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1.
Dig Dis Sci ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900712

RESUMO

BACKGROUND: In adults, post-liver transplantation anemia (PLTA) is common, but its characteristics and long-term influence on major outcomes have yet to be elucidated. AIM: We aimed to assess prevalence, characteristics, predictors, and outcomes of PLTA at 6 months (early PLTA) and at 2 years (late PLTA). METHODS: A single-center retrospective cohort study using prospectively collected data from liver transplantations in adults during January 2007-December 2015. PLTA impact on various long-term outcomes was assessed, including mortality, composites of mortality or graft failure, cardiovascular outcomes, and malignancy occurrences. RESULTS: Hundred and fifty liver transplanted individuals were included. There was a 79% prevalence of anemia pre-transplantation, whereas early and late PLTA were evident in 58% and 40% of patients, respectively. Pre-transplantation anemia was associated with development of early PLTA which was associated with late PLTA. In a multivariate analysis, early PLTA was significantly associated with mortality or graft failure at a follow-up of 3 years (odds ratio 3.838, 95% CI 1.114-13.226). Late PLTA was not significantly associated with worse long-term outcomes. CONCLUSIONS: Early and late PLTA are prevalent among liver transplanted patients. Early PLTA is associated with long-term mortality or graft failure.

2.
Dig Dis ; : 1-7, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910424

RESUMO

INTRODUCTION: Suppression of gastric acid secretion with proton-pump inhibitors (PPI) is an integral part of the treatment of Helicobacter pylori infection. Esomeprazole has been shown to be superior to other PPIs when used in the context of triple therapy; however, comparative data for PPI efficacy in quadruple therapy are lacking. Current guidelines recommend H. pylori eradication with quadruple therapy in areas with high clarithromycin resistance. OBJECTIVE: To determine whether esomeprazole is more effective than other PPIs in the context of quadruple therapy for H. pylori eradication. METHODS: We retrospectively identified 25- to 60-year-old subjects with a positive 13C-urea breath test and no prior laboratory or endoscopic test for H. pylori infection. Pharmacy dispensation data were retrieved. RESULTS: A total of 7,896 subjects including 2,856 (36.2%) males, aged 40.4 ± 10.6 years, were identified. Of those, 78.1% received omeprazole, 20.1% received lansoprazole, 1.5% received esomeprazole, and 0.34% received pantoprazole together with antibiotics for H. pylori eradication. Esomeprazole was associated with a greater proportion of successful eradication (85.0 vs. 77.5%, esomeprazole vs. omeprazole, OR 1.64; 95% CI 0.99-2.72; p = 0.05). A nonsignificant trend favored esomeprazole over omeprazole among subjects receiving quadruple therapy (90.0 vs. 82.0%, respectively, OR 1.98; 95% CI 0.68-5.72; p = 0.16). Independent predictors of treatment success included older age and quadruple therapy. CONCLUSION: Esomeprazole is more beneficial than other PPIs for H. pylori eradication. Studies with larger subgroups are necessary to confirm our findings among subjects receiving quadruple therapy.

3.
Isr Med Assoc J ; 22(1): 22-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31927801

RESUMO

BACKGROUND: Prophylactic cranial irradiation (PCI) exclusion in favor of brain magnetic resonance imaging (MRI) staging and surveillance in the management of small cell lung cancer (SCLC) is controversial yet accepted by some centers. The use of MRI suggests performing stereotactic radiosurgery (SRS) treatment for limited brain metastases. Data regarding SRS efficacy in this setting is limited. OBJECTIVES: To assess intracranial objective response rate (iORR), progression-free survival (iPFS), intracranial failure patterns, overall survival (OS) and time-to-whole-brain radiation therapy (WBRT)/death, whichever occurred first (TTWD) with SRS in SCLC. METHODS: The study comprised 10 consecutive SCLC patients with brain metastases treated with SRS and followed-up at Davidoff Cancer center between Aug 2012 and March 2019. Brain MRI images were reviewed by a neuro-radiology specialist. RESULTS: iORR was 57% as assessed by response assessment in neuro-oncology brain metastases. Intracranial progression developed in 8 patients. Median iPFS was 4.0 months (95% confidence interval [95%CI] 1.7-7.2). In-site, off-site and combined pattern of intracranial failure was seen in 0, 5, and 3 patients, respectively; median number of new brain lesions following SRS was 4 (range, 1-12). SRS was performed 10 additional times in 6 patients (median number of lesions irradiated per round was 1, range 1-5). WBRT was administered in 3 patients. Median TTWD was 20.9 months (95% CI, 1.9-26.8). Median OS since SRS administration was 23.2 months (95% CI, 4.2-not reached). CONCLUSIONS: MRI surveillance with multiple rounds of SRS may serve a reasonable alternative to PCI or therapeutic WBRT in SCLC.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Pulmonares/patologia , Radiocirurgia , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Intervalo Livre de Progressão , Radiocirurgia/métodos , Resultado do Tratamento
4.
Artigo em Inglês | MEDLINE | ID: mdl-31851128

