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OBJECTIVE: To investigate the association between oral health status and all-cause mortality in older adults using prospective cohort study design. SETTING AND PARTICIPANTS: In total, 12 809 adults aged ≥70 years (54.3% females) were participants of the ASPREE Longitudinal Study of Older Persons (ALSOP). METHODS: Participants self-reported the presence of natural teeth and oral health status. The association of self-reported oral health, edentulism and the integrative measure of the two with all-cause mortality were explored using the Cox-regression models adjusted for age, gender, socio-economic status, health-related behaviours, weight status, aspirin and polypharmacy. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. RESULTS: In total, 22.2% of participants reported edentulism and 13.8% had fair/poor oral health. After adjustment for confounders, risk of all-cause mortality was higher among those with edentulism (vs. no edentulism) HR (95% CI) 1.43 (1.18, 1.73); and those with edentulism and reporting poor/fair oral health HR (95% CI) 1.69 (1.02, 2.82), or with no edentulism but reporting poor/fair oral health HR (95% CI) 1.46 (1.19-1.80) vs. no edentulism and reporting good/very good/excellent oral health. No association was observed between self-reported oral health alone and all-cause mortality. CONCLUSIONS: The risk of all-cause mortality was 69% higher among older adults reporting both edentulism and poor/fair oral health compared with those with teeth and more favourable self-reported oral health. © 2023 Australian Dental Association.
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The Aspirin in Reducing Events in the Elderly (ASPREE) Trial recruited 19,114 participants across Australia and the United States during 2010-2014. Participants were randomized to receive either 100 mg of aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open-label aspirin use. In the placebo group, 35% and 11% ceased using study medication and commenced open-label aspirin use, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank-preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people, along with an elevated risk of clinically significant bleeding.
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Aspirina , Hemorragia , Humanos , Estados Unidos/epidemiología , Anciano , Anciano de 80 o más Años , Aspirina/uso terapéutico , Hemorragia/inducido químicamente , Australia/epidemiología , Método Doble CiegoRESUMEN
In this cross-sectional analysis of 10,071 community dwelling adults aged ≥70 years, we examined factors associated with meal skipping (self-reported) using multivariable logistic regression. Prevalence of meal skipping in this study was 19.5%. The adjusted odds (aOR [95%CI]) of meal skipping were lower in those 85+ years (vs. 70-74.9 years, 0.56 [0.45-0.70]), and in those in regional areas (vs. urban area, 0.81 [0.72-0.92]). Higher odds of meal skipping were observed for those living alone (vs. living with someone, 1.84 [1.64-2.05]), current smokers (vs. non-smokers, 2.07 [1.54-2.80]), consumers of high amounts of alcohol (vs. abstainers 1.93 [1.35-2.75]), those with poor oral health (vs. excellent oral health, 1.71 [1.07 -2.73]) diabetes (vs. not 1.26 [1.06-1.50]), or frailty (vs. not, 1.63 [1.09-2.43]). This study identified socio-demographic, social, behavioural and biomedical correlates of meal skipping in later life, which may assist in targeting interventions to address meal skipping.
