RESUMO
BACKGROUND: Data about adverse events are needed to optimise telaprevir-based therapy in a broad spectrum of patients. AIM: To investigate adverse events of telaprevir-based therapy in patients with and without advanced fibrosis or cirrhosis in a real-world setting. METHODS: Data on 174 hepatitis C-infected patients initiating telaprevir-based therapy at Mount Sinai and Montefiore medical centres were collected. Biopsy data and FIB-4 scores identified patients with advanced fibrosis. Multivariable fully adjusted models were built to assess the effect of advanced fibrosis on specific adverse events and discontinuation of treatment due to an adverse event. RESULTS: Patients with (n = 71) and without (n = 103) advanced fibrosis were similar in BMI, ribavirin exposure, gender, prior treatment history, haemoglobin and creatinine, but differed in race. Overall, 47% of patients completed treatment and 40% of patients achieved SVR. Treated patients with and without advanced fibrosis or cirrhosis had similar rates of adverse events; advanced fibrosis, however, was independently associated with ano-rectal discomfort (P = 0.03). Three patients decompensated and had advanced fibrosis. The discontinuation of all treatment medications due to an adverse event was significantly associated with older age (P = 0.01), female gender (P = 0.01) and lower platelets (P = 0.03). CONCLUSIONS: Adverse events were common, but were not significantly related to the presence of advanced fibrosis or cirrhosis. More critical monitoring in older and female patients with low platelets throughout treatment may reduce adverse event-related discontinuations.
Assuntos
Antivirais/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Cirrose Hepática/tratamento farmacológico , Oligopeptídeos/efeitos adversos , Polietilenoglicóis/efeitos adversos , Ribavirina/efeitos adversos , Anemia/induzido quimicamente , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Hepatite C Crônica/sangue , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/uso terapêutico , Contagem de Plaquetas , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêuticoRESUMO
BACKGROUND: Whether antidepressants prevent depression during interferon-alpha/ribavirin treatment for hepatitis C virus infection has yet to be established. AIM: To investigate the use of paroxetine in a prospective, double-blind, placebo-controlled study for this indication. METHODS: Sixty-one hepatitis C virus-infected patients were randomly assigned to the antidepressant, paroxetine (n = 28), or placebo (n = 33), begun 2 weeks before and continued for 24 weeks during interferon-alpha/ribavirin treatment. Primary endpoints included development of major depression and severity of depressive symptoms measured by the Montgomery Asberg Depression Rating Scale (MADRS). RESULTS: Rates of major depression during the study were low (17%) and did not differ between groups. Nevertheless, using published MADRS cut-off scores, the percent of subjects who met criteria for mild, moderate or severe depression during interferon-alpha/ribavirin therapy was significantly lower in paroxetine- vs. placebo-treated subjects (P = 0.02, Fisher's exact test). Assignment to paroxetine was also associated with significantly reduced depressive symptom severity. This effect was largely accounted for by participants with depression scores above the median (MADRS > 3) at baseline in whom paroxetine was associated with a maximal reduction in MADRS scores of 10.3 (95% CI: 2.1-18.5) compared with placebo at 20 weeks (P < 0.01). Study limitations included a small sample size and high drop-out rate. CONCLUSION: This double-blind, placebo-controlled trial provides preliminary data in support of antidepressant pre-treatment in hepatitis C virus patients with elevated depressive symptoms at baseline.
Assuntos
Antivirais/uso terapêutico , Transtorno Depressivo Maior/prevenção & controle , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/farmacocinética , Transtorno Depressivo Maior/virologia , Método Duplo-Cego , Feminino , Hepatite C Crônica/psicologia , Humanos , Interferon-alfa/farmacocinética , Masculino , Pessoa de Meia-Idade , Paroxetina/uso terapêutico , Ribavirina/farmacocinéticaRESUMO
The ischemic bowel diseases are a heterogeneous group of disorders usually seen in elderly individuals. They represent ischemic damage to different portions [figure: see text] of the bowel and produce a variety of clinical syndromes and outcomes. Colonic ischemia is the commonest of these disorders and has a favorable prognosis in most cases. In contrast, acute mesenteric ischemia, most commonly caused by a superior mesenteric artery embolus, is a disease with a poor prognosis. Acute mesenteric ischemia secondary to nonocclusive mesenteric ischemia usually is a [figure: see text] catastrophic complication of other severe medical illnesses, most notably atherosclerosis. Proper diagnosis and management of patients with ischemic bowel disease requires vigilance on the part of the physician and a willingness to embark on an aggressive plan of diagnosis and management in the appropriate setting.
