Trajectory of Humoral Responses to Two Doses of ChAdOx1 nCoV-19 Vaccination in Patients Receiving Maintenance Hemodialysis.

The ChAdOx1 nCoV-19 (AZD1222) vaccine is one of the most commonly delivered SARS-CoV-2 vaccines worldwide; however, few clinical studies have investigated its immunogenicity in dialysis patients. We prospectively enrolled 123 patients on maintenance hemodialysis at a medical center in Taiwan. All patients were infection-naive, had received two doses of the AZD1222 vaccine, and were monitored for 7 months. The primary outcomes were anti-SARS-CoV-2 receptor-binding domain (RBD) antibody concentrations before and after each dose and 5 months after the second dose and neutralization capacity against ancestral SARS-CoV-2, delta, and omicron variants. The anti-SARS-CoV-2 RBD antibody titers significantly increased with time following vaccination, with a peak at 1 month after the second dose (median titer, 498.8 U/mL; interquartile range, 162.5 to 1,050 U/mL), and a 4.7-fold decrease at 5 months. At 1 month after the second dose, 84.6, 83.7, and 1.6% of the participants had neutralizing antibodies against the ancestral virus, delta variant, and omicron variant, respectively, measured by a commercial surrogate neutralization assay. The geometric mean 50% pseudovirus neutralization titers for the ancestral virus, delta variant, and omicron variant were 639.1, 264.2, and 24.7, respectively. The anti-RBD antibody titers correlated well with neutralization capacity against the ancestral virus and delta variant. Transferrin saturation and C-reactive protein were associated with neutralization against the ancestral virus and delta variant. Although two doses of the AZD1222 vaccine initially elicited high anti-RBD antibody titers and neutralization against the ancestral virus and delta variant in hemodialysis patients, neutralizing antibodies against omicron variant were rarely detected, and the anti-RBD and neutralization antibodies waned over time. Additional/booster vaccinations are warranted in this population. IMPORTANCE Patients with kidney failure have worse immune response following vaccination compared to general population, but few clinical studies have investigated immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccination in hemodialysis patients. Here, we showed two doses of AZD1222 vaccines lead to high seroconversion rate of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies, and more than 80% patients acquired neutralizing antibodies against ancestral virus and delta variant. However, seldom did they obtain neutralizing antibodies against the omicron variant. The geometric mean 50% pseudovirus neutralization titer against the ancestral virus was 25.9-fold higher than that against the omicron variant. Also, there was a substantial decay in anti-RBD titers with time. Our findings provided evidence supporting that more protective measures, including additional/booster vaccinations, is warranted in these patients during the current COVID-19 pandemic.

Effect of dialysis modalities on risk of hospitalization for gastrointestinal bleeding.

Dialysis patients are at risk of both thromboembolic and bleeding events, while thromboembolism prevention and treatment may confer a risk of major bleeding. Gastrointestinal (GI) bleeding is a great concern which can result in high subsequent mortality rates. Our object was to clarify whether hemodialysis (HD) and peritoneal dialysis (PD) confer different incidence of GI bleeding, and further assist individualized decision-making on dialysis modalities. We conducted a population-based retrospective cohort study which included all incident dialysis patients above 18 years old derived from the National Health Insurance database from 1998 to 2013 in Taiwan. 6296 matched pairs of HD and PD patients were identified. A propensity score matching method was used to minimize the selection bias. The adjusted hazard ratio for GI bleeding was 1.13 times higher in the HD group than in the PD group, and data from the unmatched cohort and the stratified analysis led to similar results. Among subgroup analysis, we found that the use of anticoagulants will induce a much higher incidence of GI bleeding in HD patients as compared to in PD patients. We concluded that PD is associated with a lower GI bleeding risk than HD, and is especially preferred when anticoagulation is needed.

Development and validation of the dialysis dementia risk score: A retrospective, population-based, nested case-control study.

