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1.
Trials ; 25(1): 632, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334438

RESUMO

BACKGROUND: General practitioners (GP) and community pharmacists need information about hospital discharge patients' medicines to continue their management in the community. This necessitates effective communication, collaboration, and reliable information-sharing. However, such handover is inconsistent, and whilst digital systems are in place to transfer information at transitions of care, these systems are passive and clinicians are not prompted about patients' transitions. There are also gaps in communication between community pharmacists and GPs. These issues impact patient safety, leading to hospital readmissions and increased healthcare costs. METHODS: A three-phased, multi-method study design is planned to trial a multifaceted intervention to reduce 30-day hospital readmissions. Phase 1 is the co-design of the intervention with stakeholders and end-users; phase 2 is the development of the intervention; phase 3 is a stepped wedge cluster randomised controlled trial with 20 clusters (community pharmacies). Expected intervention components will be a hospital pharmacist navigator, primary care medication management review services, and a digital solution for information sharing. Phase 3 will recruit 10 patients per pharmacy cluster/month to achieve a sample size of 2200 patients powered to detect a 5% absolute reduction in unplanned readmissions from 10% in the control group to 5% in the intervention at 30 days. The randomisation and intervention will occur at the level of the patient's nominated community pharmacy. Primary analysis will be a comparison of 30-day medication-related hospital readmissions between intervention and control clusters using a mixed effects Poisson regression model with a random effect for cluster (pharmacy) and a fixed effect for each step to account for secular trends. TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry: ACTRN12624000480583p , registered 19 April 2024.


Assuntos
Serviços Comunitários de Farmácia , Alta do Paciente , Transferência da Responsabilidade pelo Paciente , Readmissão do Paciente , Farmacêuticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Transferência da Responsabilidade pelo Paciente/normas , Clínicos Gerais , Reconciliação de Medicamentos/métodos , Fatores de Tempo , Continuidade da Assistência ao Paciente
2.
Infect Dis Health ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39332981

RESUMO

INTRODUCTION: Mobile phones, contaminated with pathogenic microorganisms, have the potential to act as "trojan horses". The microbial signatures present on their surfaces most probably vary across different geographical regions. As a result, mobile phones belonging to international conference attendees may serve as a model for global microbial dissemination, posing potential risks to public health and biosecurity. AIM: This study aimed to profile the microbes present on mobile phones belonging to delegates attending an international scientific conference through use of metagenomic shotgun DNA sequencing. METHODS: Twenty mobile phones, representing ten different geographical zones from around the world, were swabbed and pooled together into ten geographical-specific samples for high definition next-generation DNA sequencing. WONCA council members were invited to participate and provided verbal consent. Following DNA extraction, next generation sequencing, to a depth of approximately 10Gbp per sample, was undertaken on a v1.5 Illumina NovaSeq6000 system. Bioinformatic analysis was performed via the CosmosID platform. RESULTS: A total of 2204 microbial hits were accumulated across 20 mobile phones inclusive of 882 bacteria, 1229 viruses, 88 fungi and 5 protozoa. Of particular concern was the identification of 65 distinct antibiotic resistance genes and 86 virulence genes. Plant, animal and human pathogens, including ESKAPE and HACEK bacteria were found on mobile phones. DISCUSSION/CONCLUSION: Mobile phones of international attendees are contaminated with many & varied microorganisms. Further research is required to characterize the risks these devices pose for biosecurity and public health. Development of new policies which appropriately address and prevent such risks maybe warranted.

3.
Australas J Ageing ; 2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39342487

RESUMO

Frailty is an important concept in the care of older adults. Over the past two decades, significant advances have been made in measuring frailty. While it is now well-recognised that frailty status is an important determinant of outcomes from medical illnesses or surgical interventions, frailty measurement is not currently routinely integrated into clinical practice. In the community setting, it is uncommon for general practitioners to deliver frailty-optimised care. In hospitals, there is substantial variability in how people living with frailty are managed. This variability is notable between and even within disciplines. Furthermore, gains from understanding frailty mechanisms and risk factors are not yet applied/implemented at scale to delay the progression of frailty in community-dwellers. The Australian Frailty Network (AFN) is a national collaborative group of researchers, clinicians, non-government organisations, consumers and policymakers, in which the engagement and active involvement of consumers has been embedded from the outset. The AFN aims to generate new knowledge to improve health outcomes, to ensure evidence-based management is translated into clinical practice and to build capacity in multidisciplinary and translational frailty research. Here, we describe the development of the AFN, highlighting important milestones: (i) securing funding for the network and flagship elements; (ii) an inaugural summit to establish the strategic vision, values and scope with end-users; (iii) sabbatical visits to learn from international examples; and (iv) developing the governance structure and an actionable plan encompassing consumer engagement, research, education and policy and practice to maximise impact.

