Heterogeneity of Asthma Care Among Hispanic Subgroups: Lower Utilization of Hospital-based Care among Spanish-speaking Hispanics.

BACKGROUND: Studies found heterogeneity of asthma prevalence among Hispanic subgroups using survey data but addressed under-diagnosis issues due to limited access to health care and diagnosis bias. OBJECTIVES: To examine heterogeneity by language in health care utilization for asthma among Hispanic subgroups. RESEARCH DESIGN: A retrospective, longitudinal cohort study of Medi-Cal claims data (2018-2019) using logistic regression to estimate the odds ratio of health care utilization for asthma. SUBJECTS: In all, 12,056 (ages 5-64) Hispanics living in Los Angeles were identified as having persistent asthma. MEASURES: Primary language is the predictor variable and outcome measures include ED visits, hospitalizations, and outpatient visits. RESULTS: The odds of ED visits among Spanish-speaking Hispanics were lower than English-speaking Hispanics in the subsequent 6 (95% CI=0.65-0.93) and 12 (95% CI=0.66-0.87) months. Spanish-speaking Hispanics were less likely than their English-speaking counterparts to utilize hospitalization in the 6 months (95% CI=0.48-0.98), while they were more likely to utilize outpatient care (95% CI=1.04-1.24). For Hispanics of Mexican origin, the odds of ED visits among Spanish-speaking Hispanics were also lower in the 6 and 12 months (95% CI=0.63-0.93, 95% CI=0.62-0.83), but their odds of outpatient visits were higher for outpatient visits in the 6 months (95% CI=1.04-1.26). CONCLUSIONS: Spanish-speaking Hispanics with persistent asthma were less likely than English-speaking Hispanics to utilize ED visits and hospitalizations but were more likely to utilize outpatient visits. The findings suggest the reduced burden of asthma among the Spanish-speaking Hispanic subgroup and contribute to explaining the protection effect, specifically among Spanish-speaking Hispanics living in highly segregated communities.

A higher Asthma Medication Ratio (AMR) predicts a decrease in ED visits among African American and Hispanic children.

INTRODUCTION: Higher rates of ED visits and hospitalizations for asthma among African American and Hispanic children may indicate suboptimal management of asthma, leading to a greater financial burden of healthcare. It is not well known if an association of race/ethnicity with controller medication and hospital-based care utilization exists. OBJECTIVE: This study examines whether the Asthma Medication Ratio (AMR) predicts healthcare utilization for asthma by race/ethnicity. METHODS: 4,584 Medi-Cal children (Ages 5-11) with persistent asthma in Los Angeles were identified and their AMRs (2018) were calculated based on the HEDIS criteria. Healthcare utilization data were used, including hospitalizations, ED visits, and pharmacy claims to examine whether a higher AMR predicts decreases in healthcare utilization by race/ethnicity in the subsequent 3,6, and 12 months (2019). RESULTS: The average AMR was lowest among African American children (0.401). In the subsequent 12 months, they were highest in ED visits (0.249) and hospitalizations (0.121), but lowest in outpatient visits (0.793). The results of logistic regression showed that a higher value of AMR (>0.5) contributed to decreases in ED visits in the subsequent 12 months only among African Americans (OR = 0.551, 95% CI 0.364-0.832) and Hispanics (OR = 0.613, 95% CI 0.489-0.770). No association between AMR and hospitalizations was found. CONCLUSIONS: Our findings indicate that increased use of controller medication contributes to a decrease in ED visits among African American and Hispanic children with persistent asthma. Increased use of controller medications and caregiver's efforts for medication adherence may contribute to a reduction in asthma disparities.

Determinants of racial and ethnic disparities in utilization of hospital-based care for asthma among Medi-Cal children in Los Angeles.

