RESUMO
RATIONALE: Roflumilast reduces exacerbations in patients with severe chronic obstructive pulmonary disease associated with chronic bronchitis and a history of exacerbations. Further characterization of patients most likely to benefit is warranted. OBJECTIVES: Define characteristics that most robustly identify patients who derive greatest exacerbation risk reduction with roflumilast. METHODS: Predefined, pooled analyses of REACT (Roflumilast in the Prevention of COPD Exacerbations While Taking Appropriate Combination Treatment; NCT01329029) and RE2SPOND (Roflumilast Effect on Exacerbations in Patients on Dual [LABA/ICS] Therapy; NCT01443845) multicenter, randomized, double-blind, placebo-controlled studies. The primary endpoint was rate of moderate or severe exacerbations per patient per year. MEASUREMENTS AND MAIN RESULTS: In the overall intention-to-treat population (n = 4,287), roflumilast reduced moderate or severe exacerbations by 12.3% (rate ratio, 0.88, 95% confidence interval, 0.80-0.97; P = 0.0086) and severe exacerbations by 16.1% (0.84; 0.71-0.99; P = 0.0409) versus placebo. The reduction in moderate or severe exacerbations with roflumilast was most pronounced in patients who had been hospitalized for an exacerbation in the prior year (0.74; 0.63-0.88; P = 0.0005); had more than two exacerbations in the prior year (0.79; 0.65-0.96; P = 0.0160); or had baseline eosinophils ≥150 cells/µl (0.81; 0.71-0.93; P = 0.0020), ≥150 to <300 cells/µl (0.84; 0.71-0.98; P = 0.0282), or ≥300 cells/µl (0.77; 0.61-0.97; P = 0.0264). Similar subgroup results were noted for severe exacerbations. In patients with prior hospitalization and higher baseline blood eosinophil concentrations, roflumilast reduced moderate or severe exacerbations by 34.5% at ≥150 cells/µl (0.65; 0.52-0.82; P = 0.0003) and 42.7% at ≥300 cells/µl (0.57; 0.37-0.88; P = 0.0111) versus placebo. CONCLUSIONS: This prespecified, pooled analysis confirms the benefit of roflumilast in decreasing exacerbations in patients with prior hospitalization for exacerbation, greater exacerbation frequency, and higher (≥150 cells/µl, ≥150 to <300 cells/µl, or ≥300 cells/µl) baseline blood eosinophil count.
Assuntos
Aminopiridinas/uso terapêutico , Benzamidas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Corticosteroides/uso terapêutico , Ciclopropanos/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
The aim of this study was to assess the quality of reporting of harms in hypertension clinical trials identified from the Cochrane Database using the Consolidated Standards of Reporting Trials (CONSORT) extension for harms reporting. Forty-one hypertension trials were included in the study. On average trials reported less than half of the items recommended by the CONSORT extension for harms (mean 9.83 items; 95% confidence interval = 8.06, 11.60). Trialists need to address the perceived shortcomings in measurement, analysis, and reporting of harms data so that the available trial data can be considered as a balanced and reliable source of evidence.
Assuntos
Anti-Hipertensivos/administração & dosagem , Hipertensão/tratamento farmacológico , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Projetos de Pesquisa , Redação/normas , Anti-Hipertensivos/efeitos adversos , Intervalos de Confiança , Humanos , Guias de Prática Clínica como Assunto/normas , Reino UnidoRESUMO
Primary Psoas abscess (PPA) is an infrequent clinical entity with obscure pathogenesis and vague clinical presentation. High index of clinical suspicion is required for the diagnosis of psoas abscess. We also emphasises the importance of bacteriological confirmation of microorganism involved, although Staphylococcus aureus remains the commonest pathogen. We report an extremely rare case of PPA caused by Streptococcus milleri. Only one case has been reported in literature so far.