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Conducta Alimentaria , Vida Independiente , Humanos , Anciano , Estudios Transversales , Comidas , Recolección de DatosRESUMEN
BACKGROUND: Pure desmoplastic melanoma (pDM) is an uncommon subtype of malignant melanoma with comparative high rates of local recurrence and low rates of sentinel lymph node positivity. The melanoma-specific survival (MSS) of pDM compared to other melanoma subtypes is unclear, with conflicting reports and lack of multivariable analyses. OBJECTIVES: We aimed to describe clinicopathological characteristics of a cohort of patients with pDM and to compare the MSS of pDM with superficial spreading melanoma (SSM). METHODS: A prospective cohort study was performed of all primary invasive cutaneous pDM with known tumour location and thickness reviewed at a tertiary referral centre over 21 years. RESULTS: A total of 119 primary cutaneous invasive pDMs from 3570 total invasive cutaneous melanomas were included. Compared to 2272 SSMs, and due largely to their greater average thickness, patients with pDM had worse MSS (unadjusted hazard ratio, HR, 2.56, 95% confidence interval, CI, 1.56-4.22). After adjustment for clinicopathologic factors (including thickness, ulceration, mitotic rate, age and sex), there was evidence that patients with pDM had an improved MSS (adjusted HR, 0.49; 95% CI, 0.28-0.87). Median thickness of head and neck pDM was greater than non-head and neck pDM (P < 0.001). There was reduced univariable MSS in head and neck pDM compared to the rest of the body. CONCLUSIONS: Decreased univariable MSS of patients with pDM compared to SSM was explained by the increased frequency of adverse clinicopathologic features at diagnosis, in particular the greater Breslow thickness of pDM. After adjustment, patients with pDM had half the chance of melanoma-specific death compared to SSM. Head and neck pDM were thicker at diagnosis compared to the rest of the body, which may account for its poorer survival compared to the rest of the body.
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Neoplasias de Cabeza y Cuello/patología , Melanoma/patología , Neoplasias Cutáneas/patología , Factores de Edad , Anciano , Anciano de 80 o más Años , Extremidades , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Melanoma/complicaciones , Persona de Mediana Edad , Índice Mitótico , Invasividad Neoplásica , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores Sexuales , Neoplasias Cutáneas/complicaciones , Úlcera Cutánea/etiología , Tasa de Supervivencia , Torso , Carga TumoralRESUMEN
BACKGROUND: The epidemiology of mucormycosis in the era of modern diagnostics is relatively under-explored. OBJECTIVES: To examine the contemporary epidemiology, clinical manifestations, diagnosis and causative pathogens of mucormycosis. DATA SOURCES: Ovid MEDLINE and Ovid EMBASE from January 2000 to January 2017. STUDY ELIGIBILITY CRITERIA: Published case reports/series of proven/probable mucormycosis. PARTICIPANTS: Patients ≥18 years old. METHODS: Patient characteristics, disease manifestations and causative pathogens were summarized descriptively. Categorical variables were assessed by chi-square test or Fischer's exact test, and continuous variables by the Wilcoxon-Mann-Whitney or Kruskal-Wallis test. Risk factors for the different clinical manifestations of mucormycosis were identified using multivariate logistic regression. RESULTS: Initial database searches identified 3619 articles of which 600 (851 individual patient cases) were included in the final analysis. Diabetes mellitus was the commonest underlying condition (340/851, 40%) and was an independent risk for rhino-orbital-cerebral mucormycosis (odds ratio (OR) 2.49; 95% CI 1.77-3.54; p < 0.001). Underlying haematological malignancy was associated with disseminated infection (OR 3.86; 95% CI 1.78-8.37; p 0.001), whereas previous solid organ transplantation was associated with pulmonary (OR 3.19; 95% CI 1.50-6.82; p 0.003), gastrointestinal (OR 4.47; 95% CI 1.69-11.80; p 0.003), or disseminated (OR 4.20; 95% CI 1.68-10.46; p 0.002) mucormycosis. Eight genera (24 species) of Mucorales organisms were identified in 447/851 (53%) cases, of which Rhizopus spp. (213/447, 48%) was the most common. Compared with other genera, Rhizopus spp. was predominantly observed in patients with rhino-orbital-cerebral mucormycosis (75/213, 35% versus 34/234, 15%; p < 0.001). Death was reported in 389/851 (46%) patients. Mortality associated with Cunninghamella infections was significantly higher than those caused by other Mucorales (23/30, 71% versus 185/417, 44%; p < 0.001). However, Cunninghamella spp. were isolated primarily in patients with pulmonary (17/30, 57%) or disseminated disease (10/30, 33%). CONCLUSIONS: Findings from the current review have helped ascertain the association between various manifestations of mucormycosis, their respective predisposing factors and causative organisms.