OBJECTIVE: We sought to identify racial/ethnic patterns of health care utilization for asthma among asthmatic children (ages 0-18) and address unequal access to optimal asthma management as a determinant of asthma disparities. METHODS: We used children Medi-Cal (California's Medicaid program) enrollees, including African American, Asian, Hispanic, and White children in Los Angeles and retrieved individual hospital utilization records of 69,118 asthmatic children (2013-2018). We applied Hierarchical Generalized Linear Models (HGMLs) to identify the patterns of health care utilization at the individual level, controlling for demographic and neighborhood characteristics. RESULTS: African American children show a higher ratio of ED to outpatient visits (OR = 1.32, 95% CI 1.08-1.62) and hospitalizations to outpatient visits (OR = 1.50, 95% CI 1.30-1.73). They also had a high ratio of ED visits (OR = 1.36, 95% CI 1.10-1.68) and hospitalizations (OR = 1.47, 95% CI 1.26-1.71) relative to PCP visits. A ratio of ED visits and hospitalizations decreased if a ratio of controller medications to total medications was greater than 0.5, but increased if children were male, under 11 years old, or living in low-income neighborhoods (Median household income < 25th percentile, $45,629) with high poverty rates (>20%). CONCLUSIONS: African American male children from disadvantaged neighborhoods are at the highest risk for higher utilization of hospital-based care for asthma. Our findings also indicate a lower ratio of controller medications contributed to increases in ED visits and hospitalizations, suggesting suboptimal management of asthma and a lack of intervention treatment through medications among minority children.

Emergency Mental Health Services for Children After the Terrorist Attacks of September 11, 2001.

Much literature documents elevated psychiatric symptoms among adults after the terrorist attacks of September 11, 2001 (9/11). We, however, know of no research in children that examines emergency mental health services following 9/11. We test whether children's emergency services for crisis mental health care rose above expected values in September 2001. We applied time-series methods to California Medicaid claims (1999-2003; N = 127,200 visits). Findings in California indicate an 8.7% increase of children's emergency mental health visits statistically attributable to 9/11. Non-Hispanic white more than African American children account for this acute rise in emergency services.

An effective strategy to prevent allopurinol-induced hypersensitivity by HLA typing.

PURPOSE: This study was conducted to evaluate the usefulness of human leukocyte antigen (HLA) typing in preventing allopurinol-induced severe cutaneous adverse reactions (SCARs) through the application of an allopurinol tolerance induction protocol or prescription of other alternative medications in high-risk patients. METHODS: HLA typing was performed in patients with chronic renal insufficiency who needed allopurinol. HLA-B*58:01-negative patients were prescribed the usual dose of allopurinol. For HLA-B*58:01-positive patients, administration of either allopurinol based on a 28-day tolerance induction protocol or alternative medications was initiated. Hypersensitivity reactions were surveyed for 90 days and compared with the result of a previous retrospective cohort study. RESULTS: Among a total of 401 study subjects, no SCARs were noted in HLA-B*58:01-positive patients with application of the tolerance induction protocol (n = 30) or alternative medications (n = 16), nor were any SCARs observed in HLA-B*58:01-negative patients who started allopurinol at the usual dose (n = 355). Compared with the previous retrospective cohort study, a significant reduction in SCARs was observed in HLA-B*58:01-positive patients (0 vs. 18%; P = 0.002). CONCLUSION: This study shows the usefulness of HLA-B*58:01 screening in identifying patients at high risk for the development of allopurinol-induced SCARs and suggests that application of a tolerance induction protocol or alternative medications could be an effective strategy to prevent allopurinol-induced SCARs in HLA-B*58:01-positive patients.

Racial/ethnic disparities in children's emergency mental health after economic downturns.

African American children-more than other race/ethnicities-rely on emergency psychiatric care. One hypothesized cause of this overrepresentation involves heightened sensitivity to economic downturns. We test whether the African American/white difference in psychiatric emergency visits increases in months when the regional economy contracts. We applied time-series methods to California Medicaid claims (1999-2008; N = 7.1 million visits). One month following mass layoffs, African American youths use more emergency mental health services than do non-Hispanic whites. Economic downturns may provoke or uncover mental disorder especially among African American youth who by and large do not participate in the labor force.

Trends of emergency department visits for cannabinoid hyperemesis syndrome in Nevada: An interrupted time series analysis.

