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OBJECTIVES: To assess changes following the 2013-21 Home Care Package (HCP) reforms in the rate of HCPs provided to Australians aged 65 years or older, the characteristics of people who have received HCPs, and the capacity of the program to meet demand for its services during 2018-21. STUDY DESIGN: Repeated cross-sectional population-based study; analysis of Australian Institute of Health and Welfare GEN Aged Care and Australian Department of Health Home Care Packages program data. SETTING, PARTICIPANTS: HCPs provided to non-Indigenous Australians aged 65 years or older, 2008-09 to 2020-21. MAIN OUTCOME MEASURES: Changes in age- and sex-standardised HCP rates (number per 1000 older people) and changes in proportions of recipients for selected characteristics, 2013-14 to 2020-21, overall and by care level; correspondence of proportional HCP supply and demand, 2018-19 to 2020-21, by care level. RESULTS: A total of 490 276 HCPs were provided during 2008-21. The age- and sex-standardised HCP rate rose from 9.23 per 1000 people aged 65 years or more in 2013-14 to 16.4 per 1000 older people in 2020-21. The increases in age- and sex-standardised HCP rate between 2013-14 and 2020-21 were greatest for level 1 (from 0.19 to 5.05 per 1000 older people) and level 3 HCPs (from 0.35 to 3.62 per 1000 older people); the rate for level 2 HCPs declined from 6.75 to 5.82 per 1000 older people, and that for level 4 HCPs did not change. The proportion of culturally and linguistically diverse recipients rose from 10.8% to 16.2%; the overall proportion of recipients living outside major cities rose slightly, from 28.1% to 28.7%, but declined for higher care level HCPs (level 3: from 30.8% to 27.8%; level 4: from 29.6% to 25.2%). During 2018-19 to 2020-21, the proportions of lower level (1 and 2) HCPs generally exceeded demand, while the supply of higher level (3 and 4) HCPs generally fell short of demand. CONCLUSIONS: Despite the increased overall availability of HCPs, the supply of higher care level HCPs is still lower than the demand, probably contributing to suboptimal support for the ageing-in-place preferences of older Australians, especially in regional and remote areas.
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Reforma de la Atención de Salud , Servicios de Atención de Salud a Domicilio , Humanos , Estudios Transversales , Anciano , Australia , Femenino , Masculino , Servicios de Atención de Salud a Domicilio/organización & administración , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Anciano de 80 o más Años , Necesidades y Demandas de Servicios de Salud , Servicios de Salud para Ancianos/estadística & datos numéricos , Servicios de Salud para Ancianos/organización & administración , Pueblos de AustralasiaRESUMEN
OBJECTIVE: Moving into a long-term care facility (LTCF) requires substantial personal, societal and financial investment. Identifying those at high risk of short-term mortality after LTCF entry can help with care planning and risk factor management. This study aimed to: (i) examine individual-, facility-, medication-, system- and healthcare-related predictors for 90-day mortality at entry into an LTCF and (ii) create risk profiles for this outcome. DESIGN: Retrospective cohort study using data from the Registry of Senior Australians. SUBJECTS: Individuals aged ≥ 65 years old with first-time permanent entry into an LTCF in three Australian states between 01 January 2013 and 31 December 2016. METHODS: A prediction model for 90-day mortality was developed using Cox regression with the purposeful variable selection approach. Individual-, medication-, system- and healthcare-related factors known at entry into an LTCF were examined as predictors. Harrell's C-index assessed the predictive ability of our risk models. RESULTS: 116,192 individuals who entered 1,967 facilities, of which 9.4% (N = 10,910) died within 90 days, were studied. We identified 51 predictors of mortality, five of which were effect modifiers. The strongest predictors included activities of daily living category (hazard ratio [HR] = 5.41, 95% confidence interval [CI] = 4.99-5.88 for high vs low), high level of complex health conditions (HR = 1.67, 95% CI = 1.58-1.77 for high vs low), several medication classes and male sex (HR = 1.59, 95% CI = 1.53-1.65). The model out-of-sample Harrell's C-index was 0.773. CONCLUSIONS: Our mortality prediction model, which includes several strongly associated factors, can moderately well identify individuals at high risk of mortality upon LTCF entry.