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Mucormicosis/epidemiología , Diabetes Mellitus/epidemiología , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/epidemiología , Humanos , Mucorales , Mucormicosis/complicaciones , Mucormicosis/mortalidad , Rhizopus , Factores de RiesgoAsunto(s)
Melanoma/mortalidad , Nevo Pigmentado/patología , Neoplasias Cutáneas/mortalidad , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Melanoma/etiología , Melanoma/patología , Persona de Mediana Edad , Nevo Pigmentado/complicaciones , Nevo Pigmentado/mortalidad , Pronóstico , Estudios Retrospectivos , Piel/patología , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/patología , Análisis de SupervivenciaRESUMEN
Human immunodeficiency virus (HIV) is membrane-enveloped, and an initial infection step is joining/fusion of viral and cell membranes. This step is catalyzed by gp41, which is a single-pass integral viral membrane protein. The protein contains an â¼170-residue ectodomain located outside the virus that is important for fusion and includes the fusion peptide (FP), N-helix, loop, C-helix, and viral membrane-proximal external region (MPER). The virion initially has noncovalent complexes between three gp41 ectodomains and three gp120 proteins. A gp120 contains â¼500 residues and functions to identify target T-cells and macrophages via binding to specific protein receptors of the target cell membrane. gp120 moves away from the gp41 ectodomain, and the ectodomain is thought to bind to the target cell membrane and mediate membrane fusion. The secondary and tertiary structures of the ectodomain are different in the initial complex with gp120 and the final state without gp120. There is not yet imaging of gp41 during fusion, so the temporal relationship between the gp41 and membrane structures is not known. This study describes biophysical and functional characterization of large gp41 constructs that include the ectodomain and transmembrane domain (TM). Significant fusion is observed of both neutral and anionic vesicles at neutral pH, which reflects the expected conditions of HIV/cell fusion. Fusion is enhanced by the FP, which in HIV/cell fusion likely contacts the host membrane, and the MPER and TM, which respectively interfacially contact and traverse the HIV membrane. Initial contact with vesicles is made by protein trimers that are in a native oligomeric state that reflects the initial complex with gp120 and also is commonly observed for the ectodomain without gp120. Circular dichroism data support helical structure for the N-helix, C-helix, and MPER and nonhelical structure for the FP and loop. Distributions of monomer, trimer, and hexamer states are observed by size-exclusion chromatography (SEC), with dependences on solubilizing detergent and construct. These SEC and other data are integrated into a refined working model of HIV/cell fusion that includes dissociation of the ectodomain into gp41 monomers followed by folding into hairpins that appose the two membranes, and subsequent fusion catalysis by trimers and hexamers of hairpins. The monomer and oligomer gp41 states may therefore satisfy dual requirements for HIV entry of membrane apposition and fusion.
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Proteína gp41 de Envoltorio del VIH/metabolismo , Infecciones por VIH/metabolismo , VIH-1/metabolismo , Fusión de Membrana , Secuencia de Aminoácidos , Proteína gp41 de Envoltorio del VIH/química , Infecciones por VIH/virología , VIH-1/química , Humanos , Concentración de Iones de Hidrógeno , Dominios Proteicos , Multimerización de Proteína , Estructura Secundaria de ProteínaRESUMEN
Human error poses significant risk for hospitalized patients causing an estimated 100,000 to 400,000 deaths in the USA annually. Medication errors contribute, with error occurring in 5.3% of medication administrations during surgery. In this study 70.3% of medication errors were deemed preventable. Given the paucity of randomized controlled studies, we undertook a rigorous review of the literature to identify recommendations supported by expert opinions. An extensive literature search pertaining to medication error, medication safety, operating room, and anaesthesia was performed. The National Guidelines Clearinghouse was searched for any anaesthesia or operating room medication safety guidelines.A total of 74 articles were included. Recommendations were tabulated and assigned points based on a scale revised from a prior study. A total of 138 unique recommendations were identified, with point tallies ranging from 4 to 190. An in-person focus meeting occurred, where the 138 recommendations were reviewed, combined and condensed. A modified Delphi process was used to eliminate items found to be unimportant or those unable to be quantified (e.g. "minimize fatigue"). A total of 35 specific recommendations remained. Adverse events as a result of medication errors occur frequently in the operative setting. There are few rigorous studies to direct medication safety strategies, but this should not lead us to do nothing. The overwhelming consensus regarding best practices should be accepted, and the recommendations implemented. Our list of recommended strategies can hopefully be used to assess local vulnerabilities and institute system solutions.
