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1.
J Negat Results Biomed ; 14: 15, 2015 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-26346300

RESUMO

BACKGROUND: Azithromycin prophylaxis has been shown to reduce COPD exacerbations but there is poor evidence for other antibiotics. We compared exacerbation rates in COPD patients with a history of frequent exacerbations (at least three moderate or severe COPD exacerbations in the past two years) during a 12-week treatment course and over a subsequent 48-week follow up period. RESULTS: 292 patients were randomised to one of three treatments for 12 weeks: roxithromycin 300 mg daily and doxycycline 100 mg daily (n = 101); roxithromycin 300 mg daily (n = 97); or matching placebos (n = 94). There were no differences in the annualised moderate and severe exacerbation rates after treatment with roxithromycin/doxycycline (2.83 (95 % CI 2.37-3.40)) or roxithromycin only (2.69 (2.26-3.21)) compared to placebo (2.5 (2.08-3.03)) (p = 0.352 and p = 0.5832 respectively). Furthermore, there were no differences in the annualised exacerbation rates during 12-week treatment with roxithromycin/doxycycline (1.64 (95 % CI 1.17-2.30)), roxithromycin only (1.75 (1.24-2.41)) or placebo (2.23 (1.68-3.03)) (p = 0.1709 and p = 0.2545 respectively). There were also no significant differences between groups for spirometry or quality of life scores over either the 12-week treatment or 48-week post-treatment periods. Both active treatments were associated with nausea but otherwise adverse events were comparable among treatment groups. CONCLUSIONS: Twelve-weeks of prophylaxis with roxithromycin/doxycycline combination or roxithromycin alone did not reduce COPD exacerbations in patients with history of frequent exacerbations. These findings do not support the use of these antibiotics to prevent exacerbations in COPD patients.


Assuntos
Progressão da Doença , Doxiciclina/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Roxitromicina/administração & dosagem , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/epidemiologia
2.
J Allergy Clin Immunol Pract ; 3(3): 335-49.e1-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25840665

RESUMO

Use of electronic monitoring devices (EMDs) for inhalers is growing rapidly because of their ability to provide objective and detailed adherence data to support clinical decision making. There is increasing potential for the use of EMDs in clinical settings, especially as cost-effectiveness is realized and device costs reduce. However, it is important for clinicians to know about the attributes of different EMDs so that they can select the right device for their patients and understand the factors that affect the reliability and accuracy of the data EMDs record. This article gives information on where to obtain EMDs, describes device specifications, and highlights useful features for the clinician and the patient, including user feedback data. We discuss the benefits and potential drawbacks of data collected by EMDs and provide device users with a set of tools to optimize the use of EMDs in clinical settings, such as advice on how to carry out brief EMD checks to ensure data quality and device reliability. New EMDs on the market require pretesting before use by patients. We provide information on how to carry out EMD pretesting in the clinic and patients' homes, which can be carried out by health professionals or in collaboration with researchers or manufacturers. Strategies for interpreting and managing common device malfunctions are also discussed.


Assuntos
Adesão à Medicação , Nebulizadores e Vaporizadores , Preparações Farmacêuticas/administração & dosagem , Tecnologia de Sensoriamento Remoto/instrumentação , Administração por Inalação , Aprovação de Equipamentos , Esquema de Medicação , Desenho de Equipamento , Falha de Equipamento , Humanos , Nebulizadores e Vaporizadores/normas , Guias de Prática Clínica como Assunto , Tecnologia de Sensoriamento Remoto/normas , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador , Fatores de Tempo , Estados Unidos , United States Food and Drug Administration
3.
Lancet Respir Med ; 3(3): 210-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25617215