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Cuidados a Largo Plazo , Humanos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Cuidados a Largo Plazo/estadística & datos numéricos , Factores de Riesgo , Medición de Riesgo , Australia/epidemiología , Sistema de Registros , Actividades Cotidianas , Casas de Salud/estadística & datos numéricos , Factores de Tiempo , Hogares para Ancianos/estadística & datos numéricos , Modelos de Riesgos ProporcionalesRESUMEN
OBJECTIVES: To examine changes in primary, allied health, selected specialists, and mental health service utilisation by older people in the year before and after accessing home care package (HCP) services. METHODS: A retrospective cohort study using the Registry of Senior Australians Historical National Cohort (≥ 65 years old), including individuals accessing HCP services between 2017 and 2019 (N = 109,558), was conducted. The utilisation of general practice (GP) attendances, health assessments, chronic disease management plans, allied health services, geriatric, pain, palliative, and mental health services, subsidised by the Australian Government Medicare Benefits Schedule, was assessed in the 12 months before and after HCP access, stratified by HCP level (1-2 vs. 3-4, i.e., lower vs. higher care needs). Relative changes in service utilisation 12 months before and after HCP access were estimated using adjusted risk ratios (aRR) from Generalised Estimating Equation Poisson models. RESULTS: Utilisation of health assessments (7-10.2%), chronic disease management plans (19.7-28.2%), and geriatric, pain, palliative, and mental health services (all ≤ 2.5%) remained low, before and after HCP access. Compared to 12 months prior to HCP access, 12 months after, GP after-hours attendances increased (HCP 1-2 from 6.95 to 7.5%, aRR = 1.07, 95% CI 1.03-1.11; HCP 3-4 from 7.76 to 9.32%, aRR = 1.20, 95%CI 1.13-1.28) and allied health services decreased (HCP 1-2 from 34.8 to 30.7%, aRR = 0.88, 95%CI 0.87-0.90; HCP levels 3-4 from 30.5 to 24.3%, aRR = 0.80, 95%CI 0.77-0.82). CONCLUSIONS: Most MBS subsidised preventive, management and specialist services are underutilised by older people, both before and after HCP access and small changes are observed after they access HCP.
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Pueblos de Australasia , Servicios de Atención de Salud a Domicilio , Servicios de Salud Mental , Humanos , Anciano , Australia , Estudios Retrospectivos , Programas Nacionales de Salud , DolorRESUMEN
BACKGROUND: The emergence of antimicrobial-resistant bacteria represents a considerable threat to human health, particularly for vulnerable populations such as those living in residential aged care. However, antimicrobial resistance carriage and modes of transmission remain incompletely understood. The Generating evidence on antimicrobial Resistance in the Aged Care Environment (GRACE) study was established to determine principal risk factors of antimicrobial resistance carriage and transmission in residential aged care facilities (RACFs). This article describes the cohort characteristics, national representation, and planned analyses for this study. METHODS: Between March 2019 and March 2020, 279 participants were recruited from five South Australian RACFs. The median age was 88.6 years, the median period in residence was 681 days, and 71.7% were female. A dementia diagnosis was recorded in 54.5% and more than two thirds had moderate to severe cognitive impairment (68.8%). 61% had received at least one course of antibiotics in the 12 months prior to enrolment. RESULTS: To investigate the representation of the GRACE cohort to Australians in residential aged care, its characteristics were compared to a subset of the historical cohort of the Registry of Senior Australians (ROSA). This included 142,923 individuals who were permanent residents of RACFs on June 30th, 2017. GRACE and ROSA cohorts were similar in age, sex, and duration of residential care, prevalence of health conditions, and recorded dementia diagnoses. Differences were observed in care requirements and antibiotic exposure (both higher for GRACE participants). GRACE participants had fewer hospital visits compared to the ROSA cohort, and a smaller proportion were prescribed psycholeptic medications. CONCLUSIONS: We have assembled a cohort of aged care residents that is representative of the Australian aged care population, and which provides a basis for future analyses. Metagenomic data isolated from participants and built environments will be used to determine microbiome and resistome characteristics of an individual and the facility. Individual and facility risk exposures will be aligned with metagenomic data to identify principal determinants for antimicrobial resistance carriage. Ultimately, this analysis will inform measures aimed at reducing the emergence and spread of antimicrobial resistant pathogens in this high-risk population.
