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1.
Chest ; 157(3): 558-565, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31759961

RESUMO

BACKGROUND: Heroin smokers have high rates of COPD, respiratory morbidity, hospital admission, and mortality. We assessed the natural history of symptoms and lung function in this population over time. METHODS: A cohort of heroin smokers with COPD was followed for 18 to 24 months. At baseline and follow-up, respiratory symptoms were measured by the Medical Research Council Dyspnea Scale (MRC) and the COPD Assessment Tool (CAT), and postbronchodilator spirometry was performed. Frequency of health-care-seeking episodes was extracted from routine health records. Parametric, nonparametric, and linear regression models were used to analyze the change in symptoms and lung function over time. RESULTS: Of 372 participants originally recruited, 161 were assessed at follow-up (mean age, 51.0 ± 5.3 years; 74 women [46%]) and 106 participants completed postbronchodilator spirometry. All participants were current or previous heroin smokers, and 122 (75.8%) had smoked crack. Symptoms increased over time (MRC score increased by 0.48 points per year, P < .001; CAT score increased by 1.60 points per year, P < .001). FEV1 declined annually by 90 ± 190 mL (P < .001). This deterioration was not associated with change in tobacco or heroin smoking status or use of inhaled medications. CONCLUSIONS: Heroin smokers experience a high and increasing burden of chronic respiratory symptoms and a decline in FEV1 that exceeds the normal age-related decline observed among tobacco smokers with COPD and healthy nonsmokers. Targeted COPD diagnostic and treatment services hosted within opiate substitution services could benefit this vulnerable, relatively inaccessible, and underserved group of people.


Assuntos
Dependência de Heroína/fisiopatologia , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fumar Produtos sem Tabaco/fisiopatologia , Broncodilatadores/uso terapêutico , Fumar Cigarros/epidemiologia , Fumar Cigarros/fisiopatologia , Fumar Cocaína/epidemiologia , Fumar Cocaína/fisiopatologia , Estudos de Coortes , Progressão da Doença , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Volume Expiratório Forçado , Dependência de Heroína/tratamento farmacológico , Dependência de Heroína/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Estudos Longitudinais , Masculino , Fumar Maconha/epidemiologia , Fumar Maconha/fisiopatologia , Programas de Rastreamento , Pessoa de Meia-Idade , Tratamento de Substituição de Opiáceos , Atenção Primária à Saúde/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Índice de Gravidade de Doença , Fumar Produtos sem Tabaco/epidemiologia , Espirometria
2.
J Allergy Clin Immunol Pract ; 7(2): 548-553.e5, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30170164

RESUMO

BACKGROUND: Patients with asthma who present with lower respiratory tract infections (LRTIs) often receive antibiotics. There is uncertainty about the need for and consequences of antibiotic administration. OBJECTIVE: To describe the demographic characteristics of and antibiotic prescriptions for adult patients with asthma with LRTI and investigate factors associated with repeat antibiotic courses. METHODS: We analyzed prescriptions of antibiotics for LRTIs in UK primary care from 2010 to 2015 using the Optimum Care Database. The primary outcome was a second antibiotic prescription for an LRTI code within 14 days of index prescription, as a proxy of initial treatment failure. A model for repeat prescriptions was derived using univariable and multivariable logistic regression analyses. RESULTS: We assessed 28,289 cases with complete data sets, 6.5% of which received a second antibiotic course. Amoxicillin and clarithromycin respectively were used most commonly as index and second agents. The most frequent course length was 7 days for both index and repeat prescriptions. Multivariable analysis demonstrated that age, index antibiotic and duration, smoking status, location, and number of consultations and oral steroid courses in the previous year were significantly associated with repeat prescriptions. The derived model predicted the binary outcome adequately (Cox-Snell R2, 0.012; area under curve, 0.62; 95% CI, 0.61-0.63). Comorbidities, vaccinations, asthma treatment, and number of exacerbations were significant only in the univariable analysis. CONCLUSIONS: The current index prescribing preference of 7 days of amoxicillin correlated to fewer repeat courses. Baseline asthma treatment was not associated with risk of further prescriptions. Antibiotic administration in older patients with a smoking history could be a target for future studies.


