin Neuropsychol ; 39(2): 175-185, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-37565493

RESUMO

OBJECTIVE: The clock drawing test (CDT) is being used regularly by medical professionals in a variety of settings to aid in assessing cognitive functioning in adults of all ages. As our technological environment has changed significantly, because of the inception of this measure, the use of and exposure to the analog clock have diminished. We investigated whether young adults, who have grown up in a mainly digital world, can draw and tell time on an analog clock. METHOD: Participants aged 18-30 years (N = 80, Mage = 24.2, SD = 3.93), who self-identified as having normal cognition, completed the CDT, as well as setting hands on a pre-drawn clock and identifying analog clock times. RESULTS: About 25% of participants received a CDT score below the expected range. There was a moderate, positive correlation between analog clock hand setting and time identification in the group who scored below the expected range on the CDT only (rs(16) = 0.472, p = .048). Most participants reported not wearing an analog watch. CONCLUSIONS: Based on these findings, the CDT should be used with caution to screen cognitive functioning in young adults (i.e., aged 18-30 years). Consideration of an alternative approach to screening cognition and modifying cognitive assessments in which the CDT is embedded is recommended for this population. These findings warrant further investigation into CDT performance in the young adult population.


Assuntos
Transtornos Cognitivos , Humanos , Adulto Jovem , Testes Neuropsicológicos , Transtornos Cognitivos/diagnóstico , Cognição
16.
Biomolecules ; 13(12)2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38136669

RESUMO

ClC-7 is a ubiquitously expressed voltage-gated Cl-/H+ exchanger that critically contributes to lysosomal ion homeostasis. Together with its ß-subunit Ostm1, ClC-7 localizes to lysosomes and to the ruffled border of osteoclasts, where it supports the acidification of the resorption lacuna. Loss of ClC-7 or Ostm1 leads to osteopetrosis accompanied by accumulation of storage material in lysosomes and neurodegeneration. Interestingly, not all osteopetrosis-causing CLCN7 mutations from patients are associated with a loss of ion transport. Some rather result in an acceleration of voltage-dependent ClC-7 activation. Recently, a gain-of-function variant, ClC-7Y715C, that yields larger ion currents upon heterologous expression, was identified in two patients with neurodegeneration, organomegaly and albinism. However, neither the patients nor a mouse model that carried the equivalent mutation developed osteopetrosis, although expression of ClC-7Y715C induced the formation of enlarged intracellular vacuoles. Here, we investigated how, in transfected cells with mutant ClC-7, the substitution of this tyrosine impinged on the morphology and function of lysosomes. Combinations of the tyrosine mutation with mutations that either uncouple Cl- from H+ counter-transport or strongly diminish overall ion currents were used to show that increased ClC-7 Cl-/H+ exchange activity is required for the formation of enlarged vacuoles by membrane fusion. Degradation of endocytosed material was reduced in these compartments and resulted in an accumulation of lysosomal storage material. In cells expressing the ClC-7 gain-of-function mutant, autophagic clearance was largely impaired, resulting in a build-up of autophagic material.


Assuntos
Osteopetrose , Camundongos , Animais , Humanos , Osteopetrose/genética , Osteopetrose/metabolismo , Mutação com Ganho de Função , Mutação , Lisossomos/metabolismo , Tirosina/metabolismo , Canais de Cloreto/genética , Canais de Cloreto/metabolismo
17.
Can J Public Health ; 114(6): 928-933, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37930628

RESUMO

Supervised consumption services have been scaled up within Canada and internationally as an ethical imperative in the context of a public health emergency. A large body of peer-reviewed evidence demonstrates that these services prevent poisoning deaths, reduce infectious disease transmission risk behaviour, and facilitate clients' connections to other health and social services. In 2019, the Alberta government commissioned a review of the socioeconomic impacts of seven supervised consumption services in the province. The report is formatted to appear as an objective, scientifically credible evaluation of these services; however, it is fundamentally methodologically flawed, with a high risk of biases that critically undermine its authors' assessment of the scientific evidence. The report's findings have been used to justify decisions that jeopardize the health and well-being of people who use drugs both in Canada and internationally. Governments must ensure that future assessments of supervised consumption services and other public health measures to address drug poisoning deaths are scientifically sound and methodologically rigorous. Health policy must be based on the best available evidence, protect the right of structurally vulnerable populations to access healthcare, and not be contingent on favourable public opinion or prevailing political ideology.