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Antibacterianos , Demencia , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Masculino , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Australia , Farmacorresistencia Bacteriana , Factores de Edad , Demencia/diagnóstico , Demencia/tratamiento farmacológico , Demencia/epidemiologíaRESUMEN
COVID-19 has had a significant impact on the global population and has produced compelling evidence of non-pulmonary organ dysfunction, including the nervous system. It is vital that specialists in ophthalmology and neurology are informed of the potential complications of COVID-19 and gain a deeper understanding of how COVID-19 can cause diseases of the nervous system. In this review we detail four possible mechanisms by which COVID-19 infection may result in neurological or neuro-ophthalmological complications: (1) Toxic and metabolic effects of severe pulmonary COVID-19 disease on the neural axis including hypoxia and the systemic hyper-inflammatory state, (2) endothelial dysfunction, (3) dysimmune responses directed again the neuroaxis, and (4) direct neuro-invasion and injury by the virus itself. We explore the pathological evidence for each of these and how they may link to neuro-ophthalmological disorders. Finally, we explore the evidence for long-term neurological and neuro-ophthalmological complications of COVID-19, with a focus on neurodegeneration.
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COVID-19 , Oftalmopatías , Enfermedades del Sistema Nervioso , Neurología , Oftalmología , Humanos , COVID-19/complicaciones , Enfermedades del Sistema Nervioso/etiología , Oftalmopatías/etiologíaRESUMEN
BACKGROUND: Otitis media (OM) is a major disease burden in Australian Aboriginal children, contributing to serious long-term health outcomes. We report a pilot analysis of OM in children attending an outreach ear and hearing clinic in a remote south Australian community over a two-year period. Our study focuses on longitudinal relationships between ear canal microbiota characteristics with nasopharyngeal microbiota, and clinical and treatment variables. RESULTS: Middle ear health status were assessed in 19 children (aged 3 months to 8 years) presenting in remote western South Australia and medical interventions were recorded. Over the two-year study period, chronic suppurative OM was diagnosed at least once in 7 children (37%), acute OM with perforation in 4 children (21%), OM with effusion in 11 children (58%), while only 1 child had no ear disease. Microbiota analysis of 19 children (51 sets of left and right ear canal swabs and nasopharyngeal swabs) revealed a core group of bacterial taxa that included Corynebacterium, Alloiococcus, Staphylococcus, Haemophilus, Turicella, Streptococcus, and Pseudomonas. Within-subject microbiota similarity (between ears) was significantly greater than inter-subject similarity, regardless of differences in ear disease (p = 0.0006). Longitudinal analysis revealed changes in diagnosis to be associated with more pronounced changes in microbiota characteristics, irrespective of time interval. Ear microbiota characteristics differed significantly according to diagnosis (P (perm) = 0.0001). Diagnoses featuring inflammation with tympanic membrane perforation clustering separately to those in which the tympanic membrane was intact, and characterised by increased Proteobacteria, particularly Haemophilus influenzae, Moraxella catarrhalis, and Oligella. While nasopharyngeal microbiota differed significantly in composition to ear microbiota (P (perm) = 0.0001), inter-site similarity was significantly greater in subjects with perforated tympanic membranes, a relationship that was associated with the relative abundance of H. influenzae in ear samples (rs = - 0.71, p = 0.0003). Longitudinal changes in ear microbiology reflected changes in clinical signs and treatment. CONCLUSIONS: Children attending the ear and hearing clinic in a remote Aboriginal community present with a broad spectrum of OM conditions and severities, consistent with other remote Aboriginal communities. Ear microbiota characteristics align with OM diagnosis and change with disease course. Nasopharyngeal microbiota characteristics are consistent with the contribution of acute upper respiratory infection to OM aetiology.