Cannabis-related emergency department visits have increased after legalization of cannabis for medical and recreational use. Accordingly, the incidence of emergency department visits due to cannabinoid hyperemesis syndrome in patients with chronic cannabis use has also increased. The aim of this study was to examine trends of emergency department visit due to cannabinoid hyperemesis syndrome in Nevada and evaluate factors associated with the increased risk for emergency department visit. The State Emergency Department Databases of Nevada between 2013 and 2021 were used for investigating trends of emergency department visits for cannabinoid hyperemesis syndrome. We compared patients visiting the emergency department due to cannabinoid hyperemesis syndrome with those visiting the emergency department due to other causes except cannabinoid hyperemesis and estimated the impact of cannabis commercialization for recreational use. Emergency department visits due to cannabinoid hyperemesis syndrome have continuously increased during the study period. The number of emergency department visits per 100,000 was 1.07 before commercialization for recreational use. It increased to 2.22 per 100,000 (by approximately 1.1 per 100,000) after commercialization in the third quarter of 2017. Those with cannabinoid hyperemesis syndrome were younger with fewer male patients than those without cannabinoid hyperemesis syndrome. A substantial increase in emergency department visits due to cannabinoid hyperemesis syndrome occurred in Nevada, especially after the commercialization of recreational cannabis. Further study is needed to explore factors associated with emergency department visits.

Economic development, intergenerational mobility, and health in South Korea.

A growing number of studies reported the association between social mobility and health. However, few studies investigated whether the association varies by age group. Drawing on the economic environment that facilitated social mobility in South Korea, we postulate each age group had a different extent of social mobility, which would vary with the extent of economic growth and affect the association between social mobility and health. We used data from KDI National Happiness Survey 2018 and measured perceived mobility using respondents' perceived social position and their parents' social position. We examined whether social mobility was associated with self-rated health and psychological well-being. The upwardly mobile individuals were more likely than the stable ones to report 'happy'. Such a positive association between upward mobility and happiness was consistently found when the sample was restricted to the ages 30-59 and 40-49. For self-rated health, the downwardly mobile individuals were less likely to report good health. However, no significant difference in self-rated health was found after the youngest and oldest age groups were excluded. We found that perceived social mobility was strongly associated with psychological well-being rather than self-rated health. Moreover, we found a stronger association between upward mobility and happiness among the aged 40-49, who had the largest proportion of upwardly mobile individuals and spent their adolescence during rapid economic growth. The findings underscore the importance of the economic and social context in which individuals perceive their social position and shape their well-being.

It takes quality improvement to cross the chasm.

Healthcare organisations in the USA rank significantly lower in quality of care compared with other developed nations. Research shows US performance emphasises expensive treatment over effective prevention programmes. This study demonstrates how a comprehensive quality improvement programme can improve health outcomes in a large county-based Medicaid health plan. The health plan serves a diverse community of members spanning racial and ethnic groups with varying levels of clinical risk and social determinants of health burdens. We used a regression discontinuity design to evaluate the impact of a comprehensive quality improvement programme vs using mainly pay-for-performance on Healthcare Effectiveness Data and Information Set (HEDIS) metrics over the course of 10 years. We found significant improvements in several HEDIS metrics that occurred after the quality improvement programme was implemented. These results demonstrate the importance of using a comprehensive quality improvement strategy along with pay-for-performance to improve health outcomes. It was determined that this research was exempt from institutional review board approval, as it used administrative healthcare data, and did not involve direct interventions with human subjects.

Changes in characteristics of inpatient respiratory conditions from 2019 to 2021 (before and during the COVID-19 pandemic).