RESUMO

BACKGROUND: Suboptimum adherence to preventive asthma treatment is associated with substantial morbidity and mortality, yet adherence often remains poor. We aimed to investigate whether use of an inhaler with audiovisual reminders leads to improved adherence and asthma outcomes in school-aged children who presented to the emergency department with an asthma exacerbation. METHODS: We did a randomised controlled trial in patients aged 6-15 years who attended the regional emergency department in Auckland, New Zealand with an asthma exacerbation and were on regular inhaled corticosteroids. Using a simple, unrestricted block randomisation with block sizes of 200, we randomly assigned patients to receive an electronic monitoring device for use with their preventer inhaler with the audiovisual reminder functions either enabled to support adherence to inhaled corticosteroids (intervention group) or disabled (control group). Participants were followed up every 2 months for 6 months. The primary outcomes were adherence to preventive inhaled corticosteroids and number of days absent from school for any reason. Asthma control was assessed as a secondary outcome. All analyses were done in the intention-to-treat population. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12613001353785. FINDINGS: The study took place between May 10, 2010, and Feb 26, 2012. We randomly assigned 220 patients, 110 to the intervention group and 110 to the control group. Median percentage adherence was 84% (10th percentile 54%, 90th percentile 96%) in the intervention group, compared with 30% (8%, 68%) in the control group (p<0·0001). The proportion of days absent from school for any reason was 1·9% (10th percentile 0·0%, 90th percentile 7·9%) in the intervention group and 1·7% (0·0%, 8·6%) in the control group. The change in asthma morbidity score from baseline to 6 months was significantly greater in the intervention group than in the control group (p=0·008), with a reduction of 2·0 points from a mean baseline score of 9·3 (SD 2·2) to 7·3 (2·1) in the intervention group, compared with a reduction of 1·2 points from a baseline of 9·2 (2·5) to 8·0 (2·2) in the control group. INTERPRETATION: Use of an electronic monitoring device with an audiovisual reminder led to significant improvements in adherence to inhaled corticosteroids in school-aged children with asthma. This intervention could be beneficial for the improvement of asthma control in patients for whom poor asthma control is related to poor adherence. FUNDING: Health Research Council of New Zealand and Cure Kids.


Assuntos
Absenteísmo , Corticosteroides/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Administração por Inalação , Adolescente , Criança , Desenho de Equipamento , Humanos , Adesão à Medicação , Monitorização Ambulatorial/instrumentação , Monitorização Ambulatorial/métodos , Nova Zelândia , Sistemas de Alerta , Instituições Acadêmicas/estatística & dados numéricos , Resultado do Tratamento
5.
Proc Am Thorac Soc ; 9(5): 304-10, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23256175

RESUMO

INTRODUCTION: Professional societies, like many other organizations, have recognized the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the last of a series of 14 articles that methodologists and researchers from around the world have prepared to advise guideline developers in respiratory and other diseases on how to achieve this. We updated a review of the literature on guideline adaptation, evaluation, and updating, focusing on four key questions. METHODS: In this review we addressed the following questions. (1) Which high-quality guidelines on chronic obstructive pulmonary disease (COPD) are available? (2) How should guidelines be adapted to the user's context and culture? (3) How should the use of guidelines be evaluated in clinical practice? and (4) How should guidelines be efficiently kept up-to-date? We did not conduct systematic reviews ourselves. We relied on a literature review published in 2006 and on a manual produced by the ADAPTE Collaboration to inform our judgments, as well as our collective experience and workshop discussions. RESULTS AND DISCUSSION: Guideline adaptation can be seen as an alternative to de novo development and as part of an implementation process, taking into consideration the user's own context. A systematic approach should be followed to ensure high quality of the resulting guidance. On the topic of COPD, many guidelines are available. Guidelines of the Global Initiative for Chronic Obstructive Lung Disease and of the American Thoracic Society and European Respiratory Society are particularly well-suited for adaptation. The adaptation process includes (1) definition of specific questions that need to be answered by the guideline; (2) assessment of guideline quality; (3) assessment of the clinical content, validity, acceptability, applicability, and transferability of the recommendations; and (4) decisions about adoption or adaptation of the recommendations. The use of the guidelines in practice can be measured with performance indicators. Adverse effects of strict adherence to guideline recommendations should be prevented, in particular when the improvement of patient outcomes is unclear. COPD guidelines should be updated at least every 2 years. Collaboration between COPD guideline developers is recommended to prevent duplication of effort.


