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D Y Lin

Publications and source records attributed to D Y Lin.

At least 73 records · Page 4Linked to original sources
PubMed1997

Non-parametric inference for cumulative incidence functions in competing risks studies.

In the competing risks problem, a useful quantity is the cumulative incidence function, which is the probability of occurrence by time t for a particular type of failure in the presence of other risks. The estimator of this function as given by Kalbfleisch and Prentice is consistent, and, properly normalized, converges weakly to a zero-mean Gaussian process with a covariance function for which a consistent estimator is provided. A resampling technique is developed to approximate the distribution of this process, which enables one to construct confidence bands for the cumulative incidence curve over the entire time span of interest and to perform Kolmogorov-Smirnov type tests for comparing two such curves. An AIDS example is provided.

AIDS-Related Opportunistic Infections↗
PubMed1997

Perspective: validating surrogate markers--are we being naive?

Because of the difficulties in conducting studies of clinical efficacy of new therapies for human immunodeficiency virus infection and other diseases, there is increasing interest in using measures of biologic activity as surrogates for clinical end points. A widely used criterion for evaluating whether such measures are reliable as surrogates requires that the putative surrogate fully captures the "net effect"-the effect aggregated over all mechanisms of action-of the treatment on the clinical end point. The variety of proposed metrics for evaluating the degree to which this criterion is met are subject to misinterpretation because of the multiplicity of mechanisms by which drugs operate. Without detailed understanding of these mechanisms, metrics of "surrogacy" are not directly interpretable. Even when all of the mechanisms are understood, these metrics are associated with a high degree of uncertainty unless either treatment effects are large in moderate-size studies or sample sizes are large in studies of moderately effective treatments.

Biomarkers↗
PubMed1997

Non-surgical treatment of hepatocellular carcinoma.

A decade ago, surgery was the only satisfactory treatment modality for hepatocellular carcinoma (HCC), but it was limited only to selected cases. For the majority of cases of HCC, systemic chemotherapy was one of the few treatment alternatives, but provided only marginal benefit. In the past 20 years, diagnostic methods have improved to an extent that small HCC less than 1 cm can be detected. Moreover, non-surgical treatment is available, of which regional therapy has been shown to prolong patients' survival, and may even replace surgical resection in some cases. Regional therapy is indicated for the treatment of HCC when there is no extrahepatic metastasis and the patient has adequate liver function reserve, thus permitting repeated therapy. Transcatheter hepatic arterial embolization (TAE) using various embolizers has been well documented to include controlled studies. However, it is not indicated for patients with thrombosed main portal veins. Its therapeutic effect is also doubtful when the tumour is infiltrative in nature or is hypovascular, too large or too small. Additional chemotherapeutic agents mixed into the embolizer with lipiodol and degraded starch microspheres or styrene-maleic acid-neocarzinostatin in which chemotherapeutic agents are embedded, are used with a better response, but the survival rate has not shown significant improvement. Ultrasound-guided local injection therapy is another new method of treatment of HCC. Of these techniques, percutaneous ethanol injection therapy (PEIT) is widely used with excellent results for small, encapsulated tumours in livers with less than three HCC. Percutaneous ethanol injection therapy can also be used in cases with portal vein thrombosis, but it is not suitable for patients having coagulopathy or ascites. Using acetic acid, OK-432, interferon or anti-cancer drugs in the injection therapy shows no further benefit over ethanol alone. Transcatheter echoguided thermotherapy or cryotherapy has been reported in small series of patients, as has target therapy with immune or radiotherapy and conformal radiotherapy. Preliminary studies show encouraging results. Systemic therapy with either single drug or multidrugs is ineffective, with a response rate of less than 20%. Immunotherapy, such as with interferon or other cytokines, is not beneficial. Hormone therapy has not been promising, except for treatment with tamoxifen, which has been reported to show some beneficial effect. Gene therapy is still in its infancy. In summary, recent progress in non-surgical treatment of HCC has resulted in a breakthrough of regional therapy looking quite promising. Moreover, a combination of different types of regional therapies may yield better outcomes in selected individuals.

Antineoplastic Agents↗
PubMed1997

Estimating medical costs from incomplete follow-up data.

