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1.
PLoS Med ; 21(3): e1004358, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38437214

RESUMEN

BACKGROUND: Population mental health in the United Kingdom (UK) has deteriorated, alongside worsening socioeconomic conditions, over the last decade. Policies such as Universal Basic Income (UBI) have been suggested as an alternative economic approach to improve population mental health and reduce health inequalities. UBI may improve mental health (MH), but to our knowledge, no studies have trialled or modelled UBI in whole populations. We aimed to estimate the short-term effects of introducing UBI on mental health in the UK working-age population. METHODS AND FINDINGS: Adults aged 25 to 64 years were simulated across a 4-year period from 2022 to 2026 with the SimPaths microsimulation model, which models the effects of UK tax/benefit policies on mental health via income, poverty, and employment transitions. Data from the nationally representative UK Household Longitudinal Study were used to generate the simulated population (n = 25,000) and causal effect estimates. Three counterfactual UBI scenarios were modelled from 2023: "Partial" (value equivalent to existing benefits), "Full" (equivalent to the UK Minimum Income Standard), and "Full+" (retaining means-tested benefits for disability, housing, and childcare). Likely common mental disorder (CMD) was measured using the General Health Questionnaire (GHQ-12, score ≥4). Relative and slope indices of inequality were calculated, and outcomes stratified by gender, age, education, and household structure. Simulations were run 1,000 times to generate 95% uncertainty intervals (UIs). Sensitivity analyses relaxed SimPaths assumptions about reduced employment resulting from Full/Full+ UBI. Partial UBI had little impact on poverty, employment, or mental health. Full UBI scenarios practically eradicated poverty but decreased employment (for Full+ from 78.9% [95% UI 77.9, 79.9] to 74.1% [95% UI 72.6, 75.4]). Full+ UBI increased absolute CMD prevalence by 0.38% (percentage points; 95% UI 0.13, 0.69) in 2023, equivalent to 157,951 additional CMD cases (95% UI 54,036, 286,805); effects were largest for men (0.63% [95% UI 0.31, 1.01]) and those with children (0.64% [95% UI 0.18, 1.14]). In our sensitivity analysis assuming minimal UBI-related employment impacts, CMD prevalence instead fell by 0.27% (95% UI -0.49, -0.05), a reduction of 112,228 cases (95% UI 20,783, 203,673); effects were largest for women (-0.32% [95% UI -0.65, 0.00]), those without children (-0.40% [95% UI -0.68, -0.15]), and those with least education (-0.42% [95% UI -0.97, 0.15]). There was no effect on educational mental health inequalities in any scenario, and effects waned by 2026. The main limitations of our methods are the model's short time horizon and focus on pathways from UBI to mental health solely via income, poverty, and employment, as well as the inability to integrate macroeconomic consequences of UBI; future iterations of the model will address these limitations. CONCLUSIONS: UBI has potential to improve short-term population mental health by reducing poverty, particularly for women, but impacts are highly dependent on whether individuals choose to remain in employment following its introduction. Future research modelling additional causal pathways between UBI and mental health would be beneficial.


Asunto(s)
Renta , Salud Mental , Adulto , Masculino , Niño , Humanos , Femenino , Estudios Longitudinales , Reino Unido/epidemiología , Inequidades en Salud
2.
Milbank Q ; 102(1): 141-182, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38294094

