RESUMO
The effect of inhaled corticosteroids (ICS) on the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to assess this risk in patients with COPD.Electronic medical record data linked to National Health Registries were collected from COPD patients and matched reference controls at 52 Swedish primary care centres from 2000 to 2014. The outcomes analysed were the effect of ICS on all fractures, fractures typically related to osteoporosis, recorded osteoporosis diagnosis, prescriptions of drugs for osteoporosis and a combined measure of any osteoporosis-related event. The COPD patients were stratified by the level of ICS exposure.A total of 9651 patients with COPD and 59â454 matched reference controls were analysed. During the follow-up, 19.9% of COPD patients had at least one osteoporosis-related event compared with 12.9% of reference controls (p<0.0001). Multivariate analysis in the COPD population demonstrated a dose-effect relationship, with high-dose ICS being significantly associated with any osteoporosis-related event (risk ratio 1.52 (95% CI 1.24-1.62)), while the corresponding estimate for low-dose ICS was 1.27 (95% CI 1.13-1.56) compared with COPD patients not using ICS. A similar dose-related adverse effect was found for all four of the specific osteoporosis-related events: all fractures, fractures typically related to osteoporosis, prescriptions of drugs for osteoporosis and diagnosis of osteoporosis.We conclude that patients with COPD have a greater risk of bone fractures and osteoporosis, and high-dose ICS use increased this risk further.
Assuntos
Fraturas Ósseas , Osteoporose , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Corticosteroides/efeitos adversos , Fraturas Ósseas/induzido quimicamente , Fraturas Ósseas/epidemiologia , Humanos , Osteoporose/induzido quimicamente , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Suécia/epidemiologiaRESUMO
BACKGROUND: Inhaled corticosteroids (ICS) are associated with an increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD). Other factors such as severity of airflow limitation and concurrent asthma may further raise the possibility of developing pneumonia. This study assessed the risk of pneumonia associated with ICS in patients with COPD. METHODS: Electronic Medical Record data linked to National Health Registries were collected from COPD patients and matched reference controls in 52 Swedish primary care centers (2000-2014). Levels of ICS treatment (high, low, no ICS) and associated comorbidities were assessed. Patients were categorized by airflow limitation severity. RESULTS: A total of 6623 patients with COPD and 48,566 controls were analyzed. Patients with COPD had a more than 4-fold increase in pneumonia versus reference controls (hazard ratio [HR] 4.76, 95% confidence interval [CI]: 4.48-5.06). ICS use increased the risk of pneumonia by 20-30% in patients with COPD with forced expiratory volume in 1 s ≥ 50% versus patients not using ICS. Asthma was an independent risk factor for pneumonia in the COPD population. Multivariate analysis identified independent predictors of pneumonia in the overall population. The highest risk of pneumonia was associated with high dose ICS (HR 1.41, 95% CI: 1.23-1.62). CONCLUSIONS: Patients with COPD have a greater risk of pneumonia versus reference controls; ICS use and concurrent asthma increased the risk of pneumonia further.
Assuntos
Registros Eletrônicos de Saúde/tendências , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Sistema de Registros , Idoso , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/tendências , Estudos Retrospectivos , Fatores de Risco , Suécia/epidemiologiaRESUMO
Cutaneous malignant melanoma (CMM) incidence is increasing globally, making a thorough understanding of the disease and its outcomes essential for optimizing care even more urgent. In this population-based, retrospective study, we investigated stage-specific survival and recurrence/progression rates of CMM among patients diagnosed in Stockholm County Council during 2005-2012, before the wide introduction of targeted therapy. A total of 3,554 CMM patients from the Stockholm Melanoma Register were included. Information on comorbidities, progression, death, and treatments was obtained from nationwide registers and hospital electronic medical records. Unadjusted 5-year survival varied from 91.4% for stage I to 24.6% for stage IV patients. Stage, age and gender were predictors of survival, with gender an independent predictor of survival for stages IA and IIA. 74.6% of patients remained recurrence/progression-free during follow-up, with 5-year recurrence/progression-free survival rates varying from 85.3% to 12.9% among stages I and IV patients, respectively. In addition to stage, male gender, and age, circulatory system comorbidities increased the risk for recurrence/progression. No statistically significant differences in progression rate for operated and non-operated patients could be detected, possibly due to high rate (98.9%) of surgery. Our estimates of survival and recurrence rates are consistent with historical and global expectations and can serve as a baseline to gauge population-level improvements with use of novel melanoma treatments.