BACKGROUND: Dementia is prevalent and underdiagnosed in the dialysis population. We aimed to develop and validate a simple dialysis dementia scoring system to facilitate identification of individuals who are at high risk for dementia. METHODS: We applied a retrospective, nested case-control study design using a national dialysis cohort derived from the National Health Insurance Research Database in Taiwan. Patients aged between 40 and 80 years were included and 2940 patients with incident dementia were matched to 29,248 non-dementia controls. All subjects were randomly divided into the derivation and validation sets with a ratio of 4:1. Conditional logistic regression models were used to identify factors contributing to the risk score. The cutoff value of the risk score was determined by Youden's J statistic and the graphic method. RESULTS: The dialysis dementia risk score (DDRS) finally included age and 10 comorbidities as risk predictors. The C-statistic of the model was 0.71 (95% confidence interval [CI] 0.70-0.72). Calibration revealed a strong linear relationship between predicted and observed dementia risk (R2  = 0.99). At a cutoff value of 50 points, the high-risk patients had an approximately three-fold increased risk of having dementia compared to those with low risk (odds ratio [OR] 3.03, 95% CI 2.78-3.31). The DDRS performance, including discrimination (C-statistic 0.71, 95% CI 0.69-0.73) and calibration (p value of Hosmer-Lemeshow test for goodness of fit = 0.18), was acceptable during validation. The OR value (2.82, 95% CI 2.37-3.35) was similar to those in the derivation set. CONCLUSION: The DDRS system has the potential to serve as an easily accessible screening tool to determine the high-risk groups who deserve subsequent neurological evaluation in daily clinical practice.

Comparison of Immunogenicity and Safety between a Single Dose and One Booster Trivalent Inactivated Influenza Vaccination in Patients with Chronic Kidney Disease: A 20-Week, Open-Label Trial.

BACKGROUND: Non-dialysis-dependent chronic kidney disease (CKD-ND) patients are recommended to receive a one-dose influenza vaccination annually. However, studies investigating vaccine efficacy in the CKD-ND population are still lacking. In this study, we aimed to evaluate vaccine efficacy between the one-dose and two-dose regimen and among patients with different stages of CKD throughout a 20-week follow-up period. METHODS: We conducted a single-center, non-randomized, open-label, controlled trial among patients with all stages of CKD-ND. Subjects were classified as unvaccinated, one-dose, and two-dose groups (4 weeks apart) after enrollment. Serial changes in immunological parameters (0, 4, 8, and 20 weeks after enrollment), including seroprotection, geometric mean titer (GMT), GMT fold-increase, seroconversion, and seroresponse, were applied to evaluate vaccine efficacy. RESULTS: There were 43, 84, and 71 patients in the unvaccinated, one-dose, and two-dose vaccination groups, respectively. At 4-8 weeks after vaccination, seroprotection rates in the one- and two-dose group for H1N1, H3N2, and B ranged from 82.6-95.8%, 97.4-100%, and 73.9-100%, respectively. The concomitant seroconversion and GMT fold-increases nearly met the suggested criteria for vaccine efficacy for the elderly population. Although the seroprotection rates for all of the groups were adequate, the seroconversion and GMT fold-increase at 20 weeks after vaccination did not meet the criteria for vaccine efficacy. The two-dose regimen had a higher probability of achieving seroprotection for B strains (Odds ratio: 3.5, 95% confidence interval (1.30-9.40)). No significant differences in vaccine efficacy were found between early (stage 1-3) and late (stage 4-5) stage CKD. CONCLUSIONS: The standard one-dose vaccination can elicit sufficient protective antibodies. The two-dose regimen induced a better immune response when the baseline serum antibody titer was low. Monitoring change in antibody titers for a longer duration is warranted to further determine the current vaccine strategy in CKD-ND population.

Can Individual Attitudes toward Aging Predict Subsequent Physical Disabilities in Older Taiwanese Individuals? A Four-Year Retrospective Cohort Study.