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Bacterias/aislamiento & purificación , Oído Medio/microbiología , Oído Medio/patología , Microbiota , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Otitis Media/microbiología , Australia/epidemiología , Bacterias/clasificación , Bacterias/genética , Bacterias/patogenicidad , Niño , Preescolar , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Nasofaringe/microbiología , Otitis Media/epidemiología , Proyectos Piloto , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/microbiología , Población Rural/estadística & datos numéricosRESUMEN
BACKGROUND: no studies have examined the impact of residential medication management review (RMMR, a 24-year government subsidised comprehensive medicines review program) in Australian residential aged care facilities (RACFs) on hospitalisation or mortality. OBJECTIVE: to examine associations between RMMR provision in the 6-12 months after RACF entry and the 12-month risk of hospitalisation and mortality among older Australians in RACFs. DESIGN: retrospective cohort study. SUBJECTS: individuals aged 65-105 years taking at least one medicine, who entered an RACF in three Australian states between 1 January 2012 and 31 December 2015 and spent at least 6 months in the RACF (n = 57,719). METHODS: Cox regression models estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for associations between RMMR provision and mortality. Adjusted subdistribution hazard ratios were estimated for associations between RMMR provision and next (i) emergency department (ED) presentation or unplanned hospitalisation or (ii) fall-related ED presentation or hospitalisation. RESULTS: there were 12,603 (21.8%) individuals who received an RMMR within 6-12 months of RACF entry, of whom 22.2% (95%CI 21.4-22.9) died during follow-up, compared with 23.3% (95%CI 22.9-23.7) of unexposed individuals. RMMR provision was associated with a lower risk of death due to any cause over 12-months (aHR 0.96, 95%CI 0.91-0.99), but was not associated with ED presentations or hospitalisations for unplanned events or falls. CONCLUSIONS: provision of an RMMR in the 6-12 months after RACF entry is associated with a 4.4% lower mortality risk over 12-months but was not associated with changes in hospitalisations for unplanned events or falls.
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Hogares para Ancianos , Hospitalización , Accidentes por Caídas/prevención & control , Anciano , Australia/epidemiología , Humanos , Estudios RetrospectivosRESUMEN
COVID-19 has demonstrated the devastating consequences of the rapid spread of an airborne virus in residential aged care. We report the use of CO2-based ventilation assessment to empirically identify potential 'super-spreader' zones within an aged care facility, and determine the efficacy of rapidly implemented, inexpensive, risk reduction measures.
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COVID-19 , Humanos , Anciano , SARS-CoV-2 , Ventilación , Conducta de Reducción del RiesgoRESUMEN
BACKGROUND: Residential Medication Management Review (RMMR) is a subsidized comprehensive medicines review program for individuals in Australian residential aged care facilities (RACFs). This study examined weekly trends in medicines use in the four months before and after an RMMR and among a comparison group of residents who did not receive an RMMR. METHODS: This retrospective cohort study included individuals aged 65 to 105 years who first entered permanent care between 1/1/2012 and 31/12/2016 in South Australia, Victoria, or New South Wales, and were taking at least one medicine. Individuals with an RMMR within 12 months of RACF entry were classified into one of three groups: (i) RMMR within 0 to 3 months, (ii) 3 to 6 months, or (iii) within 6 to 12 months of RACF entry. Individuals without RMMRs were included in the comparison group. Weekly trends in the number of defined daily doses per 1000 days were determined in the four months before and after the RMMR (or assigned index date in the comparison group) for 14 medicine classes. RESULTS: 113909 individuals from 1979 RACFs were included, of whom 55021 received an RMMR. Across all three periods examined, decreased use of statins and proton pump inhibitors was observed post-RMMR in comparison to those without RMMRs. Decreases in calcium channel blockers, benzodiazepines/zopiclone, and antidepressants were observed following RMMR provision in the 3-6 and 6-12 months after RACF entry. Negligible changes in antipsychotic use were also observed following an RMMR in the 6-12 months after RACF entry by comparison to those without RMMRs. No changes in use of opioids, ACE inhibitors/sartans, beta blockers, loop diuretics, oral anticoagulants, or medicines for osteoporosis, diabetes or the cognitive symptoms of dementia were observed post-RMMR. CONCLUSIONS: For six of the 14 medicine classes investigated, modest changes in weekly trends in use were observed after the provision of an RMMR in the 6-12 months after RACF entry compared to those without RMMRs. Findings suggest that activities such as medicines reconciliation may be prioritized when an RMMR is provided on RACF entry, with deprescribing more likely after an RMMR the longer a resident has been in the RACF.