Assuntos
Protocolos Clínicos/normas , Fidelidade a Diretrizes/organização & administração , Formulação de Políticas , Guias de Prática Clínica como Assunto/normas , Doença Pulmonar Obstrutiva Crônica , Gerenciamento Clínico , Medicina Baseada em Evidências/normas , Humanos , Revisão dos Cuidados de Saúde por Pares/métodos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Melhoria de Qualidade
6.
Cochrane Database Syst Rev ; (8): CD001287, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22895919

RESUMO

BACKGROUND: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume or purulence of sputum, or both. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference among countries in terms of prescribing of mucolytics depending on whether or not they are perceived to be effective. PRIMARY OBJECTIVE: to determine if treatment with mucolytics reduces the frequency of exacerbations, days of disability, or both, in participants with chronic bronchitis or chronic obstructive pulmonary disease, or both. SECONDARY OBJECTIVES: to determine if mucolytics lead to an improvement in lung function or quality of life and to determine the frequency of adverse effects associated with mucolytics. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register and reference lists of articles on ten separate occasions, the most recent being in July 2012. SELECTION CRITERIA: We included randomised studies that compared oral mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. DATA COLLECTION AND ANALYSIS: The review analysed summary data only, the majority from published studies. For earlier versions, one author extracted data, which was rechecked in subsequent updates. In later versions, we double-checked data extraction. We then entered data into RevMan for analysis. MAIN RESULTS: Two further trials have been added to the review for the 2012 update. There are now 30 trials in the review, recruiting a total of 7436 participants. Allocation concealment was not clearly described in the early trials, and selection bias may have inflated the results, which reduces our confidence in the findings of these trials.The likelihood of being exacerbation-free during the study period (22 trials in 4886 participants with a mean duration of 10 months) was greater in the mucolytic group for the double-blind trials (Peto odds ratio (OR) 1.84; 95% confidence interval (CI) 1.63 to 2.07). However, the more recent trials show less benefit of treatment than the earlier trials included in this review. The overall number needed to treat with mucolytics to keep an additional participant free from exacerbations over 10 months was seven (NNTB 7; 95% CI 6 to 9). The use of mucolytics was associated with a reduction of 0.04 exacerbations per participant per month (95% CI -0.04 to -0.03) compared with placebo; that is about 0.48 per year, or one exacerbation every two years. There was very high heterogeneity in this outcome (I(2) = 87%) so results need to be interpreted with caution.The number of days of disability per month also fell (mean difference (MD) -0.48; 95% CI -0.65 to -0.30) in 12 trials on 2305 participants. There was no clinically important improvement in lung function or consistent impact on quality of life with mucolytics. Mucolytic treatment was not associated with any significant increase in adverse effects, including mortality (Peto OR 0.75; 95% CI 0.35 to 1.64) in six trials on 1821 participants. AUTHORS' CONCLUSIONS: In participants with chronic bronchitis or COPD, treatment with a mucolytic may produce a small reduction in acute exacerbations, but may have little or no effect on the overall quality of life. The effects on exacerbations shown in early trials were larger than those found in the more recent studies. This may be because the earlier smaller trials were at higher risk of selection or publication bias, so the benefits of treatment may not be as large as suggested by the previous evidence.


Assuntos
Bronquite/tratamento farmacológico , Expectorantes/uso terapêutico , Pneumopatias Obstrutivas/tratamento farmacológico , Adulto , Bronquite/prevenção & controle , Doença Crônica , Progressão da Doença , Humanos , Pneumopatias Obstrutivas/prevenção & controle , Números Necessários para Tratar , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
J Cell Mol Med ; 16(7): 1522-32, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22117690

RESUMO

Chronic obstructive pulmonary disease (COPD) is characterized by loss of elastic fibres from small airways and alveolar walls, with the decrease in elastin increasing with disease severity. It is unclear why there is a lack of repair of elastic fibres. We have examined fibroblasts cultured from lung tissue from subjects with or without COPD to determine if the secretory profile explains lack of tissue repair. In this study, fibroblasts were cultured from lung parenchyma of patients with mild COPD [Global initiative for chronic Obstructive Lung Disease (GOLD) 1, n= 5], moderate to severe COPD (GOLD 2-3, n= 12) and controls (non-COPD, n= 5). Measurements were made of proliferation, senescence-associated ß-galactosidase-1, mRNA expression of IL-6, IL-8, MMP-1, tropoelastin and versican, and protein levels for IL-6, IL-8, PGE(2,) tropoelastin, insoluble elastin, and versican. GOLD 2-3 fibroblasts proliferated more slowly (P < 0.01), had higher levels of senescence-associated ß-galactosidase-1 (P < 0.001) than controls and showed significant increases in mRNA and/or protein for IL-6 (P < 0.05), IL-8 (P < 0.01), MMP-1 (P < 0.05), PGE(2) (P < 0.05), versican (P < 0.05) and tropoelastin (P < 0.05). mRNA expression and/or protein levels of tropoelastin (P < 0.01), versican (P < 0.05), IL-6 (P < 0.05) and IL-8 (P < 0.05) were negatively correlated with FEV1% of predicted. Insoluble elastin was not increased. In summary, fibroblasts from moderate to severe COPD subjects display a secretory phenotype with up-regulation of inflammatory molecules including the matrix proteoglycan versican, and increased soluble, but not insoluble, elastin. Versican inhibits assembly of tropoelastin into insoluble elastin and we conclude that the pro-inflammatory phenotype of COPD fibroblasts is not compatible with repair of elastic fibres.