RESUMEN

Policy Points Income is thought to impact a broad range of health outcomes. However, whether income inequality (how unequal the distribution of income is in a population) has an additional impact on health is extensively debated. Studies that use multilevel data, which have recently increased in popularity, are necessary to separate the contextual effects of income inequality on health from the effects of individual income on health. Our systematic review found only small associations between income inequality and poor self-rated health and all-cause mortality. The available evidence does not suggest causality, although it remains methodologically flawed and limited, with very few studies using natural experimental approaches or examining income inequality at the national level. CONTEXT: Whether income inequality has a direct effect on health or is only associated because of the effect of individual income has long been debated. We aimed to understand the association between income inequality and self-rated health (SRH) and all-cause mortality (mortality) and assess if these relationships are likely to be causal. METHODS: We searched Medline, ISI Web of Science, Embase, and EconLit (PROSPERO: CRD42021252791) for studies considering income inequality and SRH or mortality using multilevel data and adjusting for individual-level socioeconomic position. We calculated pooled odds ratios (ORs) for poor SRH and relative risk ratios (RRs) for mortality from random-effects meta-analyses. We critically appraised included studies using the Risk of Bias in Nonrandomized Studies - of Interventions tool. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework and causality using Bradford Hill (BH) viewpoints. FINDINGS: The primary meta-analyses included 2,916,576 participants in 38 cross-sectional studies assessing SRH and 10,727,470 participants in 14 cohort studies of mortality. Per 0.05-unit increase in the Gini coefficient, a measure of income inequality, the ORs and RRs (95% confidence intervals) for SRH and mortality were 1.06 (1.03-1.08) and 1.02 (1.00-1.04), respectively. A total of 63.2% of SRH and 50.0% of mortality studies were at serious risk of bias (RoB), resulting in very low and low certainty ratings, respectively. For SRH and mortality, we did not identify relevant evidence to assess the specificity or, for SRH only, the experiment BH viewpoints; evidence for strength of association and dose-response gradient was inconclusive because of the high RoB; we found evidence in support of temporality and plausibility. CONCLUSIONS: Increased income inequality is only marginally associated with SRH and mortality, but the current evidence base is too methodologically limited to support a causal relationship. To address the gaps we identified, future research should focus on income inequality measured at the national level and addressing confounding with natural experiment approaches.


Asunto(s)
Estado de Salud , Renta , Humanos , Estudios Transversales
3.
Psychol Med ; 53(13): 6271-6279, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36453184

RESUMEN

BACKGROUND: Employment and income are important determinants of mental health (MH), but the extent that unemployment effects are mediated by reduced income is unclear. We estimated the total effect (TE) of unemployment on MH and the controlled direct effect (CDE) not acting via income. METHODS: We included adults 25-64 years from nine waves of the UK Household Longitudinal Study (n = 45 497/obs = 202 297). Unemployment was defined as not being in paid employment; common mental disorder (CMD) was defined as General Health Questionnaire-12 score ≥4. We conducted causal mediation analysis using double-robust marginal structural modelling, estimating odds ratios (OR) and absolute differences for effects of unemployment on CMD in the same year, before (TE) and after (CDE) blocking the income pathway. We calculated percentage mediation by income, with bootstrapped standard errors. RESULTS: The TE of unemployment on CMD risk was OR 1.66 (95% CI 1.57-1.76), with 7.09% (6.21-7.97) absolute difference in prevalence; equivalent CDEs were OR 1.55 (1.46-1.66) and 6.08% (5.13-7.03). Income mediated 14.22% (8.04-20.40) of the TE. Percentage mediation was higher for job losses [15.10% (6.81-23.39)] than gains [8.77% (0.36-17.19)]; it was lowest for those 25-40 years [7.99% (-2.57 to 18.51)] and in poverty [2.63% (-2.22 to 7.49)]. CONCLUSIONS: A high proportion of the short-term effect of unemployment on MH is not explained by income, particularly for younger people and those in poverty. Population attributable fractions suggested 16.49% of CMD burden was due to unemployment, with 13.90% directly attributable to job loss rather than resultant income changes. Similar analytical approaches could explore how this differs across contexts, by other factors, and consider longer-term effects.