Background: The COVID-19 pandemic has resulted in an increase in the number of individuals with respiratory conditions that require hospitalization, posing new challenges for the healthcare system. Recent respiratory condition studies have been focused on the COVID-19 period, with no comparison of respiratory conditions before and during the pandemic. This study aimed to examine hospital-setting respiratory conditions regarding potential changes in length of stay (LOS), mortality, and total charge, as well as socioeconomic disparities before and during the pandemic. Methods: The study employed a pooled cross-sectional design based on the State Inpatient Data Nevada for 2019 (prior to the COVID-19 pandemic) and 2020-2021 (during the pandemic) and investigated all respiratory conditions, identified by the International Classification of Disease, 10th Revision codes (n = 227,338). Descriptive analyses were carried out for the three years. Generalized linear regression models were used for multivariable analyses. Outcome measures were hospital LOS, mortality, and total charges. Results: A total of 227,338 hospitalizations with a respiratory condition were included. Hospitalizations with a respiratory condition increased from 65,896 in 2019 to 80,423 in 2020 and 81,018 in 2021. The average LOS also increased from 7.9 days in 2019 to 8.8 days in 2020 but decreased to 8.1 days in 2021; hospital mortality among patients with respiratory conditions increased from 7.7% in 2019 to 10.2% but decreased to 9.6% in 2021; and the total charges per discharge were $159,119, $162,151, and $161,733 from 2019 to 2021, respectively (after adjustment for the inflation rate). Hispanic, Asian, and other race patients with respiratory conditions were 1-3 times more likely than white patients to have higher mortality and LOS. Medicaid patients and non-White patients were predictors of a higher respiratory-related hospital total charge. Conclusion: Demographic and socioeconomic factors were significantly associated with respiratory-related hospital utilization in terms of LOS, mortality, and total charge.

Racial and Ethnic Disparity in 4Ms among Older Adults Among Telehealth Users as Primary Care.

Telehealth has been widely accepted as an alternative to in-person primary care. This study examines whether the quality of primary care delivered via telehealth is equitable for older adults across racial and ethnic boundaries in provider-shortage urban settings. The study analyzed documentation of the 4Ms components (What Matters, Mobility, Medication, and Mentation) in relation to self-reported racial and ethnic backgrounds of 254 Medicare Advantage enrollees who used telehealth as their primary care modality in Southern Nevada from July 2021 through June 2022. Results revealed that Asian/Hawaiian/Pacific Islanders had significantly less documentation in What Matters (OR = 0.39, 95%, p = .04) and Blacks had significantly less documentation in Mobility (OR = 0.35, p < .001) compared to their White counterparts. The Hispanic ethnic group had less documentation in What Matters (OR = 0.18, p < .001) compared to non-Hispanic ethnic groups. Our study reveals equipping the geriatrics workforce merely with the 4Ms framework may not be sufficient in mitigating unconscious biases healthcare providers exhibit in the telehealth primary care setting in a provider shortage area, and, by extrapolation, in other care settings across the spectra, whether they be in-person or virtual.

Impact of Advance Care Planning on the Hospitalization-Associated Utilization and Cost of Patients with Alzheimer's Disease-Related Disorders Receiving Primary Care via Telehealth in a Provider Shortage Area: A Quantitative Pre-Study.

Telehealth has been adopted as an alternative to in-person primary care visits. With multiple participants able to join remotely, telehealth can facilitate the discussion and documentation of advance care planning (ACP) for those with Alzheimer's disease-related disorders (ADRDs). We measured hospitalization-associated utilization outcomes, instances of hospitalization and 90-day re-hospitalizations from payors' administrative databases and verified the data via electronic health records. We estimated the hospitalization-associated costs using the Nevada State Inpatient Dataset and compared the estimated costs between ADRD patients with and without ACP documentation in the year 2021. Compared to the ADRD patients without ACP documentation, those with ACP documentation were less likely to be hospitalized (mean: 0.74; standard deviation: 0.31; p < 0.01) and were less likely to be readmitted within 90 days of discharge (mean: 0.16; standard deviation: 0.06; p < 0.01). The hospitalization-associated cost estimate for ADRD patients with ACP documentation (mean: USD 149,722; standard deviation: USD 80,850) was less than that of the patients without ACP documentation (mean: USD 200,148; standard deviation: USD 82,061; p < 0.01). Further geriatrics workforce training is called for to enhance ACP competencies for ADRD patients, especially in areas with provider shortages where telehealth plays a comparatively more important role.