Assuntos
Proliferação de Células , Fibroblastos/citologia , Inflamação/genética , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Feminino , Fibroblastos/metabolismo , Humanos , Inflamação/fisiopatologia , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Tropoelastina/genética , Tropoelastina/metabolismo , Regulação para Cima , Versicanas/genética , Versicanas/metabolismo , Cicatrização , beta-Galactosidase/genética , beta-Galactosidase/metabolismo
8.
Respir Physiol Neurobiol ; 177(3): 236-40, 2011 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-21539942

RESUMO

Insufficiency of tissue repair by pulmonary fibroblasts may contribute to the decrease in elastic fibres in chronic obstructive pulmonary disease (COPD). In this study, the repair function of COPD fibroblasts was assessed by examining the response to transforming growth factor (TGF)-ß1. Primary pulmonary fibroblasts were cultured from lung tissue of COPD patients and smoking control subjects. Cellular proliferation was measured with Alamar Blue reduction method. Levels of tropoelastin mRNA and soluble elastin was measured using real-time RT-PCR and Fastin elastin assay respectively. The percentage of increase in proliferation and elastin production after TGF-ß1 (1 ng/ml) treatment was calculated for fibroblasts from each subject. COPD fibroblasts showed slower proliferation than control fibroblasts, and a reduced response to TGF-ß1 stimulation. The promotive effect of TGF-ß1 on elastin synthesis in control fibroblasts was significantly diminished in fibroblasts from COPD patients. Our findings indicate that COPD lung fibroblasts have a significantly decreased response to TGF-ß1 in terms of proliferation and elastin production.


Assuntos
Elastina/metabolismo , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Pulmão/citologia , Doença Pulmonar Obstrutiva Crônica/patologia , Fator de Crescimento Transformador beta1/farmacologia , Idoso , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Fibroblastos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Tropoelastina/genética , Tropoelastina/metabolismo
9.
Cochrane Database Syst Rev ; (5): CD002309, 2011 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-21563134

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects symptoms, lung function, quality of life and life expectancy. Apart from smoking cessation, there are no other treatments that slow lung function decline. Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE(4)) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. OBJECTIVES: To evaluate the efficacy and safety of PDE(4) inhibitors in the management of people with stable COPD. Outcomes included lung function, quality of life, symptoms, exacerbations and adverse effects. SEARCH STRATEGY: We identified randomised controlled trials (RCTs) from the Cochrane Airways Group Specialised Register of trials (date of last search 6 August 2010). We found other trials from web-based clinical trial registers. SELECTION CRITERIA: We included RCTs if they compared oral PDE(4) inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy. DATA COLLECTION AND ANALYSIS: One review author extracted data and a second review author checked the data, before entry into The Cochrane Collaboration software programme (RevMan version 5.1). We reported pooled data as mean differences (MD), standardised mean differences (SMD), or odds ratios (OR). MAIN RESULTS: Twenty-three separate RCTs studying roflumilast (nine trials, 9211 patients) or cilomilast (fourteen trials, 6457 patients) met the inclusion criteria. None of the trials exceeded a year in duration.Treatment with a PDE(4) inhibitor was associated with a significant improvement in FEV(1)over the trial period compared with placebo (MD 45.59 mL; 95% confidence interval (CI) 39.15 to 52.03), regardless of COPD severity or concomitant COPD treatment. There were some small improvements in quality of life (St George's Respiratory Questionnaire MD -1.04; 95% CI -1.66 to -0.41) and COPD-related symptoms, but no change in exercise tolerance. Treatment with a PDE(4) inhibitor was associated with a reduced likelihood of COPD exacerbation (OR 0.78; 95% CI 0.72 to 0.85). More participants in the treatment groups experienced non-serious adverse events compared with controls, particularly gastrointestinal symptoms and headache. Roflumilast was associated with weight loss during the trial period. AUTHORS' CONCLUSIONS: In people with COPD, PDE(4) inhibitors offered benefit over placebo in improving lung function and reducing likelihood of exacerbations, however, they had little impact on quality of life or symptoms. Gastrointestinal adverse effects and weight loss were common. The optimum place of PDE(4) inhibitors in COPD management remains to be defined. Longer-term trials are needed to determine whether or not PDE(4) inhibitors modify FEV(1) decline, healthcare utilisation or mortality in COPD.