RéSUMé: Les services de consommation supervisée ont été établis au Canada et à l'étranger en tant qu'impératif éthique dans le contexte d'une urgence de santé publique. Un grand nombre d'études rigoureuses démontrent que ces services préviennent les décès par empoisonnement, réduisent les comportements à risque de transmission de maladies infectieuses, et facilitent les liens avec d'autres services sociaux et de santé. En 2019, le gouvernement de l'Alberta a commandé un examen des impacts socioéconomiques de sept services de consommation supervisée dans la province. La présentation du rapport donne l'impression que l'évaluation de ces services est objective et scientifiquement crédible; cependant, il présente des faiblesses importantes au plan méthodologique, notamment en raison de la présence de biais qui compromet l'évaluation des preuves scientifiques. Ses conclusions ont été utilisées pour justifier des décisions qui mettent en péril la santé et le bien-être des personnes qui consomment des drogues, tant au Canada qu'à l'étranger. Les gouvernements doivent s'assurer que les futures évaluations des services de consommation supervisée et d'autres mesures de santé publique pour lutter contre les décès par empoisonnement dû aux drogues sont scientifiquement fondées. Les politiques en matière de santé doivent être basées sur les meilleures données disponibles, protéger les droits des populations structurellement vulnérables à accéder aux soins de santé, et ne pas dépendre de l'opinion publique ou d'une idéologie politique dominante.


Assuntos
Redução do Dano , Serviço Social , Humanos , Alberta/epidemiologia
18.
Omega (Westport) ; : 302228231196620, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37670454

RESUMO

The COVID-19 pandemic compounded isolation for patients through social distancing measures and staff shortages. We were concerned about the impact of COVID-19 on the quality of care provided at end-of-life in 2021 in a national cancer centre, and instigated the first ever review of the care of the dying. Quality of care was assessed retrospectively using a validated instrument developed by the United Kingdom's National Quality Board. Sixty-six patient deaths occurred in our cancer centre in 2021. The 'risk of dying' was documented in 65.2% of records. Palliative care services were involved in 77%, and pastoral care in 10.6%. What was important to the patient was documented in 24.2%. The 'quality-of-death' score was satisfactory for most but poor in 21.2%. Our study prompted change, including appointment of an end-of-life coordinator, development of a checklist to ensure comprehensive communication, expansion of the end-of-life committee to include junior doctors, and regular audit.

19.
J Addict Nurs ; 34(3): 166-172, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37669335

RESUMO

OBJECTIVE: The aim of this study was to explore client experiences in a community-based injectable opioid agonist therapy (iOAT) program. STUDY SETTING: The study occurred across two cities in Alberta, Canada. STUDY DESIGN: The research team conducted secondary interpretive description analysis on qualitative interview transcripts. DATA COLLECTION: Twenty-three iOAT clients were interviewed as part of a prior quality improvement initiative. Using secondary analysis of the transcripts, interviews were analyzed for themes, to create an understanding of clients' experiences. PRINCIPAL FINDINGS: Participants accessed iOAT through other health services, for treatment of opioid use disorder. Participants reported that building trusting and supportive relationships with nurses was crucial to their success in the program. Through these relationships, participants experienced stopping and starting. They stopped behaviors such as illicit drug use, having withdrawal symptoms and anxiety, and prohibited income generation activities. They started taking care of themselves, accessing housing, increasing financial stability, receiving primary care, and connecting with friends and family. The global experience of iOAT was one of positive change for participants. CONCLUSIONS: The findings of this study are largely consistent with other published examples-iOAT programs create benefits for both clients and their communities. Although clients may join the program to access the hydromorphone, the relationships between staff and clients are the key driver of success.


Assuntos
Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Canadá , Pesquisa Qualitativa
20.
Int J Drug Policy ; 120: 104157, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37574645

RESUMO

BACKGROUND: Canada is experiencing an unprecedented drug toxicity crisis driven by a highly toxic unregulated drug supply contaminated with fentanyl, benzodiazepine, and other drugs. Safer supply pilot programs provide prescribed doses of pharmaceutical alternatives to individuals accessing the unregulated drug supply and have been implemented to prevent overdose and reduce related harms. Given the recent emergence of these pilot programs and the paucity of data on implementation challenges, we sought to document challenges in their initial implementation phase. METHODS: We obtained organizational progress reports from Health Canada, submitted between 2020 and 2022 by 11 pilot programs located in British Columbia, Ontario, and New Brunswick. We analyzed the data using deductive and inductive approaches via thematic analysis. Analyses were informed by the consolidated framework for implementation research. RESULTS: We obtained 45 progress reports from 11 pilot programs. Six centres were based in British Columbia, four in Ontario, and one in New Brunswick. Four overarching themes were identified regarding the challenges faced during the establishment and implementation of pilot programs: i) Organizational features (e.g., physical space constraints, staff shortages); ii) Outer contexts (e.g., limited operational funds and resources, structural inequities to access, public perceptions); iii) Intervention characteristics (e.g., clients' unmet medication needs); and iv) Implementation process (e.g., pandemic-related challenges, overly medicalized and high-barrier safer supply models). CONCLUSIONS: Safer supply pilot programs in Canada face multiple inner and outer implementation challenges. Given the potential role of safer supply programs in addressing the drug toxicity crisis in Canada and the possibility of future scale-up, services should be well-supported during their implementation phases. Refining service provision within safer supply programs based on the feedback and experiences of clients and program administrators is warranted, along with efforts to ensure that appropriate medications are available to meet the clients' needs.

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