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Errores de Medicación/prevención & control , Quirófanos , Seguridad del Paciente , HumanosRESUMEN
AIMS: To describe the baseline characteristics of participants in the Kerala Diabetes Prevention Program. METHODS: The Kerala Diabetes Prevention Program is a cluster randomized controlled trial of lifestyle intervention for prevention of Type 2 diabetes mellitus in India. Participants in the study were those aged 30-60 years who had an Indian Diabetes Risk Score ≥ 60 and who were without Type 2 diabetes on oral glucose tolerance test. Data on demographic, lifestyle, clinical and biochemical characteristics were collected using standardized tools. RESULTS: A total of 2586 individuals were screened with the Indian Diabetes Risk Score, of these 1529 people (59.1%) had a score ≥ 60, of whom 1209 (79.1%) underwent an oral glucose tolerance test. A total of 202 individuals (16.7%) had undiagnosed Type 2 diabetes and were excluded, and the remaining 1007 individuals were enrolled in the trial (control arm, n = 507; intervention arm, n = 500). The mean participant age was 46.0 ± 7.5 years, and 47.2% were women. The mean Indian Diabetes Risk Score was 67.1 ± 8.4. More than two-thirds (69.0%) had prediabetes and 31.0% had normal glucose tolerance. The prevalence of cardiometabolic risk factors was high, including current tobacco use (34.4% in men), current alcohol use (39.3% in men), no leisure time exercise (98.0%), no daily intake of fruit and vegetables (78.7%), family history of diabetes (47.9%), overweight or obesity (68.5%), hypertension (22.3%) and dyslipidemia (85.4%). CONCLUSIONS: The Kerala Diabetes Prevention Program recruited participants using a diabetes risk score. A large proportion of the participants had prediabetes and there were high rates of cardiometabolic risk factors. The trial will evaluate the effectiveness of lifestyle intervention in a population selected on the basis of a diabetes risk score.
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Diabetes Mellitus Tipo 2/prevención & control , Estado Prediabético/terapia , Prevención Primaria/métodos , Conducta de Reducción del Riesgo , Adulto , Pueblo Asiatico , Diabetes Mellitus Tipo 2/etnología , Femenino , Humanos , India , Estilo de Vida , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Estado Prediabético/etnologíaRESUMEN
BACKGROUND: Not only is depression associated with increased inflammation but inflammation is a risk factor for the genesis of depression. Many of the environmental risk factors for depression are transduced through inflammatory signaling. Anti-inflammatory agents show promise for the management of depression in preclinical, epidemiological, and early clinical studies. This opens the door to the potential for anti-inflammatory agents to treat and prevent depression. There are no evidence-based pharmacotherapies for depression prevention. METHOD: ASPREE-D, aspirin in the prevention of depression in the elderly, is a sub study of ASPREE, which explores the potential of aspirin to prevent a range of inflammation related disorders in the elderly. With a sample size of 19,114, and a duration of 5 years, this placebo controlled study will be one of the largest randomized controlled trials in psychiatry and will provide definitive evidence on the ability of aspirin to prevent depression. RESULTS: This paper presents the rationale for the study and presents a summary of the study design. CONCLUSIONS: ASPREE-D may not only define novel therapy but will provide mechanistic proof of concept of the role of inflammation in depression.