Asunto(s)
Salud Mental , Desempleo , Adulto , Humanos , Análisis de Mediación , Estudios Longitudinales , Renta , Reino Unido/epidemiología
4.
Semin Respir Crit Care Med ; 44(2): 287-296, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36649736

RESUMEN

Nontuberculous mycobacteria (NTM) are a group of mycobacteria which represent opportunistic pathogens that are of increasing concern in people with cystic fibrosis (pwCF). The acquisition has been traditionally though to be from environmental sources, though recent work has suggested clustered clonal infections do occur and transmission potential demonstrated among pwCF attending CF specialist centers. Guidelines for the screening, diagnosis, and identification of NTM and management of pwCF have been published. The emergence of CF-specific therapies, in particular cystic fibrosis transmembrane regulator (CFTR) modulator drugs, have led to significant improvement in the health and well-being of pwCF and may lead to challenges in sampling the lower respiratory tract including to screen for NTM. This review highlights the epidemiology, modes of acquisition, screening and diagnosis, therapeutic approaches in the context of improved clinical status for pwCF, and the clinical application of CFTR modulator therapies.


Asunto(s)
Fibrosis Quística , Infecciones por Mycobacterium no Tuberculosas , Humanos , Fibrosis Quística/tratamiento farmacológico , Micobacterias no Tuberculosas , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/epidemiología
5.
BMC Pulm Med ; 23(1): 323, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37658311

RESUMEN

BACKGROUND: Cystic fibrosis (CF) is a life-limiting disorder that is characterised by respiratory tract inflammation that is mediated by a range of microbial pathogens. Small colony variants (SCVs) of common respiratory pathogens are being increasingly recognised in CF. The aim of this systematic review is to investigate the prevalence of SCVs, clinical characteristics and health outcomes for patients with CF, and laboratory diagnostic features of SCVs compared to non-small colony variants (NCVs) for a range of Gram-positive and Gram-negative respiratory pathogens. METHODS: A literature search was conducted (PubMed, Web of Science, Embase and Scopus) in April 2020 to identify articles of interest. Data pertaining to demographic characteristics of participants, diagnostic criteria of SCVs, SCV prevalence and impact on lung function were extracted from included studies for analysis. RESULTS: Twenty-five of 673 studies were included in the systematic review. Individuals infected with SCVs of Staphylococcus aureus (S. aureus) were more likely to have had prior use of the broad-spectrum antibiotic trimethoprim sulfamethoxazole (p < 0.001), and the prevalence of SCVs in patients infected with S. aureus was estimated to be 19.3% (95% CI: 13.5% to 25.9%). Additionally, patients infected with SCVs of Gram-negative and Gram-positive pathogens were identified to have a lower forced expiratory volume in one second percentage predicted (-16.8, 95% CI: -23.2 to -10.4) than those infected by NCVs. Gram-positive SCVs were commonly described as small and non-haemolytic, grown on Mannitol salt or blood agar for 24 h at 35°C and confirmed using tube coagulase testing. CONCLUSION: The findings of this systematic review demonstrate that SCVs of S. aureus have a high prevalence in the CF community, and that the occurrence of SCVs in Gram-positive and Gram-negative pathogens is linked to poorer respiratory function. Further investigation is necessary to determine the effect of infection by SCVs on the CF population.


Asunto(s)
Fibrosis Quística , Humanos , Staphylococcus aureus , Pacientes , Antibacterianos/uso terapéutico , Medios de Cultivo
6.
Immun Ageing ; 19(1): 11, 2022 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-35193613

RESUMEN

γδ T cells are a highly versatile immune lineage involved in host defense and homeostasis, but questions remain around their heterogeneity, precise function and role during health and disease. We used multi-parametric flow cytometry, dimensionality reduction, unsupervised clustering, and self-organizing maps (SOM) to identify novel γδ T cell naïve/memory subsets chiefly defined by CD161 expression levels, a surface membrane receptor that can be activating or suppressive. We used middle-to-old age individuals given immune blockade is commonly used in this population. Whilst most Vδ1+subset cells exhibited a terminal differentiation phenotype, Vδ1- subset cells showed an early memory phenotype. Dimensionality reduction revealed eight γδ T cell clusters chiefly diverging through CD161 expression with CD4 and CD8 expression limited to specific subpopulations. Comparison of matched healthy elderly individuals to bronchiectasis patients revealed elevated Vδ1+ terminally differentiated effector memory cells in patients potentially linking this population with chronic proinflammatory disease.

