Immunogenicity and safety following one dose of AS01E-adjuvanted respiratory syncytial virus prefusion F protein vaccine in older adults: a phase 3 trial.

BACKGROUND: The recently approved AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) demonstrated high efficacy against RSV-related disease in ≥60-year-olds. METHODS: This ongoing phase 3 study in ≥60-year-olds evaluates the immune persistence until three years post-RSVPreF3 OA vaccination. Here, we describe interim results on humoral and cell-mediated immunogenicity, reactogenicity, and safety until one year post-dose 1. RESULTS: In total, 1653 participants were vaccinated. One month post-dose 1, neutralization titers increased 10.5-fold (RSV-A) and 7.8-fold (RSV-B) versus pre-dose 1. Titers then declined to levels 4.4-fold (RSV-A) and 3.5-fold (RSV-B) above pre-dose 1 at month 6, and remained 3.1-fold (RSV-A) and 2.3-fold (RSV-B) above pre-dose 1 levels after one year. RSVPreF3-binding immunoglobulin G levels and CD4+ T-cell frequencies showed similar kinetics. Solicited administration-site and systemic adverse events (mostly mild to moderate and transient) were reported by 62.2% and 49.5% of participants. Serious adverse events were reported by 3.9% of participants within 6 months post-dose 1; one case was considered vaccine-related. CONCLUSIONS: One RSVPreF3 OA dose elicited cell-mediated and RSV-A and RSV-B-specific humoral immune responses that declined over time but remained above pre-dose 1 levels for at least one year. The vaccine was well tolerated with an acceptable safety profile.Clinicaltrials.gov NCT04732871.

Respiratory syncytial virus (RSV) is a major cause of illness and hospitalization in older adults. An RSV vaccine for older adults developed by GSK was recently approved. The vaccine was well tolerated and provided protection against RSV disease in adults aged 60 years and older during at least one RSV season. In this ongoing study, we are evaluating the magnitude and durability of the immune response, as well as vaccine safety, until three years after vaccination of adults aged 60 years and older from five countries. Here, we report the results of an interim analysis until one year after vaccination with one dose. In total, 1653 participants were vaccinated. We found that the vaccine induced a strong immune response that was evident one month after vaccination, after which it declined, but persisted for at least one year. Study participants most often reported pain at the injection site, muscle pain, tiredness, and headache as adverse reactions, which were mostly mild to moderate and of short duration. One serious adverse reaction was considered related to the vaccine. The long-term immune response that was observed in this study is consistent with the vaccine providing protection during at least one RSV season.

The Adjuvanted Recombinant Zoster Vaccine Confers Long-Term Protection Against Herpes Zoster: Interim Results of an Extension Study of the Pivotal Phase 3 Clinical Trials ZOE-50 and ZOE-70.

BACKGROUND: This ongoing follow-up study evaluated the persistence of efficacy and immune responses for 6 additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at age ≥50 years in 2 pivotal efficacy trials (ZOE-50 and ZOE-70). The present interim analysis was performed after ≥2 additional years of follow-up (between 5.1 and 7.1 years [mean] post-vaccination) and includes partial data for year (Y) 8 post-vaccination. METHODS: Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing ≥2 of 4 assessed activation markers) frequencies from Y5 post-vaccination. RESULTS: Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination, 67.2 years), 813, and 108 were included in the cohorts evaluating efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9-89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2-93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable through this interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells reached a plateau at approximately 6-fold above pre-vaccination levels. CONCLUSIONS: Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least 7 years post-vaccination. Clinical Trials Registration. NCT02723773.

Awareness of, attitude toward, and willingness to participate in pay for performance programs among family physicians: a cross-sectional study.