Assuntos
Aminopiridinas/administração & dosagem , Benzamidas/administração & dosagem , Ácidos Cicloexanocarboxílicos/administração & dosagem , Nitrilas/administração & dosagem , Inibidores da Fosfodiesterase 4/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração Oral , Aminopiridinas/efeitos adversos , Benzamidas/efeitos adversos , Ácidos Cicloexanocarboxílicos/efeitos adversos , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Nitrilas/efeitos adversos , Inibidores da Fosfodiesterase 4/efeitos adversos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Respir Med ; 105(3): 329-36, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21112201

RESUMO

UNLABELLED: Advanced Glycation End products (AGEs) are the products of nonenzymatic glycation and oxidation of proteins and lipids. Formation of AGEs is increased in response to hyperglycaemia, reactive oxygen species and ageing. AGEs are proinflammatory and can modify the extracellular matrix. RAGE (Receptor for Advanced Glycation End Products) mediates some of the effects of AGEs. METHODS: Formalin-fixed lung tissue from patients who had lobectomy for bronchial carcinoma was used to investigate the presence of AGEs and RAGE. Subjects were divided into those with COPD and controls. Immunostaining for AGEs and RAGE was performed and the intensity of staining measured. RESULTS: Subjects with COPD and controls were similar in age and smoking history but FEV(1)% predicted was lower for COPD than controls. Intensity of staining for AGEs was greater in the airways (p = 0.025) and alveolar walls (p = 0.004) in COPD. Intensity of staining for RAGE was also significantly increased in alveolar walls (p = 0.03) but not the airways. FEV(1)% predicted was correlated with the intensity of staining for AGEs in the airways and alveoli. CONCLUSIONS: The increased staining for both AGEs and RAGE in COPD lung raises the possibility that the RAGE-AGEs interaction may have a role in the pathogenesis of COPD.


Assuntos
Produtos Finais de Glicação Avançada/metabolismo , Pulmão/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores Imunológicos/metabolismo , Envelhecimento/fisiologia , Células Cultivadas , Feminino , Produtos Finais de Glicação Avançada/análise , Humanos , Hiperglicemia/metabolismo , Pulmão/química , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/análise , Fumar/efeitos adversos , Fumar/metabolismo
11.
Respir Med ; 105(3): 506-10, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20724130

RESUMO

BACKGROUND: Susceptibility to Chronic Obstructive Pulmonary Disease (COPD) has a genetic component. We undertook a study to determine if a genetic variant of the gene encoding the cyclooxygenase-2 gene influences the likelihood of developing COPD. METHODS: In a case control study the frequency of a single nucleotide polymorphism in the promoter region of the cyclooxygenase-2 gene (-765 G → C) was determined in 205 subjects with COPD, 171 chronic smokers with normal lung function (resistant smokers) and 95 healthy blood donors using the polymerase chain reaction and restriction enzyme fragment length polymorphism. RESULTS: The frequency of the C allele of the -765 cyclooxygenase-2 polymorphism was higher in resistant smokers (24.6%) compared with subjects with COPD (14.4%, OR = 1.98, 95% CI = 1.28-3.06, p = 0.003) and blood donors (14.7%, OR = 1.97, 95% CI = 1.14-3.41, p = 0.03). CONCLUSIONS: The -765C allele, which has been shown to be associated with decreased promoter activity of the cyclooxygenase-2 gene, is more common in resistant smokers. This raises the possibility that decreased activity of cyclooxygenase-2 may protect smokers against the development of COPD.