RESUMO

OBJECTIVES: Fontan surgery, the final surgical stage in single ventricle palliation, redirects systemic venous blood into the pulmonary circulation for gas exchange. A decrease in pulmonary blood flow can lead to major complications and grave outcomes. Alveolar dead-space fraction represents the portion of inhaled air that does not participate in gas exchange and hence quantifies ventilation-perfusion abnormalities in the lung. Increased alveolar dead-space fraction has been associated with prolonged mechanical ventilation and worse outcome after congenital heart surgery. The association of alveolar dead-space fraction with clinical outcomes in patients undergoing Fontan operation has not been reported. INTERVENTIONS: None. DESIGN, SETTING, AND PATIENTS: A retrospective charts review of all pediatric patients who underwent Fontan surgery during June 2010-November 2018 in a tertiary-care pediatric hospital. Associations between alveolar dead-space fraction and arterial oxyhemoglobin saturation to a composite outcome (surgical or catheter-based intervention, extracorporeal membrane oxygenation use, prolonged ventilation, prolonged hospital length of stay, or death) were explored. Secondary endpoints were parameters of severity of illness, chest drainage duration, and length of stay. MEASUREMENTS AND MAIN RESULTS: Of 128 patients undergoing Fontan operation, 34 met criteria for composite outcome. Alveolar dead-space fraction was significantly higher in the composite (0.33 ± 0.14) versus control (0.25 ± 0.26; p = 0.016) group. Alveolar dead-space fraction greater than or equal to 0.29 indicated a 37% increase in risk to meet composite criteria. Admission arterial oxygen saturation was significantly lower in composite versus control group (93.4% vs 97.1%; p = 0.005). Alveolar dead-space fraction was significantly associated with increased durations of mechanical ventilation, ICU length of stay, duration of thoracic drainage, and parameters of severity of illness. CONCLUSIONS: Alveolar dead-space fraction and arterial saturation may predict complicated postoperative course in patients undergoing the Fontan operation.

5.
Acta Haematol ; : 1-6, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752009

RESUMO

INTRODUCTION: A restrictive transfusion strategy of packed red blood cells (PRBCs) has been associated with at least non-inferior patient outcomes in a variety of clinical settings. In December 2014, we conducted an educational intervention which consisted of an oral presentation and computerized notifications at a single tertiary medical center. OBJECTIVE: The aim of this study was to examine the long-term effects of a simple and low-cost educational intervention aimed to promote awareness to transfusion guidelines. METHODS: We retrospectively analyzed all PRBC transfusions ordered between 2014 and 2017. The primary end point was defined as the percentage of PRBC transfused to patients with hemoglobin (Hb) ≥8 g/dL. RESULTS: Between 2014 and 2017, a total of 27,475 PRBCs were transfused in our medical center. There was a continuous reduction in the percentage of PRBCs transfused at a Hb level ≥8 g/dL between 2014 and 2017, with a matching increase in the PRBC percentage trans-fused at Hb <7 g/dL (OR reduction of 42%, 95% CI 0.54-0.62 and OR increase of 68% [95% CI 1.56-1.81], respec-tively). CONCLUSION: A simple educational intervention likely contributed to sustained improvement in the appropriateness of PRBC transfusions.

6.
Mayo Clin Proc ; 94(11): 2272-2276, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31685153

RESUMO

The International Committee of Medical Journal Editors requires authors to disclose all financial conflicts of interest (COI) that can be perceived as influencing the related trials. Undisclosed financial COI may influence the perception of the authors' scientific impartiality and erode the public trust in the reported results. Data regarding completeness of COI disclosure in high-impact-factor general medicine journals are limited. We compared payments disclosed by US-based physicians who were first or last authors of clinical drug trials published between August 2016 and August 2018 in the New England Journal of Medicine, JAMA, and Lancet, to payments reported by industry to the Centers for Medicare & Medicaid Services Open Payments Database. Of 247 included authors, 198 (80%) have not disclosed some or all received payments. The median undisclosed sum was $8409 (US Dollars) (interquartile range [IQR] $123 to $44,890). Most authors (n=170, 69%) have received more than $10,000 per year (median $120,403, IQR $58,905 to $242,014). The median undisclosed sum for these authors was $26,530 (IQR $7462 to $71,562). Median undisclosed sums for authors of papers from studies performed with and without industry funding were $20,899 (IQR $4191 to $59,883) and $149 (IQR $0 to $3276), respectively. In 10 (8%) of 125 industry-funded trials, the first or last author had not disclosed personal payments from the study sponsor (median $9741, IQR $4508 to $101,484). These findings could raise concerns about the authors' equipoise toward the trial results and influence the public perception of the credibility of reported data. Health care professionals, reviewers, and journal editors should demand more transparent reporting of financial COI.