7.
Australas J Dermatol ; 63(3): e222-e225, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35666757

RESUMEN

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous tumour of neuroendocrine cell origin, which can grow rapidly and metastasise early. Localised disease is treated with surgery and radiotherapy. Disease that reaches a more advanced stage can be treated with a variety of different treatment modalities including surgery, radiotherapy, chemotherapy, radionuclide therapy, immunotherapy, and intralesional therapy. We report a case of a patient who had exhausted all local and systemic treatment options and who subsequently had an exceptional response to intralesional injection of Talimogene laherparepvec (TVEC).


Asunto(s)
Carcinoma de Células de Merkel , Melanoma , Viroterapia Oncolítica , Neoplasias Cutáneas , Productos Biológicos , Carcinoma de Células de Merkel/terapia , Herpesvirus Humano 1 , Humanos , Melanoma/patología , Viroterapia Oncolítica/métodos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Resultado del Tratamiento
8.
Clin Infect Dis ; 73(1): e256-e259, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32910814

RESUMEN

Adverse events are frequent in nontuberculous mycobacteria pulmonary disease treatment, but evidence to support their management is scarce. An expert panel survey on management of adverse events shows consistent opinions on management of hepatoxicity, ocular toxicity, ototoxicity, tinnitus, and gastrointestinal upset. These opinions can provide assistance in individual patient management decisions.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Infección por Mycobacterium avium-intracellulare , Humanos , Enfermedades Pulmonares/inducido químicamente , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Micobacterias no Tuberculosas
9.
FASEB J ; 34(4): 5697-5714, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32141144

RESUMEN

Type 2 diabetes (T2D) manifests from inadequate glucose control due to insulin resistance, hypoinsulinemia, and deteriorating pancreatic ß-cell function. The pro-inflammatory factor Activin has been implicated as a positive correlate of severity in T2D patients, and as a negative regulator of glucose uptake by skeletal muscle, and of pancreatic ß-cell phenotype in mice. Accordingly, we sought to determine whether intervention with the Activin antagonist Follistatin can ameliorate the diabetic pathology. Here, we report that an intravenous Follistatin gene delivery intervention with tropism for striated muscle reduced the serum concentrations of Activin B and improved glycemic control in the db/db mouse model of T2D. Treatment reversed the hyperglycemic progression with a corresponding reduction in the percentage of glycated-hemoglobin to levels similar to lean, healthy mice. Follistatin gene delivery promoted insulinemia and abundance of insulin-positive pancreatic ß-cells, even when treatment was administered to mice with advanced diabetes, supporting a mechanism for improved glycemic control associated with maintenance of functional ß-cells. Our data demonstrate that single-dose intravascular Follistatin gene delivery can ameliorate the diabetic progression and improve prognostic markers of disease. These findings are consistent with other observations of Activin-mediated mechanisms exerting deleterious effects in models of obesity and diabetes, and suggest that interventions that attenuate Activin signaling could help further understanding of T2D and the development of novel T2D therapeutics.


Asunto(s)
Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/terapia , Folistatina/genética , Técnicas de Transferencia de Gen , Terapia Genética , Control Glucémico , Hiperglucemia/terapia , Administración Intravenosa , Animales , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Folistatina/administración & dosificación , Hiperglucemia/genética , Resistencia a la Insulina , Ratones
10.
Intern Med J ; 51(3): 327-333, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33738950

RESUMEN

The treatment options for patients with melanoma have expanded significantly over the past decade. In particular, the use of targeted therapy and immunotherapy has dramatically transformed the outlook for patients with advanced disease. These treatments are now being utilised as adjuvant therapy for patients with earlier stage melanoma after surgical resection. We review the latest updates for melanoma staging, surgical resection, radiotherapy and systemic therapies.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Quimioterapia Adyuvante , Terapia Combinada , Humanos , Factores Inmunológicos/uso terapéutico , Inmunoterapia , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico
11.
Intern Med J ; 50(7): 865-868, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32656984