Assuntos
Ciclo-Oxigenase 2/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Doença Pulmonar Obstrutiva Crônica/genética , Fumar/genética , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória , Fumar/fisiopatologia , População Branca/genética
12.
BMC Med Genet ; 11: 125, 2010 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-20712903

RESUMO

BACKGROUND: Individuals born small for gestational age (SGA) are at increased risk of rapid postnatal weight gain, later obesity and diseases in adulthood such as type 2 diabetes, hypertension and cardiovascular diseases. Environmental risk factors for SGA are well established and include smoking, low pregnancy weight, maternal short stature, maternal diet, ethnic origin of mother and hypertension. However, in a large proportion of SGA, no underlying cause is evident, and these individuals may have a larger genetic contribution. METHODS: In this study we tested the association between SGA and polymorphisms in genes that have previously been associated with obesity and/or diabetes. We undertook analysis of 54 single nucleotide polymorphisms (SNPs) in 546 samples from the Auckland Birthweight Collaborative (ABC) study. 227 children were born small for gestational age (SGA) and 319 were appropriate for gestational age (AGA). RESULTS AND CONCLUSION: The results demonstrated that genetic variation in KCNJ11, BDNF, PFKP, PTER and SEC16B were associated with SGA and support the concept that genetic factors associated with obesity and/or type 2 diabetes are more prevalent in those born SGA compared to those born AGA. We have previously determined that environmental factors are associated with differences in birthweight in the ABC study and now we have demonstrated a significant genetic contribution, suggesting that the interaction between genetics and the environment are important.


Assuntos
Peso ao Nascer , Diabetes Mellitus Tipo 2/etiologia , Idade Gestacional , Obesidade/complicações , Doenças Cardiovasculares/complicações , Criança , Diabetes Mellitus , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez , Fatores de Risco
13.
J Gen Intern Med ; 25(6): 537-42, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20237959

RESUMO

BACKGROUND: The inaccurate recording of medicines on admission to hospital is an important cause of medication error. Medication reconciliation has been used to identify and correct these errors. OBJECTIVE: To determine if a multimodal intervention involving medication reconciliation with real-time feedback and education would reduce the number of errors made by medical staff when recording medicines at the time of admission to hospital. DESIGN: Observational study. PARTICIPANTS: Patients admitted to the general medical wards of a teaching hospital were studied prospectively. Patients > or =75 years of age and on > or =5 medications were identified as the 'target group.' INTERVENTION: After admission, a second medication history was taken, and discrepancies were identified and communicated to the medical teams. An educational intervention to encourage prescribers to obtain accurate medication histories was conducted at the same time. MEASUREMENTS: The discrepancy rate was measured before and after the intervention. MAIN RESULTS: There were 470 admissions in the 'target group.' Three hundred and thirty-eight of the admissions (71.9%) had one or more unintentional discrepancies. Although many discrepancies had little potential to cause harm, 33% were rated as clinically significant. During the study the discrepancy rate (prior to reconciliation) fell from 2.6 (SD 2.6) to 1.0 (SD 1.1) per admission (p < 0.0001). This decline in discrepancy rate remained significant (p = 0.001) even when only clinically important discrepancies were included. The proportion of admissions with one or more clinically important discrepancies also decreased during the study from 46% to 24% (p = 0.023). CONCLUSIONS: Errors in the recording of medicines at the time of hospital admission are common. Combining the feedback provided by medication reconciliation with prescriber education reduced the error rate. This approach may be useful when the resources are not available to perform medication reconciliation for all patients admitted to hospital.