Assuntos
Autoria/normas , Compensação e Reparação/ética , Conflito de Interesses/economia , Publicações Periódicas como Assunto/normas , Médicos/psicologia , Estudos de Coortes , Políticas Editoriais , Humanos , Médicos/economia , Médicos/normas
7.
Anesth Analg ; 129(6): 1595-1606, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31743180

RESUMO

BACKGROUND: The impact of physiological adjustments throughout pregnancy on maternal vital signs and laboratory values has yet to be fully defined. The present study was designed to determine the normal range of these parameters among healthy pregnant women during the peripartum period. METHODS: This is a retrospective analysis of data collected during real-time deliveries in a single medical center. Vital signs and laboratory results from the 24 hours preceding delivery room admission and up to 72 hours postpartum were collected. Only pregnant women at term (37 to 41 weeks' gestation) with a liveborn, singleton gestation, and no chronic disease or obstetric complication that could affect the physiological parameters under study were included. The mean, range, and standard deviations of the extremes of all parameters at 3 distinct time points (prelabor, intrapartum, and postpartum) were calculated. The 2.5 and 97.5 percentiles for each parameter were reported as the normal range. RESULTS: A total of 32,161 cases fulfilled inclusion criteria. The average gestational age at delivery was 39 weeks ± 8 days, and one-third of the cases were primiparous. During labor and after delivery, the upper limits of normal blood pressure values were 147/94 and 145/94 mm Hg, respectively. The lower limits were 83/43 and 83/42 mm Hg, respectively. Normal heart rates were 60-115 beats/min prelabor, 51-120 beats/min intrapartum, and 50-120 beats/min postpartum. Lowest normal temperatures ranged between 36.0°C and 36.3°C in the 3 study time points, and highest normal temperatures were 37.2°C prelabor and 37.6°C intra- and postpartum. The normal ranges of white blood cell counts were 6.1-16.8 prelabor, 6.5-22.5 intrapartum, and 6.4-23.9 K/µL postpartum. Normal low values of hemoglobin were 9.7, 8.7, and 7.1 g/dL and of platelets were 117, 113, and 105 K/µL, respectively. CONCLUSIONS: Our findings justify the practice of using ≥2 repeated measurements for diagnosing hypertensive disorders of pregnancy. Lower normal blood pressure limits may be below those defining hypotensive shock. Normal heart rates exceed the accepted definitions of both tachy- and bradycardia. Normal temperatures at all times have a more narrow range than previously thought, and the normal range of white blood cell count has outliers exceeding the current definitions of leukocytosis or leukopenia at all times. The normal lower range of hemoglobin was constantly below 10 g/dL, and normal platelet counts were considerably lower than those previously described. The vital signs and complete blood count values thus far considered normal for the peripartum period may require some adjustment. New definitions for hypotension, tachy- and bradycardia, fever, and leukocyte quantitative disorders should be considered.

9.
J Immunother ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31498181

RESUMO

The existing data with regard to immune-related neutropenia (irN), a rare (incidence-1%) immune-related adverse event of immune checkpoint inhibitors, are scarce. Eight patients with irN were identified through internal databases of 3 participating Israeli cancer centers. In addition, 11 original articles focusing on the clinical course of 24 patients with irN were selected during the PubMed search. Descriptive analysis of clinical and pathologic factors related to irN was performed (n=32); the effect of these on the irN outcomes was assessed. An algorithm for irN evaluation and treatment was proposed. The median time-to-onset of irN (n=32) was 60 days (range, 10-465 d). Grade 3-5 irN, febrile neutropenia, and irN-related death occurred in 81%, 50%, and 9% of patients, respectively. In all, 56%, 22%, 62%, and 25% of patients received PO corticosteroids, IV corticosteroids, granulocyte colony-stimulating factor (GCSF), and intravenous immunoglobulins (IVIG), respectively, with an improvement/resolution rate of 84%. Odds ratios for irN improvement/resolution were as follows: 1.40 [95% confidence interval (CI), 0.03-68.72], 0.43 (95% CI, 0.04-4.22), 2.60 (95% CI, 0.07-97.24), 0.36 (95% CI, 0.03-4.38), 4.02 (95% CI, 0.16-99.48), 2.01 (95% CI, 0.32-12.70), 1.08 (95% CI, 0.02-49.89), 0.42 (95% CI, 0.06-2.91), and 2.73 (95% CI, 0.42-17.51) for granulocyte hyperplasia, granulocyte/all lineage hypoplasia, granulocyte maturation blockade, lymphocyte infiltration on bone marrow biopsy, IV corticosteroids, PO corticosteroids, cyclosporine, IVIG, and GCSF, respectively (P>0.05 for all factors). IrN recurrence rate following immune checkpoint inhibitors rechallenge was 80%. IrN is a rare, life-threatening, early-onset immune-related adverse event. Differentiating between the central, peripheral, and modified peripheral types allows a better prognosis definition. Corticosteroids and GCSF represent the main treatment approaches; IVIG and cyclosporine should be used as salvage treatment.

