Association between antenatal corticosteroid treatment and severe adverse events in pregnant women.

BACKGROUND: Antenatal corticosteroids are considered the standard of care for pregnant women at risk for preterm birth, but studies examining their potential risks are scarce. We aimed to estimate the associations of antenatal corticosteroids with three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding, in pregnant women. METHODS: Of 2,157,321 pregnant women, 52,119 at 24 weeks 0/7 days to 36 weeks 6/7 days of gestation were included in this self-controlled case series study during the study period of 2009-2018. We estimated incidence rates of three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding. Conditional Poisson regression was used to calculate incidence rate ratios (IRRs) for comparing incidence rates of the adverse events in each post-treatment period compared to those during the baseline period among pregnant women exposed to a single course of antenatal corticosteroid treatment. RESULTS: Among 52,119 eligible participants who received antenatal corticosteroid treatment, the estimated incidence rates per 1000 person-years were 0.76 (95% confidence interval (CI): 0.69-0.83) for sepsis, 0.31 (95% CI: 0.27-0.36) for heart failure, and 11.57 (95% CI: 11.27-11.87) for gastrointestinal bleeding. The IRRs at 5 ~ 60 days after administration of antenatal corticosteroids were 5.91 (95% CI: 3.10-11.30) for sepsis and 4.45 (95% CI: 2.63-7.55) for heart failure, and 1.26 (95% CI: 1.02-1.55) for gastrointestinal bleeding; and the IRRs for days 61 ~ 180 were 2.00 (95% CI: 1.01-3.96) for sepsis, 3.65 (95% CI: 2.14-6.22) for heart failure, and 1.81 (95% CI: 1.56-2.10) for gastrointestinal bleeding. CONCLUSIONS: This nationwide population-based study suggests that a single course of antenatal corticosteroids is significantly associated with a 1.3- to 5.9-fold increased risk of sepsis, heart failure, and gastrointestinal bleeding in pregnant women. Maternal health considerations, including recommendations for adverse event monitoring, should be included in future guidelines for antenatal corticosteroid treatment.

Gene-set integrative analysis of multi-omics data using tensor-based association test.

MOTIVATION: Facilitated by technological advances and the decrease in costs, it is feasible to gather subject data from several omics platforms. Each platform assesses different molecular events, and the challenge lies in efficiently analyzing these data to discover novel disease genes or mechanisms. A common strategy is to regress the outcomes on all omics variables in a gene set. However, this approach suffers from problems associated with high-dimensional inference. RESULTS: We introduce a tensor-based framework for variable-wise inference in multi-omics analysis. By accounting for the matrix structure of an individual's multi-omics data, the proposed tensor methods incorporate the relationship among omics effects, reduce the number of parameters, and boost the modeling efficiency. We derive the variable-specific tensor test and enhance computational efficiency of tensor modeling. Using simulations and data applications on the Cancer Cell Line Encyclopedia (CCLE), we demonstrate our method performs favorably over baseline methods and will be useful for gaining biological insights in multi-omics analysis. AVAILABILITY AND IMPLEMENTATION: R function and instruction are available from the authors' website: https://www4.stat.ncsu.edu/~jytzeng/Software/TR.omics/TRinstruction.pdf. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Cost-effectiveness evaluation of mammography screening program in Taiwan: Adjusting different distributions of age and calendar year for real world data.