Assuntos
Isquemia/etiologia , Circulação Esplâncnica , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Arteriosclerose , Colo/irrigação sanguínea , Humanos , Isquemia/diagnóstico , Isquemia/terapia , Oclusão Vascular Mesentérica/diagnóstico por imagem , Oclusão Vascular Mesentérica/etiologia , Oclusão Vascular Mesentérica/terapia , Veias Mesentéricas , Radiografia , Trombose/etiologiaRESUMO
BACKGROUND: In registration trials, zafirlukast, an asthma medication, caused asymptomatic elevated aminotransferase levels in up to 5% of participants. Until now, however, no cases of severe hepatitis attributed to zafirlukast have been reported. OBJECTIVE: To report the clinical characteristics of three patients with severe hepatitis due to zafirlukast. DESIGN: Case report. SETTING: One community hospital and two university hospitals. PATIENTS: Three middle-aged women taking zafirlukast, 20 mg twice per day. INTERVENTION: Discontinuation of zafirlukast therapy in three patients, steroid therapy in two patients, and orthotopic liver transplantation in one patient. MEASUREMENTS: Serum aminotransferase and bilirubin levels, standard blood tests for causes of hepatitis other than drug toxicity, and liver biopsy in two patients. RESULTS: Patient 1 recovered spontaneously, had a severe relapse after inadvertent rechallenge with the medication, and ultimately made a complete recovery. Patient 2 developed subfulminant hepatic failure and required liver transplantation. Patient 3 developed severe hepatitis that improved after treatment with corticosteroids. Liver tissue was available from two patients and showed histologic changes commonly associated with drug reactions. CONCLUSION: Patients receiving zafirlukast may develop severe liver injury and should be observed for signs and symptoms of hepatitis.
Assuntos
Antiasmáticos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Antagonistas de Leucotrienos , Compostos de Tosil/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Feminino , Humanos , Indóis , Fígado/enzimologia , Falência Hepática/induzido quimicamente , Falência Hepática/cirurgia , Transplante de Fígado , Pessoa de Meia-Idade , Fenilcarbamatos , SulfonamidasRESUMO
OBJECTIVE: Liver biopsies in hepatitis C virus (HCV)-positive end stage renal disease (ESRD) patients before or after renal transplantation were compared to study the effect of transplant-related immunosuppression. METHODS: In this prospective study all patients on the active transplant list and all patients with functioning renal transplants at our hospital were tested for HCV antibody (ELISA-2) over a 30-month period. HCV infection was confirmed by polymerase chain reaction in most patients. All HCV-positive patients were asked to undergo liver biopsy without regard to serum transaminase levels. Patients were interviewed, examined, and had detailed chart review. By protocol, liver histology was evaluated according to stage and inflammatory activity in a blinded fashion. RESULTS: There were 129 HCV-antibody-positive patients, of 795 tested. Sixty-seven agreed to liver biopsy. Of these, 22 patients had never been transplanted and 45 had received transplants. Mean transplant duration before biopsy was 41.2 months (range, 1-204 months). Transplant patients had significantly longer duration of ESRD and estimated duration of HCV infection than patients not transplanted. Dialysis patients had significantly more portal inflammatory activity and lymphoid follicles on biopsy whereas transplant patients had more piecemeal necrosis and steatosis. However, the total histological activity score and stage were similar between groups. Multivariate analysis confirmed the association between transplant and steatosis. But independent variables including transplant duration, HCV infection duration, and ESRD duration were not correlated with histological findings. CONCLUSION: Renal transplantation may not be associated with an increased risk of progressive liver disease in HCV-positive patients, compared with ESRD patients receiving chronic dialysis. Long-term studies with serial liver biopsies are needed to resolve this issue.