Causal Effect of Chondroitin, Glucosamine, Vitamin, and Mineral Intake on Kidney Function: A Mendelian Randomization Study.

The causal effects of chondroitin, glucosamine, and vitamin/mineral supplement intake on kidney function remain unknown, despite being commonly used. We conducted a two-sample summary-level Mendelian randomization (MR) analysis to test for causal associations between regular dietary supplement intake and kidney function. Genetic instruments for chondroitin, glucosamine, and vitamin/mineral supplement intake were obtained from a genome-wide association study of European ancestry. Summary statistics for the log-transformed estimated glomerular filtration rate (log-eGFR) were provided by the CKDGen consortium. The multiplicative random-effects inverse-variance weighted method showed that genetically predicted chondroitin and glucosamine intake was causally associated with a lower eGFR (chondroitin, eGFR change beta = -0.113%, standard error (SE) = 0.03%, p-value = 2 × 10-4; glucosamine, eGFR change beta = -0.240%, SE = 0.035%, p-value = 6 × 10-12). However, a genetically predicted vitamin/mineral supplement intake was associated with a higher eGFR (eGFR change beta = 1.426%, SE = 0.136%, p-value = 1 × 10-25). Validation analyses and pleiotropy-robust MR results for chondroitin and vitamin/mineral supplement intake supported the main results. Our MR study suggests a potential causal effect of chondroitin and glucosamine intake on kidney function. Therefore, clinicians should carefully monitor their long-term effects.

What drives variations in public health and social services expenditures? the association between political fragmentation and local expenditure patterns.

The US spends two times more than the OECD average in health expenditure but has a much smaller portion of public health spending to total health expenditure than other OECD countries. While it has been suggested that public health and social services spending is crucial to promoting health outcomes, less is known about what drives variations in public health expenditure across regions. This study aims to examine whether political fragmentation in local governance is associated with variations in public health and social services expenditures. Using the US Census of Governments, we constructed a panel dataset of political fragmentation and local government spending patterns (1997-2012) for 792 US counties (population > 60,882, top 25%) and employed Least Squares Dummy Variable (LSDV) and Generalized Estimating Equations (GEE) models. We found that per capita public health spending tended to be smaller in areas where the degree of political fragmentation was higher (Coef: - 0.034; p < 0.01), particularly when general-purpose governments were more fragmented (Coef: - 0.087; p < 0.001). The proportion of public health spending also decreased when local governments were more fragmented (Coef: - 0.012; p < 0.001). Social services expenditures and their proportions to total government expenditure fell with an increase in the degree of political fragmentation. Our findings suggest that fragmented governance settings, in which localities are more likely to face competition with others, may lead to a reduction in public spending essential for population health and that political fragmentation can also have a deterrent effect on broader categories of health-related social services spending.

Chemokine (C-C Motif) Ligand 8 and Tubulo-Interstitial Injury in Chronic Kidney Disease.

Kidney fibrosis has been accepted to be a common pathological outcome of chronic kidney disease (CKD). We aimed to examine serum levels and tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with CKD and to investigate their association with kidney fibrosis in CKD model. Serum levels and tissue expression of CCL8 significantly increased with advancing CKD stage, proteinuria level, and pathologic deterioration. In Western blot analysis of primary cultured human tubular epithelial cells after induction of fibrosis with rTGF-ß, CCL8 was upregulated by rTGF-ß treatment and the simultaneous treatment with anti-CCL8 mAb mitigated the rTGF-ß-induced an increase in fibronectin and a decrease E-cadherin and BCL-2 protein levels. The antiapoptotic effect of the anti-CCL8 mAb was also demonstrated by Annexin V/propidium iodide staining assay. In qRT-PCR analysis, mRNA expression levels of the markers for fibrosis and apoptosis showed similar expression patterns to those observed by western blotting. The immunohistochemical analysis revealed CCL8 and fibrosis- and apoptosis-related markers significantly increased in the unilateral ureteral obstruction model, which agrees with our in vitro findings. In conclusion, CCL8 pathway is associated with increased risk of kidney fibrosis and that CCL8 blockade can ameliorate kidney fibrosis and apoptosis.