Assuntos
Educação Médica , Anamnese , Prontuários Médicos , Erros de Medicação/prevenção & controle , Preparações Farmacêuticas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Admissão do Paciente , Estudos Prospectivos
14.
Cochrane Database Syst Rev ; (2): CD001287, 2010 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-20166060

RESUMO

BACKGROUND: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume and/or purulence of sputum. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference between countries in terms of prescribing of mucolytics depending on whether or not they are perceived to be effective. OBJECTIVES: To assess the effects of oral mucolytics in adults with stable chronic bronchitis or COPD. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register and reference lists of articles on eight separate occasions, the most recent being in September 2008. SELECTION CRITERIA: Randomised trials that compared oral mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. DATA COLLECTION AND ANALYSIS: One review author extracted data. We contacted study authors and drug companies for missing information. MAIN RESULTS: Twenty-eight trials involving 7042 participants were included. Compared with placebo, there was a significant reduction in the number of exacerbations per patient with oral mucolytics (weighted mean difference (WMD) -0.04 per month, 95% confidence interval -0.05 to -0.03). Using a weighted annualised rate of exacerbations in the control patients of 2.4 per year, this is a 21% reduction. The number of days of disability also fell (WMD -0.56, 95% confidence interval (CI) -0.77 to -0.35). One recent study has shown that the benefit may apply only to patients not already receiving inhaled corticosteroids. The number of patients who remained exacerbation-free was greater in the mucolytic group (odds ratio (OR) 1.93 (95% CI 1.71 to 2.17)). There is no strong evidence of improvement in lung function and treatment is not associated with any increase in adverse effects. Patients on mucolytics may be less likely to be hospitalised during the study period. AUTHORS' CONCLUSIONS: In participants with chronic bronchitis or COPD, treatment with mucolytics was associated with a small reduction in acute exacerbations and a reduction in total number of days of disability. Benefit may be greater in individuals who have frequent or prolonged exacerbations, or those who are repeatedly admitted to hospital with exacerbations with COPD. Mucolytics should be considered for use, through the winter months at least, in patients with moderate or severe COPD in whom inhaled corticosteroids (ICS) are not prescribed.


Assuntos
Bronquite/tratamento farmacológico , Expectorantes/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Adulto , Doença Crônica , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
J Paediatr Child Health ; 45(5): 291-6, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19493122

RESUMO

AIM: The aim of this study is to measure the seroprevalence of cytomegalovirus (CMV) infection in 3.5-year-old children, and identify the determinants of seropositivity. METHODS: A total of 1714 children were enrolled at birth. Approximately half were small for gestational age and half were appropriate for gestational age. Information on the children was collected at birth, 1 year and 3.5 years. At 3.5 years blood was collected and tested for CMV-specific immunoglobulin by an enzyme-linked immunosorbent assay in 530 children. RESULTS: The weighted seroprevalence of CMV was 32.8% (95% confidence interval (CI) 27.4-38.1%). The seroprevalence of CMV varied markedly by ethnicity (European: 26.5% (95% CI 20.9-32.2%); Maori: 68.0% (44.0-92.0%); Pacific: 74.5% (56.3-92.6%); Indian: 50.0% (20.2-79.8%); Chinese: 47.2% (10.8-83.5%); Other: 21.9% (0.0-52.7%); P < 0.001). Socio-economic factors, number of siblings, day care centres attendance, maternal smoking, breastfeeding and other factors examined were not related to CMV seropositivity. CONCLUSIONS: The seroprevalence of CMV in New Zealand pre-school children is similar to that reported from other developed countries. The finding of marked ethnic differences is unexplained by socio-economic factors, or other factors that were examined.


Assuntos
Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/isolamento & purificação , Estudos de Casos e Controles , Pré-Escolar , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/etnologia , Características da Família , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Masculino , Nova Zelândia/epidemiologia , Fatores de Risco , Estudos Soroepidemiológicos
17.
PLoS One ; 4(4): e5302, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19390575

RESUMO

BACKGROUND: Epidemiological and pedigree studies suggest that lung cancer results from the combined effects of age, smoking, impaired lung function and genetic factors. In a case control association study of healthy smokers and lung cancer cases, we identified genetic markers associated with either susceptibility or protection to lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: We screened 157 candidate single nucleotide polymorphisms (SNP) in a discovery cohort of 439 subjects (200 controls and 239 lung cancer cases) and identified 30 SNPs associated with either the healthy smokers (protective) or lung cancer (susceptibility) phenotype. After genotyping this 30 SNP panel in a validation cohort of 491 subjects (248 controls and 207 lung cancers) and, using the same protective and susceptibility genotypes from our discovery cohort, a 20 SNP panel was selected based on replication of SNP associations in the validation cohort. Following multivariate logistic regression analyses, including the selected SNPs from runs 1 and 2, we found age and family history of lung cancer to be significantly and independently associated with lung cancer. Numeric scores were assigned to both the SNP and demographic data, and combined to form a simple algorithm of risk. CONCLUSIONS/SIGNIFICANCE: Significant differences in the distribution of the lung cancer susceptibility score was found between normal controls and lung cancer cases, which remained after accounting for differences in lung function. Validation in other case-control and prospective cohorts are underway to further define the potential clinical utility of this model.