Individual attitudes toward aging have been regarded as a modifiable risk for physical disability. However, longitudinal cohort studies have not been carried out in countries in Asia. In the present study, we aimed to explore the association between individual attitudes toward aging and subsequent physical disabilities using a nationwide representative cohort, the Taiwan Longitudinal Study on Aging (TLSA), over a 4-year follow-up period. In 2003, a baseline survey for 10-item attitudes toward aging scale consisting of widely different domains across financial relationships with children, grandparenting, living arrangements, and remarriage was conducted. Later, physical disabilities, including mobility and activities of daily living (ADL) limitations, were evaluated in 2007. A total of 1635 participants aged 57 and over were analyzed. Older age, self-rated poor health, and those suffering from pain were found to be more likely to have higher risk of physical disabilities. The older adults who expressed a willingness to receive financial support from their adult children were reported to have a lower risk of mobility limitations (adjusted odds ratio (aOR): 0.67, 95% confidence interval (CI): 0.50-0.90), while those who did not want to assist with child care as grandparents had a higher risk of ADL difficulties (aOR: 2.46, 95% CI: 1.31-4.60). Our work shed light on the importance of individual attitudes toward aging in predicting long-term physical disabilities and illuminated the intimate role of grandparents, both financial and participatory, in Chinese families. In the future, culturally adapted attitudes toward aging scale should be developed to identify older Chinese adults at risk of physical disabilities.

Clinical Frailty Scale in Predicting Postoperative Outcomes in Older Patients Undergoing Curative Surgery for Urologic Malignancies: A Prospective Observational Cohort Study.

OBJECTIVE: To examine the utility of the Clinical Frailty Scale (CFS) in predicting outcomes in older adults with urologic malignancies undergoing curative surgeries. METHODS: This prospective observational cohort study was conducted in a university-based tertiary medical center. Patients aged 75 years or older who were scheduled to undergo curative surgery for a urologic malignancy from January 2017 to December 2017 were recruited. Patients were grouped according to the CFS scores. The primary postoperative outcome measures were a major complication within 30 days and a decline in the activities of daily living (ADL) within 30 days and 90 days. Multivariable analyses and the area under the receiver operating characteristic curve were performed to investigate the association between the CFS and postoperative outcomes. RESULTS: A total of 82 patients, 50% women, were enrolled with mean age 81.6 years. The CFS was significantly associated with postoperative outcomes in a dose-response relationship. When compared with those with a CFS <5, patients with CFS scores ≥5 had a 10.3-times higher risk for a major complication, 8.5-times and 21.4-times higher risk for a decline in ADL within 30 days and 90 days. The area under the receiver operating characteristic curves for the CFS to predict a major complication, the 30-day decline in ADL and the 90-day decline in ADL were 0.60, 0.73, and 0.79. CONCLUSION: A higher CFS score predicted a higher risk of poor outcomes in this population. It is recommended that patients with higher CFS scores, especially above 5, are needed to receive further multidisciplinary perioperative care.

A comparison of the risk of acute myocardial infarction in patients receiving hemodialysis and peritoneal dialysis: A population-based, propensity score-matched cohort study.

BACKGROUND AND AIMS: Acute myocardial infarction (AMI) remains the major cause of morbidity and mortality in the dialysis population. Traditional cardiovascular (CV) risk factors are unable to fully account for the high incidence of AMI in the dialysis population. In this study, we investigated whether dialysis modalities could be one of the uremia-specific risk factors for AMI. METHODS: Using the National Health Insurance Research Database, we recruited all incident dialysis patients from the period January 1, 1998 to December 31, 2010. The propensity score matching method was applied to form the matched pairs of hemodialysis (HD) and peritoneal dialysis (PD) patients. Incidence rate (IR), cumulative incidence rate (CIR) and multivariable subdistribution hazards models were employed to compare the risk of AMI in the HD and PD groups. RESULTS: Of the 86,215 incident dialysis patients, 5,513 matched pairs of HD and PD patients were identified. The HD patients had a higher IR of AMI than the PD patients (9.71 vs. 8.35 per 1000 patient-years, respectively, p = 0.01). The CIR was also higher in the HD patients than in the PD patients (0.09 vs. 0.05), especially 4 years after dialysis therapy was initiated (p = 0.04). In the subdistribution hazards models, HD was still significantly associated with a higher risk of developing AMI (adjusted hazard ratio:1.30, 95% confidence interval:1.02-1.65). The results remained unchanged in various stratifications as well as in the analysis of the unmatched cohorts. CONCLUSIONS: Compared to PD, HD was significantly associated with higher risk of developing AMI, especially after 4 years since dialysis was initiated. Prevention and routine surveillance programs for AMI should be individualized according to dialysis modalities and vintage.