Assuntos
Abscesso do Psoas/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus milleri (Grupo)/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Abscesso do Psoas/patologia , Radiografia Abdominal , Infecções Estreptocócicas/patologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Primary Non-Hodgkin's Lymphoma (PHNL) of the breast is a rare entity, while secondary involvement of the breast with diffuse disease of Non-Hodgkin's lymphoma (NHL) is more common. However, PNHL is the most frequent haematopoietic tumour of the breast. Diagnostic criteria for PNHL of the breast are presence of technically adequate pathologic specimens, close association of mammary tissue and lymphomatous infiltrate, no prior diagnosis of an extarammamary lymphoma, and no evidence of concurrent widespread disease, except for ipsilateral axillary lymph nodes if concomitant with the primary lesion. CASE PRESENTATION: A 57-year-old woman was recalled because her screening mammograms revealed three separate lesions in her right breast and one in the left. Histology of the lesions confirmed lymphoma in one breast with ductal carcinoma in the other. CONCLUSION: Most of reported cases in literature have been involving the right breast, and almost all the patients were females. NHLs of the breast typically present as unilateral mass; the frequency of bilateral disease at first presentation ranges from 5-25%. Our objective is to report a case of primary lymphoma of the breast involving both axillae with concomitant bilateral primary breast cancer which has not been reported yet to our best of knowledge in literature.
Assuntos
Neoplasias da Mama/patologia , Linfoma não Hodgkin/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/terapia , Mamografia , Pessoa de Meia-IdadeRESUMO
Background: The oral selective phosphodiesterase-4 inhibitor roflumilast (ROF) reduces exacerbations in patients with severe COPD. Adverse events (AEs) can cause early ROF discontinuation. Alternative dosing strategies may help patients continue their therapy. Methods: In this multicenter, double-blind trial, 1,321 patients with severe COPD were randomized 1:1:1 to 4 weeks' treatment with ROF 250 µg once daily (OD), 500 µg every other day (EOD), or 500 µg OD, each followed by ROF 500 µg OD for 8 weeks, plus standard therapy. The primary end point was the percentage of patients prematurely discontinuing study treatment. Results: Patients in the 250 µg OD/500 µg OD group had significantly fewer treatment discontinuations (odds ratio [OR] 0.66 [95% CI 0.47-0.93], p=0.017) and lower rates of AEs of interest such as diarrhea, nausea, headache, decreased appetite, insomnia and abdominal pain (OR 0.63 [95% CI 0.47-0.83], p=0.001) compared with those in the 500 µg OD group. Although rates of discontinuation and AEs of interest were numerically lower with ROF 500 µg EOD/500 µg OD, the difference was not significant (OR 0.76, p=0.114, and OR 0.78, p=0.091, respectively) compared with ROF 500 µg OD. Conclusion: A dose of ROF 250 µg OD for 4 weeks before escalation to the approved maintenance dose of 500 µg OD resulted in reduced treatment discontinuation and improved tolerability.
Assuntos
Aminopiridinas/administração & dosagem , Benzamidas/administração & dosagem , Pulmão/efeitos dos fármacos , Inibidores da Fosfodiesterase 4/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Aminopiridinas/efeitos adversos , Aminopiridinas/farmacocinética , Benzamidas/efeitos adversos , Benzamidas/farmacocinética , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Ciclopropanos/farmacocinética , Progressão da Doença , Método Duplo-Cego , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Modelos Logísticos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Inibidores da Fosfodiesterase 4/efeitos adversos , Inibidores da Fosfodiesterase 4/farmacocinética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The clinical effects of roflumilast, a selective phosphodiesterase-4 inhibitor, are well established, but little is known about the anti-inflammatory mechanisms underlying the drug's efficacy. The aim of the ROflumilast Biopsy European Research Trial (ROBERT) was to assess the anti-inflammatory effects of roflumilast on bronchial mucosal inflammation in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) and chronic bronchitis. METHODS: ROBERT was a randomised, double-blind, placebo-controlled trial done at 18 sites in five countries. Eligible patients were aged 40-80 years, had COPD, and had had a chronic productive cough for 3 months in each of the two previous years. Patients also had to have a post-bronchodilator predicted FEV1 30-80% and a post-bronchodilator FEV1/forced vital capacity ratio of 70% or less. Patients entered a 6-week run-in period before being randomly assigned (1:1) via a computerised central randomisation system to roflumilast 500 µg once daily or placebo for 16 weeks, in addition to bronchodilator therapy (inhaled corticosteroids