4.
Health Inf Manag ; : 18333583241269025, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143738

RESUMO

BACKGROUND: When a patient is discharged from hospital it is essential that their general practitioner (GPs) and community pharmacist are informed of changes to their medicines. This necessitates effective communication and information-sharing between hospitals and primary care clinicians. OBJECTIVE: To identify priority medicine handover issues and solutions to inform the co-design and development of a multifaceted intervention. METHOD: A modified nominal group technique was used to reach consensus on medicine handover priority areas. The first hour of an interactive 2-hr workshop focused on ranking pre-identified issues drawn from literature. In the second hour, participants identified solutions that they then ranked from highest to lowest priority through an online platform. Descriptive statistics were used to analyse workshop data. RESULTS: In total 32 participants attended the workshop including hospital doctors (n = 8, 25.0%), GPs and hospital pharmacists (n = 6 each, 18.8%), consumers and community pharmacists (n = 4 each, 12.5%), and both hospital and aged care facility nurses (n = 2 each 6.3%). From the list of 23 issues, the highest ranked issue was high workload and time pressures impacting the discharge process (22/32). From the list of 36 solutions, the participants identified two solutions that were equally ranked highest (12/27 each). They were mandating that patients leave hospital with a discharge summary, including medication reconciliation information and, developing an integrated information technology system where medication summary and notes are accessible for primary, secondary and tertiary health provider. CONCLUSION: The consensus process highlighted challenges in hospital procedures where potential solutions may be implemented through co-design of a multifaceted intervention to improve medicine handover quality.

5.
Gynecol Oncol ; 187: 221-226, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38821039

RESUMO

OBJECTIVE: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group. METHODS: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed). RESULTS: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). HRD rates were higher in younger participants, 59% (n = 476/802), compared to 40% (n = 78/197) of older participants (GIS ≥ 42) [p < 0.001]; similar rates demonstrated with GIS ≥ 33, 66% vs 48% [p < 0.001]. gBRCA PVs observed in 24% younger vs 8% of older participants (p < 0.001); sBRCA in 8% vs 10% (p = 0.2559), and HRD (GIS ≥ 42) not due to gBRCA was 35% vs 31% (p = 0.36). CONCLUSIONS: HRD frequency was similar in participants aged < 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications.


Assuntos
Proteína BRCA1 , Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Humanos , Feminino , Idoso , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Pessoa de Meia-Idade , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Proteína BRCA1/genética , Proteína BRCA2/genética , Idoso de 80 Anos ou mais , Fatores Etários , Adulto , Recombinação Homóloga , Estadiamento de Neoplasias , Gradação de Tumores , Testes Genéticos/métodos
6.
Prim Health Care Res Dev ; 25: e24, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38721698

RESUMO

AIM: This constructivist grounded theory study aimed to (1) explore patients' experiences of and roles in interprofessional collaborative practice for chronic conditions in primary care and (2) consider the relevance and alignment of an existing theoretical framework on patients' roles and based on the experiences of patient advocates. BACKGROUND: High-quality management of chronic conditions requires an interprofessional collaborative practice model of care considering an individual's mental, physical, and social health situation. Patients' experiences of this model in the primary care setting are relatively unknown. METHODS: A constructivist grounded theory approach was taken. Interview data were collected from primary care patients with chronic conditions across Australia in August 2020 - February 2022. Interviews were recorded, transcribed verbatim, and thematically analysed by (1) initial line-by-line coding, (2) focused coding, (3) memo writing, (4) categorisation, and (5) theme and sub-theme development. Themes and sub-themes were mapped against an existing theoretical framework to expand and confirm the results from a previous study with a similar research aim. FINDINGS: Twenty adults with chronic conditions spanning physical disability, diabetes, heart disease, cancer, autoimmune, and mental health conditions participated. Two themes were developed: (1) Adapting to Change with two sub-themes describing how patients adapt to interprofessional team care and (2) Shifting across the spectrum of roles, with five sub-themes outlining the roles patients enact while receiving care. The findings suggest that patients' roles are highly variable and fluid in interprofessional collaborative practice, and further work is recommended to develop a resource to support greater patient engagement in interprofessional collaborative practice.