BACKGROUND: The National Health Insurance Administration of Taiwan has introduced several pay-for-performance programs to improve the quality of healthcare. This study aimed to provide government with evidence-based research findings to help primary care physicians to actively engage in pay-for-performance programs. METHODS: We conducted a questionnaire survey among family physicians with age-stratified sampling from September 2016 to December 2017. The structured questionnaire consisted of items including the basic demographics of the surveyee and their awareness of and attitudes toward the strengths and/or weaknesses of the pay-for-performance programs, as well as their subjective norms, and the willingness to participate in the pay-for-performance programs. Univariate analysis and multivariate logistic regression analysis were performed to compare the differences between family physicians who participate in the pay-for-performance programs versus those who did not. RESULTS: A total of 543 family physicians completed the questionnaire. Among family physicians who participated in the pay-for-performance programs, more had joined the Family Practice Integrated Care Project [Odds ratio (OR): 2.70; 95% Confidence interval (CI): 1.78 ~ 4.09], had a greater awareness of pay-for-performance programs (OR: 2.37; 95% CI: 1.50 ~ 3.83), and a less negative attitude to pay-for-performance programs (OR: 0.50; 95% CI: 0.31 ~ 0.80) after adjusting for age and gender. The major reasons for family physicians who decided to join the pay-for-performance programs included believing the programs help enhance the quality of healthcare (80.8%) and recognizing the benefit of saving health expenditure (63.4%). The causes of unwillingness to join in a pay-for-performance program among non-participants were increased load of administrative works (79.6%) and inadequate understanding of the contents of the pay-for-performance programs (62.9%). CONCLUSIONS: To better motivate family physicians into P4P participation, hosting effective training programs, developing a more transparent formula for assessing financial risk, providing sufficient budget for healthcare quality improvement, and designing a reasonable profit-sharing plan to promote collaboration between different levels of medical institutions are all imperative.

Team-based care improves quality of diabetes care -Family Practice Integrated Care Project in Taiwan.

BACKGROUND: The Family Practice Integrated Care Project (FPICP) is a team-based program in Taiwan initiated in 2003. This study investigates the influence of FPICP on the quality of diabetes care. METHODS: This population-based cohort study used Taiwan's National Health Insurance Administration data on FPICP (fiscal year 2015-2016, with follow-up duration of one year). Participants included diabetic patients aged ≥30 in primary care clinics. We used conditional logistic regression modeling of patient characteristics and annual diabetes examinations and compared FPICP participants with non-participating candidates. Main outcome measures included completion of annual diabetes examinations, including glycated hemoglobin (A1c), low-density lipoprotein (LDL), urine microalbumin (MAU), routine urinalysis (UR), and fundus examination (FE). RESULTS: The sample included 298,208 FPICP participants and 478,778 non-participating candidates. After 1:1 propensity score matching, the examination completion rates for FPICP participants and non-participants, respectively, were 94.4% versus 93.6% in A1c, 84.2% versus 83.8% in LDL, 61.9% versus 60.1% in MAU, 59.2% versus 58.0% in UR, and 30.1% versus 32.4% in FE. CONCLUSION: Our findings indicate that a program like FPICP helps improve the quality of diabetes care through regular examinations of Alc, LDL, MAU, and UR.

Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.

BACKGROUND: A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). METHODS: This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. RESULTS: In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. CONCLUSIONS: In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.gov numbers, NCT01165177 and NCT01165229 .).

Lots of little ones: Analysis of charitable donations to a hospice and palliative care unit in Taiwan.

BACKGROUND: Charitable donations play a major role in the provision of hospice and palliative care (HPC) services, most of which are not reimbursed by health insurance programs. A good understanding of the constitution and use of donations is thus conducive to maintaining a high-quality HPC unit. METHODS: The data sources were the publicly available balance sheet, work report, and donor lists of a foundation exclusively supporting one of the best HPC units in Taiwan in the fiscal year of 2017. The analysis included the donation amounts and frequencies by donor type (individual, corporate, and group) and the categories of expenses. RESULTS: The foundation received 3033 donations worth a total of 7.8 million New Taiwan dollars (NTD) (approximately 258 thousand US dollars) in 2017. Two-thirds of the donations were allocated to the provision of direct care services. Of the 3033 donations, only 11 (0.4%) were worth 100 000 NTD or more, while 108 (3.6%) were valued between 10 000 and 99 999 NTD, 1268 (41.8%) were valued between 1000 and 9999 NTD, and 1646 (54.2%) were worth less than 1000 NTD. Of 1051 donors, 974 (92.7%) were individuals, 378 (36.0%) donated more than once, and 106 (10.1%) donated 12 or more times in one year. CONCLUSION: HPC services in Taiwan are sponsored by lots of individuals and small donations. For sustainability of standards-based and quality HPC services, the benevolence of the public should be thus cherished and adequately responded to.

Rural-urban disparities in family physician practice patterns: A nationwide survey in Taiwan.