RESUMEN

The optimal duration of immunotherapy treatment for cancer patients is unknown. As the survival data from early immunotherapy trials mature we are beginning to appreciate how durable responses can be post-discontinuation. The purpose of this brief communication is to comment on treatment duration of immunotherapy in patients with melanoma and non-small cell lung cancer and to provide practice guidance in support of discontinuation.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Melanoma , Carcinoma de Pulmón de Células no Pequeñas/terapia , Humanos , Inmunoterapia , Neoplasias Pulmonares/terapia , Melanoma/terapia
12.
Eur Respir J ; 54(1)2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30880280

RESUMEN

Treatment of Mycobacterium abscessus pulmonary disease (MAB-PD), caused by M. abscessus subsp. abscessus, M. abscessus subsp. massiliense or M. abscessus subsp. bolletii, is challenging.We conducted an individual patient data meta-analysis based on studies reporting treatment outcomes for MAB-PD to clarify treatment outcomes for MAB-PD and the impact of each drug on treatment outcomes. Treatment success was defined as culture conversion for ≥12 months while on treatment or sustained culture conversion without relapse until the end of treatment.Among 14 eligible studies, datasets from eight studies were provided and a total of 303 patients with MAB-PD were included in the analysis. The treatment success rate across all patients with MAB-PD was 45.6%. The specific treatment success rates were 33.0% for M. abscessus subsp. abscessus and 56.7% for M. abscessus subsp. massiliense For MAB-PD overall, the use of imipenem was associated with treatment success (adjusted odds ratio (aOR) 2.65, 95% CI 1.36-5.10). For patients with M. abscessus subsp. abscessus, the use of azithromycin (aOR 3.29, 95% CI 1.26-8.62), parenteral amikacin (aOR 1.44, 95% CI 1.05-1.99) or imipenem (aOR 7.96, 95% CI 1.52-41.6) was related to treatment success. For patients with M. abscessus subsp. massiliense, the choice among these drugs was not associated with treatment outcomes.Treatment outcomes for MAB-PD are unsatisfactory. The use of azithromycin, amikacin or imipenem was associated with better outcomes for patients with M. abscessus subsp. abscessus.


Asunto(s)
Antibacterianos/uso terapéutico , Enfermedades Pulmonares/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Mycobacterium abscessus/efectos de los fármacos , Anciano , Amicacina , Azitromicina , Claritromicina , Bases de Datos Factuales , Femenino , Humanos , Imipenem , Enfermedades Pulmonares/microbiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad
13.
BMC Infect Dis ; 19(1): 847, 2019 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-31615435

RESUMEN

BACKGROUND: Salmonella outbreaks in childcare facilities are relatively rare, most often occurring secondary to contaminated food products or poor infection control practices. We report an outbreak of Salmonella Saintpaul at a pre-school facility in Ayrshire, Scotland with atypical clinical and epidemiological features. METHODS: Following notification of the initial two cases, the multi-disciplinary Incident Management Team initiated enhanced active case finding and two environmental inspections of the site, including food preparation areas. Parent and staff interviews were conducted by the Public Health department covering attendance, symptomatology and risk factors for all probable and confirmed cases. Microbiological testing of stool samples and the facility water tank was conducted. Whole Genome Sequencing (WGS) was performed for positive stool samples at the national reference laboratory. Infection control measures were introduced iteratively due to the atypical progression of the outbreak. RESULTS: There were 15 confirmed cases and 3 children admitted to hospital during the outbreak. However, 35.7% of cases reported extremely mild symptoms. The attack rate was 15.2%, and age of affected children ranged from 18 to 58 months (mean 35 months). All cases were the same Multilocus Sequence Type (MLST50). Epidemiological investigation strongly suggested person-to-person spread within the facility. Existing infection control practices were found to be of a high standard, but introduction of additional evidence-based control measures was inadequate in halting transmission. Facility staff reported concerns about lack of parental disclosure of gastrointestinal symptoms, particularly where these were mild, with 50.0% of cases having attended while symptomatic against public health advice. Voluntary two-week closure of the facility was implemented to halt transmission, following which there were no new cases. WGS results were unavailable until after the decision was taken to close the facility. CONCLUSIONS: This is the first reported instance of a Salmonella Saintpaul outbreak at a childcare facility, or where person-to-person transmission is indicated. Clinicians should consider the influence of parental under-reporting on gastrointestinal outbreaks in childcare settings, particularly where perceived severity is low and financial or social pressures to attend work may reduce compliance. WGS cannot yet replace conventional microbiological techniques during short, localised outbreaks due to delays receiving results.