Assuntos
Comportamento Cooperativo , Teoria Fundamentada , Relações Interprofissionais , Atenção Primária à Saúde , Humanos , Atenção Primária à Saúde/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Doença Crônica/terapia , Idoso , Austrália , Adulto , Pesquisa Qualitativa , Equipe de Assistência ao Paciente , Entrevistas como Assunto , Participação do Paciente
7.
J Food Prot ; 87(5): 100260, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38460785

RESUMO

Ozone is a potent disinfecting agent used to treat potable water and wastewater, effectively clearing protozoa such as Giardia and Cryptosporidium spp. It is unclear whether ozone treatment of water or fresh produce can reduce the spread of the emerging parasite Cyclospora cayetanensis, which causes cyclosporiasis in humans. Obtaining viable C. cayetanensis oocysts to evaluate inactivation methods is challenging because we lack the means to propagate them in vitro, because of delays in case reporting, and because health departments typically add inactivating fixatives to clinical specimens. Research in various surrogate organisms has sought to bolster understanding of the biology of C. cayetanensis. Among these surrogates is the poultry parasite Eimeria acervulina, a closely related and easily cultured parasite of economic significance. We used this surrogate to evaluate the consequences of ozone treatment, using the sporulation state as an indicator of infectious potential. Treating with ozonated water acidified with citric acid reduced sporulation ability in a dose-dependent manner; treatment with up to 4.93 mg/L initial concentration of ozone resulted in a 93% inactivation of sporulation by 7 days posttreatment. This developmental arrest was accompanied by transcriptional changes in genes involved in regulating the response to reactive oxygen species (ROS) in a time course that is consistent with the production of oxygen free radicals. This study shows that ozone is highly effective in preventing sporulation of E. acervulina, a model coccidian used as a surrogate for Cyclospora. Furthermore, ozone exposure induced molecular responses to general oxidative stress, documented with several well-characterized antioxidant enzymes.


Assuntos
Cyclospora , Eimeria , Oocistos , Ozônio , Cyclospora/efeitos dos fármacos , Eimeria/efeitos dos fármacos , Ozônio/farmacologia , Oocistos/efeitos dos fármacos , Animais , Humanos , Água , Ciclosporíase , Desinfetantes/farmacologia
8.
Cochrane Database Syst Rev ; 3: CD013880, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426600

