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1.
Ann Oncol ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39293515

RESUMO

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) that progresses on androgen receptor pathway inhibitors (ARPIs) may continue to be driven by AR signaling. BMS-986365 is an orally administered ligand-directed degrader targeting the AR via a first-in-class dual mechanism of AR degradation and antagonism. CC-94676-PCA-001 (NCT04428788) is a phase 1 multicenter study of BMS-986365 in patients with progressive mCRPC. PATIENTS AND METHODS: Patients who progressed on androgen deprivation therapy, ≥ 1 ARPI, and taxane chemotherapy (unless declined/ineligible) were enrolled. The study included dose escalation (Part A) and expansion (Part B) of BMS-986365 up to 900 mg twice daily (BID). Primary objectives were safety, tolerability, and to define maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Key secondary endpoints included decline in prostate-specific antigen ≥50% (PSA50) and radiographic progression-free survival (rPFS). RESULTS: Parts A and B enrolled 27 and 68 patients, respectively. In Part B, the median number of prior therapies was 4 (range 2-11). The most common treatment-related adverse events (TRAEs) were asymptomatic prolonged corrected QT interval (47%) and bradycardia (34%). Part A MTD was not reached and RP2D selection is ongoing. Across Part B three highest doses (400-900 mg BID, n = 60), PSA50 was 32% (n = 19), including 50% (n = 10/20) at 900 mg; median rPFS (95% CI) was 6.3 months (5.3-12.6), including 8.3 months (3.8-16.6) at 900 mg; and rPFS was longer in patients without versus with prior chemotherapy: 16.5 months (5.5-not evaluable) versus 5.5 months (2.7-8.3), respectively. Efficacy was observed in patients with AR ligand binding domain (LBD) WT or with AR LBD mutations. CONCLUSIONS: BMS-986365 was well tolerated, with a manageable safety profile, and demonstrated activity in heavily pretreated patients with potentially higher benefit in chemotherapy-naïve patients. These data show BMS-986365's potential to overcome resistance to current ARPIs, regardless of AR LBD mutation status.

3.
Trop Biomed ; 37(2): 372-378, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33612806

RESUMO

Interleukin (IL)-1 beta (IL-1ß), IL-2, Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) in the pleural fluid are valuable biomarkers in early diagnosis of Tuberculous Pleural Effusion (TPE). This study aimed to analyze the diagnostic values of some cytokines (IFN-γ, TNF-α, IL-1ß, and IL-2) in pleural fluid for identifying TPE in Vietnam. We performed a cross-sectional study on tuberculosis (TB) patients with pleural effusion. Pleural IFN-γ, TNF-α, IL-1ß, IL-2 were measured by ELISA® Kit (Abcam, USA) on Biotek system. Receiver operating characteristic curves (ROC), an area under the curve (AUC), sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (ACC) of IFN-γ, TNF-α, IL-1ß, IL-2 in identifying TBE were assessed. Among 386 patients, 234 (60,6%) had TPE, and 152 (39,4%) did not have TPE. The median of IL-2, TNF-α, and IFN-γ levels were significantly higher in TPE compared to the non-TPE group (p<0.05). AUC for IL-1ß, IL-2, TNF-α, and IFN-γ were 0.54, 0.57, 0.62. 0.84 (p<0.05), respectively. The sensitivity of IL-1ß, IL-2, TNF-α, and IFN-γ in the diagnosis of TPE were 82.1, 53.4, 77.8, and 80.3, while the specificity was 28,4, 69.7, 47.4, and 80.9, respectively. IFN-γ and TNF-α are potential biomarkers in diagnosing TPE.