A comparison of the risk of congestive heart failure-related hospitalizations in patients receiving hemodialysis and peritoneal dialysis - A retrospective propensity score-matched study.

INTRODUCTION: Congestive heart failure (CHF) is associated with high mortality and a heavy financial and healthcare burden in the dialysis population. Determining which dialysis modality is associated with a higher risk of developing CHF might facilitate clinical decision making and surveillance programs in the dialysis population. METHODS: Using the Taiwan National Health Insurance Database, we recruited all incident dialysis patients during the period from January 1, 1998 to December 31, 2010. The propensity score matching method was applied to establish the matched hemodialysis (HD) and peritoneal dialysis (PD) cohort. Incidence rates and cumulative incidence rates of CHF-related hospitalization were first compared for the HD and PD patients. Multivariable subdistribution hazards models were then constructed to control for potential confounders. RESULTS: Among a total of 65,899 enrolled dialysis patients, 4,754 matched pairs of HD and PD patients were identified. The incidence rates of CHF in the matched HD and PD patients were 25.98 and 19.71 per 1000 patient-years, respectively (P = 0.001). The cumulative incidence rate of CHF was also higher in the matched HD patients (0.16, 95% confidence interval (CI)(0.12-0.21)] than in the corresponding PD patients (0.09, 95% CI [0.08-0.11])(P<0.0001). HD was consistently associated with an increased subdistribution hazard ratio (HR) of CHF compared with PD in the matched cohort (HR: 1.45, 95% CI [1.23-1.7]). Similar phenomenons were observed in either the subgroup analysis stratified by selected confounders or in the HD and PD group without matching. CONCLUSIONS: HD is associated with a higher risk of developing CHF-related hospitalization than PD. The surveillance program for CHF should differ in patients receiving different dialysis modalities.

Risk of dementia in patients with end-stage renal disease under maintenance dialysis-a nationwide population-based study with consideration of competing risk of mortality.

BACKGROUND: Dementia is prevalent in the end-stage renal disease (ESRD) population. However, it is still not clarified whether ESRD is one of the etiology of dementia or its attributable effect on the cumulative risk of dementia. Meanwhile, the effect of competing risk of mortality should be taken into consideration when performing epidemiologic analyses among populations with high risk of mortality. METHODS: By using the National Health Insurance Research Database (1998-2010), we identified 927,142 non-ESRD individuals and 99,158 ESRD patients to investigate the effect of ESRD on the risk of dementia. Age- and sex-specific incidence rates (IRs) and cumulative incidence rates (CIRs) were first compared between these two cohorts. Competing risk analyses including cause-specific and subdistribution proportional hazards models were then constructed with adjustments for potential confounders. RESULTS: The overall IR and CIR of dementia were much higher in the ESRD group than in the non-ESRD group (10.73 vs. 1.40 per 1000 person-years and 0.061 vs. 0.017, respectively, both P < 0.0001). Results from the multivariable cause-specific hazard models suggested that ESRD was one of the etiological factors for dementia (cause-specific hazard ratio [csHR] : 2.06 [95% CI : 1.95-2.17]). However, the subdistribution HR (sdHR) of ESRD was 0.51 (95% Cl : 0.49-0.54), which indicated the lower cumulative incidence risk of dementia in ESRD patients. The inverse relationship between csHR and sdHR could be explained by the high mortality rate in the ESRD population. These findings were also essentially consistent across various subgroup analyses according to selected confounders, as well as in the analyses that limited dementia diagnoses made by neurologists or psychologists. CONCLUSIONS: Although ESRD appears directly associated with the risk of dementia, the high competing mortality means that primary prevention of comorbidity associated with dementia may be more effective in reducing overall dementia in the general population, which may also potentially reduce the incidence of ESRD and prevent death from multimorbidity when affected by ESRD.