10.
J Clin Gastroenterol ; 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31305279

RESUMO

GOALS: The goal of this study was to examine the impact of prior treatment with a nitroimidazole antibiotic on the success of Helicobacter pylori treatment. BACKGROUND: Prior nitroimidazole exposure may increase the likelihood of nitroimidazole-resistant H. pylori. Current H. pylori treatment guidelines recommend that, in the absence of susceptibility testing, patients with prior nitroimidazole exposure should not be treated with a nitroimidazole antibiotic. Data to support this recommendation are lacking. STUDY: We searched the Clalit Health Services database to identify subjects 25 to 60 years old who underwent a first-ever C-urea breath test between 2010 and 2015. Patients who underwent a previous H. pylori stool antigen test or gastroscopy were excluded. Pharmacy dispensation data were retrieved. RESULTS: A total of 1386 subjects (34.8% male individuals, age 40.7±10.7 y) received a nitroimidazole-containing regimen including 282 (20.4%) with prior nitroimidazole exposure. Successful eradication was achieved in 58.9% and 73.8% of subjects with and without prior nitroimidazole exposure, respectively (odds ratio, 0.51; 95% confidence interval, 0.39-0.67; P<0.0001). Nitroimidazole exposure adversely impacted the success of triple therapy with nitroimidazole, proton pump inhibitor, and amoxicillin or clarithromycin (39.4% vs. 63.4% and 54.4% vs. 73.6%, P<0.01, respectively), but not quadruple therapy. Following multivariate analysis, nitroimidazole exposure was significantly associated with eradication failure (odds ratio, 1.89; 95% confidence interval, 1.43-2.50; P<0.0001). A greater time elapsed from nitroimidazole exposure, and a lower cumulative nitroimidazole dose were observed in subjects with successful eradication (P<0.0001 for both). CONCLUSION: Nitroimidazole exposure may adversely impact the success of nitroimidazole-based triple therapy, but not quadruple therapy. Clinicians should conduct a thorough patient drug history before administering empiric treatment for H. pylori infection.

11.
Isr Med Assoc J ; 21(6): 394-398, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31280508

RESUMO

BACKGROUND: The main acquired resistance mechanism to first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR mutant non-small cell lung cancer (NSCLC) is the propagation of T790M clones, which can be detected in circulating tumor DNA (ctDNA). OBJECTIVES: To analyze osimertinib outcomes according to T790M testing method. METHODS: The study comprised 33 consecutive patients with advanced EGFR mutant NSCLC who were diagnosed with a T790M mutation after progression on first- or second-generation EGFR TKIs and treated with osimertinib. The patients were divided into groups A (diagnosed by tumor testing) and B (by ctDNA testing). Osimertinib outcomes were compared between the groups. RESULTS: Objective response rate with osimertinib comprised 54% and 62% in groups A and B, respectively (P = 0.58). Median progression-free survival (PFS) with osimertinib was 8.9 months (95% confidence interval [95%CI] 1.8-17.5) and 9.1 months (95%Cl 5.3-12.6) in groups A and B, respectively (log-rank test 0.12, P = 0.73). Median overall survival (OS) was 13.8 months (95%CI 4.9-25.5) and 13.8 months (95%Cl 7.7-27.7) in groups A and B, respectively (log-rank test 0.09, P = 0.75). T790M testing technique did not affect PFS (hazard ratio [HR] 1.16, 95%CI 0.50-2.69, P = 0.73) or OS (HR = 1.16, 95%CI 0.45-3.01, P = 0.76). The proportion of patients diagnosed by ctDNA grew from 56% in 2015 to 67% in 2016-2017. CONCLUSIONS: Our study provides a ctDNA validation for the purpose of T790M testing in EGFR mutant NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , DNA Tumoral Circulante/sangue , Neoplasias Pulmonares/tratamento farmacológico , Piperazinas/uso terapêutico , Acrilamidas , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Humanos , Israel , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Intervalo Livre de Progressão , Resultado do Tratamento
12.
J Nephrol ; 32(5): 783-789, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31165981