Assuntos
Melanoma/mortalidade , Melanoma/patologia , Adulto , Idoso , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Vigilância da População , Prognóstico , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Neoplasias Cutâneas , Taxa de Sobrevida , Suécia/epidemiologia , Melanoma Maligno CutâneoRESUMO
BACKGROUND: In mild asthma exercise-induced bronchoconstriction (EIB) is usually treated with inhaled short-acting ß2 agonists (SABAs) on demand. OBJECTIVE: The hypothesis was that a combination of budesonide and formoterol on demand diminishes EIB equally to regular inhalation of budesonide and is more effective than terbutaline inhaled on demand. METHODS: Sixty-six patients with asthma (>12 years of age) with verified EIB were randomised to terbutaline (0.5 mg) on demand, regular budesonide (400 µg) and terbutaline (0.5 mg) on demand, or a combination of budesonide (200 µg) + formoterol (6 µg) on demand in a 6-week, double-blind, parallel-group study (ClinicalTrials.gov identifier: NCT00989833). The patients were instructed to perform three to four working sessions per week. The main outcome was EIB 24 h after the last dosing of study medication. RESULTS: After 6 weeks of treatment with regular budesonide or budesonide+formoterol on demand the maximum post-exercise forced expiratory volume in 1 s fall, 24 h after the last medication, was 6.6% (mean; 95% CI -10.3 to -3.0) and 5.4% (-8.9 to -1.8) smaller, respectively. This effect was superior to inhalation of terbutaline on demand (+1.5%; -2.1 to +5.1). The total budesonide dose was approximately 2.5 times lower in the budesonide+formoterol group than in the regular budesonide group. The need for extra medication was similar in the three groups. CONCLUSIONS: The combination of budesonide and formoterol on demand improves asthma control by reducing EIB in the same order of magnitude as regular budesonide treatment despite a substantially lower total steroid dose. Both these treatments were superior to terbutaline on demand, which did not alter the bronchial response to exercise. The results question the recommendation of prescribing SABAs as the only treatment for EIB in mild asthma.
Assuntos
Asma Induzida por Exercício/prevenção & controle , Broncodilatadores/administração & dosagem , Budesonida/administração & dosagem , Etanolaminas/administração & dosagem , Administração por Inalação , Adolescente , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Adulto , Asma Induzida por Exercício/fisiopatologia , Broncodilatadores/efeitos adversos , Broncodilatadores/uso terapêutico , Budesonida/efeitos adversos , Budesonida/uso terapêutico , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Etanolaminas/efeitos adversos , Etanolaminas/uso terapêutico , Teste de Esforço/métodos , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Fumarato de Formoterol , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Masculino , Terbutalina/administração & dosagem , Terbutalina/efeitos adversos , Terbutalina/uso terapêutico , Capacidade Vital/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVES: The atypical antipsychotic quetiapine is a first-line treatment for schizophrenia. This non-interventional study (NCT01212575) evaluated the clinical use of its two formulations, extended release (XR) and immediate release (IR), in outpatients with schizophrenia spectrum disorder. METHODS: Patients who had received at least one dose of quetiapine XR and/or IR were included. A dosage ≥400 mg/day was defined as antipsychotic. Medical records data were collected retrospectively. RESULTS: Of 186 enrolled patients, 99 (53%) and 87 (47%) received quetiapine XR and IR, respectively. Use in antipsychotic dosage was seen for 89% XR versus 63% IR patients (mean daily dose ≥400 mg/day; p < 0.0001). 75% XR and 53% IR patients used dosages ≥600 mg/day (p = 0.0019). Quetiapine XR was used at higher mean daily dosages than IR (748 vs 566 mg/day; p = 0.006). Forty-three patients (23%) used both formulations concomitantly; 55 patients (30%) used either XR or IR. Quetiapine IR was used as-needed in 44 patients (23%); one patient used XR as-needed. CONCLUSIONS: Quetiapine XR was used more often in higher (antipsychotic) dosages; quetiapine IR more frequently on an as-needed administration basis. Concomitant use was seen. These findings probably reflect the different profiles of XR/IR and advocate the need for both formulations to offer treatment choice.