BACKGROUND/PURPOSE: We estimated loss-of-life expectancy (LE) and lifetime medical expenditures (LME) stratified by stages to evaluate the cost-effectiveness of breast cancer (BC) screening in Taiwan. METHODS: We interlinked four national databases- Cancer Registry, Mortality Registry, National Health Insurance Claim, and Mammography Screening. A cohort of 123,221 BC was identified during 2002-2015 and followed until December 31, 2017. We estimated LE and loss-of-LE by rolling extrapolation algorithm using age-, sex-, and calendar-year-matched referents simulated from vital statistics. LME was estimated by multiplying monthly cost with survival probability and adjusted for annual discount rate. We calculated incremental cost-effectiveness ratio (ICER) by comparing the loss-of-LE of those detected by screening versus non-screening after accounting for administration fees and radiation-related excess BC. RESULTS: The LEs of stages I, II, III, and IV were 31.4, 27.2, 20.0, and 5.2 years, respectively, while the loss-of-LEs were 1.2, 4.9, 11.7, and 25.0 years with corresponding LMEs of US$ 73,791, 79,496, 89,962, and 66,981, respectively. The difference in LE between stages I and IV was 26.2 years while that of loss-of-LE was 23.8 years, which implies that a potential lead time bias may exist if diagnosis at younger ages for earlier stages were not adjusted for. The ICER of mammography seemed cost-saving after the coverage exceeded half a million. CONCLUSION: Mammography could detect BC early and be cost-saving after adjustment for different distributions of age and calendar year of diagnosis. Future studies exploring healthcare expenditure and impaired quality of life for false-positive cases are warranted.

Association Between Oral Corticosteroid Bursts and Severe Adverse Events : A Nationwide Population-Based Cohort Study.

BACKGROUND: Long-term use of oral corticosteroids has known adverse effects, but the risk from brief oral steroid bursts (≤14 days) is largely unknown. OBJECTIVE: To examine the associations between steroid bursts and severe adverse events, specifically gastrointestinal (GI) bleeding, sepsis, and heart failure. DESIGN: Self-controlled case series. SETTING: Entire National Health Insurance Research Database of medical claims records in Taiwan. PARTICIPANTS: Adults aged 20 to 64 years with continuous enrollment in the National Health Insurance program from 1 January 2013 to 31 December 2015. MEASUREMENTS: Incidence rates of severe adverse events in steroid burst users and non-steroid users, as well as incidence rate ratios (IRRs) for severe adverse events within 5 to 30 and 31 to 90 days after initiation of steroid therapy. RESULTS: Of 15 859 129 adult participants, 2 623 327 who received a single steroid burst were included. The most common indications were skin disorders and respiratory tract infections. The incidence rates per 1000 person-years in steroid bursts were 27.1 (95% CI, 26.7 to 27.5) for GI bleeding, 1.5 (CI, 1.4 to 1.6) for sepsis, and 1.3 (CI, 1.2 to 1.4) for heart failure. Rates of GI bleeding (IRR, 1.80 [CI, 1.75 to 1.84]), sepsis (IRR, 1.99 [CI, 1.70 to 2.32]), and heart failure (IRR, 2.37 [CI, 2.13 to 2.63]) significantly increased within 5 to 30 days after steroid therapy initiation and attenuated during the subsequent 31 to 90 days. LIMITATION: Persons younger than 20 years or older than 64 years were not included. CONCLUSION: Oral corticosteroid bursts are frequently prescribed in the general adult population in Taiwan. The highest rates of GI bleeding, sepsis, and heart failure occurred within the first month after initiation of steroid therapy. PRIMARY FUNDING SOURCE: National Health Research Institutes, Ministry of Science and Technology of Taiwan, Chang Gung Medical Foundation, and Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Identifying individual risk rare variants using protein structure guided local tests (POINT).

Rare variants are of increasing interest to genetic association studies because of their etiological contributions to human complex diseases. Due to the rarity of the mutant events, rare variants are routinely analyzed on an aggregate level. While aggregation analyses improve the detection of global-level signal, they are not able to pinpoint causal variants within a variant set. To perform inference on a localized level, additional information, e.g., biological annotation, is often needed to boost the information content of a rare variant. Following the observation that important variants are likely to cluster together on functional domains, we propose a protein structure guided local test (POINT) to provide variant-specific association information using structure-guided aggregation of signal. Constructed under a kernel machine framework, POINT performs local association testing by borrowing information from neighboring variants in the 3-dimensional protein space in a data-adaptive fashion. Besides merely providing a list of promising variants, POINT assigns each variant a p-value to permit variant ranking and prioritization. We assess the selection performance of POINT using simulations and illustrate how it can be used to prioritize individual rare variants in PCSK9, ANGPTL4 and CETP in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial data.

