Lymphocyte count is a universal predictor of health outcomes in COVID-19 patients before mass vaccination: A meta-analytical study.

Background: Several laboratory data have been identified as predictors of disease severity or mortality in COVID-19 patients. However, the relative strength of laboratory data for the prediction of health outcomes in COVID-19 patients has not been fully explored. This meta-analytical study aimed to evaluate the prediction capabilities of laboratory data on the prognosis of COVID-19 patients during 2020 while mass vaccination has not started yet. Methods: Two electronic databases, MEDLINE and EMBASE, from inception to October 10, 2020 were searched. Observational studies of laboratory-confirmed COVID-19 patients with well-defined severity or survival status, and with the desired laboratory data at initial hospital administrations, were selected. Meta-regression analysis with the generalized estimating equations (GEE) method for clustered data was performed sequentially. Primary outcome measures were to compare the level of laboratory data and their impact on different health outcomes (severe vs non-severe, critically severe vs non-critically severe, and dead vs alive). Results: Meta-data of 13 clinical laboratory items at initial hospital presentations were extracted from 76 selected studies with a total of 26 627 COVID-19 patients in 16 countries. After adjusting for the effect of age, 1.03 0.87 (OR = 0.0576; 95% CI = 0.0043-0.4726; P = 0.0079) had a much lower risk of severity, critical severity, and mortality from COVID-19, respectively. Conclusions: Lymphocyte count was the most powerful predictor among the 13 common laboratory variables explored from COVID-19 patients to differentiate disease severity and to predict mortality. Lymphocyte count should be monitored for the prognoses of COVID-19 patients in clinical settings in particular for patients not fully vaccinated.

The safety and immunogenicity of a cell-derived adjuvanted H5N1 vaccine - A phase I randomized clinical trial.

BACKGROUND: Development of an efficacious egg-free mock-up H5N1 vaccine is key to our preparedness against pandemic avian flu. METHODS: This is a single-center, randomized, observer-blinded phase I clinical trial evaluating the safety and immunogenicity of an alum-adjuvanted Madin-Darby canine kidney (MDCK)-derived inactivated whole-virion H5N1 influenza vaccine in healthy adults. Hemagglutination inhibition (HAI) and neutralizing antibody titers were measured using horse and turkey red blood cells (RBCs). RESULTS: Thirty-six adult subjects were randomized to receive two doses of 0.5 mL of the MDCK-derived H5N1 alum-adjuvanted vaccine containing 7.5, 15, or 30 µg of hemagglutinin (HA) 21 days apart. The candidate vaccine was well tolerated and safe across the three dosing groups. The most frequent adverse event was injection site pain (46.5%). Both HAI and neutralizing antibody titers increased after each vaccination in all three dosing groups. The best HAI responses, namely a seroconversion rate of 91.7% and a geometric mean ratio of 9.51 were achieved with the HA dose of 30 µg assayed using horse RBCs at day 42. HAI titers against H5N1 avian influenza virus was significantly higher when measured using horse RBCs compared with turkey RBCs. CONCLUSIONS: This Phase I trial showed the MDCK-derived H5N1 candidate vaccine is safe and immunogenic. The source of RBCs has a significant impact on the measurement of HAI titers (ClinicalTrials.gov number: NCT01675284.).

Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence.

AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection. METHODS: A total of 143 patients (83.1% of the 172 participants in the phase II study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase II trial. Safety parameters and the following efficacy endpoints were investigated: (1) time to recurrence; (2) disease-free survival; and (3) overall survival. RESULTS: PI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group: (1) the recurrence-free rate increased from 50% to 63%, and (2) time to recurrence at the 36th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate (11 out of 54 patients). Additionally, subgroup analyses of patients with (1) multiple tumors or a single tumor ≥ 2 cm; and (2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage (56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence. CONCLUSION: Administering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC.

Heparanase inhibitor PI-88 as adjuvant therapy for hepatocellular carcinoma after curative resection: a randomized phase II trial for safety and optimal dosage.

BACKGROUND/AIMS: Hepatocellular carcinoma recurrence after curative treatment adversely influences clinical outcome. It is important to explore adjuvant therapies. This phase II/stage 1 multi-center, randomized trial investigated the safety, optimal dosage and preliminary efficacy of PI-88, a novel heparanase inhibitor, in the setting of post-operative recurrence of HCC according to a Simon's 2-stage design. METHODS: Three groups were included: one untreated arm (Group A) and two PI-88 arms (Group B: 160 mg/day; Group C: 250 mg/day). Treatment groups received PI-88 over nine 4-week treatment cycles, followed by a 12-week treatment-free period. Safety and optimal dosage were assessed. RESULTS: Overall, 172 patients were randomized and 168 were included in the intention-to-treat (ITT) population. Treatment-related adverse effects included cytopenia, injection site hemorrhage, PT prolongation, etc. Four serious adverse events were possibly related to PI-88 treatment. One (1.8%) group B patients and six (10.5%) group C had hepatotoxicity-related withdrawals. Among the ITT population, 29 patients (50%) in Group A, 35 (63%) in Group B, and 22 (41%) in Group C remained recurrence-free at completion. Calculated T(1) value suggested 160 mg/day treatment satisfied the criteria for the next stage of the trial. CONCLUSIONS: PI-88 at 160 mg/day is optimal and safe, and shows preliminary efficacy as an adjunct therapy for post-operative HCC.