Assuntos
Citocinas/análise , Derrame Pleural/diagnóstico , Tuberculose Pleural/diagnóstico , Adulto , Idoso , Área Sob a Curva , Biomarcadores/análise , Estudos Transversais , Feminino , Humanos , Interferon gama , Interleucina-1beta , Interleucina-2 , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Fator de Necrose Tumoral alfa , Vietnã
4.
Aliment Pharmacol Ther ; 48(1): 44-54, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29797518

RESUMO

BACKGROUND: Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. METHODS: This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. RESULTS: Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). CONCLUSIONS: Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Hepatite B/tratamento farmacológico , Hepatite B/mortalidade , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Ásia/epidemiologia , Carcinoma Hepatocelular/virologia , Estudos de Coortes , Uso Indevido de Medicamentos/estatística & dados numéricos , Feminino , Mau Uso de Serviços de Saúde/estatística & dados numéricos , Hepatite B/complicações , Vírus da Hepatite B/fisiologia , Humanos , Prescrição Inadequada/estatística & dados numéricos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Estados Unidos/epidemiologia
5.
Aliment Pharmacol Ther ; 47(5): 550-562, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29327780

RESUMO

BACKGROUND: Direct-acting antiviral (DAA) regimens have shown high efficacy and tolerability for patients with HCV genotype 1/1b (GT1/1b) in clinical trials. However, robust real-world evidence of interferon (IFN)-free DAA treatment for HCV GT1-infected patients in Asia is still lacking. AIM: To systematically review and meta-analyse the effectiveness and tolerability of IFN-free DAA therapy for HCV GT1 infection in Asia. METHODS: We included studies that enrolled adult patients with HCV GT1 infection in routine clinical practice in Asia, using IFN-free DAA regimens, and reported sustained virological response (SVR) after 12/24 weeks end-of-treatment by 31 May 2017. The pooled SVR rates were computed with a random-effects model. Subgroup analysis and meta-regression as previously registered in PROSPERO were performed to determine how pre-planned variables might have affected the pooled estimates. RESULTS: We included 41 studies from eight countries and regions, comprising of 8574 individuals. The pooled SVR rates for GT1 were 89.9% (95% CI 88.6-91.1, I2  = 55.1%) with daclatasvir/asunaprevir (DCV/ASV) and 98.1% (95% CI 97.0-99.0, I2  = 41.0%) with ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV). Baseline cirrhosis but not prior treatment history and age, attenuated the effectiveness of both regimens. Baseline resistance associated substitutions (RASs) severely attenuated SVR of DCV/ASV (65.4% vs 94.3%, P < 0.001) and only minimally with LDV/SOF ± RBV (94.5% vs 99.2%, P = 0.003). Patients with renal dysfunction treated with DCV/ASV showed a higher SVR rate (93.9% vs 89.8%, P = 0.046). Patients with hepatocellular carcinoma (HCC) LDV/SOF ± RBV achieved a lower SVR than those without HCC (94.1% vs 98.7%, P = 0.001). CONCLUSION: All oral DAA treatment of HCV GT1 resulted in high cure rates in Asian patients in routine clinical practice setting including elderly patients and those with end-stage renal disease.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Adulto , Ásia/epidemiologia , Quimioterapia Combinada/efeitos adversos , Medicina Geral/estatística & dados numéricos , Genótipo , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Resultado do Tratamento
6.
Aliment Pharmacol Ther ; 46(11-12): 1061-1069, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28960360

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is expected to become a leading aetiology of hepatocellular carcinoma (HCC)-related mortality in the United States. HCC treatments with curative intent (OLT, orthotopic liver transplantation; resection; RFA, radiofrequency ablation) can improve survival in carefully selected patients. AIM: To compare survival after receipt of curative treatment for NAFLD and non-NAFLD-HCC aetiologies (HCV, chronic hepatitis C; HBV, chronic hepatitis B; ALD, alcoholic liver disease) and by treatment was performed. METHODS: A cohort of 17 664 patients was assembled using linked Surveillance, Epidemiology, and End Results and Medicare data from 1991 to 2011 with confirmed diagnosis of HCC. RESULTS: The cohort was mostly male, aged 70 (21-106) years, without cardiovascular disease, and had liver cirrhosis without decompensation, metastatic HCC or large tumour size (>5 cm). The NAFLD-HCC group was mostly female and older with more cardiovascular disease, metastatic HCC, and large tumour size and less cirrhosis and decompensated liver disease than the non-NAFLD-HCC groups. The NAFLD group was 47% less likely to receive any curative treatment as compared with non-NAFLD aetiologies (OR 0.53, P < .001). NAFLD-HCC had worse median survival after OLT (3.2, 0-12.9 years, P = .01) but had improved survival after resection (2.4, 0-12.0 years, P < .001) as compared with non-NAFLD-HCC. No significant survival differences existed for RFA by HCC aetiology. NAFLD was not an independent predictor of mortality after OLT, resection or RFA. CONCLUSION: Patients with NAFLD-HCC had worse survival after OLT but favourable survival after resection, particularly in the absence of cirrhosis, as compared with non-NAFLD-HCC aetiologies.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Feminino , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática Alcoólica/complicações , Hepatopatias Alcoólicas/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/mortalidade
7.
Aliment Pharmacol Ther ; 46(6): 605-616, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28766727

