Tai-Yuan Chiu

Hepatitis B Virus Infection in Children and Adolescents in a Hyperendemic Area: 15 Years after Mass Hepatitis B Vaccination

Hepatitis B virus (HBV) infection is an important cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma in many parts of the world, including Taiwan (1, 2). Up to 15% to 20% of the general population in Taiwan are chronic carriers of hepatitis B surface antigen (HBsAg) (3, 4). Most chronic carriage of HBV results from infection in early childhood, especially before 2 years of age (57). Taiwan launched the worlds first nationwide universal vaccination program in 1984 to prevent infection in the early years of life (8). In addition to decreasing the proportion of carriers and the prevalence of HBV infection in the current young generation (9), the universal vaccination program has also resulted in a decreased incidence of childhood hepatocellular carcinoma (10). To study the effect of this universal vaccination program, we conducted a series of prospective seroepidemiologic surveys in Chung-Cheng District, Taipei City, Taiwan. The first survey was conducted shortly before the mass vaccination program began in 1984 (6), followed by similar surveys in 1989 (11) and 1994 (12). We report findings that extend our follow-up observations to 199915 years after the start of the program. Methods National Vaccination Program The national program of universal HBV vaccination in Taiwan began on 1 July 1984 (8). At that time, only the newborn infants of mothers who were HBsAg carriers were vaccinated. The vaccination program was extended in June 1987 to include all newborn infants and in July 1987 to cover all children of preschool age. The program was further extended to school children, teenagers, and then adults from 1988 to 1990. Since 1991, the vaccination records of first-grade children have been checked, and children without a complete set of previous vaccinations have been given catch-up HBV vaccinations. Before July 1992, four doses of plasma-derived vaccine were administered in children before 1 week of age and again at 1, 2, and 12 months of age; after July 1992, three doses of recombinant (yeast-derived) vaccine were administered before 1 week and at 1 month and 6 months of age. Since 1984, newborns whose mothers test positive for hepatitis B e antigen (HBeAg) have also received hepatitis B immunoglobulin, 0.5 mL (100 IU), within 24 hours after birth. The vaccination program has been described in greater detail elsewhere (8, 12). We defined the vaccination coverage rate as the percentage of children receiving at least three doses of HBV vaccine. We assessed the vaccination histories of the studied population by examining their vaccination cards and by taking a history from their parents. We classified the vaccination status as unknown for persons with a missing vaccination card or a vague vaccination history. Participants From March 1999 to October 1999, serum samples were collected from 1916 children and adolescents from two groups: 1) 1357 apparently healthy persons younger than 15 years of age [721 male participants and 636 female participants], who were born after the launch of the universal vaccination program, and 2) 559 persons (297 male participants and 262 female participants) 15 to 20 years of age, who were born before universal vaccination. We recruited participants for the baseline and follow-up seroepidemiologic studies in Chung-Cheng District, Taipei City. In 1999, Chung-Cheng had a population of 165 388 citizens; 35 005 of the citizens were younger than 15 years of age, and 47 565 were younger than 20 years of age. From 1994 to 1999, the population was stable, with an average annual migration rate of less than 4.8%. The annual family income,

Sedation for refractory symptoms of terminal cancer patients in Taiwan.