RESUMO

BACKGROUND: The number of older people is increasing worldwide and public expenditure on residential aged care facilities (ACFs) is expected to at least double, and possibly triple, by 2050. Co-ordinated and timely care in residential ACFs that reduces unnecessary hospital transfers may improve residents' health outcomes and increase satisfaction with care among ACF residents, their families and staff. These benefits may outweigh the resources needed to sustain the changes in care delivery and potentially lead to cost savings. Our systematic review comprehensively and systematically presents the available evidence of the effectiveness, safety and cost-effectiveness of alternative models of providing health care to ACF residents. OBJECTIVES: Main objective To assess the effectiveness and safety of alternative models of delivering primary or secondary health care (or both) to older adults living in ACFs. Secondary objective To assess the cost-effectiveness of the alternative models. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases and two trials registers (WHO ICTRP, ClinicalTrials.gov) on 26 October 2022, together with reference checking, citation searching and contact with study authors to identify additional studies. SELECTION CRITERIA: We included individual and cluster-randomised trials, and cost/cost-effectiveness data collected alongside eligible effectiveness studies. Eligible study participants included older people who reside in an ACF as their place of permanent abode and healthcare professionals delivering or co-ordinating the delivery of healthcare at ACFs. Eligible interventions focused on either ways of delivering primary or secondary health care (or both) or ways of co-ordinating the delivery of this care. Eligible comparators included usual care or another model of care. Primary outcomes were emergency department visits, unplanned hospital admissions and adverse effects (defined as infections, falls and pressure ulcers). Secondary outcomes included adherence to clinical guideline-recommended care, health-related quality of life of residents, mortality, resource use, access to primary or specialist healthcare services, any hospital admissions, length of hospital stay, satisfaction with the health care by residents and their families, work-related satisfaction and work-related stress of ACF staff. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, and assessed risk of bias and certainty of evidence using GRADE. The primary comparison was any alternative model of care versus usual care. MAIN RESULTS: We included 40 randomised trials (21,787 participants; three studies only reported number of beds) in this review. Included trials evaluated alternative models of care aimed at either all residents of the ACF (i.e. no specific health condition; 11 studies), ACF residents with mental health conditions or behavioural problems (12 studies), ACF residents with a specific condition (e.g. residents with pressure ulcers, 13 studies) or residents requiring a specific type of care (e.g. residents after hospital discharge, four studies). Most alternative models of care focused on 'co-ordination of care' (n = 31). Three alternative models of care focused on 'who provides care' and two focused on 'where care is provided' (i.e. care provided within ACF versus outside of ACF). Four models focused on the use of information and communication technology. Usual care, the comparator in all studies, was highly heterogeneous across studies and, in most cases, was poorly reported. Most of the included trials were susceptible to some form of bias; in particular, performance (89%), reporting (66%) and detection (42%) bias. Compared to usual care, alternative models of care may make little or no difference to the proportion of residents with at least one emergency department visit (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.84 to 1.20; 7 trials, 1276 participants; low-certainty evidence), but may reduce the proportion of residents with at least one unplanned hospital admission (RR 0.74, 95% CI 0.56 to 0.99, I2 = 53%; 8 trials, 1263 participants; low-certainty evidence). We are uncertain of the effect of alternative models of care on adverse events (proportion of residents with a fall: RR 1.15, 95% CI 0.83 to 1.60, I² = 74%; 3 trials, 1061 participants; very low-certainty evidence) and adherence to guideline-recommended care (proportion of residents receiving adequate antidepressant medication: RR 5.29, 95% CI 1.08 to 26.00; 1 study, 65 participants) as the certainty of the evidence is very low. Compared to usual care, alternative models of care may have little or no effect on the health-related quality of life of ACF residents (MD -0.016, 95% CI -0.036 to 0.004; I² = 23%; 12 studies, 4016 participants; low-certainty evidence) and probably make little or no difference to the number of deaths in residents of ACFs (RR 1.03, 95% CI 0.92 to 1.16, 24 trials, 3881 participants, moderate-certainty evidence). We did not pool the cost-effectiveness or cost data as the specific costs associated with the various alternative models of care were incomparable, both across models of care as well as across settings. Based on the findings of five economic evaluations (all interventions focused on co-ordination of care), we are uncertain of the cost-effectiveness of alternative models of care compared to usual care as the certainty of the evidence is very low. AUTHORS' CONCLUSIONS: Compared to usual care, alternative models of care may make little or no difference to the number of emergency department visits but may reduce unplanned hospital admissions. We are uncertain of the effect of alternative care models on adverse events (i.e. falls, pressure ulcers, infections) and adherence to guidelines compared to usual care, as the certainty of the evidence is very low. Alternative models of care may have little or no effect on health-related quality of life and probably have no effect on mortality of ACF residents compared to usual care. Importantly, we are uncertain of the cost-effectiveness of alternative models of care due to the limited, disparate data available.


Assuntos
Instituição de Longa Permanência para Idosos , Atenção Primária à Saúde , Atenção Secundária à Saúde , Idoso , Humanos , Pessoal de Saúde , Qualidade de Vida
9.
BMC Prim Care ; 25(1): 49, 2024 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310217

RESUMO

BACKGROUND: Australian cardiovascular disease (CVD) prevention guidelines recommend absolute CVD risk assessment, but less than half of eligible patients have the required risk factors recorded due to fragmented implementation over the last decade. Co-designed decision aids for general practitioners (GPs) and consumers have been developed that improve knowledge barriers to guideline-recommended CVD risk assessment and management. This study used a stakeholder consultation process to identify and pilot test the feasibility of implementation strategies for these decision aids in Australian primary care. METHODS: This mixed methods study included: (1) stakeholder consultation to map existing implementation strategies (2018-20); (2) interviews with 29 Primary Health Network (PHN) staff from all Australian states and territories to identify new implementation opportunities (2021); (3) pilot testing the feasibility of low, medium, and high resource implementation strategies (2019-21). Framework Analysis was used for qualitative data and Google analytics provided decision support usage data over time. RESULTS: Informal stakeholder discussions indicated a need to partner with existing programs delivered by the Heart Foundation and PHNs. PHN interviews identified the importance of linking decision aids with GP education resources, quality improvement activities, and consumer-focused prevention programs. Participants highlighted the importance of integration with general practice processes, such as business models, workflows, medical records and clinical audit software. Specific implementation strategies were identified as feasible to pilot during COVID-19: (1) low resource: adding website links to local health area guidelines for clinicians and a Heart Foundation toolkit for primary care providers; (2) medium resource: presenting at GP education conferences and integrating the resources into audit and feedback reports; (3) high resource: auto-populate the risk assessment and decision aids from patient records via clinical audit software. CONCLUSIONS: This research identified a wide range of feasible strategies to implement decision aids for CVD risk assessment and management. The findings will inform the translation of new CVD guidelines in primary care. Future research will use economic evaluation to explore the added value of higher versus lower resource implementation strategies.