Estimation of the average total cost for treating patients with a particular disease is often complicated by the fact that the survival times are censored on some study subjects and their subsequent costs are unknown. The naive sample average of the observed costs from all study subjects or from the uncensored cases only can be severely biased, and the standard survival analysis techniques are not applicable. To minimize the bias induced by censoring, we partition the entire time period of interest into a number of small intervals and estimate the average total cost either by the sum of the Kaplan-Meier estimator for the probability of dying in each interval multiplied by the sample mean of the total costs from the observed deaths in that interval or by the sum of the Kaplan-Meier estimator for the probability of being alive at the start of each interval multiplied by an appropriate estimator for the average cost over the interval conditional on surviving to the start of the interval. The resultant estimators are consistent if censoring occurs solely at the boundaries of the intervals. In addition, the estimators are asymptotically normal with easily estimated variances. Extensive numerical studies show that the asymptotic approximations are adequate for practical use and the biases of the proposed estimators are small even when censoring may occur in the interiors of the intervals. An ovarian cancer study is provided.

Aged↗
PubMed1996

Stereological MRI volumetry of the frontal lobe.

Stereology was used to measure frontal lobe volume on magnetic resonance imaging (MRI) scans in a multi-observer repeated-measures trial in 17 adults. Prior to measurement, MR image volumes were reoriented into coronal sections perpendicular to the bicommissural plane. Three observers blinded to subject identify repeatedly used fixed grid stereology to estimate frontal lobe volumes, defined as all sections of the frontal lobe anterior to the anterior commissure. The lateral ventricles were excluded. Stereological measurement yielded high repeatability and precision, and was time efficient for the raters. The coefficient of error was 0.03. The inter-rater correlation coefficient = 0.95 for three raters; intra-rater correlation coefficients = 0.95-0.98. A comparison was made between stereological and traditional edge tracing measurement of the frontal lobe volumes. The overall correlation between the two methods was 0.95. The use of internal landmarks to define orientation and 3-D orthogonal views to define frontal lobe boundaries on 3-D images was critical to obtaining repeatable measurements. Frontal lobe volumetry by brain MR used to estimate small differences postulated to occur in certain psychiatric and neurologic disorders requires high precision and repeatability. Stereology, a semi-automated method, can reliably estimate frontal lobe volumes. This method may distinguish small frontal lobe volume differences within individuals and between groups.

Aged↗
PubMed1996

Gastrointestinal bleeding after hepatic transcatheter arterial embolization in patients with hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial embolization is a popular palliative treatment for patients with hepatocellular carcinoma, but the incidence of post-treatment gastrointestinal bleeding is not well-defined. METHODS: We retrospectively analyzed 206 patients with hepatocellular carcinoma who received transcatheter arterial embolization and compared them with 193 patients with hepatocellular carcinoma who underwent angiography along. RESULTS: Twenty-three episodes (8.5%) of gastrointestinal bleeding occurred within 3 months of hepatic transcatheter arterial embolization following 269 procedures involving 206 patients with hepatocellular carcinoma. Eight episodes (3.0%) of esophageal variceal bleeding and 15 episodes (5.5%) of nonvariceal bleeding were found. The sites of the nonvariceal bleeding episodes were the stomach (n = 7), duodenum (n = 5), and colon (n = 3). When compared with other sources, bleeding from esophageal varices took place earlier, required intensive treatment, and led to a higher mortality. Among another 193 patients with hepatocellular carcinoma who received angiography only, 6 patients developed gastrointestinal bleeding within 3 months (3.1%), and all bled from esophageal varices. CONCLUSIONS: This study suggests that esophageal variceal bleeding may occur after both angiography and transcatheter arterial embolization. Nonvariceal bleeding episodes, which were usually milder than episodes of variceal bleeding, may be related to the embolization procedure itself.

Adolescent↗
PubMed1996

Acute exacerbations in chronic hepatitis C: a clinicopathological and prognostic study.