39 963 (in U.S. dollars), was the third highest among the 12 districts in Taipei (13). From 1985 through 1990, the HBsAg carrier rate among pregnant women14% (14)was similar to the national average (3, 4). The 1916 participants in our 1999 study consisted of 1) 157 children younger than 3 years of age enrolled from the Well-Baby Clinic of the National Taiwan University Hospital Department of Pediatrics and from two day care centers; 2) 232 children 3 to 6 years of age recruited from two kindergarten classes; 3) 763 children 7 to 12 years of age enrolled from one public elementary school; 4) 205 children and adolescents 12 to 15 years of age enrolled from one public junior high school; 5) 219 adolescents 15 to 18 years of age enrolled from one high school; and 6) 340 first-year undergraduate students at the National Taiwan University, 19 to 20 years of age. We recruited the child and adolescent participants through poster advertisements and by invitation from the health staff of the Department of Pediatrics, National Taiwan University Hospital. The university student participants and the parents of enrolled children gave written, informed consent and provided the vaccination history of the participant, according to his or her personal health booklet. (The booklet, which is used to record a persons vaccination history, is provided to the parents of all newborns by the Health Bureau of City Hall.) Serologic and Statistical Analyses We analyzed serum samples for HBsAg, HBsAg antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) by using enzyme immunoassay (Abbott Laboratories, North Chicago, Illinois). We examined between-group differences in frequency by using the chi-square test with Yates correction or the Fisher exact test, where appropriate. A P value less than 0.05 was considered significant. Data analyses were performed by using GraphPad Prism, version 3.00 (GraphPad Software, Inc., San Diego, California). Role of the Funding Source The funding source had no role in the collection, analysis, and interpretation of the data or in the decision to submit the paper for publication. Results In 1999, the vaccination coverage rate was greater than 90% among children younger than 8 years of age and 80% to 86% among children 8 to 15 years of age (Table). These figures might be underestimates because some of the participants, particularly in the older age group, had missing vaccination cards; in other cases (for 23 of the 541 children younger than 8 years of age and 63 of the 766 participants 8 to 15 years of age), the parents could not recall the vaccination history. Infants had a lower coverage rate than other age groups because some of them had not yet finished their vaccination schedule (Appendix Table). Table. Seroprevalence of Hepatitis B Surface Antigen and Its Antibody in Chung-Cheng District, Taipei City, Taiwan, in 1984, 1989, 1994, and 1999 The prevalence of HBsAg in children younger than 15 years of age, 0.7% (9 of 1357), was considerably lower than the rate of 7% (39 of 559) observed in participants older than 15 years of age, who were born before the universal vaccination program (P < 0.001). Of the 9 children who were born after the vaccination program was instituted and tested positive for HBsAg, only 1 had not received the scheduled vaccinations, and the mother of this child was also HBsAg positive. According to their vaccination cards, the 8 other participants had received at least three doses of the HBV vaccine, and the first dose had been given within 1 week of birth. Seven of these 8 participants had mothers who were HBsAg carriers, and the remaining participant was living with two grandparents who were HBsAg positive. All 9 participants tested positive for anti-HBc. Eight of these 9 HBsAg carriers had received the plasma-derived vaccine, and 1 had received the yeast-derived recombinant vaccine; however, type of vaccine did not affect the rate of HBsAg seropositivity (8 of 968 persons who received the plasma-derived vaccine were carriers vs. 1 of 389 who received the yeast-derived vaccine; P > 0.2, Fisher exact test). The overall prevalence of anti-HBs in persons younger than 15 years of age in 1999 was 75.8%. We observed the highest prevalence of anti-HBs in children younger than 5 years of age (Table). The longitudinal perspective of HBsAg carriers in cohorts 0 to 1 years of age is shown in the Figure. Figure. Longitudinal perspective of the proportion of hepatitis B surface antigen carriers among the cohorts of 0 to 1 year of age in 1984 (circles) and 1989 (squares) in Chung-Cheng District, Taipei City, Taiwan. Children in the 1984 0- to 1-year age cohort, who were born before universal vaccination in Taiwan, had a carrier rate of 5.1% in 1984, 3.9% in 1989 (at age 5 to 6 years), 4.7% in 1994 (at age 10 to 11 years), and 7.5% in 1999 (at age 15 to 16 years). These proportions are significantly higher than those observed over time in the 1989 0- to 1-year age cohort, who were born since the national vaccination program started, at the corresponding age points (from the survey years 1989, 1994, and 1999, respectively). The rate of anti-HBc seropositivity was 2.9% in persons younger than 15 years of age but was 20.6% in persons 15 years of age or older (P < 0.001). In contrast, the rate of anti-HBc seropositivity among children younger than 15 years of age was 26.2% in 1984 (6), 14.5% in 1989 (11), and 4.0% in 1994 (12). Discussion The prevalence of HBsAg among children younger than 15 years of age decreased from 9.8% to 0.7% in the 15 years since implementation of the universal vaccination program. A high coverage rate for HBV vaccination is crucial for decreasing the prevalence of HBV infection. We observed a vaccination rate of at least 80% among children younger than 15 years of age and as high as 97% among children 4 years of age or younger. A nationwide series of seroepidemiologic studies of three cohorts of children 6 years of age in 1989, 1991, and 1993 reported that the vaccination rates for HBV ( 3 doses of vaccine) were 27.8%, 60.7%, and 88.7%, respectively (9). The age of these three cohorts in 1999 correspond to the age groups of 15 to 18 years, 13 to 14 years, and 11 to 12 years in our study. The data from these three national cohort studies confirm that the vaccination rate in our sample is similar to the vac