Assuntos
Doenças Cardiovasculares , Medicina Geral , Humanos , Austrália/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Técnicas de Apoio para a Decisão , Atenção Primária à Saúde
11.
BMC Med Inform Decis Mak ; 24(1): 22, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38262998

RESUMO

BACKGROUND: The linkage of primary care, hospital and other health registry data is a global goal, and a consent-based approach is often used. Understanding the attitudes of why participants take part is important, yet little is known about reasons for non-participation. The ATHENA COVID-19 feasibility study investigated: 1) health outcomes of people diagnosed with COVID-19 in Queensland, Australia through primary care health data linkage using consent, and 2) created a cohort of patients willing to be re-contacted in future to participate in clinical trials. This report describes the characteristics of participants declining to participate and reasons for non-consent. METHODS: Patients diagnosed with COVID-19 from January 1st, 2020, to December 31st, 2020, were invited to consent to having their primary healthcare data extracted from their GP into a Queensland Health database and linked to other data sets for ethically approved research. Patients were also asked to consent to future recontact for participation in clinical trials. Outcome measures were proportions of patients consenting to data extraction, permission to recontact, and reason for consent decline. RESULTS: Nine hundred and ninety-five participants were approached and 842(85%) reached a consent decision. 581(69%), 615(73%) and 629(75%) consented to data extraction, recontact, or both, respectively. Mean (range) age of consenters and non-consenters were 50.6(22-77) and 46.1(22-77) years, respectively. Adjusting for age, gender and remoteness, older participants were more likely to consent than younger (aOR 1.02, 95%CI 1.01 to 1.03). The least socio-economically disadvantaged were more likely to consent than the most disadvantaged (aOR 2.20, 95% 1.33 to 3.64). There was no difference in consent proportions regarding gender or living in more remote regions. The main reasons for non-consent were 'not interested in research' (37%), 'concerns about privacy' (15%), 'not registered with a GP' (8%) and 'too busy/no time' (7%). 'No reason' was given in 20%. CONCLUSION: Younger participants and the more socio-economically deprived are more likely to non-consent to primary care data linkage. Lack of patient interest in research, time required to participate and privacy concerns, were the most common reasons cited for non-consent. Future health care data linkage studies addressing these issues may prove helpful.


Assuntos
COVID-19 , Humanos , Austrália , Bases de Dados Factuais , Instalações de Saúde , Hospitais
12.
Nat Commun ; 14(1): 8069, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057316

RESUMO

CAR (CARSKNKDC) is a wound-homing peptide that recognises angiogenic neovessels. Here we discover that systemically administered CAR peptide has inherent ability to promote wound healing: wounds close and re-epithelialise faster in CAR-treated male mice. CAR promotes keratinocyte migration in vitro. The heparan sulfate proteoglycan syndecan-4 regulates cell migration and is crucial for wound healing. We report that syndecan-4 expression is restricted to epidermis and blood vessels in mice skin wounds. Syndecan-4 regulates binding and internalisation of CAR peptide and CAR-mediated cytoskeletal remodelling. CAR induces syndecan-4-dependent activation of the small GTPase ARF6, via the guanine nucleotide exchange factor cytohesin-2, and promotes syndecan-4-, ARF6- and Cytohesin-2-mediated keratinocyte migration. Finally, we show that genetic ablation of syndecan-4 in male mice eliminates CAR-induced wound re-epithelialisation following systemic administration. We propose that CAR peptide activates syndecan-4 functions to selectively promote re-epithelialisation. Thus, CAR peptide provides a therapeutic approach to enhance wound healing in mice; systemic, yet target organ- and cell-specific.


Assuntos
Sindecana-4 , Cicatrização , Masculino , Camundongos , Animais , Sindecana-4/genética , Sindecana-4/metabolismo , Cicatrização/fisiologia , Peptídeos/metabolismo , Epiderme/metabolismo , Células Epidérmicas/metabolismo , Movimento Celular
13.
Cell Rep ; 42(12): 113554, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-38100355

RESUMO

Cell invasion is a multi-step process, initiated by the acquisition of a migratory phenotype and the ability to move through complex 3D extracellular environments. We determine the composition of cell-matrix adhesion complexes of invasive breast cancer cells in 3D matrices and identify an interaction complex required for invasive migration. ßPix and myosin18A (Myo18A) drive polarized recruitment of non-muscle myosin 2A (NM2A) to adhesion complexes at the tips of protrusions. Actomyosin force engagement then displaces the Git1-ßPix complex from paxillin, establishing a feedback loop for adhesion maturation. We observe active force transmission to the nucleus during invasive migration that is needed to pull the nucleus forward. The recruitment of NM2A to adhesions creates a non-muscle myosin isoform gradient, which extends from the protrusion to the nucleus. We postulate that this gradient facilitates coupling of cell-matrix interactions at the protrusive cell front with nuclear movement, enabling effective invasive migration and front-rear cell polarity.


