RESUMO
Due to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country-specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.
Assuntos
Gerenciamento Clínico , Saúde Global , Hepatite C Crônica/epidemiologia , Antivirais/uso terapêutico , Política de Saúde , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/mortalidade , Hepatite C Crônica/terapia , Humanos , Transplante de Fígado , PrevalênciaRESUMO
The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.
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Gerenciamento Clínico , Saúde Global , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/mortalidade , Viremia/epidemiologia , Viremia/mortalidade , Antivirais/uso terapêutico , Política de Saúde , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Incidência , Prevalência , Viremia/diagnóstico , Viremia/tratamento farmacológicoRESUMO
Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.
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Saúde Global , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/mortalidade , Modelos Estatísticos , Viremia/epidemiologia , Viremia/mortalidade , Antivirais/uso terapêutico , Política de Saúde , Hepatite C Crônica/tratamento farmacológico , Humanos , Incidência , Prevalência , Viremia/tratamento farmacológicoRESUMO
BACKGROUND/AIMS: Simple compound of Helicobacter pylori eradication therapy may improve drug compliance of patients. The aims of this study were to compare the efficacy and tolerability of a simple combination containing levofloxacin 7-day once-daily with standard twice-daily triple therapy. PATIENTS AND METHODS: This was a prospective, randomised, open-label trial. A total of 189 consecutive patients diagnosed with peptic ulcer and H. pylori infection were enrolled. Patients were randomly divided into two groups: LEC group--levofloxacin 500 mg, esomeprazole 40 mg and clarithromycin 500 mg once daily for 7 days; AEC group--amoxicillin 1 g, esomeprazole 40 mg and clarithromycin 500 mg twice daily for 7 days. RESULTS: There were 90 patients in the LEC group and 99 patients in the AEC group. By intention-to-treat and per-protocol analysis, the H. pylori eradication rate was 78.9% [71/90; 95% confidence interval (CI), 70.3-87.5%] and 83.5% (71/85; 95% CI, 75.5-91.6%) respectively, in the LEC group; and 74.8% (74/99; 95% CI, 66.0-83.5%) and 86.0% (74/86; 95% CI, 78.6-93.5%) respectively, in the AEC group. The incidence and tolerability of side effects were similar between these two groups. CONCLUSION: The efficacy and tolerability of once-daily levofloxacin-containing triple therapy are equal to those of the standard twice-daily triple therapy in this study. However, none of the treatment regimens evaluated achieved enough eradication efficacies to be considered as a recommendable first-line treatment.
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Antibacterianos/administração & dosagem , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori , Levofloxacino , Ofloxacino/administração & dosagem , Adulto , Idoso , Amoxicilina/administração & dosagem , Antibacterianos/efeitos adversos , Antiulcerosos/administração & dosagem , Claritromicina/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada/métodos , Esomeprazol/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ofloxacino/efeitos adversos , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: The survival duration for patients diagnosed with hepatocellular carcinoma (HCC) with main portal vein thrombosis (MPVT) was usually less than 3 months. The aim of this study is to elucidate whether treatment can prolong the survival for such patients. METHODOLOGY: Retrospectively we analyzed the clinical features and outcomes of 63 patients with HCC and MPVT over a 7-year period. Three therapeutic modalities--transcatheter arterial chemotherapy (TAC) with or without radiotherapy (RT), and systemic chemotherapy--were applied. RESULTS: The patients were divided into two groups: 34 (54%) patients were treated, while the remaining 29 (46%) were not. Multivariate analysis revealed that Child-Pugh class, Okuda stage for HCC and the presence of treatment were the principal factors to predict survival. The survival was significantly longer in treated patients than those untreated both in the Child-Pugh class A or B patients. Significantly longer survival is evident in patients treated by TAC combing RT compared to those underwent TAC alone, systemic chemotherapy or no treatment. CONCLUSIONS: The survival of Child-Pugh class A or B patients can be extended by the use of an appropriate therapeutic modality. TAC combined with RT did the best benefit to prolong survival in such patients.