Symptom patterns of advanced cancer patients in a palliative care unit.

This study assessed sedation in terminal cancer patients in terms of three characteristics: frequency; relationship to intractable symptoms; and the extent to which medical staff, family, and patients found sedation to be ethically acceptable and efficacious. Two hundred seventy-six consecutive patients, who were admitted to the palliative care unit of National Taiwan University Hospital in Taiwan between August 1998 and the end of May 1999, were enrolled. A recording form was completed every day. This included demographic data, pain and common symptom scores, and the use of sedation in the terminal phase. Seventy (27.9%) of 251 patients who died received sedation. Sedation was administered to relieve agitated delirium in 40 (57.1%), dyspnea in 16 (22.8%), severe pain in 7 (10%) and insomnia in 5 (7.2%). The drugs used for sedation were haloperidol in 35 (50%), midazolam in 17 (24.3%), and rapidly increasing dosage of morphine in 9 (12.9%). In fewer than half (42.9%) of the patients, sedation was with the consent of both patient and family, and half (50%) had the consent of family alone. The overwhelming majority of medical staff and family felt the decision to use terminal sedation was ethically acceptable. There was no significant difference in survival time between sedated and non-sedated patients (28.49 vs. 24.71 days, t = -0.791, P = 0.430). Positive ethical acceptability and higher satisfaction with symptom control with terminal sedation were found in both medical staff and family in this study. Further work is needed to find the most appropriate time of intervention and to improve management of refractory symptoms in dying patients.

Determination of immune memory to hepatitis B vaccination through early booster response in college students

This study involved longitudinal evaluations of symptom severity and describes the symptom patterns of 77 terminal cancer patients (median age: 62 years; 61% female), selected from 537 consecutive patients admitted to the Palliative Care Unit of the National Taiwan University Hospital. The most common primary cancer sites in these patients were lung (23.4%), liver (15.6%), and stomach (13%). Nineteen physical and psychological symptoms were assessed using different scales. The median number of symptoms was 11 (range: 1-18) on admission, among which weakness, fatigue, anorexia, pain, and depression were the most common. A comparison of the initial symptom severity scores with those at one week after admission and two days before death suggested six symptom change patterns: A: continuous static (restless/heat, abdominal fullness, constipation, dizziness, and insomnia); B: static-increase (fatigue, weakness, nausea/vomiting, taste alteration, dysphagia, diarrhea, dry mouth, and night sweats); C: decrease-static (pain and depression); D: decrease-increase (anorexia and dyspnea); E: static-decrease (aggression); and F: gradually decrease (anxiety). These six symptom patterns can be divided into two categories on the basis of the relative severity of symptoms between one week after admission and two days before death. The first category included patterns A, C, E and F, and the symptoms improved with palliative care. However, the symptoms in the second category (patterns B and D), which were associated with the anorexia-cachexia syndrome and dyspnea, did not show improvement. As symptom management is an essential component of palliative care, holistic care, which encompasses physical, psychosocial and spiritual aspects, represents a rational approach for the relief of these incurable symptoms at the end stage of life for these patients.