Inhibiting Transglutaminase 2 Mediates Kidney Fibrosis via Anti-Apoptosis.

Transglutaminase 2 (TG2) is a calcium-dependent transamidating acyltransferase enzyme of the protein-glutamine γ-glutamyltransferase family implicated in kidney injury. In this study, we identified associations between TG2 and chronic kidney disease (CKD) identified by visualizing TG2 in kidney biopsy samples derived from CKD patients using immunohistochemistry and measuring the plasma TG2 concentrations. Our study revealed a connection between TG2 and the pathological markers of kidney disease. We showed high plasma TG2 levels in samples from patients with advanced CKD. In addition, we observed an increase in TG2 expression in tissues concomitant with advanced CKD in human samples. Moreover, we investigated the effect of TG2 inhibition on kidney injury using cystamine, a well-known competitive inhibitor of TG2. TG2 inhibition reduced apoptosis and accumulation of extracellular molecules (ECM) such as fibronectin and pro-inflammatory cytokine IL-8. Collectively, the increased expression of TG2 that was observed in advanced CKD, hence inhibiting TG2 activity, could protect kidney cells from ECM molecule accumulation, apoptosis, and inflammatory responses, thereby preventing kidney fibrosis.

Renoprotective Effect of KLF2 on Glomerular Endothelial Dysfunction in Hypertensive Nephropathy.

Kruppel-like factor 2 (KLF2) regulates endothelial cell metabolism; endothelial dysfunction is associated with hypertension and is a predictor of atherosclerosis development and cardiovascular events. Here, we investigated the role of KLF2 in hypertensive nephropathy by regulating KLF2 expression in human primary glomerular endothelial cells (hPGECs) and evaluating this expression in the kidney tissues of a 5/6 nephrectomy mouse model as well as patients with hypertension. Hypertension-mimicking devices and KLF2 siRNA were used to downregulate KLF2 expression, while the expression of KLF2 was upregulated by administering simvastatin. After 4 mmHg of pressure was applied on hPGECs for 48 h, KLF2 mRNA expression decreased, while alpha-smooth muscle actin (αSMA) mRNA expression increased. Apoptosis and fibrosis rates were increased under pressure, and these phenomena were aggravated following KLF2 knockdown, but were alleviated after simvastatin treatment; additionally, these changes were observed in angiotensin II, angiotensin type-1 receptor (AT1R) mRNA, and interleukin-18 (IL-18), but not in angiotensin type-2 receptor mRNA. Reduced expression of KLF2 in glomerular endothelial cells due to hypertension was found in both 5/6 nephrectomy mice and patients with hypertensive nephropathy. Thus, our study demonstrates that the pressure-induced apoptosis and fibrosis of glomerular endothelial cells result from angiotensin II, AT1R activation, and KLF2 inhibition, and are associated with IL-18.

Optimal target blood pressure for major adverse cardiovascular and cerebrovascular events in hypertensive patients: a nationwide population-based study.

BACKGROUND: Generalizing an 'optimal' blood pressure (BP) level for individuals with hypertension remains controversial due to the implementation of different medical guidelines. This study investigated the association of BP with major adverse cardiovascular and cerebrovascular events (MACCE) and determined the optimal BP for patients with hypertension. METHOD: A total of 934 179 individuals who received antihypertensive medications were selected from the National Health Insurance Service Examination Database between 2003 and 2011 in Korea. Their BP was measured at the index date, which was the first health examination. The study outcomes were MACCE, including acute myocardial infarction, heart failure, stroke, and all-cause mortality. The participants were monitored until in December, 2017. The hazard ratios were calculated using Cox proportional hazard models. The cumulative incidence of MACCE for each BP group was estimated using the Kaplan-Meier method. RESULTS: A lower risk of MACCE was observed at a SBP of 120-129 mmHg and a DBP of 80-89 mmHg. The endpoint-specific incidence rates and hazard ratios for acute myocardial infarction, heart failure, stroke, and all-cause mortality were the lowest at a SBP of 120-129 mmHg and a DBP of 80-89 mmHg. CONCLUSION: Even though this observational study did not support inference of a causal relationship, a SBP of 120-129 mmHg and a DBP of 80-89 mmHg may be safely recommended considering the possibility of MACCE in Korean patients with hypertension. In addition, the target BP should be tailored individually according to age, sex, and comorbidities.