RESUMO

BACKGROUND: Chronic hepatitis C (CHC) can lead to cirrhosis and hepatocellular carcinoma (HCC). A sustained virological response (SVR) is associated with improved outcomes, however, its impact on different ethnic groups is unknown. AIM: To evaluate ethnic differences in the natural history of CHC and the impact of SVR. METHODS: We conducted a cohort study of 8039 consecutive adult CHC patients seen at two medical centres in California between January 1997 and June 2016. Individual chart review confirmed CHC diagnosis. RESULTS: Asian and Hispanic but not African American patients had significantly higher cirrhosis and HCC incidence than Caucasians. On multivariate analysis, Hispanic ethnicity was independently associated with increased cirrhosis (adjusted HR 1.37, CI, confidence interval 1.10-1.71, P=.006) and HCC risk (adjusted HR 1.47, CI 1.13-1.92, P=.004) compared to Caucasian. Asian ethnicity had a significant association with cirrhosis (adjusted HR 1.28, CI 1.02-1.61, P=.034) and HCC risk (adjusted HR 1.29, CI 0.94-1.77, P=.025). In patients who achieved SVR, Hispanic ethnicity was no longer independently associated with cirrhosis (adjusted HR 1.76, CI 0.66-4.71, P=.26) or HCC (adjusted HR 1.05, CI 0.27-4.08, P=.94); nor was Asian ethnicity (adjusted HR 0.62, CI 0.21-1.82, P=.38 for cirrhosis; 2.01, CI 0.63-6.36, P=.24 for HCC). Similar findings were observed with overall survival among the ethnicities by SVR status. CONCLUSION: Hispanic and Asian ethnicity was independently associated with increased cirrhosis and HCC risk. Achieving an SVR eliminates the ethnic disparity in liver disease progression and overall survival between Hispanic and Asian vs Caucasian CHC patients.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Hepatite C Crônica/complicações , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , California , Estudos de Coortes , Progressão da Doença , Feminino , Hepatite C Crônica/etnologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
10.
Aliment Pharmacol Ther ; 44(8): 846-55, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27549411

RESUMO

BACKGROUND: Anti-viral therapy in chronic hepatitis B (CHB) is associated with a reduced risk of hepatocellular carcinoma (HCC) primary described in patients with cirrhosis. AIM: To examine the effects of treatment on HCC incidence in CHB with and without cirrhosis, after adjustment for background risks. METHODS: A total of 2255 CHB patients from a US cohort (973 received anti-viral therapy) and 3653 patients from the community-based Taiwanese REVEAL-HBV study, none of whom received treatment. We used Cox proportional hazard models to calculate the risk of developing HCC after adjustment with the previously validated REACH-B risk score. RESULTS: We found 273 incident cases of HCC. After adjustment, therapy lowered the risk of HCC development in the US treated cohort when compared to the US untreated cohort (HR 0.31; 95% CI: 0.15-0.66; P = 0.002). HCC risk reduction was also confirmed when compared to the REVEAL cohort (HR 0.22; 95% CI: 0.12-0.40; P < 0.001). Each REACH-B point was associated with a 53% increased risk of HCC (HR 1.53; 95% CI 1.46-1.59; P < 0.001). We found a significant statistical reduction in HCC incidence with therapy regardless of gender, age, cirrhosis status, HBeAg serology, alanine aminotransferase level, REACH-B score or treatment medication. Therapy was beneficial to those with mildly- to moderately elevated HBV DNA levels (>2000 IU/mL) and of even greater benefit to those with levels >200 000 IU/mL. CONCLUSION: After adjustment for background risk, anti-viral therapy was associated with a significant reduction in HCC incidence in both community and real-life clinical cohorts, including in those patients previously thought to be at low risk.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Adulto , Carcinoma Hepatocelular/etiologia , DNA Viral/sangue , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/complicações , Humanos , Incidência , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco
11.
Aliment Pharmacol Ther ; 44(4): 390-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27363288