Prevalence and severity of symptoms in terminal cancer patients: a study in Taiwan

The long‐term protection of hepatitis B (HB) vaccination has been debated for years. The purpose here was to evaluate the kinetic changes of antibody to HB surface antigen (anti‐HBs) and define immune memory of the HB vaccine among college students who had previously received full neonatal immunization against HB. In all, 127 college students aged 18‐23 years born after July 1984 who had completed HB vaccination and were seronegative for all three HB viral markers, including HB surface antigen (HBsAg), antibody to HB core protein (anti‐HBc), and anti‐HBs, were recruited. They received three doses of HB vaccine at enrollment, 1 month and 6 months after enrollment. Their anti‐HBs titers were assayed at enrollment, 7‐10 days, 1 month, 6 months, and 7 months following the first dose of HB vaccine. The anti‐HBs seroprotective rates for subjects 7‐10 days, 1 month, 6 months, and 7 months postvaccination were 20.5%, 75.6%, 94.5%, and 99.2%, respectively. Those who were seroprotective at 7 to 10 days after one dose of HB vaccine booster developed significantly higher levels of anti‐HBs at 1 and 6 months than those not developing seroprotective anti‐HBs response at an earlier timepoint. Conclusion: At least one‐quarter of HB vaccinees have lost their immune memory to the HB vaccine when entering college. Immune memory to HB vaccine was identified by early seroconversion, which was present in only 20% of vaccinees in the present study. To ensure higher than 90% anti‐HBs seroconversion rates, at least 2 doses of HB booster vaccines are recommended for at‐risk youths who received complete HB vaccinations in neonatal or infant periods but are seronegative for HBsAg, anti‐HBs, and anti‐HBc in adolescence. (Hepatology 2010;)

Ethical dilemmas in palliative care: a study in Taiwan

Abstract This paper reports a prospective study conducted between September 1997 and July 1998 in 232 consecutive patients with terminal cancer. A structured data collection form was used daily to evaluate symptoms, which were analyzed at the time of admission, 1 week after admission and 48 h before death. Terminal cancer patients in this study were polysymptomatic. There were no statistically significant differences in the prevalence of most symptoms with the primary site of cancer. The majority of symptoms improved at the end of the 1st week after admission, but many symptoms worsened just before death. The high prevalence of symptoms and lack of significant difference among primary tumor sites may be related to shorter survival times caused by late referral, which is common in Taiwan.

Social support and depressive symptoms among displaced older adults following the 1999 Taiwan earthquake

Objectives—To investigate the incidence and solution of ethical dilemmas in a palliative care unit. Design—Health care workers recorded daily all dilemmas in caring for each patient. Setting—Palliative care unit of National Taiwan University Hospital in Taiwan. Patients—Two hundred and forty-six consecutive patients with terminal cancer during 1997-8. Main measurement—Ethical dilemmas in the questionnaire were categorised as follows: telling the truth; place of care; therapeutic strategy; hydration and nutrition; blood transfusion; alternative treatment; terminal sedation; use of medication, and others. Results—The type and frequency of ethical dilemmas encountered were: place of care (33.3%); truth-telling (32.1%); hydration and nutrition (25.2%); therapeutic strategy (24.8%), and use of medication (19.1%). Ethical problems relating to the place of care and to therapeutic strategy were unlikely to be solved with increased hospital stay and some ethical dilemmas remained unsolved even in the final week in hospital, including place of care (23.2%), truth-telling (17.1%) and therapeutic strategy (11.4%). Problems of truth-telling occurred in nearly half (42.6%) of patients over sixty-five-years-old. Conflicts about blood transfusion were experienced in all patients below 18-years-old, and the dilemmas concerning the place of care occurred most frequently with head and neck cancer patients (43.8%). Conclusions—The solution of ethical dilemmas required refocusing by medical professionals on the importance of continuing communication. Improved ethical training for professionals would contribute to solving the moral dilemmas of palliative care.

