Persistent headache attributed to past ischemic stroke: A prospective cohort study.

OBJECTIVE: To assess the incidence, characteristics, and risk factors for developing persistent headache attributed to past ischemic stroke. BACKGROUND: Although the most recent International Classification of Headache Disorders has recognized the existence of persistent headache attributed to past ischemic stroke, there has been limited research in this area. METHODS: This was a prospective cohort study. We initially assessed patients hospitalized with ischemic stroke admitted within 72 h of symptom onset. All patients underwent diffusion-weighted magnetic resonance imaging. These patients were re-interviewed by telephone 1 year after the stroke. Semi-structured questionnaires, the National Institutes of Health Stroke Scale (NIHSS), and six-item Headache Impact Test were used. RESULTS: A total of 119 participants answered the interview conducted 1 year after the stroke. The mean (standard deviation) age was 64 (13.1) years, 82/119 (68.9%) were female, and the median (interquartile range) NIHSS score was 2 (1.0-4.0). The incidence rate of persistent headache attributed to past ischemic stroke was 12/119 (10.1%; 95% confidence interval [CI] 5.3-17.0%). The most frequent pattern presented was a migraine-like pattern in seven of the 12 (58.3%) patients, which had a substantial/severe impact on five of the 12 (41.7%). For most patients this headache continued, although it began to improve. Previous migraine (odds ratio 7.1, 95% CI 1.06-50.0; p = 0.043) and headache intensity in the acute phase of stroke (odds ratio 1.75, 95% CI 1.13-2.7; p = 0.012) were associated with the occurrence of persistent headache attributed to past ischemic stroke. CONCLUSION: Persistent headache attributed to past ischemic stroke is a frequent complication after stroke. It often has a significant impact on patients' lives and presents a migraine-like pattern as its most frequent phenotype.

The presence of doping agents in dietary supplements: A glimpse into the Brazilian situation.

Dietary supplements (DS) are intended for healthy people to maintain or improve their overall health. Its consumption is widespread in large part of the general population and at all levels of athletes. Nevertheless, DS use can also pose health risks to individuals and, in the case of athletes, may lead to adverse analytical findings (AAFs) due to the possibility of DS contamination or adulteration with doping agents banned by the World Anti-Doping Agency. Although educational initiatives are being performed in Brazil to warn the sports community about inadvertent doping cases, AAFs connected to the DS administration have been increasingly growing. The findings of DS analyzed by the Brazilian Doping Control Laboratory (LBCD), between 2017 and 2022, after Testing Authorities (TAs) analysis requests, showed an alarming number of tainted samples. Diuretics were the most common adulterants found in all supplement types. However, the profile of prohibited substances in manufactured and compounded dietary supplements (MDS and CDS, respectively) were distinct, with stimulants being most prevalent in MDS and anabolic agents in CDS products. Additionally, MDS samples generally presented higher estimated concentrations of banned substances (mg/g) than CDS samples (µg/g). The common practice of DS intake by athletes continues to be of great concern for a doping-free sport, given the high prevalence of prohibited substances detected in the analyzed samples by the LBCD. The current Brazilian scenario reinforces the importance of raising awareness in the sports community of the possible consequences of an unintentional doping case linked to DS use.

Genome Wide Association Study Identifies the HMGCS2 Locus to be Associated With Chlorthalidone Induced Glucose Increase in Hypertensive Patients.

BACKGROUND: Thiazide and thiazide-like diuretics are first-line medications for treating uncomplicated hypertension. However, their use has been associated with adverse metabolic events, including hyperglycemia and incident diabetes mellitus, with incompletely understood mechanisms. Our goal was to identify genomic variants associated with thiazide-like diuretic/chlorthalidone-induced glucose change. METHODS AND RESULTS: Genome-wide analysis of glucose change after treatment with chlorthalidone was performed by race among the white (n=175) and black (n=135) participants from the PEAR-2 (Pharmacogenomic Evaluation of Antihypertensive Responses-2). Single-nucleotide polymorphisms with P<5×10-8 were further prioritized using in silico analysis based on their expression quantitative trait loci function. Among blacks, an intronic single-nucleotide polymorphism (rs9943291) in the HMGCS2 was associated with increase in glucose levels following chlorthalidone treatment (ß=12.5; P=4.17×10-8). G-allele carriers of HMGCS2 had higher glucose levels (glucose change=+16.29 mg/dL) post chlorthalidone treatment compared with noncarriers of G allele (glucose change=+2.80 mg/dL). This association was successfully replicated in an independent replication cohort of hydrochlorothiazide-treated participants from the PEAR study (ß=5.54; P=0.023). A meta-analysis of the 2 studies was performed by race in Meta-Analysis Helper, where this single-nucleotide polymorphism, rs9943291, was genome-wide significant with a meta-analysis P value of 3.71×10-8. HMGCS2, a part of the HMG-CoA synthase family, is important for ketogenesis and cholesterol synthesis pathways that are essential in glucose homeostasis. CONCLUSIONS: These results suggest that HMGCS2 is a promising candidate gene involved in chlorthalidone and Hydrochlorothiazide (HCTZ)-induced glucose change. This may provide insights into the mechanisms involved in thiazide-induced hyperglycemia that may ultimately facilitate personalized approaches to antihypertensive selection for hypertension treatment. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00246519 and NCT01203852.

Novel plasma biomarker of atenolol-induced hyperglycemia identified through a metabolomics-genomics integrative approach.

INTRODUCTION: While atenolol is an effective antihypertensive agent, its use is also associated with adverse events including hyperglycemia and incident diabetes that may offset the benefits of blood pressure lowering. By combining metabolomic and genomic data acquired from hypertensive individuals treated with atenolol, it may be possible to better understand the pathways that most impact the development of an adverse glycemic state. OBJECTIVE: To identify biomarkers that can help predict susceptibility to blood glucose excursions during exposure to atenolol. METHODS: Plasma samples acquired from 234 Caucasian participants treated with atenolol in the Pharmacogenomic Evaluation of Antihypertensive Responses trial were analyzed by gas chromatography Time-Of-Flight Mass Spectroscopy. Metabolomics and genomics data were integrated by first correlating participant's metabolomic profiles to change in glucose after treatment with atenolol, and then incorporating genotype information from genes involved in metabolite pathways associated with glucose response. RESULTS: Our findings indicate that the baseline level of ß-alanine was associated with glucose change after treatment with atenolol (Q = 0.007, ß = 2.97 mg/dL). Analysis of genomic data revealed that carriers of the G allele for SNP rs2669429 in gene DPYS, which codes for dihydropyrimidinase, an enzyme involved in ß-alanine formation, had significantly higher glucose levels after treatment with atenolol when compared with non-carriers (Q = 0.05, ß = 2.76 mg/dL). This finding was replicated in participants who received atenolol as an add-on therapy (P = 0.04, ß = 1.86 mg/dL). CONCLUSION: These results suggest that ß-alanine and rs2669429 may be predictors of atenolol-induced hyperglycemia in Caucasian individuals and further investigation is warranted.