INTRODUCTION: In a world with increasing urbanization, rural-urban disparities in health care utilization have been a long-term concern. However, the details regarding the practice patterns of family physicians in Taiwan have not received sufficient attention thus far. METHODS: The National Health Insurance Research Database of Taiwan offered 0.2% of the total ambulatory visit records for Taiwan in 2013. Records from community clinics of family medicine were collected, with the clinics categorized as rural, suburban, or urban area clinics according to their locations. RESULTS: Among 100 334 visits to family medicine clinics, the median patient age was 50 years for urban clinics, 51 for suburban clinics, and 58 for rural clinics. The distributions of patient ages differed in the three areas (P < 0.001). Four types of chronic diseases (cardiovascular diseases, diabetes, chronic respiratory diseases, and cancers) accounted for 10.8%, 11.3%, and 13.6%, of the visits to urban, suburban, and rural clinics, respectively. The most common procedure was wound treatment, and the pattern of the top 10 procedures was similar in the three areas. CONCLUSION: Although rural patients in Taiwan were older and had more chronic diseases than urban and suburban patients, the pattern of procedures undertaken by rural family physicians did not differ from those of urban and suburban family physicians.

Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older.

Background: The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials. Methods: Participants (ZOE-50: ≥50; ZOE-70: ≥70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing ≥2 of 4 activation markers assessed (CD42+) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity. Results: After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD42+ T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained ≥5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Conclusions: Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination. Clinical Trials Registration: NCT01165177; NCT01165229.

Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults.

BACKGROUND: In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response. METHODS: We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults. RESULTS: A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups. CONCLUSIONS: The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups. (Funded by GlaxoSmithKline Biologicals; ZOE-50 ClinicalTrials.gov number, NCT01165177.).

Sex differences in relationships between metabolic syndrome components and factors associated with health-related quality of life in middle-aged adults living in the community: a cross-sectional study in Taiwan.

BACKGROUND: Metabolic syndrome (MetS) is a widespread condition with important effects on public health, in general. There is a lack of relevant research on possible sex differences in the relationship between MetS and health-related quality of life (HRQoL) and also the sex differences in factors associated with HRQoL. The aims of this study were to identify: 1) whether women exhibit greater negative impacts on physical domain HRQoL from MetS compared with men; 2) whether women exhibit greater mental domain impacts compared with men; and 3) whether factors associated with HRQoL scores are different for men and women. METHODS: This cross-sectional study was conducted in Taipei, Taiwan. Using random sampling, a total of 906 participants aged 35-55 years were recruited. MetS was defined according to the MetS criteria for the Taiwanese population, and HRQoL were assessed using physical component summary (PCS) and mental component summary (MCS) scores of the Short Form Health Survey (SF-36), Taiwan version. Demographics, physical activity, medical history, and blood tests as covariates were recorded and checked. The associations were assessed by multiple linear regression. RESULTS: After adjusting for covariates, women but not men with more components of MetS had significantly lower PCS scores (ß = - 0.542, p = 0.036). The number of components of MetS was not a significant factor in MCS score differences between the sexes. Furthermore, there were sex differences regarding age, education level, physical activity, and smoking status in association with PCS scores. For MCS scores, sex differences were found in education level, marital status, and habits of smoking and alcohol consumption. CONCLUSIONS: There were sex differences in the relationships between metabolic syndrome components and factors associated with HRQoL among middle-aged adults living in the community in Taiwan. Further research should be conducted to investigate mechanisms of these sex differences.

Differences in do-not-resuscitate orders, hospice care utilization, and late referral to hospice care between cancer and non-cancer decedents in a tertiary Hospital in Taiwan between 2010 and 2015: a hospital-based observational study.