Assuntos
Antibacterianos/administração & dosagem , Asma/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Infecções Respiratórias/tratamento farmacológico , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde
3.
Eur Clin Respir J ; 5(1): 1529535, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30370019

RESUMO

Antibiotic prescriptions for lower respiratory tract infections occur commonly in primary care but there is uncertainty about the most effective initial treatment strategy. Both increasing antimicrobial resistance and awareness of preventable harm from medicines make resolving this uncertainty a priority. Pragmatic, real-life epidemiological investigations are needed to inform future interventional studies. In this cross-sectional database study we analysed antibiotic prescriptions for non-pneumonic, lower respiratory tract infections (LRTI) in primary care as captured in the Optimum Care Database from 1984 to 2017. The primary outcome was a second antibiotic prescription for a LRTI code within 14 days of index prescription, the secondary outcome further antibiotic prescription for any indication. Only individuals without chronic respiratory diseases were included. We conducted univariable analysis to identify factors associated with repeat prescriptions and generate hypotheses for forthcoming projects. We analysed 367,188 index prescriptions for LRTI. Amoxicillin was the commonest used index drug (65.1%). In 6% a second antibiotic course coded for a further LRTI was prescribed (11.2% without this coding restriction). Further antibiotic prescriptions for LRTI were significantly associated with older age, previous smoking, seven day index courses and not using amoxicillin initially. The largest effect size was seen when amoxicillin was not used as index drug (odds ratio (OR) 1.15, p < 0.001). This would support current prescribing practice for amoxicillin as index drug in those without respiratory disease. Prospective studies are needed to explore the observed differences.

4.
Artigo em Inglês | MEDLINE | ID: mdl-30231523

RESUMO

Ambient air pollution is a major global health problem and commercial drivers are particularly exposed to it. As no systematic assessment of the health risks associated with occupational exposure to ambient air pollution in this population had yet been carried out, we conducted a systematic review using a protocol-driven strategy. Papers published from inception to April 20, 2018 in MEDLINE, EMBASE, CINAHL, African journals online, the Cochrane library, ISRCTN WHO ICTRP, and the Web of Science and Scopus databases were screened for inclusion by two independent reviewers. Original articles with at least an available abstract in English or French were included. The initial search retrieved 1454 published articles of which 20 articles were included. Three studies reported a significant difference in white blood cells (106/L) among commercial motorcyclists compared to rural inhabitants (5.041 ± 1.209 vs. 5.900 ± 1.213, p = 0.001), an increased risk of lung cancer (RR = 1.6, 95%CI 1.5⁻1.8) in bus drivers and an increased standardized mortality ratio (SMR) in bus drivers from Hodgkin's lymphoma (SMR 2.17, 95%CI 1.19⁻3.87) compared to white-collar workers. Other studies also found that drivers had more oxidative DNA damage and chromosome breaks. Four papers failed to demonstrate that the drivers were more exposed to air pollution than the controls. Three other studies also reported no significant difference in lung function parameters and respiratory symptoms. The genetic polymorphisms of detoxifying enzymes were also not homogeneously distributed compared to the controls. There is some evidence that occupational exposure to ambient air pollution among commercial drivers is associated with adverse health outcomes, but the existing literature is limited, with few studies on small sample size, methodological weaknesses, and contradictory findings-thus, further research is recommended.