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Aspirina/administración & dosificación , Depresión , Inflamación , Anciano , Antiinflamatorios/administración & dosificación , Depresión/fisiopatología , Depresión/prevención & control , Método Doble Ciego , Femenino , Humanos , Inflamación/tratamiento farmacológico , Inflamación/psicología , Masculino , Proyectos de InvestigaciónRESUMEN
BACKGROUND: The 2013 Global Burden of Disease Study demonstrated the increasing burden of diabetes and the challenge it poses to the health systems of all countries. The chronic and complex nature of diabetes requires active self-management by patients in addition to clinical management in order to achieve optimal glycaemic control and appropriate use of available clinical services. This study is an evaluation of a "real world" peer support program aimed at improving the control and management of type 2 diabetes (T2DM) in Australia. METHODS: The trial used a randomised cluster design with a peer support intervention and routine care control arms and 12-month follow up. Participants in both arms received a standardised session of self-management education at baseline. The intervention program comprised monthly community-based group meetings over 12 months led by trained peer supporters and active encouragement to use primary health care and other community resources and supports related to diabetes. Clinical, behavioural and other measures were collected at baseline, 6 and 12 months. The primary outcome was the predicted 5 year cardiovascular disease risk using the United Kingdom Prospective Diabetes Study (UKPDS) Risk Equation at 12 months. Secondary outcomes included clinical measures, quality of life, measures of support, psychosocial functioning and lifestyle measures. RESULTS: Eleven of 12 planned groups were successfully implemented in the intervention arm. Both the usual care and the intervention arms demonstrated a small reduction in 5 year UKPDS risk and the mean values for biochemical and anthropometric outcomes were close to target at 12 months. There were some small positive changes in self-management behaviours. CONCLUSIONS: The positive changes in self-management behaviours among intervention participants were not sufficient to reduce cardiovascular risk, possibly because approximately half of the study participants already had quite well controlled T2DM at baseline. Future research needs to address how to enhance community based programs so that they reach and benefit those most in need of resources and supports to improve metabolic control and associated clinical outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000469213 . Registered 16 June 2009.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2/complicaciones , Grupo Paritario , Evaluación de Programas y Proyectos de Salud , Características de la Residencia , Autocuidado , Apoyo Social , Anciano , Australia , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Consejo , Femenino , Procesos de Grupo , Educación en Salud , Promoción de la Salud , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Estudios Prospectivos , Calidad de Vida , Factores de RiesgoRESUMEN
INTRODUCTION: Cancer associated thromboembolism (TE) is common however the risk is heterogeneous and dynamic. AIM: To assess the TE risk profile of patients with Non-Small Cell Lung Cancer (NSCLC), though treatment phases, and generate a risk-stratified decision algorithm for appropriate thromboprophylaxis. MATERIALS AND METHODS: Single centre, prospective observational study, profiling NSCLC patients using clinical-, tumour- and treatment-related risk factors, in conjunction with an extensive thrombogenic biomarker panel, during treatment (surgery, chemotherapy, targeted therapy and/ or radiotherapy) and disease phases. Biomarkers include: FBC, APTT, PT, D-dimer, fibrinogen, FVIIIc, TM, TAT, vWF, prothrombin fragments 1+ 2, fibrin monomers, TEG, microparticles, OHP. Cancer management is per clinician discretion and/or concurrent interventional study protocol. Biomarkers are assessed at baseline; weeks 1, 4 and 12 after commencing cancer treatment; 3 monthly until 12 months. RESULTS: The interim cohort for analysis included 68 patients, 43 (63%) males, median age 67 years (range 43-67) and with median follow-up 5 months (range 0.2-11). Importantly, 21 patients (15% of patients screened) were ineligible for this study, having presented with TE at diagnosis of NSCLC, while a further 15 patients (15% of study cohort) developed TE while on study. Median time to TE on study was 2.4 months (range 0.1-7). Patients who developed TE demonstrated a biomarker profile indicative of a hypercoagulable state. Khorana score did not adequately stratify or predict TE in this cohort (PPV 20%, NPV 80%), with more than half of patients classified as low or intermediate risk (score 1 (44%), 2 (29%). However, D-dimer ≥1.44mg/L+Fibrinogen ≥4g/L+TEG-MA ≥69mm, as a single measurement at baseline, predicted TE (OR 4.2, p=0.005) and at 4-weeks after commencing cancer treatment (OR 6.7, p=0.005). Predictive power increased further, when considering longitudinal measurements from baseline to 12-weeks after commencing cancer treatment, with OR 14.0 (p<0.001) and PPV 40%, NPV 95%. Inclusion of other Khorana parameters in this model, did not improve predictive performance. CONCLUSIONS: Interim study results reveal a high TE risk among patients with NSCLC. Simple, routine, algorithmic thrombogenic biomarkers demonstrate the capacity to stratify risk and predict TE. Ongoing analyses with the planned larger cohort, expanded biomarker panel and longer follow-up, with longitudinal assessments, are likely to provide greater insight and enhance predicative power. The results will contribute to the development of a simple clinical and biomarker risk stratification tool, to facilitate real-time and dynamic decision-making for appropriate thromboprophylaxis strategies.