Health inequality: a longitudinal study on geographic variations in lung cancer incidence and mortality in Taiwan.

BACKGROUND: This study is aimed toward an analysis of the variations in lung cancer incidence and mortality, adjusted by population factors (age, gender, and year), between administrative areas. METHODS: This is a retrospective study, using 2005-2014 data in each administrative area from the Taiwan Cancer Registry database organized by the Health Promotion Administration. The yearly age-standardized (overall) and crude (stratified by gender and age) incidence/mortality (and their growth rates) for each administrative area were collected and calculated. We used a mixed model to analyze the repeated measurements of yearly incidence and mortality rates and used general linear regression to analyze their growth rates. RESULTS: It was found that male and elderly populations had significantly higher lung cancer incidence and mortality in Taiwan. After adjusting for gender, age, and calendar year, there were no significant variations in incidence among the administrative areas, while the mortality in Yilan County was significantly higher than that in Taipei City (the capital city of Taiwan). On the other hand, the incidence in the female and younger population and mortality growth rates were higher. The incidence growth rate in Keelung City was significantly lower than that in Taipei City, while there were no significant variations in mortality growth rate among administrative areas. CONCLUSIONS: This study found an inequality in the lung cancer burden among cities in Taiwan, which can serve as the basis for future resource allocations for lung cancer prevention and treatment in Taiwan.

Predictors of caregiver burden and care costs for older persons with dementia in Taiwan.

ABSTRACTObjectives:As a degenerative disease, the progression of dementia needs continued care provision and poses both psychological and financial burden for family caregivers of persons with dementia (PWD). This study seeks to compare predictors of care costs and caregiver burden, and to identify modifiable factors that could alleviate the burden faced by dementia caregivers. METHODS: This study interviewed 231 PWD-caregiver dyads in a dementia clinic at a teaching hospital in southern Taiwan in 2013. A follow-up study was conducted a year later, and 167 dyads completed the second interview. Data collected included PWD characteristics, caregiver characteristics, relationship to PWD, and social support to caregivers. Caregiver burden was measured with the Zarit Burden Interview instrument. The association between each predictor variable and cost of care and caregiver burden scores was examined using linear mixed models. RESULTS: Predictors of care costs were found to be different from predictors of caregiver burden: functional declines measured by Katz's activities of daily living (ADL) scale were associated with total cost as compared to behavioral disturbance measured by Neuropsychiatric Inventory (NPI), which showed no impact on care costs. However, NPI was a significant predictor of caregiver burden. Caregivers who were better-off financially also reported significantly lower caregiver burden. CONCLUSIONS: Since predictors of care costs were different from the predictors of caregiver burden, providing training to caregivers in addressing PWD's behavioral disturbance and proving financial assistance to low income caregivers could be effective in reducing caregiver burden.

Geographic Variations and Time Trends in Cancer Treatments in Taiwan.

BACKGROUND: Targeted therapies have become important treatment options for cancer care in many countries. This study aimed to examine recent trends in utilization of antineoplastic drugs, particularly the use of targeted therapies for treatment of cancer, by geographic region in Taiwan (northern, midwestern, southern, and eastern regions and the outer islands). METHODS: This was a retrospective observational study of antineoplastic agents using 2009-2012 quarterly claims data from Taiwan's National Health Insurance Research Database. Yearly market shares by prescription volume and costs for targeted therapies among total antineoplastic agents by region were estimated. We used multivariate regression model and ANOVA to examine variations in utilization of targeted therapies between geographic regions and used ARIMA models to estimate longitudinal trends. RESULTS: Population-adjusted use and costs of antineoplastic drugs (including targeted therapies) were highest in the southern region of Taiwan and lowest in the outer islands. We found a 4-fold difference in use of antineoplastic drugs and a 49-fold difference in use of targeted therapies between regions if the outer islands were included. There were minimal differences in use of antineoplastic drugs between other regions with about a 2-fold difference in use of targeted therapies. Without considering the outer islands, the market share by prescription volume and costs of targeted therapies increased almost 2-fold (1.84-1.90) and 1.5-fold (1.26-1.61) respectively between 2009 and 2012. Furthermore, region was not significantly associated with use of antineoplastic agents or use of targeted therapies after adjusting for confounders. Region was associated with costs of antineoplastic agents but it was not associated with costs of targeted therapies after confounding adjustments. CONCLUSIONS: Use of antineoplastic drugs overall and use of targeted therapies for treatment of cancer varied somewhat between regions in Taiwan; use was notably low in the outer islands. Strategies might be needed to ensure access to cancer care in each region as economic burden of cancer care increase due to growing use of targeted therapies.