BACKGROUND: In 2009, the Taiwanese national health insurance system substantially expanded hospice coverage for terminal cancer patients to include patients with end-stage brain, dementia, heart, lung, liver, and kidney diseases. This study aimed to evaluate differences in do-not-resuscitate (DNR) status and hospice care utilization between terminal cancer patients and advanced non-cancer patients after the policy change. METHODS: Data were obtained from the Death and Hospice Palliative Care Database of Taipei Veterans General Hospital in Taiwan. The differences between cancer and non-cancer patients who died in this hospital between 2010 and 2015 were analyzed in terms of patient characteristics, rates of DNR orders, hospice care utilization, number of living days after DNR order, duration of survival (DOS) after hospice care enrollment, and the rate of late referral to hospice care. RESULTS: Data for 8459 patients who died of cancer and major non-cancer terminal diseases were included. DNR order rate, hospice care utilization rate, and DOS were significantly higher for cancer patients than for non-cancer patients (p < 0.001, p < 0.001, and p < 0.001, respectively). The number of living days after DNR order and the late referral rate were significantly higher for non-cancer decedents than for cancer decedents (p < 0.001 and p < 0.001, respectively). From 2010 to 2015, there were significantly increasing trends in the hospice utilization rate, number of living days after DNR order, and rate of late referral for the cancer group (p < 0.001, p = 0.001, and p < 0.001, respectively). For the non-cancer group, there were significantly increasing trends in the rate of DNR order, hospice utilization rate, and number of living days after DNR order (p < 0.001, p < 0.001, and p = 0.029, respectively). CONCLUSIONS: Further guidelines should be developed to help clinicians to promptly refer terminal cancer and non-cancer patients to hospice care. Considering the lower hospice utilization rate and the growing need for hospice care among terminal non-cancer patients, policymakers should consider how to improve the relevant levels of professional care to enhance the accessibility and availability of hospice care in Taiwan.

Cancer patient autonomy and quality of dying-a prospective nationwide survey in Taiwan.

BACKGROUND: Patient autonomy is an essential factor in the measurement of quality of dying. We aimed to conduct a study to investigate the factors affecting the autonomy of advanced cancer patients in Taiwan. METHODS: We conducted a prospective, multicenter study and recruited 574 advanced cancer patients from four inpatient hospice wards in Taiwan; their quality of dying was measured using the validated good death scale and the audit scale. Physician-assessed autonomy and the other scales were measured in a team conference by the primary care physician and the team 1 week after the patient had passed away. The good death scale was measured twice, once at admission and then after the patient had passed away for comparison. We measured factors affecting the improvement in quality of dying of these patients initially by applying multiple linear regression analysis. Then, taking physician-assessed autonomy as a dependent variable, we identified the factors that affected this variable. RESULTS: The good death score at admission, clear consciousness, number of admission days beyond 7, better physical care, higher physician-assessed autonomy, better emotional support, better communication, better continuity of life, and physician-reported rate of closure were factors affecting the quality of dying. Further analysis identified age (p = 0.031), consciousness (p = 0.01), and total good death scale score at death (p < 0.001) as determinants of physician-assessed autonomy. CONCLUSIONS: We concluded that physician-assessed autonomy would affect a good death and was highly correlated with age, consciousness level, and quality of dying at the end for advanced cancer patients in Taiwan.

How different is the care of terminal pancreatic cancer patients in inpatient palliative care units and acute hospital wards? A nationwide population-based study.

BACKGROUND: Inpatient palliative care is important for patients with terminal pancreatic cancer. However, the differences between inpatient palliative care and acute hospital care for inpatients with pancreatic cancer have not been explored in a population-based study. METHODS: This population-based nationwide study was conducted using data from the Taiwan National Health Insurance database to analyze the differences between inpatient palliative care and acute hospital care for inpatients with pancreatic cancer. We identified 854 patients with terminal pancreatic cancer, who had received in-hospital end-of-life care between January 2003 and December 2006. These patients were then sub-divided and matched 1:1 (using propensity score matching) according to whether they received inpatient palliative care (n = 276) or acute hospital care (n = 276). These groups were subsequently compared to evaluate any differences in the use of aggressive procedures, prescribed medications, and medical costs. RESULTS: Inpatient palliative care was typically provided by family physicians (39%) and oncologists (25%), while acute hospital care was typically provided by oncologists (29%) and gastroenterologists (24%). The inpatient palliative care group used natural opium alkaloids significantly more frequently than the acute hospital care group (84.4% vs. 56.5%, respectively; P < 0.001). The inpatient palliative care group also had shorter hospital stays (10.6 ± 11.1 days vs. 20.6 ± 16.3 days, respectively; P < 0.001), fewer aggressive procedures, and lower medical costs (both, P < 0.005). CONCLUSIONS: Compared to patients in acute hospital wards, patients with pancreatic cancer in inpatient palliative care units received more frequent pain control treatments, underwent fewer aggressive procedures, and incurred lower medical costs. Therefore, inpatient palliative care should be considered a viable option for patients with terminal pancreatic cancer.

Respiratory syncytial virus and other respiratory viral infections in older adults with moderate to severe influenza-like illness.