RESUMO

BACKGROUND: High concentrations of homocysteine are considered a risk factor for developing atherosclerosis and coronary artery disease. The aim of this study was to assess the concentrations of homocysteine in subjects with chronic kidney disease (CKD). METHODS: Data were collected from medical records of individuals examined at a screening center in Israel between the years 2000-2014. Cross sectional analysis was carried out on 17,010 subjects; 67% were men. RESULTS: Significant differences were observed between four quartiles of homocysteine concentrations and estimated glomerular filtration rate (eGFR)-the higher the homocysteine concentration, the lower the eGFR (p < 0.0001). In subjects with CKD, homocysteine plasma levels were correlated with the stage of renal impairment. Mean (SD) homocysteine concentrations in subjects with eGFR < 60 mL/min per 1.73 m2 compared to subjects with eGFR ≥ 60 mL/min per 1.73 m2 were: 16.3 (5.9) vs. 11.5 (5.5) µmol/L respectively. These findings remained significant after adjustment for age, smoking status, body mass index, hypertension and diabetes mellitus (p < 0.0001). Compared to subjects with homocysteine concentrations less than 15 µmol/L, those with homocysteine concentrations equal and above 15 µmol/L, had a significantly higher odds ratio (95% CI) of having an eGFR < 60 mL/min per 1.73 m2; non adjusted model, 8.30 (6.17-11.16); adjusted model for age smoking status, body mass index, hypertension and diabetes mellitus, 7.43 (5.41-10.21). CONCLUSION: Plasma homocysteine concentrations are higher in subjects with CKD. This may contribute to an increased risk for developing atherosclerosis and coronary artery disease in these patients.

13.
Clin Lung Cancer ; 20(4): 278-286.e1, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31060855

RESUMO

BACKGROUND: Real-life comparative data on BRAF inhibitors (BRAFi) and BRAFi + MEK inhibitors (MEKi) combination in BRAF-mutant (BRAFm) non-small-cell lung cancer (NSCLC) is lacking. PATIENTS AND METHODS: Consecutive BRAFm advanced NSCLC patients (n = 58) treated in 9 Israeli centers in 2009-2018 were identified. These were divided according to mutation subtype and treatment into groups A1 (V600E, BRAFi; n = 5), A2 (V600E, BRAFi + MEKi; n = 15), A3 (V600E, no BRAFi; n = 7), B1 (non-V600E, BRAFi ± MEKi; n = 7), and B2 (non-V600E, no BRAFi; n = 23); one patient received both BRAFi and BRAFi + MEKi. Safety, objective response rate, progression-free survival with BRAFi ± MEKi, and overall survival were assessed. RESULTS: Objective response rate was 40%, 67%, and 33% in groups A1, A2, and B1, respectively (P = .5 for comparison between groups A1 and A2). In group B1, G469A and L597R mutations were associated with response to BRAFi + MEKi. Median progression-free survival was 1.2 months (95% confidence interval [CI], 0.5-5.3), 5.5 months (95% CI, 0.7-9.3), and 3.6 months (95% CI, 1.5-6.7) for groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .04). Median overall survival with BRAFi ± MEKi was 1.7 months (95% CI, 0.5-NR), 9.5 months (95% CI, 0.2-14.9), and 7.1 months (95% CI, 1.8-NR) in groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .6). Safety profiles differed slightly, and similar treatment discontinuation rates were observed with BRAFi and BRAFi + MEKi. CONCLUSION: In the real-life setting, activity and safety of BRAFi + MEKi in V600E BRAFm NSCLC are comparable to those observed in prospective clinical trials; the combination of BRAFi + MEKi is superior to monotherapy with a BRAFi. Further research should be done to explore the impact of BRAFi + MEKi treatment on the natural history of BRAFm NSCLC.