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Instituciones de Vida Asistida , Hogares para Ancianos , Anciano , Humanos , Cuidados a Largo Plazo , Estudios Retrospectivos , VictoriaRESUMEN
The gut microbiome is an established regulator of aspects of host metabolism, such as glucose handling. Despite the known impacts of the gut microbiota on host glucose homeostasis, the underlying mechanisms are unknown. The gut microbiome is also a potent mediator of gut-derived serotonin synthesis, and this peripheral source of serotonin is itself a regulator of glucose homeostasis. Here, we determined whether the gut microbiome influences glucose homeostasis through effects on gut-derived serotonin. Using both pharmacological inhibition and genetic deletion of gut-derived serotonin synthesis, we find that the improvements in host glucose handling caused by antibiotic-induced changes in microbiota composition are dependent on the synthesis of peripheral serotonin.
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Microbioma Gastrointestinal , Glucosa/metabolismo , Homeostasis , Serotonina/fisiología , Animales , Antibacterianos/farmacología , Área Bajo la Curva , Glucemia/metabolismo , Eliminación de Gen , Prueba de Tolerancia a la Glucosa , Masculino , Ratones , Ratones Endogámicos C57BL , Distribución AleatoriaRESUMEN
BACKGROUND: Understanding current patterns of antibiotic use in residential aged care facilities (RACFs) is essential to inform stewardship activities, but limited utilization data exist. This study examined changes in prevalence and consumption of antibiotics in Australian RACFs between 2005-2006 and 2015-2016. METHODS: This population-based, repeated cross-sectional analysis included all long-term permanent residents of Australian RACFs between July 2005 and June 2016 who were agedâ ≥â 65 years. The yearly prevalence rate of antibiotic use and number of defined daily doses (DDDs) of systemic antibiotics per 1000 resident-days were determined annually from linked pharmaceutical claims data. Trends were assessed using ordinary least squares regression. RESULTS: This study included 502â 752 residents from 3218 RACFs, with 424.9 million resident-days analyzed. Antibiotics were dispensed on 5â 608â 126 occasions during the study period, of which 88% were for oral use. Cefalexin, amoxicillin-clavulanic acid, and trimethoprim were the most commonly dispensed antibiotics. The annual prevalence of antibiotic use increased from 63.8% (95% confidence interval [CI], 63.3%-64.4%) to 70.3% (95% CI, 69.9%-70.7%) between 2005-2006 and 2015-2016 (0.8% average annual increase, Pâ <â .001). There was a 39% relative increase in total consumption of systemic antibiotics, with utilization increasing from 67.6 to 93.8 DDDs/1000 resident-days during the study period (average annual increase of 2.8 DDDs/1000 resident-days, Pâ <â .001). CONCLUSIONS: This nationwide study showed substantial increases in both prevalence of use and total consumption of antibiotics in Australian RACFs between 2005 and 2016. The increasingly widespread use of antibiotics in Australian RACFs is concerning and points to a need for enhanced efforts to optimize antibiotic use in this setting.
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Antibacterianos , Hogares para Ancianos , Anciano , Antibacterianos/uso terapéutico , Australia/epidemiología , Estudios Transversales , HumanosRESUMEN
OBJECTIVES: To examine national variation in systemic antibiotic use in long-term care facilities (LTCFs) and identify facility characteristics associated with antibiotic utilization. METHODS: This retrospective cohort study included 312â375 residents of 2536 Australian LTCFs between 2011 and 2016. LTCFs were categorized as low, medium or high antibiotic use facilities according to tertiles of DDDs of systemic antibiotics dispensed per 1000 resident-days. Multivariable logistic regression estimated the associations between facility characteristics (ownership, size, location, medication quality indicator performance, prevalence of after-hours medical practitioner services) and antibiotic use (low versus high). RESULTS: LTCFs in the lowest and highest antibiotic use categories received a median of 54.3 (IQR 46.5-60.5) and 106.1 (IQR 95.9-122.3) DDDs/1000 resident-days, respectively. Compared with not-for-profit LTCFs in major cities, government-owned non-metropolitan LTCFs were less likely to experience high antibiotic use [adjusted OR (aOR) 0.47, 95% CI 0.24-0.91]. LTCFs with 69-99 residents were less likely to experience high antibiotic use (aOR 0.69, 95% CI 0.49-0.97) than those with 25-47 residents annually. Greater prevalence of medical practitioner services accessed after-hours was associated with high antibiotic use [aOR 1.10 (per 10% increase in after-hours services), 95% CI 1.01-1.21]. South Australian LTCFs (aOR 2.17, 95% CI 1.38-3.39) were more likely, while Queensland (0.43, 95% CI 0.30-0.62) and Western Australian (aOR 0.34, 95% CI 0.21-0.57) LTCFs were less likely to experience high antibiotic use than New South Wales LTCFs. CONCLUSIONS: Considerable facility level variation in systemic antibiotic use was observed across Australian LTCFs. Identification of facility characteristics associated with antibiotic use provides a basis for targeted stewardship initiatives.
