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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.
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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.
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Proteína BRCA1 , Cistadenocarcinoma Seroso , Neoplasias Ováricas , Humanos , Femenino , Anciano , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Persona de Mediana Edad , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Proteína BRCA1/genética , Proteína BRCA2/genética , Anciano de 80 o más Años , Factores de Edad , Adulto , Recombinación Homóloga , Estadificación de Neoplasias , Clasificación del Tumor , Pruebas Genéticas/métodosRESUMEN
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.
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Conducta Cooperativa , Teoría Fundamentada , Relaciones Interprofesionales , Atención Primaria de Salud , Humanos , Atención Primaria de Salud/métodos , Femenino , Masculino , Persona de Mediana Edad , Enfermedad Crónica/terapia , Anciano , Australia , Adulto , Investigación Cualitativa , Grupo de Atención al Paciente , Entrevistas como Asunto , Participación del PacienteRESUMEN
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.
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Hogares para Ancianos , Atención Primaria de Salud , Atención Secundaria de Salud , Anciano , Humanos , Personal de Salud , Calidad de VidaRESUMEN
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.
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Cyclospora , Eimeria , Oocistos , Ozono , Cyclospora/efectos de los fármacos , Eimeria/efectos de los fármacos , Ozono/farmacología , Oocistos/efectos de los fármacos , Animales , Humanos , Agua , Ciclosporiasis , Desinfectantes/farmacologíaRESUMEN
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.
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Enfermedades Cardiovasculares , Medicina General , Humanos , Australia/epidemiología , Enfermedades Cardiovasculares/prevención & control , Técnicas de Apoyo para la Decisión , Atención Primaria de SaludRESUMEN
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.
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COVID-19 , Humanos , Australia , Bases de Datos Factuales , Instituciones de Salud , HospitalesRESUMEN
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.
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Sindecano-4 , Cicatrización de Heridas , Masculino , Ratones , Animales , Sindecano-4/genética , Sindecano-4/metabolismo , Cicatrización de Heridas/fisiología , Péptidos/metabolismo , Epidermis/metabolismo , Células Epidérmicas/metabolismo , Movimiento CelularRESUMEN
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.
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Citoesqueleto de Actina , Actomiosina , Retroalimentación , Movimiento Celular/fisiología , Actomiosina/metabolismo , Citoesqueleto de Actina/metabolismo , Miosinas/metabolismo , Adhesión Celular/fisiología , Matriz Extracelular/metabolismoRESUMEN
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.
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Medicina General , Médicos Generales , Adulto , Humanos , Calidad de Vida , Antidepresivos/efectos adversos , Servicios de Salud , Análisis Costo-Beneficio , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
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.
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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.
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Actividades Cotidianas , Cuidadores , Humanos , Cuidadores/psicología , Teoría Fundamentada , Investigación Cualitativa , Enfermedad Crónica , Atención Primaria de SaludRESUMEN
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.
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Carcinoma , Endometriosis , Neoplasias Ováricas , Neoplasias Peritoneales , Femenino , Humanos , Endometriosis/genética , Histonas/genética , Neoplasias Ováricas/genéticaRESUMEN
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.
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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.
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Prisioneros , Trastornos por Estrés Postraumático , Trastornos Relacionados con Sustancias , Veteranos , Humanos , Trastornos por Estrés Postraumático/psicología , Veteranos/psicología , Prisiones , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
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.