Assuntos
Hepatite C/patologia , Falência Renal Crônica/patologia , Transplante de Rim , Fígado/patologia , Diálise Renal , Feminino , Hepatite C/complicações , Hepatite C/diagnóstico , Anticorpos Anti-Hepatite C/análise , Humanos , Terapia de Imunossupressão , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos ProspectivosRESUMO
Gray scale ultrasonographic images of the liver were correlated with histologic findings in patients with chronic hepatitis C virus infection. The gray scale patterns of 64 livers with chronic hepatitis C virus infection were categorized as normal, fatty, fibrofatty, fibrotic, or inflammatory and were graded as mild, moderate, or severe. Liver biopsy specimens also were analyzed for the presence of fat, inflammation, and fibrosis and graded similarly. No correlation was found between fatty and fibrofatty sonographic findings with any of the three histologic patterns. Correlations were found between fibrotic sonographic findings and both fibrotic and inflammatory histologic findings (r = 0.27; P = 0.03). Although some pathologic features of liver disease were detected by ultrasonography, no useful correlation was noted between results of sonography and histologic examination.
Assuntos
Hepatite C Crônica/diagnóstico por imagem , Fígado/diagnóstico por imagem , Adolescente , Adulto , Idoso , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Humanos , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , UltrassonografiaRESUMO
OBJECTIVE: Crohn's disease frequently affects the perineum, but it is unknown if such involvement poses a heightened risk to a woman with Crohn's disease undergoing vaginal delivery and possibly episiotomy. This study attempts to elucidate whether vaginal delivery with or without episiotomy: 1) predisposes to perineal involvement in women with Crohn's disease; 2) reactivates quiescent perineal Crohn's disease; or 3) worsens preexisting perineal Crohn's disease. METHODS: Data were culled from questionnaires returned by 117 respondents contacted through newsletters of the Crohn's and Colitis Foundation of America. These surveys were then reviewed and tabulated to determine if any temporal and causal relationship existed between perineal Crohn's disease and vaginal delivery. RESULTS: Four groups were identified: group 1 (n = 56), with 128 pregnancies, had no history of perineal disease or subsequent perineal complication. Group 2 (n = 24) had 51 pregnancies. This group had no preexisting perineal disease, but 67.6% said they developed perineal Crohn's disease postpartum, 60% of which occurred within 2 months of vaginal delivery. Groups 3 and 4 were too small to evaluate (n = 4 and 5, respectively) and represented patients with preexisting perineal disease who had varying results after delivery. Overall, the rate of developing perineal involvement after vaginal delivery, usually with episiotomy, in patients with Crohn's disease and no preexisting perineal involvement (combining groups 1 and 2) was 17.9%. CONCLUSIONS: A high rate of perineal involvement seems to follow vaginal delivery with episiotomy in patients with Crohn's disease. Although this study has substantial methodological limitations, it does raise questions as to the proper obstetrical management of patients with Crohn's disease and highlights an intriguing relationship that deserves further and more rigorous study.
Assuntos
Doença de Crohn/complicações , Parto Obstétrico/efeitos adversos , Episiotomia/efeitos adversos , Complicações na Gravidez , Transtornos Puerperais/etiologia , Adulto , Estudos de Casos e Controles , Doença de Crohn/epidemiologia , Coleta de Dados , Feminino , Humanos , Pessoa de Meia-Idade , Períneo , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Transtornos Puerperais/epidemiologia , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Chorioamnionitis, a common cause of second-trimester abortion, is usually secondary to an ascending infection. Recurrent chorioamnionitis with second-trimester abortion secondary to an occult enterouterine fistula has not been reported previously. CASE: A 26-year-old Indian woman, para 0-0-2-0, presented with two spontaneous second-trimester losses. Her third pregnancy carried to 24 weeks, but she delivered after the development of pneumonia, bacteremia, preterm labor, and chorioamnionitis. The patient passed melena containing blood clots after the delivery. After the last pregnancy, laparoscopy and laparotomy revealed an ileal-uterine fistula and a foreign body (necrotic cartilage). The blind loop of bowel was resected and the fistulous tract excised. CONCLUSION: Our patient's recurrent pregnancy wastage was caused by chorioamnionitis secondary to an enterouterine fistula resulting from foreign body ingestion. A complete reversal of this problem is anticipated.