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Antibacterianos , Cuidados a Largo Plazo , Antibacterianos/uso terapéutico , Australia/epidemiología , Estudios de Cohortes , Humanos , Nueva Gales del Sur , Queensland , Estudios RetrospectivosRESUMEN
BACKGROUND: The gut microbiota influences many aspects of host physiology, including immune regulation, and is predictive of outcomes in cancer patients. However, whether conventional myelosuppressive chemotherapy affects the gut microbiota in humans with non-haematological malignancy, independent of antibiotic exposure, is unknown. METHODS: Faecal samples from 19 participants with non-haematological malignancy, who were receiving conventional chemotherapy regimens but not antibiotics, were examined prior to chemotherapy, 7-12 days after chemotherapy, and at the end of the first cycle of treatment. Gut microbiota diversity and composition was determined by 16S rRNA gene amplicon sequencing. RESULTS: Compared to pre-chemotherapy samples, samples collected 7-12 days following chemotherapy exhibited increased richness (mean 120 observed species ± SD 38 vs 134 ± 40; p = 0.007) and diversity (Shannon diversity: mean 6.4 ± 0.43 vs 6.6 ± 0.41; p = 0.02). Composition was significantly altered, with a significant decrease in the relative abundance of gram-positive bacteria in the phylum Firmicutes (pre-chemotherapy median relative abundance [IQR] 0.78 [0.11] vs 0.75 [0.11]; p = 0.003), and an increase in the relative abundance of gram-negative bacteria (Bacteroidetes: median [IQR] 0.16 [0.13] vs 0.21 [0.13]; p = 0.01 and Proteobacteria: 0.015 [0.018] vs 0.03 [0.03]; p = 0.02). Differences in microbiota characteristics from baseline were no longer significant at the end of the chemotherapy cycle. CONCLUSIONS: Conventional chemotherapy results in significant changes in gut microbiota characteristics during the period of predicted myelosuppression post-chemotherapy. Further study is indicated to link microbiome changes during chemotherapy to clinical outcomes.
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Antineoplásicos/efectos adversos , Microbioma Gastrointestinal/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Médula Ósea/efectos de los fármacos , ADN Bacteriano/aislamiento & purificación , Heces/microbiología , Femenino , Microbioma Gastrointestinal/genética , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , ARN Ribosómico 16S/genéticaRESUMEN
Despite the success of combination antiretroviral therapy (cART), HIV persists in long lived latently infected cells in the blood and tissue, and treatment is required lifelong. Recent clinical studies have trialed latency-reversing agents (LRA) as a method to eliminate latently infected cells; however, the effects of LRA on the central nervous system (CNS), a well-known site of virus persistence on cART, are unknown. In this study, we evaluated the toxicity and potency of a panel of commonly used and well-known LRA (panobinostat, romidepsin, vorinostat, chaetocin, disulfiram, hexamethylene bisacetamide [HMBA], and JQ-1) in primary fetal astrocytes (PFA) as well as monocyte-derived macrophages as a cellular model for brain perivascular macrophages. We show that most LRA are non-toxic in these cells at therapeutic concentrations. Additionally, romidepsin, JQ-1, and panobinostat were the most potent at inducing viral transcription, with greater magnitude observed in PFA. In contrast, vorinostat, chaetocin, disulfiram, and HMBA all demonstrated little or no induction of viral transcription. Together, these data suggest that some LRA could potentially activate transcription in latently infected cells in the CNS. We recommend that future trials of LRA also examine the effects of these agents on the CNS via examination of cerebrospinal fluid.