Assuntos
Antipsicóticos/uso terapêutico , Dibenzotiazepinas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/administração & dosagem , Preparações de Ação Retardada , Dinamarca , Dibenzotiazepinas/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Fumarato de Quetiapina , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The importance of identifying chronic obstructive pulmonary disease (COPD) at an early stage is recognised. Improved and easily accessible identification of individuals at risk of COPD in primary care is needed to select patients for spirometry more accurately. AIMS: To explore whether use of a mini-spirometer can predict a diagnosis of COPD in patients at risk of COPD in primary care, and to assess its cost-effectiveness in detecting patients with COPD. METHODS: Primary care patients aged 45-85 years with a smoking history of >15 pack-years were selected. Data were collected on the Clinical COPD Questionnaire (CCQ), Medical Research Council (MRC) dyspnoea scale and smoking habits. Lung function (forced expiratory volume in 1 and 6 s; FEV1 and FEV6, respectively) was measured by mini-spirometer (copd-6), followed by diagnostic standard spirometry (COPD diagnosis post-bronchodilation ratio of FEV1 to forced vital capacity (FVC) <0.7). Time consumed was recorded. Univariate logistic regression and receiver operating characteristic (ROC) curves were used. RESULTS: A total of 305 patients (57% females) of mean (SD) age 61.2 (8.4) years, mean (SD) total CCQ 1.0 (0.8) and mean (SD) MRC 0.8 (0.8) were recruited from 21 centres. COPD was diagnosed in 77 patients (25.2%) by standard diagnostic spirometry. Using the copd-6 device, mean (SD) FEV1/FEV6 was 68 (8)% in patients with COPD and 78 (10)% in patients without COPD. Sensitivity and specificity at a FEV1/FEV6 cut-off of 73% were 79.2% and 80.3%, respectively. The area under the ROC curve was 0.84. Screening with the copd-6 device significantly predicted COPD. Gender, CCQ, and MRC were not found to predict COPD. CONCLUSIONS: Using the copd-6 as a pre-screening device, the rate of COPD diagnoses by standard diagnostic spirometry increased from 25.2% to 79.2%. Although the sensitivity and specificity of the copd-6 could be improved, it might be an important device for prescreening of COPD in primary care and may reduce the number of unnecessary spirometric tests performed.
Assuntos
Doença Pulmonar Obstrutiva Crônica/diagnóstico , Espirometria , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Volume Expiratório Forçado , Custos de Cuidados de Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/economia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Curva ROC , Fatores de Risco , Fumar/efeitos adversos , Espirometria/economia , Espirometria/métodos , Capacidade VitalRESUMO
Background: Patients with mild chronic obstructive pulmonary disease (COPD) account for more than half of the total COPD population but are often undiagnosed and sparsely studied. This real-world, longitudinal study compared the socioeconomic burden, clinical characteristics and treatment patterns in patients with mild COPD and age- and gender-matched controls. Patients and methods: Our population included mild COPD patients (forced expiratory volume in one second ≥80% of predicted value) and reference controls from 52 Swedish primary care centres over 15 years (2000-2014). We linked electronic medical record (EMR) data to Sweden's National Health Registries. The outcomes analyzed were socioeconomic status including annual income from work, presence of comorbidities and the use of medications. Results: 844 patients with mild COPD were included in this study and matched with 844 reference controls. Compared with the reference controls, mild COPD patients had a significantly lower annual income from work (mean difference, men: 12,559 and women: 7143) and were significantly less likely to be married or employed. The presence of comorbidities, including cardiovascular disease, anxiety and depression (only women) was significantly higher in mild COPD patients. The use of medications, such as proton pump inhibitors, antidepressants, central painkillers and sleep medications, was significantly higher in the mild COPD group. Conclusion: Mild COPD presents a considerable socioeconomic and clinical burden compared with reference controls The findings suggest that COPD constitutes a condition that influences health status even in mild disease clearly demanding an increased need for early detection and treatment.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Feminino , Volume Expiratório Forçado , Humanos , Estudos Longitudinais , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos , Classe Social , Suécia/epidemiologiaRESUMO
Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown both anti-proliferative and anti-tumoral activity in breast cancer. This study was designed to determine the effect of adding gefitinib to neoadjuvant epirubicin and cyclophosphamide (EC) on tumor response rates. Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer ≥ 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib (250 mg daily) or placebo. Primary endpoint was pathologic complete response (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI -7.19 to 6.33; P = 0.44). CR was observed in 10% of patients in both the gefitinib (7/71) and the placebo group (7/73) (0.27% difference, 95% CI -9.6 to 10.2; P = 0.96). There was no significant difference in OR (5.96%; 95% CI -9.9 to 21.9; P = 0.45) between the two groups. Post hoc subgroup analysis showed a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment. More patients in the gefitinib group discontinued treatment because of AE.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Terapia Neoadjuvante , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/metabolismo , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Método Duplo-Cego , Epirubicina/administração & dosagem , Feminino , Febre/induzido quimicamente , Gefitinibe , Humanos , Leucopenia/induzido quimicamente , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Quinazolinas/administração & dosagem , Projetos de Pesquisa , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacosRESUMO
PURPOSE: The aim of this study was to assess the association between exacerbation frequency and clinical and economic outcomes in patients with COPD. PATIENTS AND METHODS: Electronic medical record data linked to National Health Registries were collected from COPD patients at 52 Swedish primary care centers (2000-2014). The outcomes analyzed were exacerbation rate, mortality, COPD treatments, lung function and healthcare costs during the follow-up period. Based on the exacerbation rate two years before index date, the patients were initially classified into three groups, either 0, 1 or ≥2 exacerbations per year. After the index date, the classification into exacerbation groups was updated each year based on the exacerbation rate during the last year of follow-up. A sensitivity analysis was conducted excluding patients with asthma diagnosis from the analysis. RESULTS: In total 18,586 COPD patients were analyzed. A majority of the patients (60-70%) who either have had no exacerbation or frequent exacerbations (≥2/year) during the pre-index period remained in their group (ie, with 0 or ≥2 annual exacerbations) during up to 11 years of follow-up. Compared with having no exacerbation, mortality was higher in patients having 1 (HR; 2.06 [1.93-2.20]) and ≥2 (4.58 [4.33-4.84]) exacerbations at any time during the follow-up. Lung function decline was more rapid in patients with frequent exacerbations and there was an almost linear relationship between exacerbations frequency and mortality. Total healthcare costs were higher in the frequent exacerbation group (≥2/year) than in patients with no or one exacerbation annually (p<0.0001 for both). The results did not differ from the main analysis after exclusion of patients with a concurrent asthma diagnosis. CONCLUSION: In addition to faster lung function decline and increased mortality, frequent exacerbations in COPD patients imply a significant economic burden.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Progressão da Doença , Custos de Cuidados de Saúde , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Suécia/epidemiologia , Fatores de TempoRESUMO
BACKGROUND: The electronic medical record (EMR) offers unique possibilities for clinical research, but some important patient attributes are not readily available due to its unstructured properties. We applied text mining using machine learning to enable automatic classification of unstructured information on smoking status from Swedish EMR data. METHODS: Data on patients' smoking status from EMRs were used to develop 32 different predictive models that were trained using Weka, changing sentence frequency, classifier type, tokenization, and attribute selection in a database of 85,000 classified sentences. The models were evaluated using F-score and accuracy based on out-of-sample test data including 8500 sentences. The error weight matrix was used to select the best model, assigning a weight to each type of misclassification and applying it to the model confusion matrices. The best performing model was then compared to a rule-based method. RESULTS: The best performing model was based on the Support Vector Machine (SVM) Sequential Minimal Optimization (SMO) classifier using a combination of unigrams and bigrams as tokens. Sentence frequency and attributes selection did not improve model performance. SMO achieved 98.14% accuracy and 0.981 F-score versus 79.32% and 0.756 for the rule-based model. CONCLUSION: A model using machine-learning algorithms to automatically classify patients' smoking status was successfully developed. Such algorithms may enable automatic assessment of smoking status and other unstructured data directly from EMRs without manual classification of complete case notes.
Assuntos
Registros Eletrônicos de Saúde , Aprendizado de Máquina , Processamento de Linguagem Natural , Fumar , Tabagismo/diagnóstico , Algoritmos , Automação , Teorema de Bayes , Mineração de Dados , Reações Falso-Positivas , Humanos , Informática Médica , Variações Dependentes do Observador , Reconhecimento Automatizado de Padrão , Curva ROC , Reprodutibilidade dos Testes , Projetos de Pesquisa , Software , Máquina de Vetores de Suporte , Suécia/epidemiologia , Tabagismo/epidemiologiaRESUMO
This study reports the association of ICS use and the risk of type 2 diabetes mellitus (T2DM) in Swedish patients with COPD using data from real-world, primary care settings. A total of 7078 patients with COPD were included in this analysis and the 5-year cumulative incidence rate per 100,000 person years was 1506.9. The yearly incidence rate per 100,000 person years ranged from 850 to 1919. Use of ICS especially at a high dose in patients with COPD was related to an increased risk of T2DM.