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To identify hospital-level factors associated with post-cardiac surgical pneumonia for assessing their impact on standardized infection rates (SIRs), we studied 43 691 patients in a cardiac surgery registry (2001-2011) in 16 hospitals. In a logistic regression model for pneumonia following cardiac surgery, associations with hospital characteristics were quantified with adjustment for patient characteristics while allowing for clustering of patients by hospital. Pneumonia rates varied from 0·7% to 12·4% across hospitals. Seventy percent of variability in the pneumonia rate was attributable to differences in hospitals in their long-term rates with the remainder attributable to within-hospital differences in rates over time. After adjusting for patient characteristics, the pneumonia rate was found to be higher in hospitals with more registered nurses (RNs)/100 intensive-care unit (ICU) admissions [adjusted odds ratio (aOR) 1·2, P = 0·006] and more RNs/available ICU beds (aOR 1·4, P < 0·001). Other hospital characteristics had no significant association with pneumonia. SIRs calculated on the basis of patient characteristics alone differed substantially from the same rates calculated on the basis of patient characteristics and the hospital characteristic of RNs/100 ICU admissions. Since SIRs using patient case-mix information are important for comparing rates between hospitals, the additional allowance for hospital characteristics can impact significantly on how hospitals compare.
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Procedimientos Quirúrgicos Cardíacos/efectos adversos , Infección Hospitalaria/epidemiología , Hospitales/estadística & datos numéricos , Neumonía/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Infección Hospitalaria/microbiología , Infección Hospitalaria/virología , Hospitalización/estadística & datos numéricos , Humanos , Modelos Logísticos , Persona de Mediana Edad , Nueva Zelanda/epidemiología , Neumonía/microbiología , Neumonía/virologíaRESUMEN
BACKGROUND: Age-related hearing loss (ARHL) is a leading cause of disability in the elderly. Low-grade inflammation and microvessel pathology may be responsible for initiating or exacerbating some of the hearing loss associated with aging. A growing body of evidence demonstrates an association of hearing loss with cognitive decline. A shared etiological pathway may include a role of inflammation, alongside vascular determinants. The ASPREE-HEARING study aims to determine whether low-dose aspirin decreases the progression of ARHL, and if so, whether this decrease in progression is also associated with retinal microvascular changes and/or greater preservation of cognitive function. DESIGN AND METHODS: A three year double-blind, randomized controlled trial of oral 100mg enteric-coated aspirin or matching placebo, enrolling 1262 Australians aged ≥70years with normal cognitive function and no overt cardiovascular disease. The primary outcome is the change in mean pure tone average hearing threshold (decibels) in the better ear, over a 3-year period. Secondary outcomes consist of changes in retinal microvascular indicators, and changes in cognitive function. Participants are recruited from a larger trial, ASPirin in Reducing Events in the Elderly (ASPREE), which is designed to assess whether daily low dose aspirin will extend disability-free life. DISCUSSION: ASPREE-HEARING will determine whether aspirin slows development or progression of ARHL, and will interrogate the relationship between inflammatory and microvascular mechanisms that may underlie the effects of aspirin on ARHL. This study will improve understanding of the patterns of comorbidity with, and the relationships between, aging and ARHL, alongside modeling the impacts of ARHL.