BACKGROUND: Few studies have prospectively assessed viral etiologies of acute respiratory infections in community-based elderly individuals. We assessed viral respiratory pathogens in individuals ≥65 years with influenza-like illness (ILI). METHODS: Multiplex reverse-transcriptase polymerase chain reaction identified viral pathogens in nasal/throat swabs from 556 episodes of moderate-to-severe ILI, defined as ILI with pneumonia, hospitalization, or maximum daily influenza symptom severity score (ISS) >2. Cases were selected from a randomized trial of an adjuvanted vs nonadjuvanted influenza vaccine conducted in elderly adults from 15 countries. RESULTS: Respiratory syncytial virus (RSV) was detected in 7.4% (41/556) moderate-to-severe ILI episodes in elderly adults. Most (39/41) were single infections. There was a significant association between country and RSV detection (P = .004). RSV prevalence was 7.1% (2/28) in ILI with pneumonia, 12.5% (8/64) in ILI with hospitalization, and 6.7% (32/480) in ILI with maximum ISS > 2. Any virus was detected in 320/556 (57.6%) ILI episodes: influenza A (104/556, 18.7%), rhinovirus/enterovirus (82/556, 14.7%), coronavirus and human metapneumovirus (each 32/556, 5.6%). CONCLUSIONS: This first global study providing data on RSV disease in ≥65 year-olds confirms that RSV is an important respiratory pathogen in the elderly. Preventative measures such as vaccination could decrease severe respiratory illnesses and complications in the elderly.

Long-term booster schedules with AS03A-adjuvanted heterologous H5N1 vaccines induces rapid and broad immune responses in Asian adults.

BACKGROUND: The pandemic potential of avian influenza A/H5N1 should not be overlooked, and the continued development of vaccines against these highly pathogenic viruses is a public health priority. METHODS: This open-label extension booster study followed a Phase III study of 1206 adults who had received two 3.75 µg doses of primary AS03A-adjuvanted or non-adjuvanted H5N1 split-virus vaccine (A/Vietnam/1194/2004; clade 1) (NCT00449670). The aim of the extension study was to evaluate different timings for heterologous AS03A-adjuvanted booster vaccination (A/Indonesia/5/2005; clade 2.1) given at Month 6, 12, or 36 post-primary vaccination. Immunogenicity was assessed 21 days after each booster vaccination and the persistence of immune responses against the primary vaccine strain (A/Vietnam) and the booster strain (A/Indonesia) was evaluated up to Month 48 post-primary vaccination. Reactogenicity and safety were also assessed. RESULTS: After booster vaccination given at Month 6, HI antibody responses to primary vaccine, and booster vaccine strains were markedly higher with one dose of AS03A-H5N1 booster vaccine in the AS03A-adjuvanted primary vaccine group compared with two doses of booster vaccine in the non-adjuvanted primary vaccine group. HI antibody responses were robust against the primary and booster vaccine strains 21 days after boosting at Month 12 or 36. At Month 48, in subjects boosted at Month 6, 12, or 36, HI antibody titers of ≥1:40 against the booster strain persisted in 39.2%, 61.2%, and 95.6% of subjects, respectively. Neutralizing antibody responses and cell-mediated immune responses also showed that AS03A-H5N1 heterologous booster vaccination elicited robust immune responses within 21 days of boosting at Month 6, 12, or 36 post-primary vaccination. The booster vaccine was well tolerated, and no safety concerns were raised. CONCLUSIONS: In Asian adults primed with two doses of AS03A-adjuvanted H5N1 pandemic influenza vaccine, strong cross-clade anamnestic antibody responses were observed after one dose of AS03A-H5N1 heterologous booster vaccine given at Month 6, 12, or 36 after priming, suggesting that AS03A-adjuvanted H5N1 vaccines may provide highly flexible prime-boost schedules. Although immunogenicity decreased with time, vaccinated populations could potentially be protected for up to three years after vaccination, which is likely to far exceed the peak of the a pandemic.

Chinese herbal prescriptions for osteoarthritis in Taiwan: analysis of National Health Insurance dataset.