Asunto(s)
Infecciones por Salmonella/diagnóstico , Salmonella/aislamiento & purificación , Guarderías Infantiles , Preescolar , ADN Bacteriano/química , ADN Bacteriano/metabolismo , Brotes de Enfermedades , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Tipificación de Secuencias Multilocus , Salud Pública , Salmonella/genética , Infecciones por Salmonella/epidemiología , Escocia/epidemiología , Secuenciación Completa del Genoma
14.
Respirology ; 24(10): 980-987, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30919511

RESUMEN

BACKGROUND AND OBJECTIVE: Aerosol transmission of Pseudomonas aeruginosa has been suggested as a possible mode of respiratory infection spread in patients with cystic fibrosis (CF); however, whether this occurs in other suppurative lung diseases is unknown. Therefore, we aimed to determine if (i) patients with bronchiectasis (unrelated to CF) or chronic obstructive pulmonary disease (COPD) can aerosolize P. aeruginosa during coughing and (ii) if genetically indistinguishable (shared) P. aeruginosa strains are present in these disease cohorts. METHODS: People with bronchiectasis or COPD and P. aeruginosa respiratory infection were recruited for two studies. Aerosol study: Participants (n = 20) underwent cough testing using validated cough rigs to determine the survival of P. aeruginosa aerosols in the air over distance and duration. Genotyping study: P. aeruginosa sputum isolates (n = 95) were genotyped using the iPLEX20SNP platform, with a subset subjected to the enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) assay to ascertain their genetic relatedness. RESULTS: Aerosol study: Overall, 7 of 20 (35%) participants released P. aeruginosa cough aerosols during at least one of the cough aerosol tests. These cough aerosols remained viable for 4 m from the source and for 15 min after coughing. The mean total aerosol count of P. aeruginosa at 2 m was two colony-forming units. Typing study: No shared P. aeruginosa strains were identified. CONCLUSION: Low viable count of P. aeruginosa cough aerosols and a lack of shared P. aeruginosa strains observed suggest that aerosol transmission of P. aeruginosa is an unlikely mode of respiratory infection spread in patients with bronchiectasis and COPD.


Asunto(s)
Aerosoles , Bronquiectasia/complicaciones , Tos/microbiología , Infecciones por Pseudomonas/complicaciones , Pseudomonas aeruginosa , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Anciano , Recuento de Colonia Microbiana , Tos/etiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/aislamiento & purificación , Esputo/microbiología
15.
Lung ; 197(6): 803-810, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31691027

RESUMEN

PURPOSE: Australian data regarding the management of patients with bronchiectasis is scarce. We sought to compare the management of adults with bronchiectasis attending tertiary Australian centres with recent national and international guidelines. METHODS: The Australian Bronchiectasis Registry is a centralised database of patients with radiologically confirmed bronchiectasis unrelated to cystic fibrosis recruited from 14 tertiary Australian hospitals. We excluded children (<18 years) and those with incomplete data, leaving 589 adults for cross-sectional analyses. We compared the proportion of patients receiving certain therapies, as compared to the proportion eligible for those treatments according to the current guidelines and baseline clinical information available from the registry. RESULTS: Pulmonary rehabilitation was attended by 22%, although it was indicated in 67% of the cohort. Airway clearance was undertaken in 52% of patients, although 71% reported chronic productive cough. Sputum bacterial culture results were available for 59%, and mycobacterial culture results were available for 29% of the cohort. Inhaled antibiotics were used in half of potentially eligible patients. Despite guideline recommendations against routine use, inhaled corticosteroids were used in 48% of patients. Long-term macrolides were used in 28% of participants. CONCLUSIONS: Discrepancies exist between guideline recommendations and real-world treatment of bronchiectasis in Australia, even in tertiary centres. These findings suggest the need for increased patient referral to pulmonary rehabilitation, increased attention to airway clearance, increased collection of sputum samples (especially for mycobacterial culture) and rationalisation of inhaled corticosteroid use. These findings encourage a review of treatment access and will inform ongoing education to promote evidence-based care for people living with bronchiectasis.