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VIH-1/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Neuronas/efectos de los fármacos , Activación Viral/efectos de los fármacos , Latencia del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Acetamidas/farmacología , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Astrocitos/virología , Azepinas/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Depsipéptidos/farmacología , Disulfiram/farmacología , Feto , VIH-1/genética , VIH-1/metabolismo , Humanos , Ácidos Hidroxámicos/farmacología , Indoles/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/virología , Neuronas/metabolismo , Neuronas/virología , Panobinostat , Piperazinas/farmacología , Cultivo Primario de Células , Transcripción Genética/efectos de los fármacos , Triazoles/farmacología , Activación Viral/genética , Latencia del Virus/genética , Replicación Viral/genética , VorinostatAsunto(s)
COVID-19 , Pandemias , Australia/epidemiología , Humanos , Atención Primaria de Salud , SARS-CoV-2RESUMEN
Human immunodeficiency virus type-1 (HIV-1) invades the central nervous system (CNS) during acute infection which can result in HIV-associated neurocognitive disorders in up to 50% of patients, even in the presence of combination antiretroviral therapy (cART). Within the CNS, productive HIV-1 infection occurs in the perivascular macrophages and microglia. Astrocytes also become infected, although their infection is restricted and does not give rise to new viral particles. The major barrier to the elimination of HIV-1 is the establishment of viral reservoirs in different anatomical sites throughout the body and viral persistence during long-term treatment with cART. While the predominant viral reservoir is believed to be resting CD4(+) T cells in the blood, other anatomical compartments including the CNS, gut-associated lymphoid tissue, bone marrow, and genital tract can also harbour persistently infected cellular reservoirs of HIV-1. Viral latency is predominantly responsible for HIV-1 persistence and is most likely governed at the transcriptional level. Current clinical trials are testing transcriptional activators, in the background of cART, in an attempt to purge these viral reservoirs and reverse viral latency. These strategies aim to activate viral transcription in cells constituting the viral reservoir, so they can be recognised and cleared by the immune system, while new rounds of infection are blocked by co-administration of cART. The CNS has several unique characteristics that may result in differences in viral transcription and in the way latency is established. These include CNS-specific cell types, different transcription factors, altered immune surveillance, and reduced antiretroviral drug bioavailability. A comprehensive understanding of viral transcription and latency in the CNS is required in order to determine treatment outcomes when using transcriptional activators within the CNS.
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Encéfalo/virología , Reservorios de Enfermedades/virología , Infecciones por VIH/virología , VIH-1/fisiología , Activación Transcripcional/fisiología , Humanos , Latencia del Virus/fisiologíaRESUMEN
Probiotics have gained significant attention as a potential strategy to improve health by modulating host-microbe interactions, particularly in situations where the normal microbiota has been disrupted. However, evidence regarding their efficacy has been inconsistent, with considerable interindividual variability in response. We aimed to explore whether a common genetic variant that affects the production of mucosal α(1,2)-fucosylated glycans, present in around 20% of the population, could explain the observed interpersonal differences in the persistence of commonly used probiotics. Using a mouse model with varying α(1,2)-fucosylated glycans secretion (Fut2WT or Fut2KO), we examined the abundance and persistence of Bifidobacterium strains (infantis, breve, and bifidum). We observed significant differences in baseline gut microbiota characteristics between Fut2WT and Fut2KO littermates, with Fut2WT mice exhibiting enrichment of species able to utilize α(1,2)-fucosylated glycans. Following antibiotic exposure, only Fut2WT animals showed persistent engraftment of Bifidobacterium infantis, a strain able to internalize α(1,2)-fucosylated glycans, whereas B. breve and B. bifidum, which cannot internalize α(1,2)-fucosylated glycans, did not exhibit this difference. In mice with an intact commensal microbiota, the relationship between secretor status and B. infantis persistence was reversed, with Fut2KO animals showing greater persistence compared to Fut2WT. Our findings suggest that the interplay between a common genetic variation and antibiotic exposure plays a crucial role in determining the dynamics of B. infantis in the recipient gut, which could potentially contribute to the observed variation in response to this commonly used probiotic species.