BACKGROUND/METHODS: To examine the incidence, predisposing factors, clinicopathological characteristics and implications of acute exacerbations in chronic hepatitis C, a consecutive series of 194 biopsy-verified, anti-HCV-positive and hepatitis B surface antigen-negative patients were followed up and studied for the events of acute exacerbations, sustained biochemical resolution and development of cirrhosis. RESULTS: During a mean period of 6.2 +/- 3.5 (1.0-14.0) years, 151 episodes of acute exacerbations were recorded in 78 patients (40.2%). The estimated annual incidence of acute exacerbations was 11.9%. Fifty-five percent of acute exacerbations were asymptomatic. Histological study of acute exacerbations showed mild to moderate lobular inflammatory activities without bridging hepatic necrosis in all and periportal piecemeal in 23 (42.6%). The clinicopathological features of acute exacerbations in patients with chronic hepatitis C were less severe than those in patients with chronic hepatitis B. The route of infection, sex, age, mode of clinical presentation and the initial histology did not influence the occurrence of acute exacerbations. Only those with alanine aminotransferase > or = 300 U/l at entry tended to develop acute exacerbations more frequently (p < 0.001, odds ratio = 3.6, 95% confidence interval: 1.9-6.5). Acute exacerbations per se did not influence the subsequent development of cirrhosis or sustained biochemical resolution. Cirrhosis developed more frequently in patients with chronic active hepatitis at entry (p < 0.001, odds ratio = 6.5, 95% confidence interval: 2.6-16.0). Compared with baseline HCV-RNA level, HCV-RNA increased in 61% of acute exacerbations but the genotype remained unchanged in 75%. CONCLUSIONS: These results suggest that acute exacerbations also occur frequently in patients with chronic hepatitis C. They are clinically indolent, histologically less severe and not likely to be followed by sustained remission or development of cirrhosis.

Adult↗
PubMed1996

A prospective randomized trial of colchicine in prevention of liver cirrhosis in chronic hepatitis B patients.

BACKGROUND: The clinical course of chronic hepatitis B is variable. Patients with hepatic decompensation, bridging necrosis or an alpha-fetoprotein level greater than 100 ng/mL during an exacerbation of hepatitis have a high risk of developing cirrhosis. This study was conducted to evaluate the effect of colchicine in the prevention of cirrhosis in such patients. METHODS: Patients with risk factor(s) were randomized to receive either colchicine 5 mg/week or no specific treatment, the end point being development of cirrhosis. RESULTS: After a follow up period of 4 years, the treatment group had a marked reduction in exacerbations of acute hepatitis (32% vs. 63%/patient/year, P < 0.005). Seven out of 38 patients in the treatment group and 10 out of 27 patients in the control group developed cirrhosis. The calculated cumulative incidence of cirrhosis by the end of first, second, third and fourth years in the treatment group was 8.7, 18.6, 32 and 32%, respectively. The corresponding figures in the control group were 30, 35.5, 46.3 and 73.2%, respectively, with a P-value of 0.057. CONCLUSIONS: The results suggest that colchicine may prevent cirrhosis in chronic hepatitis B patients with risk factor(s), possibly by suppressing exacerbations of hepatitis through an anti-inflammatory effect.

Adult↗
PubMed1996

Non-O1 Vibrio cholerae bacteremia in patients with cirrhosis: 5-yr experience from a single medical center.

OBJECTIVES: To assess the clinical features and susceptibility of cirrhotic patients to non-O1 Vibrio cholerae bacteremia and to provide our therapeutic experiences in this rare and high lethal infection. METHODS: Twenty-eight blood culture isolates of non-O1 V. cholerae were identified by our clinical microbiology laboratory between July 1989 and June 1994. Patients with underlying cirrhosis and the aforementioned bacteremia were retrospectively reviewed. RESULTS: Twenty-one cirrhotic patients (16 male, five female; mean age, 50.9 yr; range 28-67 yr) were identified and classified as Child B (6 cases) and Child C (15 cases). Bacteremic episodes occurred most often from March to September. Seafood ingestion (seven cases) and seawater exposure (two cases) were risk factors, but nosocomial infections were also noted in six cases. Presenting symptoms and signs included ascites (95.2%), fever (81%), abdominal pain (52.4%), diarrhea (33.3%), and cellulitis with bullae formation (19%). Concurrent spontaneous bacterial peritonitis was determined in 10 cases, seven with positive ascites cultures. Antibiotic therapy (either cephalothin with gentamicin or ceftriaxone alone) cured most of the bacteremic episodes. The overall case-fatality rate was 23.8%, but 75% of the deaths were observed in patients with skin manifestation. CONCLUSIONS: Patients with decompensated cirrhosis are susceptible to non-O1 V. cholerae bacteremia and should not ingest raw seafood or expose skin wounds to salt water. A high index of suspicion and early administration of antibiotics may lower the mortality rate.

Adult↗
PubMed1996

Group sequential designs for monitoring survival probabilities.