Asunto(s)
Corticoesteroides/uso terapéutico , Antibacterianos/uso terapéutico , Bronquiectasia/terapia , Medicina Basada en la Evidencia , Adhesión a Directriz/estadística & datos numéricos , Modalidades de Fisioterapia/estadística & datos numéricos , Terapia Respiratoria/estadística & datos numéricos , Centros de Atención Terciaria , Administración por Inhalación , Anciano , Australia , Bronquiectasia/complicaciones , Broncodilatadores/uso terapéutico , Femenino , Infecciones por Haemophilus/complicaciones , Infecciones por Haemophilus/tratamiento farmacológico , Accesibilidad a los Servicios de Salud , Humanos , Macrólidos/uso terapéutico , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/tratamiento farmacológico
16.
Am J Respir Crit Care Med ; 198(12): 1559-1569, 2018 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-30216086

RESUMEN

Rationale: Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives: To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Methods: Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite at least 6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS + GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture conversion, defined as three consecutive monthly MAC-negative sputum cultures by Month 6. Measurements and Main Results: Enrolled patients (ALIS + GBT, n = 224; GBT-alone, n = 112) were a mean 64.7 years old and 69.3% female. Most had underlying bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with ALIS + GBT and 10 of 112 (8.9%) with GBT alone (odds ratio, 4.22; 95% confidence interval, 2.08-8.57; P < 0.001). Patients in the ALIS + GBT arm versus GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% confidence interval, 2.00-7.60). Respiratory adverse events (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients receiving ALIS + GBT and 50.0% receiving GBT alone; serious treatment-emergent adverse events occurred in 20.2% and 17.9% of patients, respectively. Conclusions: Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved significantly greater culture conversion by Month 6 than GBT alone, with comparable rates of serious adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT02344004).


Asunto(s)
Amicacina/uso terapéutico , Antibacterianos/uso terapéutico , Enfermedades Pulmonares/tratamiento farmacológico , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Administración por Inhalación , Amicacina/administración & dosificación , Antibacterianos/administración & dosificación , Femenino , Humanos , Liposomas , Enfermedades Pulmonares/microbiología , Masculino , Persona de Mediana Edad , Complejo Mycobacterium avium , Estudios Prospectivos , Resultado del Tratamiento
17.
Lancet ; 399(10331): 1210-1211, 2022 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-35298904
18.
Emerg Infect Dis ; 23(11): 1919-1922, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-29048290

RESUMEN

Nontuberculous mycobacteria are human pathogens with increasing incidence and prevalence worldwide. Mycobacterium shimoidei is a rare cause of pulmonary disease, with only 15 cases previously reported. This series documents an additional 23 cases of M. shimoidei from Queensland, Australia, and highlights the pathogenicity and clinical role of this species.