Assuntos
Aborto Habitual/etiologia , Corioamnionite/microbiologia , Infecções por Escherichia coli , Fístula/complicações , Fístula Intestinal/complicações , Doenças Uterinas/complicações , Adulto , Infecções por Escherichia coli/complicações , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , RecidivaRESUMO
Lower intestinal hemorrhage, defined as bleeding originating below the ligament of Treitz, is a common clinical problem frequently requiring hospital admission. The two chief causes, vascular ectasia and diverticulosis, are degenerative diseases usually found in the elderly. This article focuses on those disease entities that potentially can result in significant lower intestinal blood loss. It also discusses a generalized approach to the diagnostic evaluation leading to specific management of the patient presenting with this problem.
Assuntos
Doenças do Colo , Hemorragia Gastrointestinal , Doenças Retais , Doenças do Colo/diagnóstico , Doenças do Colo/etiologia , Doenças do Colo/terapia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Humanos , Doenças Retais/diagnóstico , Doenças Retais/etiologia , Doenças Retais/terapiaRESUMO
OBJECTIVE: To identify sensitive epidemiologic predictors of a positive hepatitis C virus antibody test in asymptomatic persons, and to compare the cost of testing only persons with an epidemiologic predictor to that of universal screening. METHODS: Seventeen hundred consecutive pregnant women were tested by enzyme-linked immunosorbent assay for antibody to hepatitis C virus. Seventy-five subjects tested positive and were compared with 257 pregnant women who tested negative. Cohort and control patients were interviewed and their medical records were reviewed to identify those with chosen predictors of a positive hepatitis C virus antibody test. RESULTS: Seventy-four of 75 cohort patients and 108 of 257 controls had one or more predictors of a positive antibody test. Cohort patients were significantly more likely (P < .001) to have the following: human immunodeficiency virus infection, a sex partner with a risk factor for hepatitis, age greater than 30 years, and a history of drug use, blood transfusion, sexually transmitted disease, hepatitis, or incarceration. The sensitivity and specificity of a single predictor in identifying a person with a positive test were 99 and 58%, respectively. The cost of finding a single individual with a positive antibody test by universal screening was $674, compared to $303 by selectively screening persons with one or more predictors of a positive antibody test. CONCLUSIONS: Most individuals with positive hepatitis C virus antibody tests can be identified on the basis of epidemiologic predictors, reducing the cost of testing by 55%. These patients may receive appropriate medical therapy, and their children may be evaluated for possible infection by vertical transmission of hepatitis C virus.
Assuntos
Hepacivirus/imunologia , Anticorpos Anti-Hepatite/sangue , Hepatite C/epidemiologia , Programas de Rastreamento/economia , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Estudos de Coortes , Custos e Análise de Custo , Feminino , Hepatite C/sangue , Anticorpos Anti-Hepatite C , Humanos , Recém-Nascido , Modelos Logísticos , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez/sangue , Fatores de Risco , Sensibilidade e Especificidade , Estudos SoroepidemiológicosRESUMO
Lower intestinal bleeding is an important medical problem frequently responsible for hospital admission in the United States. The two most common causes of this type of bleeding are colonic diverticula and vascular ectasias. Because ectasias are difficult to diagnose and because many older individuals have asymptomatic diverticula, it is often impossible to be certain that one of these lesions is the source of blood loss in a given patient. Fortunately, bleeding from an ectasia or a diverticulum usually stops spontaneously. A conservative approach to therapy, therefore, is strongly recommended. Should a careful evaluation fail to reveal the source of bleeding and treatment become necessary because of recurrent hemorrhage, the patient should undergo an elective right hemicolectomy. The extent of resection is not altered by the presence of diverticulosis in the left colon.