In the present paper we derive the asymptotic joint distribution of the Nelson-Aalen estimators for the cumulative hazard function (or the Kaplan-Meier estimators for the survival function) calculated at different (possibly random) calendar time points of a survival study. This result is used to develop group sequential designs for clinical trials in which patients are enrolled over an extended period and the survival probability at a given failure time point is the parameter of primary interest. The proposed designs allow monitoring the survival probability (or probabilities) at interim looks so that the study can be terminated when there is sufficient evidence for a positive or negative result. A detailed illustration is provided with a problem from the National Wilms Tumor Study Group, which motivated this research.

Adolescent↗
PubMed1996

Hypoxemia in a cirrhotic patient caused by hepatopulmonary syndrome: a case report.

Hepatopulmonary syndrome (HPS) is the triad of liver disease, pulmonary vascular dilatation, and abnormal arterial oxygenation. We report a case with progressive orthodeoxia and platypnea who was proven to have HPS after serial investigations, including autopsy. This 61-year-old male is a case of alcoholic liver cirrhosis without any documented cardiopulmonary disorders before. However, he suffered from progressive dyspnea in his last one-year life. During that period, progressive severe hypoxemia, orthodeoxia and platypnea were detected. Serial non-invasive diagnostic approaches, including two-dimensional contrast enhanced echocardiography and technetium-99m labeled macroaggregated albumin (MAA) lung perfusion scanning, were performed and showed positive evidence of intrapulmonary shunting. Direct evidence of intrapulmonary vascular dilatation was finally proven by autopsy. Although this syndrome is not rare, clinical awareness of the association between liver disease and arterial oxygen desaturation is still inadequate. We report a case proved by typical clinical manifestation and complete investigation and review the literature to emphasize this important disorder.

Cyanosis↗
PubMed1996

The effect of meal intake on hepatic feeding vessels-color Doppler ultrasonographic assessment in normal Chinese adults.

To evaluate the response of hepatic vessels, the hepatic artery and portal vein were measured before and after a meal by color Doppler ultrasonography in 14 normal Chinese adults. Portal vein can be identified in all instance with diameter, velocity and flow volume in fasting as 1.17 +/- 0.22 cm, 16.29 +/- 3.68 cm/sec and 18.7 +/- 11.8 ml/sec respectively. These parameters are significantly increased to 1.38 +/- 0.25, 22.72 +/- 4.88 and 33.91 +/- 12.63 respectively (all with p < 0.01) after the meal. Successful visualization of hepatic artery was achieved in all except one (7.1%) in fasting, but only in 8 out of 14 after the meal. In fasting, hepatic artery peak systolic, mean and peak diastolic flow were 47.44 +/- 14.49, 28.81 +/- 10.10 and 18.36 +/- 6.85 cm/sec. respectively. These values did not alter significantly after the meal. In contrast, pulsatility index increased from 1.12 +/- 0.36 to 1.58 +/- 0.55 (p < 0.05), and resistance index rose from 0.61 +/- 0.07 to 0.71 +/- 0.08 (p = 0.06). The results suggest that the hepatic artery examination is not always successful, especialy in heavier-build person and after meal. Compared with hepatic artery, hemodynamics of portal vein is more easily affected by meal.

Adolescent↗
PubMed1995

Serum carboxy terminal propeptide of type I procollagen to amino terminal propeptide of type III procollagen ratio is a better indicator than each single propeptide and 7S domain type IV collagen for progressive fibrogenesis in chronic viral liver diseases.

Twenty chronic viral hepatitis patients, mainly with hepatitis B related with progression to liver cirrhosis were included for an assay of serum collagen markers: PICP (carboxy terminal propeptide of type I procollagen), PIIINP (amino terminal propeptide of type III procollagen), and 7S-IV (7S-domain type IV collagen). PICP is increased in 20% of chronic hepatitis patients with a mean of 190.3 ng/ml, which is not different from that of the follow-up concentration in liver cirrhosis, where 35% of cases were abnormal with a mean of 220.5 ng/ml. The serum level and percent of abnormality of PIIICP in chronic hepatitis and in liver cirrhosis are 23.5 ng/ml vs 14.8 ng/ml and 90% vs 100%, respectively (P > 0.05). PICP/PIIINP is significantly higher during liver cirrhosis (15.11 vs 10.08, P < 0.05). PICP during chronic hepatitis is not related to serum biochemical changes, while PICP during liver cirrhosis and PIIINP are correlated with hepatic enzymes. 7S-IV in chronic hepatitis and in liver cirrhosis is 14.0 ng/ml vs 10.9 ng/ml, respectively; both were positively correlated with hepatic enzymes. These results suggest that PICP/PIIINP is a better indicator of hepatic fibrogenesis than either PICP or PIIINP alone in viral hepatitis. A ratio of more than 12 is suggestive of liver cirrhosis.

