Allopurinol‐induced Stevens‐Johnson syndrome and toxic epidermal necrolysis: Signal detection and preventability from Vietnam National pharmacovigilance database

alexandrossfakianakis shared this article with you from Inoreader Allopurinol‐induced Stevens‐Johnson syndrome and toxic epidermal necrolysis: Signal detection and preventability from Vietnam National pharmacovigilance database via Journal of Clinical Pharmacy and Therapeutics Among 72,822 spontaneous ADR reports submitted to the Vietnam National Drug Information and Adverse Drug Reaction Monitoring Centre, 392 reports were on SJS/TEN, of which, 65 cases (16.6%) were related to allopurinol. The signals of allopurinol-induced SJS/TEN in Vietnam started in 2014 (ROR of 3.531, 95% CI: 1.830–6.810) and annually increased until 2019 (ROR of 11.923, 95% CI: 8.508–16.710). The preventability assessment showed that no allopurinol-induced SJS/TEN case was definitely unpreventable. 61.6% of the SJS/TEN cases were avoidable because they were associated with inappropriate prescribing such as unapproved indications, too high initial dose and even rechallenging in patients with a history of allopurinol allergy. Abstract What Is Known and Objective Allopurinol, the first-line medication for hyperuricemia is well-known for its association with severe cutaneous adverse reactions, especially Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In the current study, we analysed the Vietnamese spontaneous reporting database to identify signals and preventability of allopurinol-induced SJS/TEN in Vietnam from 2010 to 2019. Methods Signal generation was assessed using the case/non-case method. Reporting odds ratios (RORs) and 95% confidence intervals (95% CI) were calculated. Results Among 72,822 spontaneous ADR reports submitted to the Vietnam National Drug Information and Adverse Drug Reaction Monitoring Centre, 392 reports were on SJS/TEN, of which, 65 cases (16.6%) were related to allopurinol. The signals of allopurinol-induced SJS/TEN in Vietnam started in 2014 (ROR of 3.531, 95% CI: 1.830–6.810) and annually increased until 2019 (ROR of 11.923, 95% CI: 8.508–16.710). The preventability assessment showed that no allopurinol-induced SJS/TEN case was definitely unpreventable. 61.6% of the SJS/TEN cases were avoidable because they were associated with inappropriate prescribing such as unapproved indications, too high initial dose and even rechallenging in patients with a history of allopurinol allergy. What Is New and Conclusion The signals of allopurinol-induced SJS/TEN in Vietnam started in 2014 and annually increased until 2019. Our first report specifically focusing on the ADR preventability of allopurinol showed that correction of medical errors relating to prescription could prevent more than 60% of SJS/TEN cases in Vietnamese allopurinol users. This is a feasible and practical solution, provided that there would be a systematic change in both healthcare systems and public awareness. View on Web

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Long-term exposure to low-level air pollution, genetic susceptibility and risk of dementia

alexandrossfakianakis shared this article with you from Inoreader Long-term exposure to low-level air pollution, genetic susceptibility and risk of dementia via International Journal of Epidemiology - Advance Access Abstract BackgroundWe aimed to assess the association between low-level air pollution and the risk of dementia, and examine the modification effect by genetic susceptibility on the relationship. Methods A total of 164 447 participants who were free of dementia at baseline and aged ≥60 years were included. Annual average concentrations of particulate matter (PM) with diameters of ≤2.5 μm (PM2.5), between 2.5 and 10 μm (PMcoarse), PM2.5 absorbance and nitrogen dioxides (NO2) were evaluated using the Land Use Regression models. Cox proportional hazards regression was used to estimate the association between air pollutants and incident dementia. Results The adjusted hazard ratio (HR) of dementia for a 5-μg/m3 increase in NO2 was 1.09 (95% CI, 1.05–1.14); the adjusted HR of dementia for a 1-μg/m3 increase in PM2.5 was 1.10 (1.04–1.17). Such significant associations were present even within concentration ranges well below the present World Health Organization, US and European annual mean limit values. In addition, higher PM2.5 absorbance, a marker closely related to motorized traffic, was associated with higher risk of dementia. We found the risk of dementia associated with a combination of air pollutants (NO2 or PM2.5) and high genetic susceptibility (APOE-ε4 alleles or overall genetic susceptibility) was greater than the addition of the risk associated with each individual factor, indicating significant interactions on an additive scale (all P-interaction < 0.05). Conclusion Long-term exposure to PM2.5 or NO2, even at relatively low levels, is associated with a higher risk of dementia. Air pollution may additively interact with the genetic susceptibility on dementia risk. View on Web

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Gestational Weight Gain and Birth Outcomes: A Comparison of Methods to Account for Gestational Age

alexandrossfakianakis shared this article with you from Inoreader Gestational Weight Gain and Birth Outcomes: A Comparison of Methods to Account for Gestational Age via American Journal of Epidemiology - Advance Access Abstract Cross-sectional studies of total gestational weight gain (GWG) and perinatal outcomes have used different approaches to operationalize GWG and adjust for gestational duration. Using birth records from California (2007-2017), Nevada (2010-2017), and Oregon (2008-2017) we compared three commonly used approaches to estimate associations between GWG and cesarean delivery (C-section), small for gestational age (SGA), and low birth weight (LBW)]: (1) the Institute of Medicine r ecommended GWG ranges at a given gestational week, (2) total weight gain categories directly adjusting for gestational age as a covariate, and (3) weight-gain-for-gestational-age z-scores derived from an external longitudinal reference population. Among 5,461,130 births, the three methods yielded similar conclusions for C-section and SGA. However, for LBW, some associations based on z-scores were in the opposite direction of methods 1 and 2, paradoxically suggesting higher GWG increases risk of LBW. This was due to a greater proportion of preterm births among those with high z-scores, and controlling for gestational age in the z-score model brought the results in line with the other methods. We conclude that the use of externally-derived GWG z-scores based on ongoing pregnancies can yield associations confounded by duration of pregnancy when the outcome is strongly associated with gestational age at delivery. View on Web

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