Assuntos
Angiodisplasia/complicações , Doenças do Colo/etiologia , Divertículo/complicações , Hemorragia Gastrointestinal/etiologia , Idoso , Angiodisplasia/terapia , Divertículo/terapia , Hemorragia Gastrointestinal/terapia , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To search for transmission of hepatitis C virus (HCV) from infected mothers to their infants. DESIGN: Prospective clinical, serologic, and molecular biologic follow-up (at least 3 months) of the infants of mothers with anti-HCV antibody. SETTING: A county hospital providing primary and referral care in high-risk obstetrics (perinatology). PATIENTS: Twenty-three mothers with anti-HCV antibody and their 24 infants. METHODS: An enzyme-linked immunosorbent assay (EIA) and a four-antigen recombinant immunoblot assay (RIBA) were used to test for anti-HCV antibody; serum HCV RNA was measured in two independent laboratories by reverse transcription and polymerase chain reaction (PCR) using nested primers in the 5'-noncoding region. Infant samples were tested for HCV RNA by PCR at delivery and after 3 to 6 months of follow-up. Each sample was tested at least four times in two independent laboratories. RESULTS: Twenty-nine of 648 mothers (4.5%; 95% Cl, 3.0% to 6.4%) had anti-HCV antibody; these women had 30 babies. Twenty-three mothers and their 24 babies were followed at least 3 months (mean follow-up, 52 weeks). Of the 23 mothers, 21 (91%; Cl, 72% to 99%) had a reactive RIBA; one woman had an indeterminate RIBA and was positive for HCV RNA by PCR. In 16 of 23 mothers (70%; Cl, 47% to 87%), PCR yielded a positive result in both laboratories. The mean maternal alanine aminotransferase (ALT) level was 1.6 times the normal value. All the babies had anti-HCV antibody in cord-blood samples, but antibody disappeared or diminished in strength in interval samples, and no infant had evidence of active production of anti-HCV antibody. Only 1 of 24 (4%; Cl, 0.1% to 21%) cord-blood samples was HCV RNA positive, and none of 24 (0%; Cl, 0% to 14%) follow-up samples was positive for HCV RNA by PCR in either laboratory. Four mothers and one baby had antibody to HIV. CONCLUSIONS: Infant anti-HCV antibody is most likely acquired passively in utero, and vertical transmission of HCV is uncommon.
Assuntos
Hepatite C/congênito , Hepatite C/transmissão , Complicações Infecciosas na Gravidez , Feminino , Hepacivirus/genética , Hepacivirus/imunologia , Anticorpos Anti-Hepatite/sangue , Hepatite C/diagnóstico , Humanos , Técnicas Imunoenzimáticas , Recém-Nascido , Reação em Cadeia da Polimerase , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Estudos Prospectivos , RNA Viral/sangue , Testes SorológicosRESUMO
To clarify the prevalence and characteristics of gastrointestinal malignancy in patients with AIDS, we reviewed the demographics and clinical features of patients with AIDS and gastrointestinal neoplasms seen at North Central Bronx Hospital and Montefiore Medical Center during the past 8 yr. Malignant neoplasia complicated AIDS in 108/869 (12%) of the cases in our study. Most common was Kaposi's sarcoma (KS) (60%), followed by lymphoma (35%) and miscellaneous tumors (6.5%). The gastrointestinal tract was involved in 35/108 (32%) of patients with AIDS and neoplasia. Gastrointestinal tract involvement with KS usually was silent, although present, in every patient with KS who underwent autopsy. Lymphoma was most commonly non-Hodgkin's, and often produced symptoms. Uncommonly, the gastrointestinal tract was the primary site of neoplasms other than KS or lymphoma.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Neoplasias Gastrointestinais/complicações , Linfoma/complicações , Sarcoma de Kaposi/complicações , Adulto , Idoso , Feminino , Neoplasias Gastrointestinais/epidemiologia , Humanos , Linfoma/epidemiologia , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Prevalência , Estudos Retrospectivos , Sarcoma de Kaposi/epidemiologiaRESUMO
Lower intestinal bleeding in the elderly is a common problem with numerous and varied causes. Its diagnosis and treatment require a careful, systematic approach by physicians with special expertise. Under the proper circumstances, elderly patients with lower intestinal bleeding do well, even when surgery is required. An individual's age, by itself, should not preclude aggressive medical care.