Incidence and survival impact of pulmonary arterial hypertension among patients with systemic lupus erythematosus: a nationwide cohort study.

BACKGROUND: No population-based study has investigated the cumulative incidence of pulmonary arterial hypertension (PAH) in patients with newly diagnosed systemic lupus erythematosus (SLE) or the survival impact of PAH in this population. METHOD: We used a nationwide database in Taiwan and enrolled incident SLE patients between January 1, 2000, and December 31, 2013. The cumulative incidence of PAH in the SLE patients and the survival of these patients were estimated by the Kaplan-Meier method. Potential predictors of the development of PAH were determined using a Cox proportional hazards regression model. RESULTS: Of 15,783 SLE patients, 336 (2.13%) developed PAH. The average interval from SLE diagnosis to PAH diagnosis was 3.66 years (standard deviation [SD] 3.36, range 0.1 to 13.0 years). Seventy percent of the patients developed PAH within 5 years after SLE onset. The 3- and 5-year cumulative incidence of PAH were 1.2% and 1.8%, respectively. Systemic hypertension was an independent predictor of PAH occurrence among the SLE patients (adjusted hazard ratio 2.27, 95% confidence interval 1.59-2.97). The 1-, 3-, and 5-year survival rates of SLE patients following the diagnosis of PAH were 87.7%, 76.8%, and 70.1%, respectively. CONCLUSIONS: PAH is a rare complication of SLE and the majority of PAH cases occur within the first 5 years following SLE diagnosis. Systemic hypertension may be a risk factor for PAH development in the SLE population. The overall 5-year survival rate after PAH diagnosis was 70.1%.

Associations Between Geriatric Syndromes and Mortality in Community-Dwelling Elderly: Results of a National Longitudinal Study in Taiwan.

OBJECTIVE: Although geriatric syndromes have been studied extensively, their interactions with one another and their accumulated effects on life expectancy are less frequently discussed. This study examined whether geriatric syndromes and their cumulative effects are associated with risks of mortality in community-dwelling older adults. METHODS: Data were collected from the Taiwan Longitudinal Study in Aging in 2003, and the participant survival status was followed until December 31, 2007. A total of 2744 participants aged ≥65 years were included in this retrospective cohort study; 634 died during follow-up. Demographic factors, comorbidities, health behaviors, and geriatric syndromes, including underweight, falls, functional impairment, depressive condition, and cognitive impairment, were assessed. Cox proportional hazard regression analysis was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the probability of survival according to the cumulative number of geriatric syndromes. RESULTS: The prevalence of geriatric syndromes increased with age. Mortality was significantly associated with age ≥75 years; male sex; ≤6 years of education; history of stroke, malignancy; smoking; not drinking alcohol; and not exercising regularly. Geriatric syndromes, such as underweight, functional disability, and depressive condition, contributed to the risk of mortality. The accumulative model of geriatric syndromes also predicted higher risks of mortality (N = 1, HR 1.50, 95% CI 1.19-1.89; N = 2, HR 1.69, 95% CI 1.25-2.29; N ≥ 3, HR 2.43, 95% CI 1.62-3.66). CONCLUSIONS: Community-dwelling older adults who were male, illiterate, receiving institutional care, underweight, experiencing a depressive condition, functionally impaired, and engaging in poor health behavior were more likely to have a higher risk of mortality. The identification of geriatric syndromes might help to improve comprehensive care for community-dwelling older adults.