Assuntos
Citoesqueleto de Actina , Actomiosina , Retroalimentação , Movimento Celular/fisiologia , Actomiosina/metabolismo , Citoesqueleto de Actina/metabolismo , Miosinas/metabolismo , Adesão Celular/fisiologia , Matriz Extracelular/metabolismo
14.
Trials ; 24(1): 615, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37770893

RESUMO

BACKGROUND: Many people experience withdrawal symptoms when they attempt to stop antidepressants. Withdrawal symptoms are readily misconstrued for relapse or ongoing need for medication, contributing to long-term use (> 12 months). Long-term antidepressant use is increasing internationally yet is not recommended for most people. Long-term use is associated with adverse effects including weight gain, sexual dysfunction, lethargy, emotional numbing and increased risk of falls and fractures. This study aims to determine the effectiveness of two multi-strategy interventions (RELEASE and RELEASE+) in supporting the safe cessation of long-term antidepressants, estimate cost-effectiveness, and evaluate implementation strategies. METHODS: DESIGN: 3-arm pragmatic cluster randomised controlled trial effectiveness-implementation hybrid type-1. SETTING: primary care general practices in southeast Queensland, Australia. POPULATION: adults 18 years or older taking antidepressants for longer than 1 year. Practices will be randomised on a 1.5:1:1 ratio of Usual care:RELEASE:RELEASE+. INTERVENTION: RELEASE for patients includes evidence-based information and resources and an invitation to medication review; RELEASE for GPs includes education, training and printable resources via practice management software. RELEASE+ includes additional internet support for patients and prescribing support including audit and feedback for GPs. OUTCOME MEASURES: the primary outcome is antidepressant use at 12 months self-reported by patients. Cessation is defined as 0 mg antidepressant maintained for at least 2 weeks. SECONDARY OUTCOMES: at 6 and 12 months are health-related quality of life, antidepressant side effects, well-being, withdrawal symptoms, emotional numbing, beliefs about antidepressants, depressive symptoms, and anxiety symptoms; and at 12 months 75% reduction in antidepressant dose; aggregated practice level antidepressant prescribing, and health service utilisation for costs. SAMPLE SIZE: 653 patients from 28 practices. A concurrent evaluation of implementation will be through mixed methods including interviews with up to 40 patients and primary care general practitioners, brief e-surveys, and study administrative data to assess implementation outcomes (adoption and fidelity). DISCUSSION: The RELEASE study will develop new knowledge applicable internationally on the effectiveness, cost-effectiveness, and implementation of two multi-strategy interventions in supporting the safe cessation of long-term antidepressants to improve primary health care and outcomes for patients. TRIAL REGISTRATION: ANZCTR, ACTRN12622001379707p. Registered on 27 October 2022.


Assuntos
Medicina Geral , Clínicos Gerais , Adulto , Humanos , Qualidade de Vida , Antidepressivos/efeitos adversos , Serviços de Saúde , Análise Custo-Benefício , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
J Infect Public Health ; 16(11): 1750-1760, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37738691

RESUMO

BACKGROUND: Mobile phones, used in billions throughout the world, are high-touch devices subject to a dynamic contamination of microorganisms and rarely considered as an important fomite to sanitise systematically. The emergence of SARS-CoV-2 resulted in the COVID-19 pandemic, arguably the most impactful pandemic of the 21st century with millions of deaths and disruption of all facets of modern life globally. AIM: To perform a systematic review of the literature exploring SARS-CoV-2 presence as a contaminant on mobile phones. METHODS: A systematic search (PubMed and Google Scholar) of literature was undertaken from December 2019 to March 2023 identifying English language studies. Studies included in this review specifically identified or tested for the contamination of the SARS-CoV-2 virus or genome on mobile phones while studies testing for SARS-COV-2 in environments and/or other fomites samples than but not mobile phones were excluded. RESULTS: A total of 15 studies with reports of SARS-CoV-2 contamination on mobile phones between 2020 and 2023 were included. Amongst all studies, which encompassed ten countries, 511 mobile phones were evaluated for the presence of SARS-CoV-2 contamination and 45% (231/511) were positive for SARS-CoV-2. All studies were conducted in the hospital setting and two studies performed additional testing in residential isolation rooms and a patient's house. Four studies (3 in 2020 and one in 2021) reported 0% contamination while two other studies (in 2020 and 2022) reported 100% of mobile phone contamination with SARS-COV-2. All other studies report mobile phones positive for the virus within a range of 4-77%. CONCLUSION: A total of 45% of mobile phones are contaminated with SARS-CoV-2 virus. These devices might be an important fomite vector for viral dissemination worldwide. Competent health authorities are advised/recommended to start a global implementation of mobile phone decontamination by introducing regulations and protocols in public health and health care settings such as the 6th moment of hand washing.