were not permitted). Randomisation was stratified by concomitant use of long-acting ß agonist. Both participants and investigators were masked to group assignment. Roflumilast and placebo were supplied as identical yellow, triangular tablets. Airway inflammation was assessed by quantification of inflammatory cells in bronchial biopsy samples and induced sputum samples. The primary endpoint was the change in the number of CD8 inflammatory cells in bronchial biopsy submucosa from randomisation to week 16 in the intention-to-treat population. Changes in cell counts of additional inflammatory markers, including eosinophils, were assessed as secondary endpoints. This trial is registered with ClinicalTrials.gov, number NCT01509677, and is closed to new participants, with follow-up completed. FINDINGS: Between Jan 4, 2012, and Feb 11, 2016, 158 patients were randomly assigned: 79 to the roflumilast group, and 79 to the placebo group. At week 16, the change in the number of CD8 cells in the bronchial submucosa did not differ significantly between the roflumilast and placebo groups (treatment ratio 1·03 [95% CI 0·82-1·30]; p=0·79). However, compared with placebo, roflumilast was associated with a significant reduction in eosinophils in bronchial biopsy samples at week 16 (treatment ratio 0·53 [95% CI 0·34-0·82]; p=0·0046). Significant reductions in both absolute (p=0·0042) and differential (p=0·0086) eosinophil cell counts in induced sputum were also noted with roflumilast compared with placebo, but peripheral blood eosinophil counts were not significantly affected. We noted no other significant effects of roflumilast on bronchial mucosal inflammatory cells. The most common (ie, occurring in >5% patients) moderate adverse events were worsening of COPD (three [4%] patients in the roflumilast group vs seven [9%] in the placebo group), cough (six [8%] vs four [5%]), diarrhoea (four [5%] vs three [4%]), and nasopharyngitis (three [4%] vs five [6%]). Severe adverse events included worsening of COPD, which occurred in four (5%) patients in the roflumilast group and two (3%) in the placebo group. No deaths occurred during the study. Serious adverse events occurred in eight (10%) patients in the roflumilast group and five (6%) in the placebo group. INTERPRETATION: 16 weeks of treatment with roflumilast did not affect the number of CD8 cells in bronchial submucosa compared with placebo. However, we noted significant reductions in eosinophil cell counts in bronchial biopsy samples and induced sputum, generating the hypothesis that the effect of roflumilast in COPD could be mediated by an effect on lung eosinophils. FUNDING: Takeda and AstraZeneca.
Assuntos
Aminopiridinas/administração & dosagem , Benzamidas/administração & dosagem , Eosinófilos/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Aminopiridinas/efeitos adversos , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Benzamidas/efeitos adversos , Biópsia , Broncodilatadores/uso terapêutico , Linfócitos T CD8-Positivos , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/patologia , Sistema Respiratório/efeitos dos fármacosRESUMO
Endometriosis is the ectopic growth of viable endometrium outside the uterus, affecting approximately 7% of females. It commonly affects pelvic structures including the bowel. Perforation of the colon by endometriosis is very rare and the patients generally present with an asymptomatic or painful pelvic mass, often in the left iliac fossa. Our patient presented acutely unwell and her symptoms were more suggestive of pyelonephritis or diverticulitis. We therefore report an unusual cause of acute abdomen. The purpose of the following case report is to elucidate certain diagnostic and therapeutic problems of the disease, concerning both surgeons and gynaecologists. In summary, intestinal endometriosis should be considered in the differential diagnosis of all post-menarche women with episodic gastrointestinal symptoms. A past history of endometriosis or co-existent gynaecological symptoms should increase the index of suspicion, and laparoscopy prior to formal laparotomy should be considered. Our patient, in retrospect, had a history of mild endometriosis, but we feel that this case serves as a reminder of a rare, but important, differential diagnosis of acute abdomen in females.
Assuntos
Doenças do Colo/etiologia , Endometriose/complicações , Enteropatias/complicações , Perfuração Intestinal/etiologia , Adulto , Doenças do Colo/patologia , Endometriose/patologia , Feminino , Humanos , Enteropatias/patologia , Mucosa Intestinal/patologia , Perfuração Intestinal/patologiaRESUMO
There has been a recent increase in the use of endovascular prostheses resulting in complex surgical and interventional complications not previously recognised. We report a case of Superior vena cava stenosis treated with a wallstent which migrated to the right atrium, necessitating a combined radiological and surgical approach to retrieve it.