Exploring the relationship between nursing hours per patient day and mortality rate of hospitalised patients in Taiwan.

AIM: To investigate the relationship between nursing hours per patient day and the inpatient mortality rate in Taiwan. BACKGROUND: Nursing hours per patient day has been associated with better patient outcomes. The literature is inconclusive on the relationship between nursing hours per patient day and the inpatient mortality rate, and no studies have yet examined this issue in Taiwan. METHODS: A retrospective longitudinal study analysed data from the 'Nursing Utilization of Resources, Staffing and Environment on Outcome Study: NURSE-outcome study'. Hierarchical regression estimated the relationship between nursing hours per patient day and in-hospital mortality rate after controlling for confounding variables. RESULTS: The mean nursing hours per patient day in Taiwan was 2.3, while the mean inpatient mortality rate was 0.73% higher nursing hours per patient day was associated with a lower inpatient mortality rate after controlling for confounding variables. The total explained variance of this study in inpatient mortality rate was 19.9%. Significant relationships to inpatient mortality were found in levels of hospitals, seasonal variation and nurses' work experience. CONCLUSION: Nursing hours per patient day affects the mortality rate among hospitalised patients in Taiwan. IMPLICATIONS FOR NURSING MANAGEMENT: According to the results, we suggested the government and managers in Taiwan double the nursing hours per patient day so that the inpatient mortality rate will decline by 1.1%. This might be the optimal nurse configuration that could provide a balance between cost-effectiveness and patient safety.

Confidence intervals for the ratio of two median residual lifetimes with left-truncated and right-censored data.

The confidence intervals for the ratio of two median residual lifetimes are developed for left-truncated and right-censored data. The approach of Su and Wei (1993) is first extended by replacing the Kaplan-Meier survival estimator with the estimator of the conditional survival function (Lynden-Bell, 1971). This procedure does not involve a nonparametric estimation of the probability density function of the failure time. However, the Su and Wei type confidence intervals are very conservative even for larger sample size. Therefore, this article proposes an alternative confidence interval for the ratio of two median residual lifetimes, which is not only without nonparametric estimation of the density function of failure times but is also computationally simpler than the Su and Wei type confidence interval. A simulation study is conducted to examine the accuracy of these confidence intervals and the implementation of these confidence intervals to two real data sets is illustrated.

Age and gender differences in misperceptions of body shape in a Taiwanese population.