RESUMO

BACKGROUND: Hepatitis B surface antigen (HBsAg) positivity is associated with increased risk for cirrhosis and hepatocellular carcinoma (HCC). HBsAg seroclearance is thought to be rare in general, but cohort data from US patients are limited. AIM: To determine the incidence of HBsAg seroclearance in a real-life US cohort. METHODS: In total, 4737 patients with chronic hepatitis B from five primary care, gastroenterology and multispecialty centres, and a university medical centre were retrospectively enrolled between 2001 and 2014 with data obtained by manual review of individual patient medical records. Seroclearance was determined by loss of HBsAg seropositivity. Persistent HBsAg was confirmed by direct serology or by proxy with positive hepatitis B e-antigen (HBeAg) or HBV DNA levels. RESULTS: HBsAg seroclearance occurred in 52 patients over 16 844 person-years (0.31% annually, 1.2% overall). Median follow-up was 32 months, and mean age 45 ± 14 years. Incidence of HBsAg seroclearance was higher in non-Asians, age >45, males, and those with baseline HBV DNA ≤10 000 IU/mL. On multivariate Cox proportional modelling, non-Asian ethnicity (HR 2.8), male sex (HR 2.1), baseline HBVDNA ≤10 000 (HR 2.0) and age >45 (HR 1.8) were significant independent predictors of seroclearance. CONCLUSION: HBsAg seroclearance rates were lower than previously described in this real-life cohort of patients with chronic hepatitis B, especially among Asian, female and younger patients.


Assuntos
Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/sangue , Adulto , DNA Viral/sangue , Etnicidade , Feminino , Vírus da Hepatite B/genética , Hepatite B Crônica/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos
12.
Aliment Pharmacol Ther ; 43(1): 134-44, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26510638

RESUMO

BACKGROUND: Entecavir (ETV) has been shown to be safe and efficacious in randomised controlled trials in highly selected patients with hepatitis B virus (HBV) infection. AIM: To determine the safety and effectiveness of ETV in 'real-world' HBV patients in the United States (US). METHODS: Treatment-naïve HBV patients ≥18 years old who received ETV for ≥12 months between 2005 and 2013 were included in a retrospective, cohort study. Rates of ALT normalisation, undetectable HBV DNA, HBeAg and HBsAg loss/seroconversion, adverse events (AE) and clinical outcomes were evaluated. RESULTS: Of 841 patients, 658 [65% male, 83% Asian; median age 47 years] met the inclusion criteria. 36% were HBeAg+ and 9.3% cirrhotic. 89% had abnormal ALT. Baseline median HBV DNA was 5.8 log 10 IU/mL. Median duration of ETV treatment was 4 years. Rates of ALT normalisation at 1, 3 and 5 years were 37.2%, 48.7% and 56.2% in HBeAg+ and 39.6%, 46.8% and 55.6% in HBeAg- patients. HBV DNA was undetectable at 1, 3 and 5 years in 34.6%, 64.7% and 84.6% in HBeAg+ patients, and 81.9%, 90.3% and 96.2% in HBeAg patients. Five-year cumulative probability of HBeAg loss and seroconversion was 46% and 33.7% and HBsAg loss was 4.6%. ETV was discontinued due to adverse events in 1.2% of patients. Hepatic decompensation occurred in 0.8%, liver cancer in 2.7% and death in 0.6%. CONCLUSION: Entecavir treatment was safe in a large cohort of US patients, but ALT normalisation and hepatitis B virus DNA suppression rates were lower than previously reported in clinical trials.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Feminino , Guanina/administração & dosagem , Guanina/efeitos adversos , Guanina/uso terapêutico , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
13.
Andrologia ; 47(2): 178-85, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24612408