14.
Am J Gastroenterol ; 114(6): 900-906, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31095531

RESUMO

OBJECTIVES: Helicobacter pylori (H. pylori) guidelines, including the recent ACG clinical guideline, recommend avoiding clarithromycin-based triple therapy (TT-C) among patients with past macrolide exposure. Data to support this recommendation are scarce, and the impact of macrolide exposure on quadruple therapies is unclear. We aimed to determine the impact of macrolide exposure on the efficacy of H. pylori treatment in our region. METHODS: We searched the Clalit Health Services database to identify subjects aged 25-60 years who underwent the first-ever C-urea breath test between 2010 and 2015. Patients who underwent a previous H. pylori stool antigen test or gastroscopy were excluded. Pharmacy dispensation data were retrieved. RESULTS: We identified 7,842 subjects (36.1% male individuals, age: 40.3 ± 10.5 years), including 3,062 (39.0%) with previous macrolide exposure. The efficacy of TT-C was 74.3% and 82.4% among subjects with and without macrolide exposure, respectively (odds ratio (OR), 0.62; 95% confidence interval (CI), 0.55-0.70; P < 0.0001). TT success was adversely affected by exposure to clarithromycin (55.5%; OR, 0.31; 95% CI, 0.24-0.39; P < 0.0001), roxythromycin (74.4%; OR, 0.65; 95% CI, 0.58-0.74; P < 0.0001), and erythromycin (73.9%; OR, 0.72; 95% CI, 0.57-0.89; P < 0.01) but not by exposure to azithromycin. A greater time elapsed because exposure to clarithromycin and roxythromycin was associated with higher eradication (OR, 1.007; 95% CI, 1.002-1.012; P < 0.01 and OR, 1.004; 95% CI, 1.002-1.006; P < 0.0001). A higher dose of clarithromycin and roxythromycin was associated with a lower likelihood of successful eradication (OR, 0.99988; 95% CI, 0.99982-0.99996; P < 0.01 and OR, 0.99981; 95% CI, 0.99971-0.99992; P < 0.001). The efficacies of sequential and concomitant therapies were 82.7% and 81.3%, respectively, and were not significantly affected by macrolide exposure. CONCLUSIONS: TT-C is adversely affected by previous exposure to macrolide antibiotics. Sequential, concomitant, and bismuth-based treatment may be preferred in this setting.

15.
Diagn Microbiol Infect Dis ; 95(1): 80-83, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31129007

RESUMO

INTRODUCTION: Risk factors for candidemia in the internal medicine wards (IMW) are poorly characterized. Their elucidation might assist in early diagnosis and treatment. OBJECTIVES: We aimed to elucidate predictors of candidemia in the IMWs comparing them to patients with gram-negative bacteremia (GNB). METHODS: A retrospective study of consecutive patients with candidemia in IMWs in Beilinson hospital (2007-2016) was performed. Patient demographics, comorbidities, and clinical characteristics were documented. The comparator group was GNB patients. RESULTS: Sixty-two patients with candidemia were compared with 178 patients with GNB. Candidemic patients were younger and with less body mass index > 20 kg/m2 (73 ±â€¯15 vs. 78 ±â€¯10, P = 0.01; 44% vs. 60%, P = <0.0001,respectively). In multivariate model, underweight, prior cephalosporin use, and central venous catheters (CVCs) were significantly associated with candidemia [odds ratio (OR) = 0.2, 95% confidence interval (CI) 0.07-0.4; OR = 4, 95% CI 1.3-11; and OR = 4, 95% CI 1.5-12, respectively]. CONCLUSION: Underweight, recent cephalosporin exposure, and CVCs were statistically significant predictors of candidemia in the IMW. Using these predictors might aid in recognizing high-risk patients for candidemia in the IMWs, leading to earlier appropriate empirical treatment.


Assuntos
Bacteriemia/epidemiologia , Candidemia/epidemiologia , Medicina Interna/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Hemocultura , Candida/isolamento & purificação , Candidemia/diagnóstico , Feminino , Bactérias Gram-Negativas/fisiologia , Hospitais , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco
16.
Oncol Res Treat ; 42(5): 275-282, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30955009

RESUMO

BACKGROUND: Little is known regarding the anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) efficacy and safety in the elderly. OBJECTIVES AND METHODS: Consecutive patients (n = 53) with ALK-positive advanced non-small cell lung cancer treated with an ALK TKI were identified through internal databases of three cancer centers and divided into groups A (< 65 years old; n = 34) and B (≥65 years old; n = 19). Progression-free survival (PFS), ALK TKI safety and overall survival (OS) were assessed. Uni- and multivariate PFS and OS analyses were performed. RESULTS: Crizotinib, ceritinib, and alectinib were administered in 94 and 100%, 35 and 31%, 38 and 52% of patients in groups A and B, respectively. The median PFS (months) was 5.4 (95% CI, 3.4-12.4) and 5.6 (95% CI, 2.5-14.7) with crizotinib (log-rank 0.0009, p = 0.9), 4.7 (95% CI, 1.0-11.5) and 23.0 (95% CI, 0.8-27.7) with ceritinib (log-rank 0.44, p = 0.5), and 21.2 (95% CI, 1.2 to not reached, NR) and 5.6 (95% CI, 0.5 to NR) with alectinib (log-rank 0.53, p = 0.5) in groups A and B, respectively. The median OS (months) comprised 29.8 (95% CI, 21.0 to NR) and 25.1 (95% CI, 10.8-53.6) in groups A and B, respectively (log-rank 0.57, p = 0.4). Age affected neither PFS nor OS. 19 and 37%, 50 and 40%, and 0 and 0% of patients in groups A and B, treated with crizotinib, ceritinib, and alectinib, respectively, developed high-grade adverse events. The treatment discontinuation rate was 9 and 21%, 16 and 60%, 0 and 0% with crizotinib, ceritinib, and alectinib in groups A and B, respectively. CONCLUSIONS: In the elderly, crizotinib, ceritinib, and alectinib treatments are associated with similar efficacy but different safety profiles; alectinib is associated with a lower rate of high-grade adverse events and a lower treatment discontinuation rate.