OBJECTIVES: Most studies of body size perception have been performed in adolescents, and most focus on gender differences in accurate perception of body size. This study investigated misperceptions of body sizes among males and females at different stages of adulthood in Taiwan. DESIGNS: In-person home interviews were used to proportionally and randomly select 2095 adult men and women to answer the East Asian Social Survey. Participants were divided into 18-39, 40-64, and 65 + age groups. The main variables analyzed were self-perceived body size and standardized BMI. RESULTS: Women, unlike men, were more likely to misperceive their body size as being overweight (OR = 2.92; p < .001). People with higher self-perceived social status were less likely to misperceive themselves as overweight (OR = 0.91; p = .01). People with college educations were 2.35 times more likely to overestimate their body size as being heavier than they were (p < .001) and less likely to underestimate it as being thinner than they were (OR = 0.45; p < .001). Women 18-35 and 36-64 years old were 6.96 and 4.31 times more likely (p < .001) to misperceive themselves as being overweight than women 65 or older, who were more likely to misperceive themselves as being too thin. There were no significant differences in body size misperceptions among the three age groups of adult men (p > .05). We found no different significant discrepancies between self-perceived body size and actual BMI between the older men and women (p = .16). However, younger and middle-aged men were 6.67 and 3.1 times more likely to misperceive themselves as being too thin than women in their same age groups (OR = 0.15 and OR = 0.32, respectively). CONCLUSIONS: Age and gender affect self-perceptions of body size in Taiwan. Overall, women are more likely than men to misperceive themselves as being too big, and men are more likely than women to misperceive themselves as too thin. Older women, however, were more likely to misperceive themselves as being too thin. Clinicians and health educators should know that people's perceptions and concerns regarding their body size vary by age and gender.

Association between antenatal corticosteroids and risk of serious infection in children: nationwide cohort study.

OBJECTIVE: To investigate the associations between exposure to antenatal corticosteroids and serious infection in children during the first three, six, and 12 months of life. DESIGN: Nationwide cohort study. SETTING: National Health Insurance Research Database, Birth Reporting Database, and Maternal and Child Health Database, 1 January 2008 to 31 December 2019, to identify all pregnant individuals and their offspring in Taiwan. PARTICIPANTS: 1 960 545 pairs of pregnant individuals and their singleton offspring. 45 232 children were exposed and 1 915 313 were not exposed to antenatal corticosteroids. MAIN OUTCOME MEASURES: Incidence rates were estimated for overall serious infection, sepsis, pneumonia, acute gastroenteritis, pyelonephritis, meningitis or encephalitis, cellulitis or soft tissue infection, septic arthritis or osteomyelitis, and endocarditis during the first three, six, and 12 months of life in children exposed versus those not exposed to antenatal corticosteroids. Cox proportional hazards models were performed to quantify adjusted hazard ratios with 95% confidence intervals for each study outcome. RESULTS: The study cohort was 1 960 545 singleton children: 45 232 children were exposed to one course of antenatal corticosteroids and 1 915 313 children were not exposed to antenatal corticosteroids. The adjusted hazard ratios for overall serious infection, sepsis, pneumonia, and acute gastroenteritis among children exposed to antenatal corticosteroids were significantly higher than those not exposed to antenatal corticosteroids during the first six months of life (adjusted hazard ratio 1.32, 95% confidence interval 1.18 to 1.47, P<0.001, for overall serious infection; 1.74, 1.16 to 2.61, P=0.01, for sepsis; 1.39, 1.17 to 1.65, P<0.001, for pneumonia; and 1.35, 1.10 to 1.65, P<0.001, for acute gastroenteritis).Similarly, the adjusted hazard ratios for overall serious infection (P<0.001), sepsis (P=0.02), pneumonia (P<0.001), and acute gastroenteritis (P<0.001) were significantly higher from birth to 12 months of life. In the sibling matched cohort, the results were comparable with those observed in the whole cohort, with a significantly increased risk of sepsis in the first six (P=0.01) and 12 (P=0.04) months of life. CONCLUSIONS: This nationwide cohort study found that children exposed to one course of antenatal corticosteroids were significantly more likely to have an increased risk of serious infection during the first 12 months of life. These findings suggest that before starting treatment, the long term risks of rare but serious infection associated with antenatal corticosteroids should be carefully weighed against the benefits in the perinatal period.

Approaching person-centered long-term care: The trajectories of intrinsic capacity and functional decline in Taiwan.