Assuntos
Poluição do Ar/efeitos adversos , Poluição do Ar/estatística & dados numéricos , Condução de Veículo/estatística & dados numéricos , Veículos Automotores/estatística & dados numéricos , Exposição Ocupacional/efeitos adversos , Poluição Relacionada com o Tráfego/efeitos adversos , Poluição Relacionada com o Tráfego/estatística & dados numéricos , Adulto , Dano ao DNA/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/efeitos dos fármacos , Medição de Risco
5.
Pediatr Pulmonol ; 53(9): 1179-1192, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29870146

RESUMO

BACKGROUND: Asthma attacks are common and have significant physical, psychological, and financial consequences. Improving the assessment of a child's risk of subsequent asthma attacks could support front-line clinicians' decisions on augmenting chronic treatment or specialist referral. We aimed to identify predictors for emergency department (ED) or hospital readmission for asthma from the published literature. METHODS: We searched MEDLINE, EMBASE, AMED, PsycINFO, and CINAHL with no language, location, or time restrictions. We retrieved observational studies and randomized controlled trials (RCT) assessing factors (personal and family history, and biomarkers) associated with the risk of ED re-attendance or hospital readmission for acute childhood asthma. RESULTS: Three RCTs and 33 observational studies were included, 31 from Anglophone countries and none from Asia or Africa. There was an unclear or high risk of bias in 14 of the studies, including 2 of the RCTs. Previous history of emergency or hospital admissions for asthma, younger age, African-American ethnicity, and low socioeconomic status increased risk of subsequent ED and hospital readmissions for acute asthma. Female sex and concomitant allergic diseases also predicted hospital readmission. CONCLUSION: Despite the global importance of this issue, there are relatively few high quality studies or studies from outside North America. Factors other than symptoms are associated with the risk of emergency re-attendance for acute asthma among children. Further research is required to better quantify the risk of future attacks and to assess the role of commonly used biomarkers.


Assuntos
Asma/terapia , Hospitalização/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , América do Norte , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Poluição por Fumaça de Tabaco , Resultado do Tratamento
6.
J Clin Endocrinol Metab ; 93(6): 2390-401, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18381572

RESUMO

CONTEXT: Mutations have been identified in the aryl hydrocarbon receptor-interacting protein (AIP) gene in familial isolated pituitary adenomas (FIPA). It is not clear, however, how this molecular chaperone is involved in tumorigenesis. OBJECTIVE: AIP sequence changes and expression were studied in FIPA and sporadic adenomas. The function of normal and mutated AIP molecules was studied on cell proliferation and protein-protein interaction. Cellular and ultrastructural AIP localization was determined in pituitary cells. PATIENTS: Twenty-six FIPA kindreds and 85 sporadic pituitary adenoma patients were included in the study. RESULTS: Nine families harbored AIP mutations. Overexpression of wild-type AIP in TIG3 and HEK293 human fibroblast and GH3 pituitary cell lines dramatically reduced cell proliferation, whereas mutant AIP lost this ability. All the mutations led to a disruption of the protein-protein interaction between AIP and phosphodiesterase-4A5. In normal pituitary, AIP colocalizes exclusively with GH and prolactin, and it is found in association with the secretory vesicle, as shown by double-immunofluorescence and electron microscopy staining. In sporadic pituitary adenomas, however, AIP is expressed in all tumor types. In addition, whereas AIP is expressed in the secretory vesicle in GH-secreting tumors, similar to normal GH-secreting cells, in lactotroph, corticotroph, and nonfunctioning adenomas, it is localized to the cytoplasm and not in the secretory vesicles. CONCLUSIONS: Our functional evaluation of AIP mutations is consistent with a tumor-suppressor role for AIP and its involvement in familial acromegaly. The abnormal expression and subcellular localization of AIP in sporadic pituitary adenomas indicate deranged regulation of this protein during tumorigenesis.


Assuntos
Adenoma/genética , Neoplasias Hipofisárias/genética , Proteínas/fisiologia , Acromegalia/genética , Acromegalia/metabolismo , Adenoma/metabolismo , Adolescente , Adulto , Idoso , Proliferação de Células , Criança , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Testes Genéticos , Hormônio do Crescimento Humano/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/metabolismo , Ligação Proteica , Proteínas/genética , Proteínas/metabolismo , Transfecção , Células Tumorais Cultivadas
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