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Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Trombose Venosa/tratamento farmacológico , Trombose Venosa/radioterapia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Distribuição de Qui-Quadrado , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Veia Porta/patologia , Modelos de Riscos Proporcionais , Radioterapia Conformacional , Estudos Retrospectivos , Análise de Sobrevida , Trombose Venosa/complicações , Trombose Venosa/patologiaRESUMO
BACKGROUND: Both spontaneous and nucleos(t)ide analogue (Nuc)-treated hepatitis B surface antigen (HBsAg) seroclearance are associated with excellent clinical outcomes. AIM: To conduct a case-control study to explore whether there is difference of clinical outcomes between these two groups. METHODS: A total of 312 chronic hepatitis B patients with spontaneous HBsAg seroclearance and 110 patients with Nuc-treated HBsAg seroclearance were recruited retrospectively. Propensity score (PS) matching method produced 98 patients in each group for comparison. The development of hepatocellular carcinoma (HCC), hepatic complications and cumulative incidence of antibody to HBsAg (anti-HBs) was compared. RESULTS: During a mean follow-up period of 107 months after HBsAg seroclearance, five patients developed HCC after a mean period of 75.3 months (four and one patients with spontaneous and Nuc-treated HBsAg seroclearance, respectively) in overall population. One died of pneumonia with sepsis and one experienced variceal bleeding in Nuc-treated patients but none in spontaneous group. The incidence of anti-HBs seroconversion was comparable between spontaneous and Nuc-treated HBsAg seroclearance (69.6% vs. 66.4%, respectively, P = 0.617). There were no significant differences in HCC development (2% vs. 1.1%), overall mortality (0% vs. 1%), variceal bleeding (0% vs. 4.2%) and 6-year cumulative incidence of anti-HBs seroconversion (62.3% vs. 61.5%) among PS-matched patients with spontaneous and Nuc-treated HBsAg seroclearance. CONCLUSIONS: The clinical outcomes between patients with spontaneous and Nuc-treated HBsAg seroclearance are comparable. HCC can develop at a low rate during long-term follow-up and periodic surveillance after HBsAg seroclearance is still mandatory.
Assuntos
Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Nucleotídeos/uso terapêutico , Adulto , Anticorpos Antivirais/sangue , Carcinoma Hepatocelular/epidemiologia , Estudos de Casos e Controles , Varizes Esofágicas e Gástricas/epidemiologia , Feminino , Hemorragia Gastrointestinal/epidemiologia , Antígenos de Superfície da Hepatite B/imunologia , Hepatite B Crônica/epidemiologia , Humanos , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
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Hepatite B Crônica/diagnóstico , Hepatite B Crônica/terapia , Hepatite B/diagnóstico , Hepatite B/terapia , Doença Aguda , África , Antivirais/uso terapêutico , Ásia , Gerenciamento Clínico , Feminino , Vírus da Hepatite B/isolamento & purificação , Humanos , MasculinoRESUMO
BACKGROUND: Long-term nucleos(t)ide analogues therapy may reduce hepatocellular carcinoma (HCC) in chronic hepatitis B patients with advanced fibrosis or cirrhosis. AIM: To investigate in a retrospective-prospective study whether this beneficial effect would be reduced in cirrhotic patients who discontinued a successful course of entecavir (ETV) therapy. METHODS: The study included 586 hepatitis B e antigen (HBeAg)-negative patients with compensated cirrhosis, mean age of 53.8 ± 10 years and 81% males, treated with ETV for at least 12 months. After ETV therapy for 46.5 ± 22.9 months, 205 patients who achieved hepatitis B virus (HBV) DNA suppression discontinued therapy. The clinical outcomes were assessed and HCC incidence was compared between propensity score (PS)-matched patients who continued and patients who discontinued ETV therapy by Asian Pacific Association for the Study of Liver stopping rule. RESULTS: During a mean duration of 59.3 ± 19 months after start of ETV therapy, nine and six HCC developed in an estimated annual incidence of 2.3% and 1.6% in 154 PS-matched patients who continued and who discontinued ETV therapy, respectively (P = 0.587). Multivariate Cox proportional hazards regression analyses showed that age (HR 1.065, P < 0.001) and HBV DNA (HR 1.216, P = 0.048) were the significant factors for HCC development. The rates of adverse clinical outcomes were comparable. CONCLUSIONS: The clinical outcomes, including HCC, after cessation of a successful course of entecavir therapy in patients with compensated cirrhosis were comparable to those who continued therapy. The results suggest that this strategy of finite therapy is safe and a feasible alternative to indefinite therapy, especially in a low resources setting.