AIM: To examine the longitudinal trajectory of intrinsic capacity over a 3-year period among long-term care recipients in Taiwan, its association with functional decline and the onset of severe dependency. METHODS: A total of 9448 individuals aged ≥50 years utilizing home and community-based long-term care services with complete data from three separate evaluations in Taiwan were included in the study. We carried out a latent class linear mixed model to identify heterogeneous patterns of intrinsic capacity over time, a mixed-effects model to investigate their impact on activities of daily living and a Kaplan-Meier analysis to examine the onset year of severe dependency among different intrinsic capacity classes. RESULTS: The results identified four classes sharing similar longitudinal the intrinsic capacity trajectories: "high-stable" (20.13%), "normal-stable" (40.58%), "sensory-dysfunction" (29.53%) and "all-dysfunction" (9.76%). Individuals with predisposing characteristics were associated with lower activities of daily living, with the exception of age and education level. In addition, the poor intrinsic capacity class (b from -16.94 to -6.61, P < 0.001) had a worse evolution in terms of activity of daily living scores, and was associated with an earlier onset of severe dependency in 2.5 years in the all-dysfunction class. CONCLUSIONS: Heterogeneous patterns of intrinsic capacity that delay further functional decline are promising markers of function trajectories for a person-centered care approach in long-term care services. Targeting the needs of intrinsic capacity groups to prevent functional decline offer insights into: (i) strengthening function-centered care modalities to delay severe dependency as individuals get older; and (ii) validating regular monitoring intrinsic capacity as an early warning system to achieve healthy aging. Geriatr Gerontol Int 2022; 22: 516-522.

Mapping algorithms for predicting EuroQol-5D-3L utilities from the assessment test of chronic obstructive pulmonary disease.

To predict 3-Level version of European Quality of Life-5 Dimensions (EQ-5D-3L) questionnaire utility from the chronic obstructive pulmonary disease (COPD) assessment test (CAT), the study attempts to collect EQ-5D-3L and CAT data from COPD patients. Response mapping under a backward elimination procedure was used for EQ-5D score predictions from CAT. A multinomial logistic regression (MLR) model was used to identify the association between the score and the covariates. Afterwards, the predicted scores were transformed into the utility. The developed formula was compared with ordinary least squares (OLS) regression models and models using Mean Rank Method (MRM). The MLR models performed as well as other models according to mean absolute error (MAE) and root mean squared error (RMSE) evaluations. Besides, the overestimation for low utility patients (utility ≤ 0.6) and underestimation for near health (utility > 0.9) in the OLS method was improved through the means of the MLR model based on bubble chart analysis. In conclusion, response mapping with the MLR model led to performance comparable to the OLS and MRM models for predicting EQ-5D utility from CAT data. Additionally, the bubble charts analysis revealed that the model constructed in this study and MRM could be a better predictive model.

Dynamic Changes of Generic Quality of Life after Different Treatments for Localized Prostate Cancer.

Generic quality of life (QoL) is an important issue in decision making related to the primary treatment of localized prostate cancer (PC). This study assessed the dynamic changes of QoL in patients with localized PC under different treatment modalities. From 2013 to 2018, we prospectively assessed QoL scores in patients with localized PC under unitary treatment using the World Health Organization Quality of Life (WHOQOL) BREF version. The trajectories of the QoL scores after different treatments were estimated using a kernel-smoothing method. Dynamic changes in the major determinants were analyzed using a mixed effects model. The clinical features of the participants in our institute were compared with PC patients in Taiwan's cancer registry. A total of 196 patients were enrolled with 491 repeated assessments. The participants shared similar clinical characteristics with the PC patients in Taiwan as a whole. Patients with lower household incomes showed statistically significant lower scores on all four domains and related facets, while PC survivors with comorbidities of anxiety and/or diabetes appeared to be affected on the physical domain and related facets. After controlling for these determinants, patients under active surveillance or observation demonstrated significantly higher QoL scores in the physical and social domains, as well as several facets belonging to these domains, in mixed models compared with patients undergoing radical prostatectomy or radiotherapy within the first year. The generic QoL scores were higher within the first year in patients receiving active surveillance or observation after controlling other significant factors. The difference diminished after one year of post management. More studies are needed to corroborate our findings.

Association of Oral Corticosteroid Bursts With Severe Adverse Events in Children.