Asunto(s)
Antibacterianos , Fucosiltransferasas , Galactósido 2-alfa-L-Fucosiltransferasa , Microbioma Gastrointestinal , Probióticos , Animales , Ratones , Fucosiltransferasas/genética , Fucosiltransferasas/metabolismo , Probióticos/administración & dosificación , Antibacterianos/farmacología , Bifidobacterium longum subspecies infantis/genética , Bifidobacterium longum subspecies infantis/metabolismo , Polisacáridos/metabolismo , Interacciones Microbiota-Huesped , Ratones Endogámicos C57BL , Ratones Noqueados , Bifidobacterium/genética , Bifidobacterium/metabolismoRESUMEN
BACKGROUND: Urinary tract infections (UTI) are the most frequently diagnosed infection in residents of long-term care and are a major risk factor for urosepsis, hospitalisation, and death. Translocation of gut pathobionts into the urinary tract is the presumed cause of most UTIs. While specific gut microbiota characteristics have been linked to UTI risk in younger adults, their relevance in aged care residents remains uncertain. METHODS: The faecal microbiome was assessed in 54 long-term aged care residents with a history of UTIs and 69 residents without a UTI history. Further comparisons were made to microbiome characteristics in 20 younger adults without UTIs. Microbiome characteristics were examined in relation to prior and subsequent UTIs, as well as antibiotic therapy. RESULTS: In long-term aged care residents, prior UTI history and exposure to UTI-exclusive antibiotics do not significantly affect microbiome composition or functional capacity. However, exposure to antibiotics unrelated to UTI treatment is associated with distinct microbiota compositional traits. Adjustment for dementia, incontinence, diabetes, and prior antibiotic use finds no microbiota characteristic linked to UTI development. However, prior UTI is identified as a predictor of future UTIs. Comparison with younger adults identifies greater within-participant dispersion in aged care residents, as well as lower microbiota diversity and altered microbiome functional potential. CONCLUSIONS: No association between the gut microbiome and UTI incidence, as has been reported in younger individuals, is evident in long-term aged care residents. Considerable variability in gut microbiome characteristics, relating to high antibiotic exposure and age-related physiological and immunological factors, could mask such a relationship. However, it cannot be discounted that increased UTI risk in the elderly is independent of microbiome-mediated mechanisms.
Urinary tract infections (UTIs) are common in residents of long-term aged care facilities, posing serious health risks. Harmful bacteria moving from the gut to the urinary tract is thought to cause most UTIs. It is still unclear, however, how differences in gut bacteria contribute to UTI risk in older adults. Here, we investigate the gut bacteria of aged care residents, both with and without a history of UTIs, and compare them to younger adults. While prior UTIs did not alter gut bacteria, antibiotic use did. We observed greater variability in gut bacteria among aged care residents compared to younger adults. These observations suggest that both high antibiotic exposure and age-related factors may mask any potential relationship between gut bacteria and UTI risk in this population. Understanding these factors could lead to improved UTI prevention and treatment strategies for elderly individuals.
RESUMEN
BACKGROUND: The impact of Home Medicines Reviews (HMRs) on long-term health outcomes among individuals receiving long-term in-home aged care services is unknown. OBJECTIVES: To examine associations between HMR provision and hospitalization, long-term care facility (LTCF) entry and mortality among older people receiving long-term in-home aged care services. METHODS: This retrospective cohort study included individuals aged 65-105 years from three Australian states who accessed in-home aged care services between 2013 and 2017. Using propensity score matching, HMR recipients (n = 1530) were matched to individuals who did not receive an HMR (n = 1530). Associations between HMR provision and outcomes were estimated using multivariable regression models. RESULTS: Over a median of 414 days (interquartile range 217-650) of follow-up, HMR provision was not associated with hospitalizations for unplanned events (subdistribution hazard ratio (sHR) 1.04, 95%CI 0.96-1.14), falls-related hospitalizations (sHR 0.97, 95%CI 0.83-1.13), LTCF entry (sHR 0.97, 95%CI 0.83-1.13), or all-cause mortality (adjusted HR 0.86, 95%CI 0.72-1.01). CONCLUSIONS: In a cohort of older people receiving long-term in-home aged care services, no differences in unplanned hospitalizations, falls, LTCF entry or mortality were observed those with HMRs compared to those that did not receive an HMR.