Assuntos
Predisposição Genética para Doença , Variação Genética , Neoplasias Pulmonares/genética , Idoso , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Fumar
19.
BMC Clin Pharmacol ; 8: 9, 2008 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-18823561

RESUMO

BACKGROUND: Prescribing errors are common in hospital settings. Regular review of medication charts is recommended as a way to reduce errors but it is not clear how often this happens. The aim of this study was to determine the frequency with which specialist physicians reviewed medication charts during ward rounds. METHODS: An observer noted how often consultant physicians at Auckland City Hospital reviewed medication charts during ward rounds. The physicians were not aware that they were being observed. RESULTS: Twenty-one physicians were observed over a 26 week period. The general physicians reviewed the medication charts on 77% of occasions (range: 45% - 100%) during routine ward rounds and 65% of the time (range: 41% - 80%) on post admission rounds. Subspecialty physicians who did not see more than 8 patients on their rounds reviewed medication charts more frequently (88%) than those specialties where more than 8 patients were seen on average (61%). CONCLUSION: The physicians did not review medication charts on all ward rounds and there was considerable variation in how often they did this. There is some evidence that the frequency with which charts are reviewed decreases as the number of patients seen increases. More efforts should be made to encourage regular review of medication charts.


Assuntos
Prescrições de Medicamentos , Corpo Clínico Hospitalar , Erros de Medicação/prevenção & controle , Padrões de Prática Médica/estatística & dados numéricos , Humanos , Prontuários Médicos , Medicina , Nova Zelândia , Especialização
20.
Aust N Z J Public Health ; 32(5): 454-60, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18959550

RESUMO

OBJECTIVE: To compare dietary intakes of European, Maori, Pacific, and Asian men and women living in Auckland. METHODS: Daily nutrient intakes were calculated from a self-administered food frequency questionnaire from participants in a cross-sectional health screening study carried out between 2002 and 2003. Participants were 4,007 Maori, Pacific, Asian and European people (1,915 men, 2,092 women) aged 35 to 74 years. RESULTS: Compared with Europeans, Maori and Pacific men had higher total energy intakes per day, while Asians had lower intakes. A similar pattern was observed for carbohydrate and fat consumption. While protein and cholesterol consumption tended to be lower in Europeans than the other three ethnic groups, alcohol consumption and calcium intakes were highest among Europeans. Many of the differences between ethnic groups were attenuated when nutrient consumption was expressed as their percentage contribution to total energy intake suggesting that total food consumption was the major determinant of ethnic differences in nutrient intakes. CONCLUSIONS: There were substantial differences in dietary habits, food selections and cooking practices between European, Maori, Pacific and Asian participants. However, the observed differences were in the area of serving sizes and frequency of consumption of certain foods than to major differences in the range of foods and nutrients consumed or the percentage contribution of carbohydrate, fat or protein to total energy intake. IMPLICATIONS: The development of strategies to reduce serving sizes and the frequency of consumption of certain foods will be required to help address the major nutrition-related health problems in New Zealand.


Assuntos
Inquéritos sobre Dietas , Ingestão de Alimentos/etnologia , Ingestão de Energia/etnologia , Preferências Alimentares/etnologia , Grupos Populacionais/etnologia , Adulto , Idoso , Povo Asiático , Culinária , Diabetes Mellitus/etnologia , Diabetes Mellitus/metabolismo , Ingestão de Alimentos/fisiologia , Ingestão de Energia/fisiologia , Feminino , Preferências Alimentares/fisiologia , Cardiopatias/etnologia , Cardiopatias/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Havaiano Nativo ou Outro Ilhéu do Pacífico , Nova Zelândia , Grupos Populacionais/classificação , Grupos Populacionais/estatística & dados numéricos , Fatores de Risco , Inquéritos e Questionários , População Branca
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