Assuntos
Antivirais/administração & dosagem , Carcinoma Hepatocelular/epidemiologia , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Adulto , Idoso , Antivirais/uso terapêutico , Feminino , Guanina/administração & dosagem , Guanina/uso terapêutico , Antígenos E da Hepatite B/imunologia , Humanos , Incidência , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Hec1 (highly expressed in cancer 1) or Nek2 (NIMA-related kinase 2) is often overexpressed in cancers with poor prognosis. Both are critical mitotic regulators, and phosphorylation of Hec1 S165 by Nek2 is required for proper chromosome segregation. Therefore, inactivation of Hec1 and Nek2 by targeting their interaction with small molecules represents an ideal strategy for tackling these types of cancers. Here we showed that new derivatives of INH (inhibitor for Nek2 and Hec1 binding) bind to Hec1 at amino acids 394-408 on W395, L399 and K400 residues, effectively blocking Hec1 phosphorylation on S165 by Nek2, and killing cancer cells at the nanomolar range. Mechanistically, the D-box (destruction-box) region of Nek2 specifically binds to Hec1 at amino acids 408-422, immediately adjacent to the INH binding motif. Subsequent binding of Nek2 to INH-bound Hec1 triggered proteasome-mediated Nek2 degradation, whereas the Hec1 binding defective Nek2 mutant, Nek2 R361L, resisted INH-induced Nek2 degradation. This finding unveils a novel drug-action mechanism where the binding of INHs to Hec1 forms a virtual death-trap to trigger Nek2 degradation and eventually cell death. Furthermore, analysis of the gene expression profiles of breast cancer patient samples revealed that co-elevated expressions of Hec1 and Nek2 correlated with the shortest survival. Treatment of mice with this kind of tumor with INHs significantly suppressed tumor growth without obvious toxicity. Taken together, the new INH derivatives are suitable for translation into clinical application.
Assuntos
Neoplasias/metabolismo , Neoplasias/patologia , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Benzamidas/química , Benzamidas/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Proteínas do Citoesqueleto , Modelos Animais de Doenças , Progressão da Doença , Expressão Gênica , Xenoenxertos , Humanos , Indóis , Concentração Inibidora 50 , Mitose/efeitos dos fármacos , Modelos Moleculares , Conformação Molecular , Quinases Relacionadas a NIMA , Neoplasias/genética , Neoplasias/mortalidade , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/química , Proteínas Nucleares/genética , Fosforilação/efeitos dos fármacos , Prognóstico , Ligação Proteica/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Proteólise/efeitos dos fármacos , Tiazóis/química , Tiazóis/farmacologia , ValeratosRESUMO
Patients with dual infection with hepatitis B virus (HBV) and delta virus (HDV) responded poorly to interferon (IFN) therapy. Little is known about the effect of IFN therapy in patients with HBV and hepatitis C virus (HCV) dual infection. The patients in two randomized controlled trials with chronic HBV infection were retrospectively assayed for HCV markers. The HBV responses to IFN therapy in patients with and without HCV markers were compared. An open trial was conducted in 4 patients who had lost their serum HBV surface antigen (HBsAg) but had continuing HCV viremia and hepatitis. Of the 15 patients seropositive for HCV marker(s), only 1 (6.7%) responded with seroclearance of HBV DNA and HBV e antigen, as compared with 46 (28%) of 164 HCV-negative patients (p = 0.058). Icteric hepatitis developed in 1 patient on emergence of serum HCV RNA in association with seroclearance of HBV DNA. In contrast, good response was demonstrated in 3 of the 4 patients who had lost serum HBsAg before therapy. The results suggest that IFN therapy is not only of limited value in patients with dual infection with HBV and HCV but also has a potential risk of severe hepatitis if the clearance of one virus removes its suppressive effect on and facilitates the emergence of the other. However, patients with continuing HCV hepatitis after termination of the chronic HBsAg carrier state responded well to IFN therapy.