RESUMO

Complex chromosome rearrangements (CCRs) are structural rearrangements involving at least three chromosomes and three or more chromosome breakpoints. Generally, balanced CCR carriers have a normal phenotype but they are at a higher reproductive risk. Azoospermia was discovered in the male partner of a couple with primary infertility. Conventional cytogenetics identified a CCR refined by fluorescent in situ hybridisation. The CCR involved three chromosomes, four breakpoints and an insertion. A literature search identified 43 phenotypically normal males referred for reproductive problems presenting a CCR. More males were ascertained because of spermatogenesis failure or disturbances than because of repeated abortions and/or birth of a malformed child. Male carriers of CCR produce a high frequency of chromosomally abnormal spermatozoa due to the aberrant segregation of the rearranged chromosomes. The number of chromosomes and breakpoints involved in the rearrangement, the position of breakpoints, the relative size of the resultant chromosomes and the presence or absence of recombination inside the paired-rearranged segments are presumed to affect the fertility of the carrier. Testicular biopsy should not be performed in males with azoospermia. Intracytoplasmic sperm injection should not be proposed as a procedure for treating the infertility of CCR male carriers as a successful result is unlikely.


Assuntos
Azoospermia/genética , Pontos de Quebra do Cromossomo , Rearranjo Gênico/genética , Infertilidade Masculina/genética , Adulto , Azoospermia/complicações , Azoospermia/diagnóstico , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 5/genética , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/etiologia , Masculino , Mutagênese Insercional/genética , Fenótipo
14.
Eur J Clin Microbiol Infect Dis ; 33(6): 1053-61, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24500598

RESUMO

Our objective was to model the cost-effectiveness and economic value of routine peri-operative Staphylococcus aureus screening and decolonization of lung and heart-lung transplant recipients from hospital and third-party payer perspectives. We used clinical data from 596 lung and heart-lung transplant recipients to develop a model in TreeAge Pro 2009 (Williamsport, MA, USA). Sensitivity analyses varied S. aureus colonization rate (5-15 %), probability of infection if colonized (10-30 %), and decolonization efficacy (25-90 %). Data were collected from the Cardiothoracic Transplant Program at the University of Pittsburgh Medical Center. Consecutive lung and heart-lung transplant recipients from January 2006 to December 2010 were enrolled retrospectively. Baseline rates of S. aureus colonization, infection and decolonization efficacy were 9.6 %, 36.7 %, and 31.9 %, respectively. Screening and decolonization was economically dominant for all scenarios tested, providing more cost savings and health benefits than no screening. Savings per case averted (2012 $US) ranged from $73,567 to $133,157 (hospital perspective) and $10,748 to $16,723 (third party payer perspective), varying with the probability of colonization, infection, and decolonization efficacy. Using our clinical data, screening and decolonization led to cost savings per case averted of $240,602 (hospital perspective) and averted 6.7 S. aureus infections (4.3 MRSA and 2.4 MSSA); 89 patients needed to be screened to prevent one S. aureus infection. Our data support routine S. aureus screening and decolonization of lung and heart-lung transplant patients. The economic value of screening and decolonization was greater than in previous models of other surgical populations.


Assuntos
Portador Sadio/diagnóstico , Portador Sadio/tratamento farmacológico , Programas de Rastreamento/economia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/isolamento & purificação , Transplantados , Centros Médicos Acadêmicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Simulação por Computador , Análise Custo-Benefício , Feminino , Transplante de Coração , Humanos , Lactente , Transplante de Pulmão , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Pennsylvania , Estudos Retrospectivos , Adulto Jovem
15.
Aliment Pharmacol Ther ; 39(4): 349-58, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24387289

