Sofosbuvir and daclatasvir therapy in patients with hepatitis C-related advanced decompensated liver disease (MELD ≥ 15).

BACKGROUND: Antiviral therapy for hepatitis C has the potential to improve liver function in patients with decompensated cirrhosis. AIMS: To examine the virological response and effect of viral clearance in patients with decompensated hepatitis C cirrhosis all with MELD scores ≥15 following sofosbuvir/daclatasvir ± ribavirin. METHODS: We prospectively collected data on patients who commenced sofosbuvir/daclatasvir for 24-weeks under the Australian patient supply program (TOSCAR) and analysed outcomes including sustained viral response at 12 weeks (SVR12), death and transplant. RESULTS: 108 patients (M/F, 79/29; median age 56years; Child-Pugh 10; MELD 16; genotype 1/3, 55/47) received sofosbuvir/daclatasvir and two also received ribavirin. On intention-to-treat, the SVR12 rate was 70% (76/108). Seventy-eight patients completed 24-weeks therapy. SVR12 was achieved in 56 of these patients on per-protocol-analysis (76%). SVR12 was 80% in genotype 1 compared to 69% in genotype 3. Thirty patients failed to complete therapy. In patients achieving SVR12, median MELD and Child-Pugh fell from 16(IQR15-17) to 14(12-17) and 10(9-11) to 8(7-9), respectively (P<.001). In those who died, MELD increased from 16 to 23 at death (P=.036). Patients who required transplantation had a significantly higher baseline MELD (20) compared to those patients completing treatment (16) (P=.0010). The odds ratio for transplant in patients with baseline MELD ≥20 was 13.8(95%CI 2.78-69.04). CONCLUSIONS: SVR12 rates with sofosbuvir/daclatasvir in advanced liver disease are lower than in compensated disease. Although treatment improves MELD and Child-Pugh in most patients, a significant proportion will die or require transplantation. In those with MELD ≥20, it may be better to delay treatment until post-transplant.

Markers of coagulation activation after hepatic resection for cancer: evidence of sustained upregulation of coagulation.

We investigated the possibility that despite postoperative derangements of routine laboratory coagulation tests, markers of coagulation activation and thrombin generation would be normal or increased in patients undergoing hepatic resection for cancer In addition to the conventional coagulation tests prothrombin time and activated partial thromboplastin time, we measured select markers of coagulation activation prothrombin fragments 1 and 2 (PF1 + 2), thrombin-antithrombin complexes and plasma von Willebrand Factor antigen in 21 patients undergoing hepatic resection. The impact of hepatic resection on coagulation and fibrinolysis was studied with thromboelastography. Preoperatively, routine laboratory coagulation and liver function tests were normal in all patients. On the first postoperative day, prothrombin time was prolonged (range 16 to 22 seconds) in eight patients (38%). For these patients, thromboelastography was normal in six (75%), PF1 + 2 was elevated in four (50%), and thrombin-antithrombin complexes and von Willebrand Factor antigen were elevated in all, which was evidence of acute phase reaction, sustained coagulation factor turnover and activation. By the fifth postoperative day, despite normalisation of prothrombin time, markers of increased coagulation activity remained greater than 85% of baseline values. The findings indicate that in patients undergoing liver resection for cancer, there is significant and prolonged postoperative activation of the haemostatic system despite routine coagulation tests being normal or even prolonged. Before considering therapeutic interventions an integrated approach to interpreting haematological data with clinical correlation is essential.

The association between cardiovascular response tasks and future blood pressure levels in children: Bogalusa Heart Study.

Children were selected from a total community survey and categorized into three blood pressure (BP) groups (low less than 10 percentile, midrange 10 to 90 percentile, high greater than 90 percentile) based on resting diastolic pressure (DBP). To examine the relationship of cardiovascular reactivity with BP levels 4 years later, three cardiovascular response tasks (orthostatic, handgrip, and cold pressor) were administered. Partial correlations, adjusted for initial resting BP, showed that peak BP responses to the three tasks were related to future resting systolic and diastolic BP. Further analyses showed that DBP reactivity was related to future BP tracking in children with high DBP levels. In the high DBP group, while resting DBP levels did not differ for trackers vs nontrackers, peak DBP responses to each of the three tasks did (orthostatic, p less than 0.001; handgrip, p less than 0.05; cold pressor, p less than 0.01). The combination of resting and peak BP levels may provide more powerful predictions of future BP levels in children.

Longitudinal patterns of cigarette smoking and smokeless tobacco use in youth: the Bogalusa Heart Study.

Tobacco use was studied during 1977-76 (n = 2880) and 1981-82 (n = 2158) in a total biracial community of children, aged 8-17 years, in Bogalusa, Louisiana. White males were the early adopters of tobacco products in both surveys. Cigarette smoking decreased in all race and gender groups while smokeless tobacco use increased in White males. Studies which find a decline in male adolescent smoking should investigate a possible concurrent increase in smokeless tobacco.

Factors associated with adolescent participation in a cardiovascular risk factor assessment program.