BACKGROUND: Chinese herbal medicine (CHM) has been commonly used for treating osteoarthritis in Asia for centuries. This study aimed to conduct a large-scale pharmaco-epidemiologic study and evaluate the frequency and patterns of CHM used in treating osteoarthritis in Taiwan. METHODS: A complete database (total 22,520,776 beneficiaries) of traditional Chinese medicine (TCM) outpatient claims offered by the National Health Insurance program in Taiwan for the year 2002 was employed for this research. Patients with osteoarthritis were identified according to the diagnostic code of the International Classification of Disease among claimed visiting files. Corresponding prescription files were analyzed, and an association rule was applied to evaluate the co-prescription of CHM for treating osteoarthritis. RESULTS: There were 20,059 subjects who visited TCM clinics for osteoarthritis and received a total of 32,050 CHM prescriptions. Subjects between 40 and 49 years of age comprised the largest number of those treated (19.2%), followed by 50-59 years (18.8%) and 60-69 years group (18.2%). In addition, female subjects used CHMs for osteoarthritis more frequently than male subjects (female: male = 1.89: l). There was an average of 5.2 items prescribed in the form of either an individual Chinese herb or formula in a single CHM prescription for osteoarthritis. Du-zhong (Eucommia bark) was the most commonly prescribed Chinese single herb, while Du-huo-ji-sheng-tang was the most commonly prescribed Chinese herbal formula for osteoarthritis. According to the association rule, the most commonly prescribed formula was Du-huo-ji-sheng-tang plus Shen-tong-zhu-yu-tang, and the most commonly prescribed triple-drug combination was Du-huo-ji-sheng-tang, Gu-sui-pu (Drynaria fortune (Kunze) J. Sm.), and Xu-Duan (Himalaya teasel). Nevertheless, further clinical trials are needed to evaluate the efficacy and safety of these CHMs for treating osteoarthritis. CONCLUSIONS: This study conducted a large scale pharmaco-epidemiology survey of Chinese herbal medicine use in OA patients by analyzing the NHIRD in Taiwan in year 2002.

The rural - urban divide in ambulatory care of gastrointestinal diseases in Taiwan.

BACKGROUND: The utilization of medical care for gastrointestinal diseases increased over the past decade worldwide. The aim of the study was to investigate the difference between rural and urban patients in seeking medical service for gastrointestinal diseases at ambulatory sector in Taiwan. METHODS: From the one-million-people cohort datasets of the National Health Insurance Research Database, the utilization of ambulatory visits for gastrointestinal diseases in 2009 was analyzed. Rural patients were compared with urban and suburban patients as to diagnosis, locality of visits and choice of specialists. RESULTS: Among 295,056 patients who had ambulatory visits for gastrointestinal diseases in 2009, rural patients sought medical care for gastrointestinal diseases more frequently than urban and suburban patients (1.60 ± 3.90 vs. 1.17 ± 3.02 and 1.39 ± 3.47). 83.4% of rural patients with gastrointestinal diseases were treated by non-gastroenterologists in rural areas. Rural people had lower accessibility of specialist care, especially for hepatitis, esophageal disorders and gastroduodenal ulcer. CONCLUSION: The rural-urban disparity of medical care for gastrointestinal diseases in Taiwan highlighted the importance of the well communication between rural physicians and gastroenterologists. Besides the establishment of the referral system, the medical teleconsultation system and the arrangement of specialist outreach clinics in rural areas might be helpful.

The Effects of Switching from Dipeptidyl Peptidase-4 Inhibitors to Glucagon-Like Peptide-1 Receptor Agonists on Bone Mineral Density in Diabetic Patients.

Purpose: Diabetes increases the risk of fragility fractures. As a result, when choosing a diabetes treatment, whether the drug affects bone density should be taken into account. The goal of this study was to determine how switching from dipeptidyl peptidase-4 inhibitors (DPP-4i) to glucagon-like peptide-1 receptor agonists (GLP-1RA) influenced bone mineral density (BMD) in diabetic patients. Patients and Methods: In this retrospective cohort study, diabetic patients with osteoporosis or osteopenia who used DPP-4i but not anti-osteoporosis medications were divided into two groups: those who switched to GLP-1RA (n = 132) and those who did not (control group, n = 133). We compared changes in glycemic control and BMD with and without conversion from DPP-4i to GLP-1RA. Results: Prior to switching, there was no difference between the groups in terms of age, gender, glycosylated hemoglobin (HbA1c), or BMD. HbA1c was 8.7% in the participants (mean age 62.7 years, 17.4% female). Despite the fact that there was no difference in femoral neck BMD, the GLP-1RA group had a greater decrease in lumbar spine BMD (-0.028 g/cm2 versus -0.019 g/cm2, p = 0.041) than the control group. Furthermore, HbA1c levels in the GLP-1RA-treated group were considerably lower than in the control group (7.5% versus 8.0%, p = 0.027). Conclusion: While switching to GLP-1RA improves glycemic control, it appears to have a less favorable effect on bone density than continuing DPP-4i. More research is needed, however, to determine whether diabetic patients with low bone density should be switched from DPP-4i to GLP-1RA.