Assuntos
Quinase do Linfoma Anaplásico/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carbazóis/efeitos adversos , Carbazóis/uso terapêutico , Crizotinibe/efeitos adversos , Crizotinibe/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Sulfonas/efeitos adversos , Sulfonas/uso terapêutico , Adulto Jovem
17.
Eur J Clin Microbiol Infect Dis ; 38(4): 689-693, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30685806

RESUMO

An unabsorbed dietary iron supplementation can modify the colonic microbiota equilibrium and favor the growth of pathogenic strains over barrier strains. Nevertheless, the impact of oral iron supplements (OIS) use on the clinical outcomes of patients with gram-negative bacteremia (GNB) has not been evaluated. To explore the impact of OIS on the outcomes of patients with GNB. A retrospective study conducted in a tertiary hospital including patients with GNB during 2011-2016. The entire cohort was divided into chronic OIS users (study group) and nonusers (control group). The two groups were compared for the study outcomes, septic shock at presentation, length of hospital stay (LOS), and short-term mortality. The study cohort included 232 patients; 44 patients in the study group and 188 in the control one. There was no any significant difference in demographic and comorbidities characteristics between the two groups. Escherichia coli comprised the majority of bacteria (69%), while the urinary tract was the main source of the bacteremia. OIS alone and after adjustment was significantly associated with septic shock at presentation (OR = 2, CI95% [1.03-5], p = 0.04 and OR = 5, CI95% [1.4-15], p = 0.01, respectively). By multivariate analysis, OIS was significantly associated with 30-day mortality (OR = 3, CI95% [1.05-7], p = 0.04), but had no impact on LOS (16 + 23 vs. 12 + 15, p = 0.9). There is a significant association between chronic OIS exposure and increased adverse outcomes in patients with GNB. These findings might have important clinical implications.


Assuntos
Bacteriemia/patologia , Suplementos Nutricionais/efeitos adversos , Infecções por Bactérias Gram-Negativas/patologia , Ferro na Dieta/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/complicações , Estudos de Casos e Controles , Escherichia coli , Infecções por Escherichia coli/etiologia , Feminino , Infecções por Bactérias Gram-Negativas/complicações , Mortalidade Hospitalar , Humanos , Ferro na Dieta/administração & dosagem , Masculino , Registros Médicos , Pessoa de Meia-Idade , Estudos Retrospectivos , Choque Séptico/etiologia , Choque Séptico/mortalidade , Centros de Atenção Terciária/estatística & dados numéricos , Infecções Urinárias/complicações , Infecções Urinárias/microbiologia
18.
Ann Thorac Surg ; 107(2): 539-545, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30617023

RESUMO

BACKGROUND: Late tricuspid regurgitation is a common finding in patients with rheumatic valvular disease after mitral valve replacement surgery. However, the long-term benefit of concomitant tricuspid valve annuloplasty has not been established in this population. METHODS: This was a single-center retrospective study in a tertiary hospital. The final cohort included 285 rheumatic patients who underwent either isolated mitral valve replacement (147 patients) or mitral valve replacement with concomitant tricuspid valve annuloplasty (138 patients). Tricuspid regurgitation severity grade was assessed according to current echocardiography guidelines and graded using a 0 to 3 scale (none or trivial, mild, moderate, severe). RESULTS: Patients were followed for a total median duration of 10.8 (interquartile range, 6.8 to 14.5) years. The majority of patients undergoing mitral valve replacement were women, with a median age at operation of 59 (interquartile range, 48 to 68) years. Patients undergoing concomitant tricuspid valve annuloplasty had a 3.4-fold odds of improving their tricuspid regurgitation grade at long-term follow-up by multivariate logistic regression. Furthermore, concomitant tricuspid valve annuloplasty was independently associated with a long-term survival benefit in patients with preoperative moderate or severe tricuspid regurgitation (hazard ratio, 0.44; 95% confidence interval, 0.23 to 0.87; p = 0.018). CONCLUSIONS: This study demonstrates good long-term results in patients with rheumatic heart disease undergoing mitral valve replacement with concomitant tricuspid valve annuloplasty.