16.
Health Expect ; 26(6): 2302-2311, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37515464

RESUMO

BACKGROUND: Chronic conditions can lead to physical, cognitive and social decline; thus, increasing an individual's dependence on family who assist with activities of daily living. Interprofessional collaborative practice (IPCP), involving two or more health professionals working with the patient and their family, is one model of care for the high-quality management of individuals with chronic conditions in primary care. Nevertheless, family carers have reported a disconnect between themselves and healthcare providers in previous research. This study aimed to explore the experiences and perspectives of family carers for individuals with chronic conditions, regarding their involvement in IPCP. METHODS: Aspects of constructivist grounded theory methodology were used. Family carers of individuals with chronic conditions were invited to participate in a one-on-one, semistructured interview about their experiences with IPCP in the care of their loved one. Interview transcripts were analysed using Charmaz's four-step iterative process: (1) line-by-line coding, (2) focused coding, (3) categorisation of codes and (4) potential theme and subtheme development with memo writing to support each phase of analysis. The research team collaborated on reflexivity exercises, the conceptualisation of categories and the development of themes. RESULTS: Constructivist data analysis of interviews (average 40 min) with 10 family carers resulted in two themes. (1) Stepping in for my loved one represents the notion that carers take on external roles on behalf of their loved ones (subthemes: working with interprofessional teams, supporting independence and learning as I go). (2) Taking on the carer role, represents the internal factors that influence the external roles described in theme 1 (subthemes: feeling obligated to be involved and changing relationship dynamics). CONCLUSION: This study outlines the external actions and internal influences on family carer involvement in an interprofessional team. The required knowledge and support to care for their loved ones is currently learned in an ad hoc manner, and carers' resources should be better promoted by health professionals. Additionally, the relationship dynamics between a carer and their loved one change as the carer becomes more involved in IPCP and influences how and the extent health professionals involve family carers. PATIENT OR PUBLIC CONTRIBUTION: Carers were the study population involved in this qualitative study. Patient advocates who have chronic conditions, and are informal family carers, were involved in the creation and design of this study, including a review of the research question, participant information sheet and the interview guide.


Assuntos
Atividades Cotidianas , Cuidadores , Humanos , Cuidadores/psicologia , Teoria Fundamentada , Pesquisa Qualitativa , Doença Crônica , Atenção Primária à Saúde
17.
JCI Insight ; 8(12)2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37345659

RESUMO

Epigenetic aberrations, including posttranslational modifications of core histones, are major contributors to cancer. Here, we define the status of histone H2B monoubiquitylation (H2Bub1) in clear cell ovarian carcinoma (CCOC), low-grade serous carcinoma, and endometrioid carcinomas. We report that clear cell carcinomas exhibited profound loss, with nearly all cases showing low or negative H2Bub1 expression. Moreover, we found that H2Bub1 loss occurred in endometriosis and atypical endometriosis, which are established precursors to CCOCs. To examine whether dysregulation of a specific E3 ligase contributes to the loss of H2Bub1, we explored expression of ring finger protein 40 (RNF40), ARID1A, and UBR7 in the same case cohort. Loss of RNF40 was significantly and profoundly correlated with loss of H2Bub1. Using genome-wide DNA methylation profiles of 230 patients with CCOC, we identified hypermethylation of RNF40 in CCOC as a likely mechanism underlying the loss of H2Bub1. Finally, we demonstrated that H2Bub1 depletion promoted cell proliferation and clonogenicity in an endometriosis cell line. Collectively, our results indicate that H2Bub1 plays a tumor-suppressive role in CCOCs and that its loss contributes to disease progression.