Assuntos
Corticosteroides/efeitos adversos , Broncodilatadores/efeitos adversos , Diabetes Mellitus Tipo 2/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Idoso , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Incidência , Masculino , Fatores de Risco , Suécia/epidemiologiaRESUMO
Binary tetracycline-regulated polyomavirus large T antigen transgenic mice were generated to study immunological tolerance for nucleosomes. Expression of T antigen resulted in binding of the protein to chromatin, and released T antigen-nucleosome complexes from dying cells maintained anti-dsDNA and anti-nucleosome antibody-production by activating autoimmune nucleosome-specific B cells and CD4+ and CD8+ T antigen specific T cells. Glomerular T antigen expression was observed in these mice. Here, we demonstrate that this expression was linked to glomerular cell apoptosis, release of nucleosomes and association of nucleosomes with glomerulus basement membranes, detected as electron dense structures. Immune electron microscopy (IEM) revealed that these structures were glomerular targets for induced anti-dsDNA and anti-T antigen antibodies. Co-localization IEM demonstrated that in vivo-bound auto-antibodies co-localized with experimental monoclonal antibodies to dsDNA and to T antigen. A comparative analysis of glomeruli from nephritic (NZWxNZB)F1 and T antigen expressing transgenic mice revealed deposition of nucleosomes in glomerular capillary and mesangial matrix membranes and binding of anti-nucleosome antibodies in both mice strains. A controlled experimental model that may elucidate the initial events accounting for nucleosome-mediated nephritis has not been available. The transgenic mouse may be important to describe early immunological and cellular events accounting for the enigmatic lupus nephritis.
Assuntos
Antígenos Virais de Tumores/imunologia , Apoptose/imunologia , Membrana Basal Glomerular/imunologia , Mesângio Glomerular/imunologia , Nefrite Lúpica/imunologia , Polyomavirus/imunologia , Animais , Anticorpos Antinucleares/imunologia , Antígenos Virais de Tumores/genética , Apoptose/genética , Linfócitos B/imunologia , Linfócitos B/patologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Modelos Animais de Doenças , Membrana Basal Glomerular/patologia , Mesângio Glomerular/patologia , Nefrite Lúpica/genética , Camundongos , Camundongos Transgênicos , Nucleossomos/imunologia , Polyomavirus/genéticaRESUMO
Objective: This retrospective, single-centre, non-interventional, registry-based study evaluated patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide in daily clinical practice at Skåne University Hospital, Malmö, Sweden.Materials and methods: Registry data were reviewed for patients treated with enzalutamide pre- or post-chemotherapy initiated between December 2013 and June 2017. The primary endpoint was overall survival (OS) in post-chemotherapy patients. Secondary endpoints were enzalutamide treatment duration in the pre- and post-chemotherapy setting. This study was approved by the Lund regional Ethics Review Board (Dnr:2017/716) and is registered with ClinicalTrials.gov (NCT03328364).Results: A total of 102 pre-chemotherapy and 98 post-chemotherapy patients were included. Median age was higher in the pre- than in the post-chemotherapy group (77 vs 72 years, respectively). Median OS in post-chemotherapy patients from initiation of enzalutamide until death from any cause was 14.3 months [95% confidence interval (CI) = 11.00-18.20]. Median treatment duration was 13.8 months (95% CI = 11.4-20.2) and 7.6 months (95% CI = 6.3-10.2) for pre- and post-chemotherapy patients, respectively.Conclusion: Enzalutamide can be used to effectively treat mCRPC patients in daily clinical settings, despite the patients being older and less healthy than those enrolled in the previous randomised, clinical registration studies.
Assuntos
Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Sistema de Registros , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Duração da Terapia , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/secundário , Estudos Retrospectivos , Taxa de Sobrevida , SuéciaRESUMO
Purpose: Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD. Patients and methods: In a retrospective, observational cohort study, electronic medical record data (2000-2014) were collected from Swedish primary care patients with COPD. COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis). Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization. Results: More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; P<0.0001). Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83-1.96; P<0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54-1.69; P<0.0001). Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02-1.18; P=0.0095). Late diagnosis was also associated with higher direct costs than early diagnosis. Conclusion: Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis. The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD.