RESUMO

BACKGROUND: Chronic hepatitis B (CHB) may lead to cirrhosis, hepatocellular carcinoma and premature death. Elevated alanine transaminase (ALT) levels ≥ the upper limit of normal (ULN) are a major determinant for initiating anti-viral therapy; however, ALT levels alone may not be predictive of hepatic fibrosis. AIM: To determine the proportion of CHB patients with ALT ≤ 40 IU/L and liver fibrosis stage ≥ 2. Secondary goals include subgroup analysis by hepatitis B e antigen (HBeAg) status, high hepatitis B virus (HBV) DNA levels, Asian ethnicity, lower ULN of ≤ 30 IU/L (males) and 19 IU/L (females), and advanced age. METHODS: Studies identified in EMBASE and MEDLINE (1/1990-6/2012) using the search criteria: "Hepatitis B"[Mesh] OR "Hepatitis B virus"[Mesh] OR "Hepatitis B, Chronic"[Mesh])) AND "Alanine Transaminase"[Mesh]) and abstracts containing the term 'hepatitis' from recent major U.S. gastroenterology and liver society meetings were considered. RESULTS: Among nine studies (N = 830 patients), a significant proportion (20.7%; 95% CI: 16.2-26.0%) of CHB patients with ALT levels ≤ 40 IU/L had significant fibrosis irrespective of HBeAg status, high HBV DNA levels, ethnicity or age, although this proportion may be higher in patients older than 30-40 years old. The corresponding proportion was 27.8% even when the newer ULN of 30 IU/L (males) and 19 IU/L (females) was applied. CONCLUSIONS: Approximately one fifth of CHB patients with ALT ≤ 40 IU/L may have significant hepatic fibrosis. The approach to such patients should be individualised, as further evaluation and treatment may be appropriate.


Assuntos
Alanina Transaminase/sangue , Hepatite B Crônica/fisiopatologia , Cirrose Hepática/etiologia , Adulto , DNA Viral/sangue , Feminino , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade
16.
Rev Med Suisse ; 9(400): 1780, 1782-4, 2013 Oct 02.
Artigo em Francês | MEDLINE | ID: mdl-24187752

RESUMO

The hearing is routinely tested in all newborns in most European countries. Thereafter, no hearing test is performed in a systematic way, despite the many conditions that can cause hearing loss in the first years of life. If language acquisition is possible with only one ear, even a unilateral hearing loss can be the cause of learning difficulties at school. In Geneva, a screening program for hearing deficit was introduced in 1955 in all primary schools of the canton. This paper shows the efficiency of the program, which can detect unnoticed deafness, sometimes in children whose neonatal screening had proved normal. Such a program should be applied to all private schools and to schools for disabled children.


Assuntos
Transtornos da Audição/diagnóstico , Testes Auditivos/estatística & dados numéricos , Programas de Rastreamento/métodos , Instituições Acadêmicas , Idade de Início , Criança , Pré-Escolar , Eficiência Organizacional , Feminino , Transtornos da Audição/epidemiologia , Humanos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Serviços de Saúde Escolar , Índice de Gravidade de Doença
17.
Am J Transplant ; 13(8): 2137-45, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23710593

RESUMO

We conducted a retrospective study of deep surgical site infections (SSIs) among consecutive patients who underwent lung transplantation (LTx) at a single center from 2006 through 2010. Thirty-one patients (5%) developed SSIs at median 25 days after LTx. Empyema was most common (42%), followed by surgical wound infections (29%), mediastinitis (16%), sternal osteomyelitis (6%), and pericarditis (6%). Pathogens included Gram-positive bacteria (41%), Gram-negative bacteria (41%), fungi (10%) and Mycobacterium abscessus, Mycoplasma hominis and Lactobacillus sp. (one each). Twenty-three percent of SSIs were due to pathogens colonizing recipients' native lungs at time of LTx, suggesting surgical seeding as a source. Patient-related independent risk factors for SSIs were diabetes and prior cardiothoracic surgery; procedure-related independent risk factors were LTx from a female donor, prolonged ischemic time and number of perioperative red blood cell transfusions. Mediastinitis and sternal infections were not observed among patients undergoing minimally invasive LTx. SSIs were associated with 35% mortality at 1 year post-LTx. Lengths of stay and mortality in-hospital and at 6 months and 1 year were significantly greater for patients with SSIs other than empyema. In conclusion, deep SSIs were uncommon, but important complications in LTx recipients because of their diverse microbiology and association with increased mortality.