Assuntos
Carcinoma , Endometriose , Neoplasias Ovarianas , Neoplasias Peritoneais , Feminino , Humanos , Endometriose/genética , Histonas/genética , Neoplasias Ovarianas/genética
18.
PEC Innov ; 2: 100140, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37214489

RESUMO

Objective: Patient decision aids (DA) facilitate shared decision making, but implementation remains a challenge. This study tested the feasibility of integrating a cardiovascular disease (CVD) prevention DA into general practice software. Methods: We developed a desktop computer application (app) to auto-populate a CVD prevention DA from general practice medical records. 4 practices received monthly practice reports from July-Nov 2021, and 2 practices use the app with limited engagement. CVD risk assessment data and app use were monitored. Results: The proportion of eligible patients with complete CVD risk assessment data ranged from 59 to 94%. Monthly app use ranged from 0 to 285 sessions by 13 individual practice staff including GPs and nurses, with staff using the app an average of 67 sessions during the study period. High users in the 5-month study period continued to use the app for 10 months. Low use was attributed to reduced staff capacity during COVID-19 and technical issues. Conclusion: High users sustained interest in the app, but additional strategies are required for low users. The study will inform implementation plans for new guidelines. Innovation: This study showed it is feasible to integrate patient decision aids with Australian general practice software, despite the challenges of COVID-19 at the time of the study.

19.
Int J Offender Ther Comp Criminol ; 67(13-14): 1401-1424, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37132536

RESUMO

Military veterans have been shown to differ demographically from non-veterans in the criminal justice system. However, relatively little is known about their psychological adjustment, institutional misbehavior, and the efficacy of programing received while incarcerated. Using data taken from a national sample of prison inmates, this study investigates how traumatic events experienced during military service can impact the intensity of negative affect among veterans. Additionally, we examine whether prison misconduct is influenced by military service history and the receipt of substance abuse treatment. Controlling for a host of relevant variables, our results indicate that traumatic events show a significant effect on psychological adjustment only indirectly through veterans who developed post-traumatic stress disorder and that misconduct is lower among those who received an honorable discharge. Overall, these findings suggest that the ability of veterans to resist adverse outcomes may depend on a variety of factors both within and outside the prison environment.


Assuntos
Prisioneiros , Transtornos de Estresse Pós-Traumáticos , Transtornos Relacionados ao Uso de Substâncias , Veteranos , Humanos , Transtornos de Estresse Pós-Traumáticos/psicologia , Veteranos/psicologia , Prisões , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
20.
Clin Cancer Res ; 29(15): 2800-2807, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37097611

RESUMO

PURPOSE: Addition of ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) to PARP inhibitors (PARPi) overcomes PARPi resistance in high-grade serous ovarian cancer (HGSOC) cell and mouse models. We present the results of an investigator-initiated study of combination PARPi (olaparib) and ATRi (ceralasertib) in patients with acquired PARPi-resistant HGSOC. PATIENTS AND METHODS: Eligible patients had recurrent, platinum-sensitive BRCA1/2 mutated or homologous recombination (HR)-deficient (HRD) HGSOC and clinically benefited from PARPi (response by imaging/CA-125 or duration of maintenance therapy; > 12 months first-line or > 6 months ≥ second-line) before progression. No intervening chemotherapy was permitted. Patients received olaparib 300 mg twice daily and ceralasertib 160 mg daily on days 1 to 7 of a 28-day cycle. Primary objectives were safety and objective response rate (ORR). RESULTS: Thirteen patients enrolled were evaluable for safety and 12 for efficacy; 62% (n = 8) had germline BRCA1/2 mutations, 23% (n = 3) somatic BRCA1/2 mutations, and 15% (n = 2) tumors with positive HRD assay. Prior PARPi indication was treatment for recurrence (54%, n = 7), second-line maintenance (38%, n = 5) and first-line treatment with carboplatin/paclitaxel (8%, n = 1). There were 6 partial responses yielding an ORR of 50% (95% confidence interval, 0.15-0.72). Median treatment duration was 8 cycles (range 4-23+). Grade (G) 3/4 toxicities were 38% (n = 5); 15% (n = 2) G3 anemia, 23% (n = 3) G3 thrombocytopenia, 8% (n = 1) G4 neutropenia. Four patients required dose reductions. No patient discontinued treatment due to toxicity. CONCLUSIONS: Combination olaparib and ceralasertib is tolerable and shows activity in HR-deficient platinum-sensitive recurrent HGSOC that benefited and then progressed with PARPi as the penultimate regimen. These data suggest that ceralasertib resensitizes PARPi-resistant HGSOCs to olaparib, warranting further investigation.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Antineoplásicos/uso terapêutico , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Recombinação Homóloga , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ftalazinas , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
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