ChatGPT failed Taiwan's Family Medicine Board Exam.

BACKGROUND: Chat Generative Pre-trained Transformer (ChatGPT), OpenAI Limited Partnership, San Francisco, CA, USA is an artificial intelligence language model gaining popularity because of its large database and ability to interpret and respond to various queries. Although it has been tested by researchers in different fields, its performance varies depending on the domain. We aimed to further test its ability in the medical field. METHODS: We used questions from Taiwan's 2022 Family Medicine Board Exam, which combined both Chinese and English and covered various question types, including reverse questions and multiple-choice questions, and mainly focused on general medical knowledge. We pasted each question into ChatGPT and recorded its response, comparing it to the correct answer provided by the exam board. We used SAS 9.4 (Cary, North Carolina, USA) and Excel to calculate the accuracy rates for each question type. RESULTS: ChatGPT answered 52 questions out of 125 correctly, with an accuracy rate of 41.6%. The questions' length did not affect the accuracy rates. These were 45.5%, 33.3%, 58.3%, 50.0%, and 43.5% for negative-phrase questions, multiple-choice questions, mutually exclusive options, case scenario questions, and Taiwan's local policy-related questions, with no statistical difference observed. CONCLUSION: ChatGPT's accuracy rate was not good enough for Taiwan's Family Medicine Board Exam. Possible reasons include the difficulty level of the specialist exam and the relatively weak database of traditional Chinese language resources. However, ChatGPT performed acceptably in negative-phrase questions, mutually exclusive questions, and case scenario questions, and it can be a helpful tool for learning and exam preparation. Future research can explore ways to improve ChatGPT's accuracy rate for specialized exams and other domains.

To explore the effects of herbal medicine among cancer patients in Taiwan: A cohort study.

BACKGROUND: Traditional Chinese medicine (TCM) is widely used by ethnic Chinese communities. TCM is covered by Taiwan's National Health Insurance (NHI) program. We evaluated the efficacy and outcomes of complementary Chinese herbal medicine (CHM) therapy in patients with cancer. METHODS: This population-based cohort study was conducted using the data of patients who received a cancer diagnosis between 2005 and 2015 in Taiwan. Eligible patients were divided into standard and complementary CHM therapy groups. The complementary CHM therapy group was further divided into low cumulative dosage (LCD), medium cumulative dosage (MCD), and high cumulative dosage (HCD) subgroups. Overall survival (OS), mortality risk, cancer recurrence, and metastasis were analyzed for all cancers and five major cancers (lung, liver, breast, colorectal, and oral cancers). RESULTS: We included 5707 patients with cancer (standard therapy, 4797 [84.1%]; complementary CHM therapy, 910 [15.9%]; LCD, 449 [7.9%]; MCD, 374 [6.6%], and HCD, 87 [1.5%]). For the LCD, MCD, and HCD subgroups, the mortality risk was 0.83, 0.64, and 0.45, and the 11-year OS, 5-year cumulative cancer recurrence, and 5-year cumulative cancer metastasis rates were 6.1 ± 0.2, 6.9 ± 0.2, and 8.2 ± 0.4 years; 39.2%, 31.5%, and 18.8%; and 39.5%, 32.8%, and 16.6%, respectively. The cumulative cancer recurrence and metastasis rates of the standard therapy group were 40.9% and 32.8%, respectively. The cumulative recurrence and metastasis rates of all cancers, lung cancer, and liver cancer and all cancers, colorectal cancer, and breast cancer, respectively, were significantly lower in the HCD subgroup than in the other subgroups and standard therapy group ( p < 0.05). CONCLUSION: Patients receiving complementary CHM therapy may have prolonged OS and reduced risks of mortality, recurrence, and metastasis. A dose-response relationship was noted between CHM therapy and mortality risk: increased dosage was associated with improved OS and reduced mortality risk.