Importance: The adverse effects from the long-term use of oral corticosteroids are known, but, to our knowledge, few studies have reported the risk of corticosteroid bursts, particularly among children. Objective: To quantify the associations of corticosteroid bursts with severe adverse events, including gastrointestinal (GI) bleeding, sepsis, pneumonia, and glaucoma, in children. Design, Setting, and Participants: This study used data derived from the National Health Insurance Research Database in Taiwan from January 1, 2013, to December 31, 2017, on children younger than 18 years of age and used a self-controlled case series design. Data were analyzed from January 1 to July 30, 2020. Exposure: Oral corticosteroid bursts (defined as oral corticosteroid use for ≤14 days). Main Outcomes and Measures: Incidence rates were calculated of 4 severe adverse events (GI bleeding, sepsis, pneumonia, and glaucoma) in children who did or did not receive corticosteroid bursts. Conditional fixed-effect Poisson regression was used to estimate incidence rate ratios (IRRs) of severe adverse events within 5 to 30 days and 31 to 90 days after initiation of corticosteroid bursts. Results: Among 4 542 623 children, 23% (1 064 587; 544 268 boys [51.1%]; mean [SD] age, 9.7 [5.8] years) were prescribed a single corticosteroid burst. The most common indications were acute respiratory tract infections and allergic diseases. The incidence rate differences per 1000 person-years between children administered a single corticosteroid burst and those not prescribed corticosteroids were 0.60 (95% CI, 0.55-0.64) for GI bleeding, 0.03 (95% CI, 0.02-0.05) for sepsis, 9.35 (95% CI, 9.19-9.51) for pneumonia, and 0.01 (95% CI, 0.01-0.03) for glaucoma. The IRRs within 5 to 30 days after initiating corticosteroid bursts were 1.41 (95% CI, 1.27-1.57) for GI bleeding, 2.02 (95% CI, 1.55-2.64) for sepsis, 2.19 (95% CI, 2.13-2.25) for pneumonia, and 0.98 (95% CI, 0.85-1.13) for glaucoma; the IRRs within the subsequent 31 to 90 days were 1.10 (95% CI, 1.02-1.19) for GI bleeding, 1.08 (95% CI, 0.88-1.32) for sepsis, 1.09 (95% CI, 1.07-1.11) for pneumonia, and 0.95 (95% CI, 0.85-1.06) for glaucoma. Conclusions and Relevance: This study suggests that corticosteroid bursts, which are commonly prescribed for children with respiratory and allergic conditions, are associated with a 1.4- to 2.2-fold increased risk of GI bleeding, sepsis, and pneumonia within the first month after initiation of corticosteroid therapy that is attenuated during the subsequent 31 to 90 days.

Gene-trait similarity regression for multimarker-based association analysis.

We propose a similarity-based regression method to detect associations between traits and multimarker genotypes. The model regresses similarity in traits for pairs of "unrelated" individuals on their haplotype similarities, and detects the significance by a score test for which the limiting distribution is derived. The proposed method allows for covariates, uses phase-independent similarity measures to bypass the needs to impute phase information, and is applicable to traits of general types (e.g., quantitative and qualitative traits). We also show that the gene-trait similarity regression is closely connected with random effects haplotype analysis, although commonly they are considered as separate modeling tools. This connection unites the classic haplotype sharing methods with the variance-component approaches, which enables direct derivation of analytical properties of the sharing statistics even when the similarity regression model becomes analytically challenging.

Dynamic Changes Of Body Image And Quality Of Life In Breast Cancer Patients.