Assuntos
Antivirais/uso terapêutico , Hepatite B/terapia , Hepatite C/terapia , Interferon-alfa/uso terapêutico , Adulto , Idoso , Biomarcadores , Feminino , Hepatite B/virologia , Hepatite C/virologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes , Estudos RetrospectivosRESUMO
BACKGROUND: Prognosis of pyogenic liver abscesses in patients with malignant disease is generally considered poor. The discrepancy between the outcomes of liver abscesses caused by hepatopancreatobiliary malignant disease and those caused by other malignant diseases, however, to our knowledge has never been investigated. OBJECTIVES: To clarify the clinical course of pyogenic liver abscess in patients with different types of cancer, and to compare outcomes in abscesses caused by hepatopancreatobiliary malignant disease and other malignant disease. DESIGN: Retrospective review of case series in our experience from 1980 through 1993. SETTING: Tertiary care university teaching hospital. PATIENTS: Fifty-two patients with pyogenic liver abscess related to the underlying cancer were divided into 2 groups. Group 1 (n=32) was composed of patients with cancer originating from the hepatic parenchyma, bile duct, and pancreas; group 2 (n=20) was composed of patients with cancer originating from other sites. INTERVENTIONS: Parenteral antibiotics, percutaneous drainage, surgical drainage, or hepatectomy, in combinations, were employed. MAIN OUTCOME MEASURES: Patient characteristics, symptoms, laboratory data, abscess characteristics, microbiological study, management, and outcome of the 2 groups were analyzed. RESULTS: Thirteen patients (41%) in group 1 and 16 patients (80%) in group 2 had undergone prior anticancer treatment. Jaundice was encountered more often in group 1 than in group 2 (29 patients [91%] vs 6 patients [30%], respectively, P=.001), whereas nausea and vomiting were more frequently seen in group 2 than in group 1 (17 patients [52%] vs 6 patients[31%], respectively, P=.04). Leukocytosis, hypoalbuminemia, hyperbilirubinemia, and reversed albumin-globulin ratio were more pronounced in group 1 than in group 2 (P=.001, .02, .003, and .03, respectively). Abscesses communicating with the intrahepatic biliary tree were more frequently encountered in group 1 than in group 2 (11 patients [34%] vs 2 patients [10%], respectively, P=.03). Escherichia coli and Klebsiella pneumoniae predominated in group 1, while the bacteria species in group 2 were more diverse. The hospital mortality rates of group 1 and group 2 were 28% (9 of 32 patients) vs 10% (2 of 20 patients) (P=.04), respectively. Twenty-three patients (72%) of group 1 died of uncontrolled biliary sepsis or progressive cancer or both within 6 months after the diagnosis, while 17 patients (85%) of group 2 survived longer than 1 year without relapse of the abscess and continued with anticancer treatment. CONCLUSIONS: Pyogenic liver abscess could be a presentation of hepatopancreatobiliary malignant disease at the preterminal stage, and carries a grave prognosis. Pyogenic liver abscess in patients with nonhepatopancreatobiliary malignant disease has a better chance of favorable outcome.
Assuntos
Abscesso Hepático/diagnóstico , Abscesso Hepático/etiologia , Neoplasias/complicações , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Abscesso Hepático/microbiologia , Abscesso Hepático/mortalidade , Abscesso Hepático/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Supuração , Análise de Sobrevida , Resultado do TratamentoRESUMO
Sample stacking is a very important sample concentration technique. It has been used widely in capillary electrophoresis (CE). There are many different stacking techniques. One of the most popular techniques is called "field-amplified sample stacking" where an electric field discontinuity is set up across a concentration boundary. Charged analytes will then automatically stacked due to velocity changes after they cross the concentration boundary. There are several different strategies to perform sample stacking in microfluidic laboratory-on-a-chip devices. One could simply inject a plug of low concentration buffer containing sample into a channel surrounded by high concentration buffer. The electric field is then applied to stack the sample and move the whole plug into the separation channel. One could also stack the sample in a side channel adjacent to the separation channel. The disadvantage of this sample stacking technique is the difficulty in control of the precise location of stacked sample. We present a new sample stacking technique applied specifically to microfluidic laboratory-on-a-chip devices. Up to hundreds of fold increases in sample concentration can be achieved. We have also combined this stacking with electrophoretic separation in the same device.
Assuntos
Eletroforese Capilar/métodos , Indicadores e Reagentes , MiniaturizaçãoRESUMO
This paper introduces two new edge detection algorithms. One uses multiple difference-based edge detectors. This scheme selects peak center by absolute maximum or center of mass techniques. The other algorithm is motivated by the observation that second-order enhancement improves human contour extraction, but generally confuses difference-based edge detectors. This algorithm translates intensity images into three state images (plus one, zero, and minus one), then uses multiple three-state edge masks to find edge positions. The second scheme has a multiple hardware implementation and interesting biological analogs. Finally, the two operators introduced are compared to some popular edge detection techniques from the literature.