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Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Cognición , Presbiacusia/prevención & control , Vasos Retinianos/patología , Anciano , Anciano de 80 o más Años , Audiometría de Tonos Puros , Australia , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Masculino , Escala del Estado Mental , Percepción del HablaRESUMEN
BACKGROUND: The clinical behaviour and prognosis of primary melanomas harbouring BRAF mutations is not fully understood. OBJECTIVES: To investigate the effect of mutation status on primary melanoma growth rate and melanoma-specific survival (MSS). METHODS: A prospective cohort of 196 patients with stage I-III primary cutaneous melanoma were followed for a median of 92 months, pre-dating the institution of BRAF inhibitor therapy. Clinicopathological variables were correlated with mutation status and hazard ratios (HRs) estimated for MSS. RESULTS: Of 196 tumours, 77 (39.2%) were BRAF V600E, 10 (5.1%) BRAF V600K and 33 (16.8%) were NRAS mutant. BRAF V600E mutant melanomas were associated with favourable clinical characteristics and tended to be slower growing compared with BRAF V600K, NRAS mutant or BRAF/NRAS wild-type tumours (0.12 mm per month, 0.61 mm per month, 0.36 mm per month and 0.23 mm per month, respectively; P = 0.05). There were 39 melanoma deaths, and BRAF mutant melanomas were associated with poorer MSS in stage I-III disease [HR 2.60, 95% confidence interval (CI) 1.20-5.63; P = 0.02] and stage I-II disease (HR 3.39, 95% CI 1.12-10.22; P = 0.03) after adjusting for other prognostic variables. Considered separately, BRAF V600E mutant melanomas were strongly associated with MSS independently of thickness and nodal status (HR 3.89, 95% CI 1.67-9.09; P < 0.01) but BRAF V600K mutant tumours were not (HR 1.19, 95% CI 0.36-3.92; P = 0.77). CONCLUSIONS: The presence of a BRAF mutation does not necessarily 'drive' more rapid tumour growth but is associated with poorer MSS in patients with early-stage disease.
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Melanoma/genética , Mutación/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/genética , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patologíaRESUMEN
Lengthening of the conjoined tendon of the gastrocnemius aponeurosis and soleus fascia is frequently used in the treatment of equinus deformities in children and adults. The Vulpius procedure as described in most orthopaedic texts is a division of the conjoined tendon in the shape of an inverted V. However, transverse division was also described by Vulpius and Stoffel, and has been reported in some clinical studies. We studied the anatomy and biomechanics of transverse division of the conjoined tendon in 12 human cadavers (24 legs). Transverse division of the conjoined tendon resulted in predictable, controlled lengthening of the gastrocsoleus muscle-tendon unit. The lengthening achieved was dependent both on the level of the cut in the conjoined tendon and division of the midline raphé. Division at a proximal level resulted in a mean lengthening of 15.2 mm (sd 2.0, (12 to 19), which increased to 17.1 mm (sd 1.8, (14 to 20) after division of the midline raphé. Division at a distal level resulted in a mean lengthening of 21.0 mm (sd 2.0, (18 to 25), which increased to 26.4 mm (sd 1.4, (24 to 29) after division of the raphé. These differences were significant (p < 0.001).