A Student Attitude Survey was administered to high school seniors to determine attitudinal and behavioral factors associated with participation in a longitudinal cardiovascular risk factor screening program. Health beliefs, attitudes, and practices were assessed as were altruism, social skills, self-concept, conformity, and academic class standing. Male participants showed higher self-concept scores than non participants. Black participants were younger than black nonparticipants and black participants also showed greater perceived control over their health and more optimistic appraisals of the worth of medical research and practice. White male participants tended to be more likely to remain home from school or to see a doctor when ill. These observations suggest that attitudinal and behavioral factors related to participation in a health-related program can be assessed in childhood.

Transitions of cardiovascular risk from adolescence to young adulthood--the Bogalusa Heart Study: I. Effects of alterations in lifestyle.

Adolescence and young adulthood represents a transition period for biologic and lifestyle characteristics. In a preliminary investigation of young adults (ages 18-20 years), the Bogalusa Heart Study documented patterns of alcohol, tobacco, and oral contraceptive use, as well as changes in education, occupational, marital and parenting status. Such behaviors accelerate the cardiovascular disease process and may differentially influence risk factor patterns of race and sex groups. Adverse levels of systolic blood pressure and alpha-lipoprotein cholesterol were more frequent in married vs single men; elevated triglyceride levels were more frequent in married vs single whites. However adverse levels of beta- and alpha-lipoprotein cholesterol were more frequent in nonparents than in parents. Cigarette smoking and oral contraceptive use were independently related to elevated beta-lipoprotein cholesterol and decreased alpha-lipoprotein cholesterol levels of young white women. Alcohol consumption was highest among white males, with 32% reporting daily consumption of the equivalent of two or more beers or one mixed drink. Alcohol consumption was negatively correlated with blood pressure in white males and positively correlated with alpha-lipoprotein cholesterol in black males. Since such lifestyle factors are related to physiologic risk factors that result in heart disease and adult cardiovascular morbidity and mortality in the older ages, early targeting during adolescence and young adulthood is important.

Relationship between mood and blood pressure in the natural environment: an adolescent population.

We examined the relation between psychological variables and blood pressure (BP) as 28 adolescents engaged in their customary activities over a 24-hr period in their natural environment. Each subject had previously participated in a laboratory study of cardiovascular reactivity. During the ambulatory monitoring period, subjects monitored mood state, perceptions of the environment, and ambulatory BP at 30-min intervals. Mood ratings and BP were averaged across the waking hours. Systolic blood pressure (SBP) reactivity to laboratory stressors was significantly correlated with average SBP in the home environment. Ambulatory SBP was positively associated with worried, hostile, depressed, and tense mood ratings as well as perceptions of the environment as hostile, demanding, and noisy. Ambulatory diastolic blood pressure was correlated with hostile, depressed, and upset mood ratings as well as with hostile and demanding perceptions of the environment. In general, average ambulatory BP appeared to be associated with negative emotions and perceptions of the environment.

Measurement assessment of the type A coronary prone behavior pattern and hyperactivity/problem behaviors in children: are they related? The Bogalusa Heart Study.

The purpose of this study was to contribute to concept clarification regarding identification of the Type A behavior pattern in children. To accomplish this, two measurement techniques for assessing Type A behavior in children (MYTH and Hunter-Wolf) were compared to a third (a teacher-rated measure of hyperactivity: the Conners), since this latter measure, although often used to diagnose hyperactive children, seemed also to measure some Type A-like behaviors. The Hunter-Wolf also included a self-assessment of Type A behavior. The conceptual and measurement issue was: Are teachers rating Type A or hyperactive/problem behaviors in children? Fifty-five teachers participated. They rated 253 students, aged 8 to 17 years, in a biracial community. The clear overlap between teacher-assessed Type A and the Conners hyperactivity measure was demonstrated when the best predictor of teacher-assessed Type A measure was the Conners. This was especially true for black males and white females. Little relationship existed between teacher-assessed Type A and self-assessment. The conclusions suggest that implications drawn from teacher-assessed Type A behavior in children may be inadequate because of potential ethnic and gender artifactual measurement error.

Recruitment and participation of children in a long-term study of cardiovascular disease: The Bogalusa Heart Study, 1973-1982.

The Bogalusa Heart Study has been highly successful in recruitment and screening of children and adolescents in Bogalusa, Louisiana. From 1973 to 1982 in four cardiovascular risk factor surveys, 80-93% of the biracial pediatric population was examined. Overall participation rates compare favorably with those of similar studies. The authors examine methods and strategies involved in obtaining community support, identifying and contacting the eligible population, and implementing recruitment campaigns. Several of the more successful motivational efforts are described. Attrition and the broader problem of decreasing participation rates in older adolescents are examined. Recommendations are advanced for dealing with this problem age group.

A behavioral program for disruptive Junior High school students: results and follow-up.

The 5-year annual and 4-year follow-up results of a collaborative community mental health center--junior high school program for disruptive students are presented. The program is a comprehensive, behavioral, in-school, regular education project characterized by a token economy, parent contracting, major subjects taught in the morning, small class enrollment, small group and individualized instruction, an early release from school contingency option and frequent parent-school communications. Annual controlled outcome results revealed that the program led to significant and consistent reductions in expulsions, suspensions, and grade failure, and variable, often significant, gains in attendance and achievement. Follow-up findings indicated that former program students in senior high school achieved a significantly higher entry rate, greater attendance, better classroom conduct, and a lower frequency of withdrawal from school.