Assuntos
Anuloplastia da Valva Cardíaca/métodos , Previsões , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Cardiopatia Reumática/cirurgia , Insuficiência da Valva Tricúspide/cirurgia , Valva Tricúspide/cirurgia , Idoso , Ecocardiografia , Feminino , Seguimentos , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/etiologia , Reoperação , Estudos Retrospectivos , Cardiopatia Reumática/complicações , Cardiopatia Reumática/mortalidade , Taxa de Sobrevida/tendências , Resultado do Tratamento , Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/diagnóstico , Insuficiência da Valva Tricúspide/etiologia
19.
Drugs Aging ; 36(2): 165-177, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30460518

RESUMO

BACKGROUND: There is a paucity of data on apixaban levels among octogenarians with non-valvular atrial fibrillation (NVAF). We aimed to compare apixaban levels between octogenarians (with and without dose reduction) and younger patients, to assess the frequency of high and above-range drug levels. METHODS: A cross-sectional, prospective study of 80 patients treated with apixaban for NVAF was conducted. Apixaban levels were compared among octogenarians treated with 5 mg twice daily (bid), octogenarians with appropriately reduced dose (2.5 mg bid), octogenarians with inappropriately reduced dose and younger patients (age < 70 years). Trough and peak levels were measured by a chromogenic assay calibrated for apixaban and compared to predicted manufacturer levels. RESULTS: A significant proportion of the cohort had above-range trough [n = 11 (13.8%)] and peak [n = 16 (20%)] levels, especially octogenarians with the 5-mg bid dosage [n = 6 (30%) for trough and n = 8 (40%) for peak]. No significant differences were found in the trough or peak geometric mean (GM) levels among the groups, apart from the peak GM levels between the 5-mg octogenarian group and the other two 2.5-mg bid octogenarian groups (p = 0.0004). The frequency of apixaban peak levels within the upper quartile was significantly higher in the 5-mg octogenarian group compared to the other groups [n = 12 (60%) of measurements, p = 0.019), whereas trough levels were comparable between groups. CONCLUSION: High and above-range peak apixaban steady-state levels are highly prevalent in octogenarians receiving the appropriate dosage of 5 mg bid for NVAF stroke prevention. Age above 80 strongly affects apixaban levels. TRIAL REGISTRATION: ClinicalTrials.gov Identifier number NCT02623049.


Assuntos
Fibrilação Atrial/sangue , Pirazóis/sangue , Piridonas/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/sangue , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Estudos de Coortes , Estudos Transversais , Inibidores do Fator Xa/sangue , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle
20.
Am J Med ; 132(1): 81-87, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30367857

RESUMO

PURPOSE: We initiated this study to evaluate the prevalence and clinical significance of tricuspid regurgitation in patients with left ventricular dysfunction. METHODS: A single-center analysis of all echocardiographic studies between 2000 and 2013 was performed. Patients with ejection fraction <35% were included, and those with mechanical valves, mitral stenosis, or significant aortic valve pathology were excluded. Patients were grouped based on tricuspid regurgitation severity (nonsignificant, moderate, and severe). Demographic and echocardiographic findings and survival were compared. RESULTS: The study included 3943 patients (74% male, age 69 ± 14 years); 70% had nonsignificant, 24% had moderate, and 6% had severe tricuspid regurgitation. In a multivariate model, tricuspid regurgitation was independently associated with older age (odds ratio [OR] 1.009; 95% confidence interval [CI], 1.001-1.017; P = .022), female sex (OR 1.644; 95% CI, 1.329-2.035; P < .001), atrial fibrillation (OR 1.764; 95% CI, 1.429-2.134; P < .001), tricuspid regurgitation gradient (OR 1.051; 95% CI, 1.045-1.058; P < .001 per mm Hg), right ventricular dysfunction (OR 3.492; 95% CI, 2.870-4.248; P < .001), left atrial area (cm2, OR 1.031; 95% CI, 1.013-1.049; P < .001), mitral regurgitation severity (P < .001), and lack of hypertension (OR 0.760; 95% CI, 0.616-0.936; P = .010) or obesity (OR 0.583; 95% CI, 0.427-0.796; P < .001). Patients were followed for a median of 8.15 years (interquartile range 4.75-11.42). Median survival was 4.88 years for nonsignificant, 2.3 years for moderate, and 1.6 years for patients with severe tricuspid regurgitation, significantly associated with tricuspid regurgitation severity (hazard ratio 1.513; 95% CI, 1.383-1.656 for moderate, hazard ratio 1.857; 95% CI, 1.606-2.148 for severe tricuspid regurgitation; P < .001), the association persisted after multiple adjustments. CONCLUSIONS: Significant tricuspid regurgitation is common in patients with left ventricular dysfunction. It is linked to various cardiac pathologies and independently associated with increased mortality.


Assuntos
Insuficiência da Valva Tricúspide/mortalidade , Disfunção Ventricular Esquerda/complicações , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Insuficiência da Valva Tricúspide/complicações , Insuficiência da Valva Tricúspide/diagnóstico por imagem
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