Solving family-related barriers to truthfulness in cases of terminal cancer in Taiwan. A professional perspective.

This longitudinal study examines changes in depressive symptoms among displaced older Taiwanese adults (N = 54, M = 68 years), and the impact of various social supports for them at between 6 and 12 months after an earthquake. The average depression score between 6 and 12 months following the earthquake was unchanged and kept high score. Child and extended family support levels related to depressive symptoms after 6 months. In contrast, after 12 months, significant factors associated with a lessening of the depressive symptoms were social support from the extended family and neighbors, and social participation. Intervention to promote increased social networks and social participation, within their new environment in a temporary community, is highly recommended for older adults.

Good death study of elderly patients with terminal cancer in Taiwan

The study investigated the puzzling factors and solutions of family-related barriers to truthfulness with patients with terminal cancer through a nationwide survey conducted in Taiwan. Two-hundred twenty-nine valid questionnaires were retrieved (91.6%) from 250 palliative care workers at 15 Taiwan hospices. Most of the respondents were nursing staff (72.5%), and only 38 respondents were physicians (16.6%). Canonical correlation analysis was used to examine the association between the puzzling factors and solutions, which revealed that the value of the first variate was 0.39 (P < .05). Results showed that the puzzling factors of barriers and canonical loadings were families do not know how to tell the truth (.85), families believe it is unnecessary to tell aged patients the truth (.71), and patients can be happier without knowing the truth (.70). The valid solutions correlated significantly with the above puzzling factors and were ranked in the following order: communicate with and encourage families to accept patients’ prognoses (.83), discuss the sickness gently with patients and determine what patients know (.76), and tell the families about the possible emotional reactions in patients and how to provide support (.72). In conclusion, for solving family-related barriers to truthfulness in cases of terminal cancer, the results suggest that health professionals communicate with families first and discuss the possible emotional reactions from patients, give patients enough time to reflect on their sicknesses and discuss further what patients have been told, and then disclose information based on patients’ expectations and support them.

The practicalities of terminally ill patients signing their own DNR orders—a study in Taiwan

Objectives: Over half of all terminal cancer patients in Taiwan are 65 or older, thus demonstrating the importance of terminal care for elderly people. This study investigates the good death status of elderly patients with terminal cancer, comparing the differences in the degree of good death among elderly and younger groups, and exploring the factors related to the good death score. Methods: Three hundred and sixty-six patients with terminal cancer admitted to a palliative care unit were enrolled. Two structured measurements, the good death scale and the audit scale for good death services, were used as the instruments in the study. Results: The scores of individual items and of the good death scale were increased significantly in both elderly (n = 206, 56.3%) and younger (n = 160, 43.7%) groups from the time of admission to just prior to death. However, the elderly group had significantly lower scores in ‘awareness’ (t = −3.76, P < 0.001), ‘propriety’ (t = −2.92, P < 0.01) and ‘timeliness’ (t = −2.91, P < 0.01) than the younger group prior to death. Furthermore, because of a lack of truth-telling, the elderly group also had significantly lower scores than the younger group in both ‘respect for autonomy’ and ‘decision-making participation’ (t = –2.17, P < 0.05; t = –2.21, P < 0.05, respectively). Multiple regression analysis revealed that ‘respect for autonomy’ (OR = 1.22, 95% CI = 0.76–1.67) and ‘verbal support ‘(OR = 0.93, 95% CI = 0.34–1.51) were two independent correlates of the good death score in the elderly group. Conclusion: The dilemma of truth-telling compromises the autonomy of the elderly patients with terminal cancer and consequently affects their good death scores. The palliative care team should emphasize the issue of truth-telling in the process of caring for terminally ill cancer patients, especially elderly patients.