Assuntos
Custos de Cuidados de Saúde , Atenção Primária à Saúde/economia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/economia , Idoso , Comorbidade , Progressão da Doença , Diagnóstico Precoce , Registros Eletrônicos de Saúde , Feminino , Nível de Saúde , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/mortalidade , Estudos Retrospectivos , Fatores de Risco , Suécia/epidemiologia , Fatores de TempoRESUMO
The present study aimed to generate real-world evidence regarding gender differences among chronic obstructive pulmonary disease (COPD) patients, especially as regards the diagnosis and outcomes in order to identify areas for improvement and management and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients and a matched reference population from 52 primary care centers in 2000-2014. The incidence of COPD, prevalence of asthma and other comorbidities, risk of exacerbations, mortality rate, COPD drug prescriptions, and healthcare resource utilization were analyzed. In total, 17,479 patients with COPD were included in the study. During the study period, COPD was more frequent among women (53.8%) and women with COPD experienced more exacerbations vs. men (6.66 vs. 4.66). However, the overall mortality rate was higher in men compared with women (45% vs. 38%), but no difference for mortality due to COPD was seen between genders over the study period. Women seemed to have a greater susceptibility to asthma, fractures, osteoporosis, rheumatoid arthritis, rhinitis, depression, and anxiety, but appeared less likely to have diabetes, kidney diseases, and cardiovascular diseases. Furthermore, women had a greater risk of COPD-related hospitalization and were likely to receive a significantly higher number of COPD drug prescriptions compared with men. These results support the need to reduce disease burden among women with COPD and highlight the role of healthcare professionals in primary care who should consider all these parameters in order to properly diagnose and treat women with COPD.
Assuntos
Previsões , Glucocorticoides/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Idoso , Vias de Administração de Medicamentos , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Retrospectivos , Distribuição por Sexo , Fatores Sexuais , Taxa de Sobrevida/tendências , Suécia/epidemiologiaRESUMO
Coronary arteriograhy in patients with ischemic heart disease often shows spasm of the coronary arteries. The question is whether spasm is a triggering factor for thrombosis in a stenotic artery. If so, what are the mechanisms for this? A stenosing teflon ring was applied to the right common carotid artery of anesthetized rabbits and 1-nor-epinephrine was dripped over the outer surface of both carotid arteries, causing spasm. In control animals an indifferent solution did not cause spasm. Nineteen rabbits were killed 30 min or 24 h after treatment. Microscopically, arteries with stenosis and spasm contained thrombi nearby the stenosis significantly more often than arteries in control animals. In another 14 rabbits, killed at 30 min, the number of platelets on the intimal surface away from the stenosis was quantified. In arteries with both stenosis and spasm the counts were significantly greater than in arteries with no treatment. The intimal surface in stenotic and spastic arteries showed assumed imprints of eddying flow and endothelial injury downstream and upstream of the stenosis. Spastic arteries showed increased folding of the internal elastic membrane, altered endothelial cells, and adhering platelets. Spasm in a rabbit artery with a preformed stenosis facilitates thrombosis probably by creating increased flow disturbances. Spasm may induce endothelial injury, causing adherence of platelets.
Assuntos
Plaquetas/patologia , Artéria Carótida Primitiva/patologia , Estenose das Carótidas/sangue , Espasmo/sangue , Animais , Trombose das Artérias Carótidas/sangue , Artéria Carótida Primitiva/ultraestrutura , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Norepinefrina/farmacologia , Agregação Plaquetária/fisiologia , Contagem de Plaquetas , Coelhos , Vasoconstritores/farmacologiaRESUMO
This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014. These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population. A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population. A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs. 30.7%). Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001). Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients. Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke. The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients (27,692) vs. reference population (5141) (p < 0.0001). The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.