Adult↗
PubMed1995

Risk factors of hepatocellular carcinoma with familial tendency.

Family history of hepatocellular carcinoma (HCC) has been identified as a risk factor of HCC. The pathogenesis is still uncertain. In order to evaluate the risk factors and to detect the small HCC. 721 asymptomatic family members (419 males and 302 females with a mean age of 40.21 years) of the index cases of HCC received a series of examinations including: serum GOT, GPT, alpha-fetoprotein (AFP). HBsAg, Anti-HCV, and abdominal ultrasonography (US). Of the 18 patients with liver tumor detected by US. 6 were proved to be HCC, 8 were hemangioma, and the nature of the rest was undetermined. The US found 22 with cirrhosis, 24 with chronic liver disease, 133 with fatty liver, and 14 with a liver cyst. The incidence of HCC in our study was 0.96% in males (4 of 419 cases), and 0.66% in females (2 of 302 cases) which was much higher than that in the general population of Taiwan (0.025% in males and 0.01% in females). The positive rate of HBsAg in the participants, including all the newly detected HCC patients, was 46.5% (335 cases) which was also higher than the prevalence in Taiwan (15-20%). Male, sibling and liver cirrhosis seemed to have higher risk. These results suggest that family members of patients with HCC have a high risk of developing HCC. The hepatitis B virus may be the most important link. Early diagnosis is possible by screening the family members by means of AFP and abdominal US.

Adult↗
PubMed1994

Cox regression analysis of multivariate failure time data: the marginal approach.

Multivariate failure time data are commonly encountered in scientific investigations because each study subject may experience multiple events or because there exists clustering of subjects such that failure times within the same cluster are correlated. In this paper, I present a general methodology for analysing such data, which is analogous to that of Liang and Zeger for longitudinal data analysis. This approach formulates the marginal distributions of multivariate failure times with the familiar Cox proportional hazards models while leaving the nature of dependence among related failure times completely unspecified. The baseline hazard functions for the marginal models may be identical or different. Simple estimating equations for the regression parameters are developed which yield consistent and asymptotically normal estimators, and robust variance-covariance estimators are constructed to account for the intra-class correlation. Simulation results demonstrate that the large-sample approximations are adequate for practical use and that ignoring the intra-class correlation could yield rather misleading variance estimators. The proposed methodology has been fully implemented in a simple computer program which also incorporates several alternative approaches. Detailed illustrations with data from four clinical or epidemiologic studies are provided.

Adolescent↗
PubMed1994

Displacement of hepatitis B virus by hepatitis C virus as the cause of continuing chronic hepatitis.

BACKGROUND/AIMS: It has been shown that hepatitis C virus (HCV) superinfection may suppress hepatitis B virus (HBV) leading to hepatitis B surface antigen (HBsAg) clearance and that hepatitis may persist after HBsAg clearance in a few patients. The role of HCV in continuing hepatitis after termination of chronic HBsAg antigenemia remains to be explored in a series of patients. METHODS: HCV markers were studied using second generation enzyme immunoassay and polymerase chain reaction with reverse transcription and were compared between 41 patients with persistent alanine aminotransferase (ALT) elevation (hepatitis group) and 82 age/sex-matched patients with normal ALT (control group) after HBsAg clearance. RESULTS: Twenty-six (63%) of the 41 hepatitis group patients were seropositive for antibodies to HCV (anti-HCV) compared with only 4 (5%) of 82 controls (P < 0.0001). Six patients of the hepatitis group and 1 control had an episode of acute hepatitis C with seroconversion of anti-HCV 1-68 months before HBsAg clearance. Of those seropositive for anti-HCV, serum HBV DNA was not detectable, and serum HCV RNA was detected in 23 (88.5%) of the 26 hepatitis patients but none of the 4 controls (P < 0.001). Liver biopsy in 6 anti-HCV positive patients with continuing hepatitis showed features compatible with chronic hepatitis C. HCV RNA, but not HBV DNA, was detected in liver tissues of these 6 patients. CONCLUSIONS: The results suggest that HCV may usurp the role of HBV in chronic hepatitis and act as the major cause of continuing hepatitis or ALT elevation after HBV/HBsAg clearance.

Adult↗