PURPOSE: Dynamic changes of body image and quality of life (QoL) in breast cancer patients were not commonly investigated. We aimed to compare the dynamic changes in QoL and body image of breast cancer survivors receiving breast-conserving surgery or total mastectomy within 5-10 years after surgery. METHODS: Patients with non-metastatic breast cancer who received surgery were invited to complete the World Health Organization Quality of Life-Brief (WHOQOL-BREF) questionnaire and the Body Image Scale (BIS) within 10 years after surgery. We applied kernel smoothing methods to capture the dynamic changes of the patients' QoL and body image within 5 years after surgery. We also constructed multiple linear regression models to identify predictive factors for QoL and body image. RESULTS: A total of 581 patients were collected, and 211 of them received breast-conserving surgery. There were no statistically significant differences in QoL and body image for breast-conserving surgery versus total mastectomy, but the former showed fluctuating trends. BIS was a predictor of every item and domain in the WHOQOL-BREF in the multiple linear regression model, and explanatory of the trends of dynamic change over time. Patients without lymph node dissection seemed to have less positive feelings but were more satisfied with sexual activities. CONCLUSION: Body image is predictive of the QoL of breast cancer patients. Dynamic changes of body image and QoL would be useful for shared decision-making regarding surgery in breast cancer patients.

Dynamic Changes of Health Utility in Lung Cancer Patients Receiving Different Treatments: A 7-Year Follow-up.

INTRODUCTION: This study aimed to estimate the utility values of all subtypes of lung cancer. The trajectories after different kinds of treatments and their major determinants were explored on the basis of real-world data and repeated measurements. METHODS: From 2011 to 2017, all patients with lung cancer who visited a medical center were invited to fill out the EuroQol Five-Dimension and WHO Quality of Life-Brief questionnaires at each visit. Utility values of quality of life (QoL) after diagnosis and treatments were depicted using a kernel smoothing method. We constructed linear mixed models to predict health utility in each time period and cross-validated them with domain scores of the WHO Quality of Life-Brief. RESULTS: A total of 1715 patients were enrolled, with 6762 QoL measurements. Utility values were lower in patients with advanced-stage disease and older patients. Patients receiving second-line targeted therapy showed higher utility values at 0 to 3 months, 3 to 6 months, and 6 months and beyond (0.89, 0.90, and 0.88, respectively) than did those undergoing chemotherapy (0.81, 0.85, and 0.80, respectively). After using mixed models to control confounders, including poor performance status and disease progression, patients receiving second-line chemotherapy showed health utility similar to that at quasi-baseline, whereas utility values related to second-line targeted therapy were higher at 3 to 6 months and 6 months and beyond (ß = 0.07, p = 0.010 and ß = 0.07, p < 0.001, respectively). There was convergent validity between the utility values and scores of the physical and psychological domains. CONCLUSION: Targeted therapy provided treated patients with a higher health utility value than was provided to those treated with chemotherapy. Development of the longitudinal trajectory may help predict changes in QoL and improve the care of lung cancer survivors.

Reference equations for spirometry in healthy Asian children aged 5 to 18 years in Taiwan.

BACKGROUND AND OBJECTIVE: This study aimed to establish reference equations for spirometry in healthy Taiwanese children and assess the applicability of the Global Lung Function Initiative (GLI)-2012 equations to Taiwanese children. METHODS: Spirometric data collected from 757 healthy Taiwanese children aged 5 to 18 years in a population-based cohort study. Prediction equations derived using linear regression and the generalized additive models for location, scale and shape (GAMLSS) method, respectively. RESULTS: The GLI-2012 South East Asian equations did not provide a close fit with mean ± standard error z-scores of -0.679 ± 0.030 (FVC), -0.186 ± 0.044 (FEV1), -0.875 ± 0.049 (FEV1/FVC ratio) and -2.189 ± 0.063 (FEF25-75) for girls; and 0.238 ± 0.059, -0.061 ± 0.053, -0.513 ± 0.059 and -1.896 ± 0.077 for boys. The proposed GAMLSS models took age, height, and weight into account. GAMLSS models for boys and girls captured the characteristics of spirometric data in the study population closely in contrast to the linear regression models and the GLI-2012 equations. CONCLUSION: This study provides up-to-date reference values for spirometry using GAMLSS modeling in healthy Taiwanese children aged 5 to 18 years. Our study provides evidence that the GLI-2012 reference equations are not properly matched to spirometric data in a contemporary Taiwanese child population, indicating the urgent need for an update of GLI reference values by inclusion of more data of non-Caucasian decent.