Assuntos
Rejeição de Enxerto/mortalidade , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Pneumopatias/complicações , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias , Infecção da Ferida Cirúrgica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Bactérias Gram-Negativas/patogenicidade , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/mortalidade , Bactérias Gram-Positivas/patogenicidade , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/mortalidade , Humanos , Pneumopatias/mortalidade , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/mortalidade , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
18.
Aliment Pharmacol Ther ; 37(10): 921-36, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23557103

RESUMO

BACKGROUND: Chronic hepatitis C (CHC) infection is a risk factor for both the development of end-stage liver disease and hepatocellular carcinoma (HCC). Globally, approximately 170 million people are chronically infected with the hepatitis C virus (HCV), and the majority of these individuals come from the western Pacific and Southeast Asia regions (94.6 million persons combined). CHC is an understudied and underappreciated health problem in many Asian countries and in the US, where Asians represent one of the fastest growing groups of new Americans. AIM: To perform a systematic review of the current literature on the epidemiology, diagnosis and screening, clinical characteristics and response to anti-viral therapy of Asians with CHC. METHODS: Using a PubMed search of 'hepatitis C' and 'Asia,' 341 original manuscripts published in peer-reviewed journals were identified, and 99 were selected based on their relevance. RESULTS: Many Asian CHC patients do not have easily identifiable risk factors and may be underdiagnosed. Rates of HCV infection in Asians on community screening in the US are unexpectedly high, and there is a high prevalence of HCV genotype 6 in Southeast Asia and Southern China. HCV-infected Asians tend to present at older age and may have higher risk of HCC; however, they respond better to anti-viral therapy than non-Asians across all HCV genotypes. CONCLUSIONS: Given the high HCV endemicity in Asia, lack of identifiable risk factors and favourable treatment response rates in Asians, we advocate the screening for HCV infection of all Asians who come from areas where HCV prevalence is ≥2%.


Assuntos
Povo Asiático/etnologia , Hepatite C Crônica , Fatores Etários , Antivirais/uso terapêutico , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/etnologia , Humanos , Prevalência , Fatores de Risco
19.
J Viral Hepat ; 19(2): e105-11, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22239506

RESUMO

Commonly known risk factors for infection with hepatitis C virus (HCV) include blood transfusion, injection drug use, intranasal cocaine use, and body tattoos. We hypothesized that Asian Americans infected with HCV may not identify with these established risk factors present in Caucasians and Hispanics, and our aim was to conduct a survey of risk factors in HCV-infected patients in these ethnic groups. In this prospective study, 494 patients infected with HCV completed a detailed risk assessment questionnaire at a liver centre in Northern California from 2001 to 2008. Among subjects participating in this study, 55% identified themselves as Caucasian, 20% as Hispanic, and 25% as Asian. Asian Americans were older, less likely to smoke or consume alcohol, and have a family history of cancer compared with Caucasians and Hispanics. The laboratory profiles were similar, and genotype 1 was the most common infection in all groups (74-75%). The great majority of Caucasians (94%) and Hispanics (86%) identified with commonly known risk factors, which was in contrast to 67% of Asians (P < 0.0001). The most common risk factors in Asians were blood transfusions (50%) and acupuncture (50%). Furthermore, 74% of Caucasians and 66% of Hispanics identified more than one major risk factor, while only 20% of Asians reported having more than one risk factor (P < 0.0001). Survey for established risk factors for acquisition of HCV may be more appropriate for risk assessment of Caucasians and Hispanics, but not for Asian Americans. These findings may guide the development of HCV screening in our increasingly diverse population.


Assuntos
Hepatite C/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Asiático , California/epidemiologia , Estudos Transversais , Feminino , Hispânico ou Latino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , População Branca
20.
Transpl Infect Dis ; 12(2): 146-50, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19781019

RESUMO

Purulent pericarditis due to Mycoplasma hominis is rare, and is usually associated with mediastinitis or pleuritis following cardiothoracic surgery. We report the first case to our knowledge of isolated purulent pericarditis caused by M. hominis in a lung transplant recipient and review previously reported cases of this disease.


Assuntos
Transplante de Pulmão , Infecções por Mycoplasma/etiologia , Mycoplasma hominis , Pericardite/microbiologia , Complicações Pós-Operatórias/microbiologia , Adulto , Ecocardiografia , Feminino , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Infecções por Mycoplasma/diagnóstico , Derrame Pericárdico/microbiologia , Pericardite/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Radiografia
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