RESUMO
A theory for planning collision-free paths of a moving object among obstacles is described. Using the concepts of state space and rotation mapping, the relationship between the positions and the corresponding collision-free orientations of a moving object among obstacles is represented as some set of a state space. This set is called the rotation mapping graph (RMG) of that object. The problem of finding collision-free paths for an object translating and rotating among obstacles is thus transformed to that of considering the connectivity of the RMG. Since the connectivity of the graph can be solved by topological methods, the problem of planning collision-free paths is easily solved in theory. Using this theory, a topological method for planning collision-free paths of a rod-object translating and rotating among obstacles is presented. If a nonrigid robotic arm is viewed as a composite rod with some degrees of freedom, the planning of collision-free paths of a robotic arm can be solved in a similar way to a rod.
RESUMO
Declining hospital utilization has created excess hospital capacity in rural areas, has depressed occupancy rates, and threatens the financial viability of rural hospitals. Access to hospital care could be reduced and rural economies damaged if rural hospitals close. The federal Essential Access Community Hospital (EACH) demonstration program is an attempt to address these issues by establishing regional hospital networks. A preliminary analysis of the impact of state-wide implementation of the EACH program in Iowa suggests that about 60% of rural hospital beds and about 28% of all hospital beds would be eliminated. The EACH program could well prove difficult to implement because of the need to select hospitals for reduced services.
Assuntos
Hospitais Comunitários/organização & administração , Hospitais Rurais/organização & administração , Regionalização da Saúde/organização & administração , Ocupação de Leitos/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Hospitais Comunitários/classificação , Hospitais Comunitários/estatística & dados numéricos , Hospitais Rurais/classificação , Hospitais Rurais/estatística & dados numéricos , Iowa , Afiliação Institucional , Transferência de Pacientes , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , ViagemRESUMO
Chronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse chronic sequalae such as cirrhosis and hepatocellular carcinoma. Over the past 20 years, many antiviral or immunomodulatory agents, or both, have been used in patients with chronic HBV infection. Among immunomodulatory agents, levamisole, BCG, picibanil and interleukin-2 have been shown to be ineffective. Corticosteroid therapy is also ineffective and can cause deleterious effects in chronic HBV infection. Thymosin-alpha 1 therapy is currently in phase III clinical trial. Among antiviral agents, acyclovir, dideoxynucleosides, suramin, zidovudine and ganciclovir have been shown to be ineffective and have intolerable side effects. While adenine arabinoside (Ara-A) and its monophosphate derivative (Ara-AMP) are effective agents if the treatment course is long enough, they have been withdrawn from investigative use because of their substantial neuromuscular toxicity. Interferon-alpha may directly inhibit HBV replication and enhance hepatocyte HLA class I antigen expression with subsequent increase of T-cell mediated cytotoxicity. Randomized, controlled clinical trials have shown that 25% to 50% of adult patients with elevated alanine transaminase (ALT) levels lost HBeAg and HBV-DNA when treated with IFN-alpha at a dose of 5MU daily or 10 MU three times a week for 3 to 6 months. In view of the fact that the response rate is far from satisfactory, particularly in Asian patients, combination therapies including interferon alpha with Ara-AMP, acyclovir, didoxynucleoside or interferon-gamma have been studied. Most forms of combination therapy have been shown to be of limited effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Hepatite B/tratamento farmacológico , Corticosteroides/uso terapêutico , Adulto , Doença Crônica , Quimioterapia Combinada , Humanos , Interferons/uso terapêuticoRESUMO
Herpes esophagitis presents as dysphagia and odynophagia in the majority of cases. Rarely has hematemesis been reported. We report a case of herpes esophagitis presenting with hematemesis in an immunocompetent patient. This 67-year-old man suffered from herpes esophagitis, proven by a panendoscopic examination, with characteristic histological findings. He presented with hematemesis and passage of tarry stools, but was otherwise healthy with normal humoral, cell-mediated immunity and was negative for human immunodeficiency virus antibody. Only supportive treatment was given. He has been well for the past nine months since the initial diagnosis.