Asunto(s)
Enfermedades Pulmonares/microbiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas/aislamiento & purificación , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Queensland/epidemiología
19.
Immunogenetics ; 69(5): 287-293, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28233049

RESUMEN

Despite widespread exposure to potentially pathogenic mycobacteria present in the soil and in domestic water supplies, it is not clear why only a small proportion of individuals contract pulmonary nontuberculous mycobacterial (NTM) infections. Here, we explore the impact of polymorphisms within three genes: P2X ligand gated ion channel 7 (P2X7R), P2X ligand gated ion channel 4 (P2X4R) and calcium/calmodulin-dependent protein kinase kinase 2 beta (CAMKK2) on susceptibility. Thirty single nucleotide polymorphisms (SNPs) were genotyped in NTM patients (n = 124) and healthy controls (n = 229). Weak associations were found between individual alleles in P2X7R and disease but were not significant in multivariate analyses adjusted to account for gender. Haplotypes spanning the three genes were derived using the fastPHASE algorithm. This yielded 27 haplotypes with frequencies >1% and accounting for 63.3% of the combined cohort. In univariate analyses, seven of these haplotypes displayed associations with NTM disease above our preliminary cut-off (p ≤ 0.20). When these were carried forward in a logistic regression model, gender and one haplotype (SH95) were independently associated with the disease (model p < 0.0001; R 2  = 0.05). Examination of individual alleles within these haplotypes implicated P2X7R and CAMKK2 in pathways affecting pulmonary NTM disease.


Asunto(s)
Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/genética , Enfermedades Pulmonares/genética , Infecciones por Mycobacterium no Tuberculosas/genética , Mycobacterium , Polimorfismo de Nucleótido Simple , Receptores Purinérgicos P2X4/genética , Receptores Purinérgicos P2X7/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/microbiología , Masculino , Persona de Mediana Edad , Mycobacterium/patogenicidad , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/microbiología
20.
Med J Aust ; 206(6): 251-257, 2017 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-28359007

RESUMEN

OBJECTIVE: To determine whether the prevalence of physical comorbidities in Australian Vietnam War veterans with post-traumatic stress disorder (PTSD) is higher than in trauma-exposed veterans without PTSD. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of the health status (based on self-reported and objective clinical assessments) of 298 Australian Vietnam War veterans enrolled by the Gallipoli Medical Research Institute (Brisbane) during February 2014 - July 2015, of whom 108 were confirmed as having had PTSD and 106 served as trauma-exposed control participants.Main outcomes and measures: Diagnostic psychiatric interview and psychological assessments determined PTSD status, trauma exposure, and comorbid psychological symptoms. Demographic data, and medical and sleep history were collected; comprehensive clinical examination, electrocardiography, spirometry, liver transient elastography, and selected pathology assessments and diagnostic imaging were performed. Outcomes associated with PTSD were identified; regression analysis excluded the effects of potentially confounding demographic and risk factors and comorbid symptoms of depression and anxiety. RESULTS: The mean total number of comorbidities was higher among those with PTSD (17.7; SD, 6.1) than in trauma-exposed controls (14.1; SD, 5.2; P < 0.001). For 24 of 171 assessed clinical outcomes, morbidity was greater in the PTSD group, including for conditions of the gastrointestinal, hepatic, cardiovascular, and respiratory systems, sleep disorders, and laboratory pathology measures. In regression analyses including demographic factors, PTSD remained positively associated with 17 adverse outcomes; after adjusting for the severity of depressive symptoms, it remained significantly associated with ten. CONCLUSION: PTSD in Australian Vietnam veterans is associated with comorbidities in several organ systems, independent of trauma exposure. A comprehensive approach to the health care of veterans with PTSD is needed.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Enfermedades del Sistema Digestivo/epidemiología , Trastornos Mentales/epidemiología , Enfermedades Respiratorias/epidemiología , Trastornos por Estrés Postraumático/epidemiología , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Enfermedades Cardiovasculares/psicología , Estudios de Casos y Controles , Comorbilidad , Estudios Transversales , Enfermedades del Sistema Digestivo/psicología , Humanos , Masculino , Trastornos Mentales/psicología , Persona de Mediana Edad , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/psicología , Exposición Profesional , Prevalencia , Análisis de Regresión , Enfermedades Respiratorias/psicología , Trastornos por Estrés Postraumático/etiología , Veteranos/psicología , Veteranos/estadística & datos numéricos , Guerra de Vietnam
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