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Antineoplásicos , Neoplasias Ováricas , Animales , Femenino , Humanos , Ratones , Antineoplásicos/uso terapéutico , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Recombinación Homóloga , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Ftalazinas , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéuticoRESUMEN
BACKGROUND: During the COVID-19 pandemic, telehealth emerged as a means of safely providing primary healthcare (PHC) consultations. In Australia, changes to telehealth funding led to the reconsideration of the role of telehealth in the ongoing provision of PHC services. AIM: To investigate GPs', registered nurses' (RNs), nurse practitioners' (NPs), and allied health (AH) clinicians perceptions of the sustainability of telehealth in PHC post-pandemic. DESIGN & SETTING: Semi-structured interviews were undertaken with 33 purposively selected clinicians, including GPs (n = 13), RNs (n = 5), NPs (n = 9), and AH clinicians (n = 6) working in PHC settings across Australia. Participants were drawn from responders to a national survey of PHC providers (n = 217). METHOD: The thematic analysis approach reported by Braun and Clarke was used to analyse the interview data. RESULTS: Data analysis revealed that the perception of providers was represented by the following two themes: lessons learnt; and the sustainability of telehealth. Lessons learnt included the need for rapid adaptation to telehealth, use of technology, and the pandemic being a catalyst for long-term change. The sustainability of telehealth in PHC comprised four subthemes around challenges: the funding model, maintaining patient and provider safety, hybrid service models, and access to support. CONCLUSION: Providers required resilience and flexibility to adapt to telehealth. Funding models must reward providers from an outcome focus, rather than placing limits on telehealth's use. Hybrid approaches to service delivery will best meet the needs of the community but must be accompanied by support and education for PHC professionals.
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OBJECTIVE: This study aimed to investigate Australian primary healthcare professionals' experiences of the rapid upscaling of telehealth during COVID-19. DESIGN: A cross-sectional survey. PARTICIPANTS AND SETTING: Two hundred and seventeen general practitioners, nurses and allied health professionals employed in primary healthcare settings across Australia were recruited via social media and professional organisations. METHODS: An online survey was disseminated between December 2020 and March 2021. The survey comprised items about individual demographics, experiences of delivering telehealth consultations, perceived quality of telehealth consultations and future perceptions of telehealth. RESULTS: Telephone was the most widely used method of providing telehealth, with less than 50% of participants using a combination of telephone and video. Key barriers to telehealth use related to the inability to undertake physical examination or physical intervention. Telehealth was perceived to improve access to healthcare for some vulnerable groups and those living in rural settings, but reduced access for people from non-English-speaking backgrounds. Quality of telehealth care was considered mostly or somewhat the same as care provided face-to-face, with actual or perceived negative outcomes related to missed or delayed diagnosis. Overwhelmingly, participants wanted telehealth to continue with guaranteed ongoing funding. Some 43.7% of participants identified the need to further improve telehealth models of care. CONCLUSION: The rapid shift to telehealth has facilitated ongoing care during the COVID-19 pandemic. However, further work is required to better understand how telehealth can be best harnessed to add value to service delivery in usual care.
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COVID-19 , Telemedicina , Humanos , COVID-19/epidemiología , Estudios Transversales , Pandemias , Australia , Telemedicina/métodos , Atención Primaria de SaludRESUMEN
OBJECTIVE: Investigate outcomes for advanced stage epithelial ovarian cancer (EOC) patients based on facility-level utilization of neoadjuvant chemotherapy (NACT). METHODS: Stage III-IV EOC patients diagnosed between 2010 and 2016 were identified in the National Cancer Database. Percentage of patients managed with NACT was calculated for facilities, reporting ≥120 patients. Facilities with lowest and highest quartile of NACT rate comprised the low and high-utilizing groups. Clinico-pathological characteristics were collected, and appropriate statistical analysis performed. RESULTS: High- and low-utilizing facilities managed on average 54.1% and 25.4% of patients with NACT respectively. Patients managed at high-utilizing facilities were significantly more likely to be >65 (p = 0.029), have stage IV disease (p < 0.001) and comorbidities (p < 0.001). Patients managed with primary debulking surgery (PDS) at low-utilizing facilities were significantly more likely to be >65, have stage IV disease, and have comorbidities (all, p < 0.001). Patients undergoing PDS at low-utilizing facilities were significantly less likely to achieve complete gross resection (p < 0.001), and were significantly more likely to experience 90-day mortality (p < 0.001), and unplanned 30-day readmission (p < 0.001). After controlling for age, comorbidities, race, insurance status, stage, grade and histology, high-utilizing facilities trended towards better overall survival (OS) (HR: 0.92, 95% CI: 0.85-0.99). Overall, patients undergoing PDS had better OS compared to those who had NACT (median 42 vs 27 months, p < 0.001). CONCLUSIONS: Despite treating an EOC population with more advanced disease and comorbidities, high-utilizing facilities have lower surgical morbidity and mortality with no detrimental impact on long-term survival. Careful patient selection to minimize the morbidity and mortality associated with PDS is pivotal.