HLA-B58 can help the clinical decision on starting allopurinol in patients with chronic renal insufficiency.

BACKGROUND: Although allopurinol is a very effective urate-lowering drug for complicated hyperuricemia, in some patients, it can induce severe cutaneous adverse reactions (SCARs). Recent investigations suggest that HLA-B*5801 is a very strong marker for allopurinol-induced SCARs, especially in the population with a high frequency of HLA-B*5801. Korea is one of the countries with a high frequency of HLA-B*5801 which is the only subtype of HLA-B58 in the Korean population. Objective. This study was conducted to find out the incidence of allopurinol-induced hypersensitivity on patients with chronic renal insufficiency (CRI) according to HLA-B58 and the clinical implications of HLA-B58 as a risk marker for the development of allopurinol-induced hypersensitivity. METHODS: We retrospectively reviewed the medical records of patients with CRI who took allopurinol and carried out serologic human leukocyte antigen (HLA) typing for kidney transplantation between January 2003 and May 2010. RESULTS: Among a total of 448 patients with CRI, 16 (3.6%) patients experienced allopurinol hypersensitivity. Nine of these patients (2.0%) were diagnosed with SCARs (two Stevens-Johnson syndrome and seven allopurinol hypersensitivity syndrome) and seven patients (1.6%) had simple maculopapular rashes. The HLA-B58 allele was present in all patients with allopurinol-induced SCARs, while the frequency of HLA-B58 was only 9.5% in allopurinol-tolerant patients (P < 0.05). The incidence of allopurinol-induced SCARs in CRI shows a wide disparity according to HLA-B58 [18% in HLA-B58 (+) versus 0% in HLA-B58 (-)]. Among patients without HLA-B58, most (98.2%) of the CRI patients were tolerant to allopurinol and only 1.8% experienced simple rashes after taking allopurinol. CONCLUSIONS: In this study, the incidence of allopurinol-induced SCARs was considerably high in CRI patients with HLA-B58. This finding indicates that the presence of HLA-B58 may increase the risk of allopurinol-induced SCARs. Screening tests for HLA-B58 in CRI patients will be clinically helpful in preventing severe allopurinol hypersensitivity reactions.

Causal Effects of Serum Levels of n-3 or n-6 Polyunsaturated Fatty Acids on Coronary Artery Disease: Mendelian Randomization Study.

We aimed to investigate the causal effects of n-3 and n-6 polyunsaturated fatty acids (PUFAs) on the risk of coronary artery disease (CAD) through Mendelian randomization (MR) analysis. This MR study utilized a genetic instrument developed from previous genome-wide association studies for various serum n-3 and n-6 PUFA levels. First, we calculated the allele scores for genetic predisposition of PUFAs in individuals of European ancestry in the UK Biobank data (N = 337,129). The allele score-based MR was obtained by regressing the allele scores to CAD risks. Second, summary-level MR was performed with the CARDIoGRAMplusC4D data for CAD (N = 184,305). Higher genetically predicted eicosapentaenoic acid and dihomo-gamma-linolenic acid levels were significantly associated with a lower risk of CAD both in the allele-score-based and summary-level MR analyses. Higher allele scores for linoleic acid level were significantly associated with lower CAD risks, and in the summary-level MR, the causal estimates by the pleiotropy-robust MR methods also indicated that higher linoleic acid levels cause a lower risk of CAD. Arachidonic acid showed significant causal estimates for a higher risk of CAD. This study supports the causal effects of certain n-3 and n-6 PUFA types on the risk of CAD.