Exploration into the variance in self-reported health-related quality of life between the chronically-ill elderly and their family caregivers.

Differences in perspective with regard to Health-Related Quality of Life (HRQOL) may significantly affect long-term care preferences. This study was developed to quantify the direction and magnitude of such differences and to explore factors accounting for HRQOL reporting differences between two groups, namely elderly individuals with chronic conditions and their primary family caregivers. Nurses in seven Taiwanese counties and cities interviewed 267 matched pairs of elderly individuals and primary family caregivers using a 28-item version of the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) adapted for use in Taiwan. Our study used the standardized response mean (SRM)--the ratio of the mean difference to the SD of that difference--to compare scores assigned by the two groups. Family caregivers assigned higher scores in all four HRQOL domains, with scores "moderately higher" in the physical domain and "slightly higher" in the other three. In addition to gender, several activities of daily livings (ADLs) in the physiological, environmental and psychological domains were identified as predictors of HRQOL differences. Marital status and presence of a primary caregiver were the two predictors in the social relationship domain. This study found elderly ADLs, gender, marital status, and the presence of a primary caregiver to be significant predictors of HRQOL differences. Study findings offer guidance to elderly individuals with chronic conditions and their family caregivers with regard to long-term care program arrangement in order to enhance elderly ADLs and family relationships and to achieve a better overall HRQOL for the elderly.

WHOQOL-BREF as predictors of mortality: a two-year follow-up study at veteran homes.

The main purpose of this study was to evaluate the effectiveness of the brief version of the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire as a predictor of mortality amongst the elderly. A total of 689 male residents of veteran homes, all above the age of 65 years, were randomly selected in 2001. The Taiwan version of the WHOQOL-BREF was administered as the baseline, with each of these subjects being interviewed and subsequently followed up for mortality until the end of 2003. Data on self-reported global health, life satisfaction, medical status, physical performance and health behavior was also collected. Following the death of 105 of the 689 subjects during the 2-year follow-up period, the relative risk (RR) of death was subsequently assessed using Cox's proportional hazard regression analyses. After adjusting for other predictors (age group, chronic diseases, emergency visits, hospitalization, physical performance, regular exercise, self-reported global health and life satisfaction), almost all of the WHOQOL-BREF items and domains failed to predict mortality; the one exception was working capacity levels (score 1-2 vs. score 4-5) which, after adjusting for other predictors, did demonstrate the ability to predict mortality (RR = 1.96, p < 0.05).

Health-related quality of life and health utility for the institutional elderly in Taiwan.

OBJECTIVE: To explore the health-related quality of life (HRQOL) and health utility in an institutional elderly population. METHODS: Four hundred sixty-five elderly persons living in long-term care institutions in Taiwan were interviewed using Taiwan's abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF), rating scale (RS) and the Time-Trade-Off (TTO) utility measurement. RESULTS: The WHOQOL-BREF showed acceptable internal consistency (alpha range: 0.75-0.80 across domains) and validity. The sexual activity facet had the lowest response rate. Educational level, number of chronic diseases, physical performance, and number of caregivers had significant (p < 0.05) impacts on the domain scores of the WHOQOL-BREF. Physical performance had the strongest impact on the physical domain (R2 = 0.40) and accounted for significant percentages of the variance on the other three domains (R2 = 0.06-0.13). The mean RS score (score 0-100) was 61.3 +/- 16.2 (mean +/- SD). The mean TTO utility (score 0-1) was 0.92 +/- 0.22. CONCLUSIONS: Results indicate that the WHOQOL-BREF, excepting the sexual activity item, is useful for evaluating HRQOL of conscious elderly in institutions. The validity of TTO utility for studying the institutionalized elderly needs further evaluation.

Preferences of the elderly and their primary family caregivers in the arrangement of long-term care.

BACKGROUND AND PURPOSE: Long-term care policies and networks in Taiwan are still in the early stages of development and as such it is important to establish comprehensive care models which clearly define the needs of the elderly and their family members. This study examined the preferences of the elderly and their primary family caregivers in long-term care arrangements. METHODS: Using multi-stage sampling, a total of 1180 subjects (n = 593 elderly people [age > or = 65 years] and n = 587 caregivers) from 7 counties/cities in the north of Taiwan were interviewed by local public health nurses. RESULTS: Home care was the first choice for both elderly people and their primary caregivers (59.2% of both groups combined). Institutional care was considered the second choice; however, only 9.2% found this choice acceptable. Community-based care was the least preferred mode of long-term care (4.2%). Among the sample subjects, elderly people born in China, those not living in the Taipei metropolitan area, and those not receiving a financial subsidy from the government, indicated that they would be more inclined to accept institutional care. All other elderly people between the ages of 65 and 74 years indicated greater preference for community-based care. Primary caregivers born in China, those with only an elementary school level of education, and those with previous unpleasant experiences in caring for the elderly were more inclined to accept community and institutional care. CONCLUSIONS: Most elderly people and their primary family caregivers preferred home care. This study also revealed that previous experiences with care for the elderly, educational level, and socioeconomic status were important factors influencing preferences for long-term care arrangements.