Assuntos
Efeitos Psicossociais da Doença , Doença Pulmonar Obstrutiva Crônica/complicações , Estudos de Coortes , Progressão da Doença , Registros Eletrônicos de Saúde , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/economia , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/terapia , Estudos Retrospectivos , SuéciaRESUMO
Background: We assessed direct and indirect costs associated with COPD in Sweden and examined how these costs vary across time, age, and disease stage in a cohort of patients with COPD and matched controls in a real-world, primary care (PC) setting. Patients and methods: Data from electronic medical records linked to the mandatory national health registers were collected for COPD patients and a matched reference population in 52 PC centers from 2000 to 2014. Direct health care costs (drug, outpatient or inpatient, PC, both COPD related and not COPD related) and indirect health care costs (loss of income, absenteeism, loss of productivity) were assessed. Results: A total of 17,479 patients with COPD and 84,514 reference controls were analyzed. During 2013, direct costs were considerably higher among the COPD patient population (13,179) versus the reference population (2,716), largely due to hospital nights unrelated to COPD. Direct costs increased with increasing disease severity and increasing age and were driven by higher respiratory drug costs and non-COPD-related hospital nights. Indirect costs (~28,000 per patient) were the largest economic burden in COPD patients of working age during 2013. Conclusion: As non-COPD-related hospital nights represent the largest direct cost, management of comorbidities in COPD would offer clinical benefits and relieve the financial burden of disease.
Assuntos
Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Gastos em Saúde , Atenção Primária à Saúde/economia , Doença Pulmonar Obstrutiva Crônica/economia , Doença Pulmonar Obstrutiva Crônica/terapia , Absenteísmo , Fatores Etários , Idoso , Feminino , Custos de Cuidados de Saúde/tendências , Gastos em Saúde/tendências , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Atenção Primária à Saúde/tendências , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Licença Médica/economia , Suécia , Fatores de Tempo , Resultado do TratamentoRESUMO
The aim of this study was to examine whether there are morphological signs in spasm in the coronary arteries at autopsy in persons with coronary artery disease dying suddenly. From a forensic autopsy service, 48 cases of sudden and unexpected deaths were selected: 24 cases with a preliminary diagnosis of coronary heart disease and 24 cases involving persons dying of noncoronary causes. A complete autopsy according to a preset protocol was followed with particular emphasis on the heart examination. The myocardium and the coronary arteries were sampled and examined without knowledge to which group the case belonged. The degree of folding of the internal elastic lamina of the proximal and distal parts of the coronary arteries was measured by picture analysis of elastin-stained cross sections of the arteries. The degree of folding was significantly greater in the distal section of the right coronary artery in cases of the coronary group compared to the folding in the same section in cases of the noncoronary group. In the proximal part of the right coronary artery and in the left coronary artery with its two branches, there were no differences in the folding of the internal elastic membrane between the groups. Our findings indicate that a spasmic contracture of an artery may be diagnosed postmortem. The spasm of the distal part of the right coronary artery may have caused focal ischemia in the central parts of the cardiac conducting system, precipitating a lethal arrhythmia.
Assuntos
Doença das Coronárias/patologia , Vasoespasmo Coronário/patologia , Vasos Coronários/patologia , Morte Súbita Cardíaca/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Estudos de Casos e Controles , Doença das Coronárias/complicações , Vasoespasmo Coronário/complicações , Morte Súbita Cardíaca/etiologia , Tecido Elástico/patologia , Feminino , Patologia Legal , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Pericárdio/patologiaRESUMO
The effect of rosuvastatin or atorvastatin on urinary albumin excretion (UAE) was determined in type 2 diabetic patients. A randomized, double-blind, parallel-group, response-based design compared rosuvastatin 10mg (titrated to 40 mg) with atorvastatin 10mg (titrated to 80 mg) in type 2 diabetic patients with dyslipidemia, with dose titration to an LDL-C target of <3.0 mmol/L. Overnight timed urine collections were obtained at baseline, 8 and 16 weeks to UAE. Glomerular filtration rate (GFR) was determined using the Modification of Diet in Renal Disease formula. Patients with paired, UAE collections of at least 8h duration were analyzed (n=344). No significant change from baseline in UAE was observed for either treatment group or between-treatment groups at 16 weeks, and median UAE for both treatment groups remained within normal limits (rosuvastatin 4.5 microg/min, atorvastatin 5.0 microg/min). A similar absence of change from baseline was observed for 51 patients with UAE above the normal range at study entry (>20 microg/min). No significant change in GFR from baseline after 16 weeks was observed for either treatment group. These data provide reassurance that type 2 diabetic patients can be treated with higher efficacy statins without clinically meaningful effects on urinary albumin excretion.