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Esofagite/complicações , Hemorragia Gastrointestinal/etiologia , Herpes Simples/complicações , Idoso , Esofagite/microbiologia , Herpes Simples/imunologia , Humanos , Imunocompetência , MasculinoRESUMO
Twenty-two patients with clinical, biochemical, immunological and pathological characteristics compatible with primary biliary cirrhosis were studied. There were 17 women and 5 men with a mean age of 57.4 +/- 15.2 years and a mean follow-up of 24.1 +/- 20.1 months. Four of them expired during the follow-up and eighteen patients now survive. The most common complaints were fatigue (63.6%) and itching (59.1%). Only one case (4.5%) was asymptomatic in this series. The major physical findings were jaundice (50%) and hepatomegaly (50%). The significant laboratory findings were: elevation of alkaline phosphatase (91% of the cases greater than 3 times the upper limit of normal), gamma-glutamyl transpeptidase (100% of the cases greater than 4 times the upper limit of normal), aspartate transaminase (95%) and alanine transaminase (100%), presence of anti-mitochondrial antibodies (91%), antinuclear antibodies (73%) and the elevation of IgM (88%). One case was associated with ulcerative colitis. Pathological staging in this series revealed 57.9% of stage II, 26% of stage III, 10% of stage IV and 5.3% of stage I. All patients with granuloma survived but 4 of the 5 patients with cholestasis died during follow-up. The results show that the features in this series of PBC were similar to those observed in western countries. The very high ALP and gamma-GT level as well as only one asymptomatic case in this series, suggest that our patients were diagnosed at a late stage. The reason(s) for the higher positivity of ANA, particularly the speckled type and a lower rate of associated auto-immune disease requires further study. Liver biopsy in predicting a prognosis is valuable.
Assuntos
Cirrose Hepática Biliar/patologia , Adulto , Idoso , Feminino , Humanos , Cirrose Hepática Biliar/enzimologia , Cirrose Hepática Biliar/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Limited data are available on the efficacy and safety of antiviral therapy in geriatric patients with chronic hepatitis C virus (HCV) infection. AIM: To evaluate the efficacy and safety of pegylated interferon (pegIFN) plus ribavirin (RBV) therapy in geriatric HCV-infected patients. METHODS: Ninety-one geriatric patients (age ≥65 years; the elderly group) with HCV infection and 91 gender- and HCV genotype-matched middle-aged patients (age 50-64 years; the younger group) were assigned to receive weekly pegIFN injection plus weight-based oral RBV for 24 weeks. The on- and off-treatment virological responses were evaluated for treatment efficacy. RESULTS: In intention-to-treat analysis, the sustained virological response (SVR) rate was substantially decreased in the elderly patients (elderly group vs. younger group, 40.7% vs. 61.5%, respectively; P = 0.005). The SVR rate was significantly lower in geriatric patients than in middle-aged patients with HCV genotype non-1 (54.3% vs. 82.9%; P = 0.01), but the difference was not significant with HCV genotype 1 (32.1% vs. 48.2%; P = 0.083). Furthermore, the older patients infected with HCV genotype non-1 who achieved a rapid virological response had a similar SVR rate to that of the younger patients. The withdrawal rate was 13.2% in the elderly group and 7.7% in the younger group. CONCLUSIONS: Compared with middle-aged patients, the therapeutic efficacy of pegylated interferon plus ribavirin therapy is lower in hepatitis C virus-infected geriatric patients with an acceptable withdrawal rate. Considering prolonged lifespan in geriatric patients, we recommend treating geriatric hepatitis C virus-infected patients who have significant hepatic fibrosis and no other health problems.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polietilenoglicóis/efeitos adversos , Estudos Prospectivos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Ribavirina/efeitos adversos , Resultado do Tratamento , Carga ViralRESUMO
Multiferroic BiFeO(3) (BFO) ceramics with electrodes of indium tin oxide (ITO) and Au thin films exhibit significant photovoltaic effects under near-ultraviolet illumination (λ = 405 nm) and show strong dependences on light wavelength, illumination intensity, and sample thickness. The correlation between photovoltaic responses and illumination intensity can be attributed to photo-excited and thermally generated charge carriers in the interface depletion region between BFO ceramic and ITO thin film. A theoretical model is developed to describe the open-circuit photovoltage and short-circuit photocurrent density as a function of illumination intensity. This model can be applied to the photovoltaic effects in p-n junction type BFO thin films and other systems. The BFO ceramic exhibits stronger photovoltaic responses than the ferroelectric Pb(1-x)La(x)(Zr(y)Ti(1-y))(1-x/4)O(3) (PLZT) ceramics under near-ultraviolet illumination. Comparisons are made with other systems and models for the photovoltaic effect.