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Músculo Esquelético/anatomía & histología , Músculo Esquelético/cirugía , Tenotomía/métodos , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Cadáver , Parálisis Cerebral/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Espasmo/cirugía , Tendones/fisiopatología , Tendones/cirugíaRESUMEN
INTRODUCTION: Thromboembolism is common in lung cancer. Current thromboprophylaxis guidelines lack specific recommendations for appropriate strategies in this high thrombotic risk patient cohort. We profiled lung cancer patients receiving anti-cancer therapy. Thromboembolism incidence and thromboembolism-related mortality rates are reported and we explored patient, disease, and treatment-related risk factors associated with higher thrombotic rates. METHODS: Retrospective review of lung cancer patients referred to a Comprehensive Cancer Centre between 01/07/2011 and 30/06/2012 for anti-cancer therapy. Data were collected from medical, pharmacy, pathology and diagnostic imaging electronic records. RESULTS: After a median follow up of 10 months (range: 0.03-32 months), 24/222 patients (10.8%) had developed radiologically confirmed thromboembolism; 131 events per 1000 person-years (95%CI 87-195). Thromboembolism occurred equally in patients with non-small cell and small cell lung cancer (10.8% and 10.5% respectively), and more frequently among patients with adenocarcinoma compared to squamous cell carcinoma (14.7% and 5.3% respectively). Chemotherapy-treated patients experienced thromboembolism more often than patients who did not receive chemotherapy (HR 5.7 95%CI 2.2-14.8). Radiotherapy was also associated with more frequent thromboembolism (HR 5.2 95%CI 2.0-13.2). New lung cancer diagnosis, presence of metastatic disease, second primary malignancy and Charlson Index ≥ 5 were also associated with higher rates of thromboembolism. Importantly, pharmacological thromboprophylaxis (P-TP) was not routinely or systematically prescribed for ambulant lung cancer patients during any treatment phase, at this institution. The majority (83%) of thromboembolic events occurred in the ambulatory care setting. CONCLUSION: Morbidity and mortality from thromboembolism occurs frequently in lung cancer. Thromboprophylaxis guidelines should be developed for the ambulatory care setting.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Neoplasias Pulmonares/complicaciones , Carcinoma Pulmonar de Células Pequeñas/complicaciones , Tromboembolia/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tromboembolia/etiologíaRESUMEN
The aim of this study was to evaluate the impact of serious sport and active recreation injury on 12-month physical activity levels. Adults admitted to hospital with sport and active recreation-related injuries, and captured by the Victorian Orthopaedic Trauma Outcomes Registry were recruited to the study. Changes between preinjury and 12 month post-injury physical activity was assessed using the short International Physical Activity Questionnaire (IPAQ). Independent demographic, injury, and hospital variables were assessed for associations with changes in physical activity levels, using multivariate linear regression. A total of 324 patients were recruited, of which 98% were followed up at 12 months. Mean short IPAQ scores decreased from 7650 METS (95% CI: 7180, 8120) preinjury to 3880 METS; (95% CI: 3530, 4250) post-injury, independent of functional recovery. Education level and occupation group were the only variables independently associated with changes in physical activity levels post-injury. These results highlighted that sport and active recreation injuries lead to significant reductions in physical activity levels. Hence, the prevention of sport and active recreation injuries is important when considering promotion of activity at a population level.
Asunto(s)
Traumatismos en Atletas/complicaciones , Traumatismos en Atletas/fisiopatología , Actividad Motora/fisiología , Recreación , Adolescente , Adulto , Anciano , Industria de la Construcción , Escolaridad , Femenino , Estudios de Seguimiento , Humanos , Industrias , Masculino , Equivalente Metabólico , Persona de Mediana Edad , Ocupaciones , Recuperación de la Función , Encuestas y Cuestionarios , Victoria , Adulto JovenRESUMEN
The generalizability of a prediction model from North America for incident nosocomial pneumonia following coronary artery bypass graft surgery was assessed for 23247 patients on the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) registry. The performance of the North American model was evaluated using measures of calibration and discrimination. The model had reasonable discrimination (area under the receiver-operating characteristic curve, AUC=0·69), but unsatisfactory calibration (Hosmer-Lemeshow test, P<0·001) in the ANZSCTS patients. An update of the model coefficients yielded a model with AUC=0·71 and good calibration (P=0·46).