Risk of serious skin disorders among users of oral antifungals: a population-based study

BACKGROUND: Serious skin disorders have been associated with the use of oral antifungals in a number of case reports and series of cases. However the incidence of these disorders remains unknown. METHODS: We estimated the risk of serious skin disorders in a cohort of users of oral antifungals identified in the general population of the General Practice Research Database in the UK. The cohort included 61,858 patients, 20 to 79 years old, who had received at least one prescription for either oral fluconazole, griseofulvin, itraconazole, ketoconazole, or terbinafine. RESULTS: The background rate of serious cutaneous adverse reactions (the one corresponding to non use of oral antifungals) was 3.9 per 10,000 person-years (95% CI 2.9–5.2). Incidence rates for current use were 15.4 per 10,000 person-years (1.9–55.7) for itraconazole, 11.1 (3.0–28.5) for terbinafine, 10.4 (1.3–37.5) for fluconazole, and 4.6 (0.1–25.8) for griseofulvin. Itraconazole was the antifungal associated with the highest relative risk, 3.9 (0.5–15.0), when compared to the risk among non users, followed by terbinafine and fluconazole, with relative risks of 2.8 (0.7–7.8) and 2.6 (0.3–10.1), respectively. CONCLUSIONS: We conclude that cutaneous disorders associated with the use of oral antifungals in this study were all of mild severity and that the risk associated with the use of oral antifungals was slightly higher than the risk in non-users. The safety profile of terbinafine regarding cutaneous disorders is similar to other antifungals and in the very low range of risks associated with other drugs

Miocardiopatía por estrés: takotsubo

Clinic. A 83-year-old woman who presented with acute chest pain after an intense emotional stimulus. Diagnostic tests. EKG showed negative T waves in anterior and ultrasensitive troponins were raised. The echocardiogram showed an intensely depressed with akinesia media and distal segments of all sides and apex, with conventional coronary angiography systolic function without significant lesions. The MRI was consistent with stress cardiomyopathy (ECM) takotsubo. Discussion. of uncertain origin, the ECM can mimic myocardial infarction with normal coronary arteries and good prognosis.Clínica. Mujer de 83 años que consultó por dolor torácico agudo tras un estímulo emocional intenso. Pruebas diagnósticas. El electrocardiograma mostró ondas T negativas en cara anterior y las troponinas ultrasensibles estaban elevadas. El ecocardiograma mostró una función sistólica global intensamente deprimida con acinesia de los segmentos medios y distales de todas las caras y el ápex, con coronariografía convencional sin lesiones significativas. La imagen por RM era compatible con miocardiopatía de estrés (MCE-takotsubo). Discusión. De origen incierto, la MCE puede remedar un infarto de miocardio con coronarias normales y buen pronóstico

Calculation of the efficacy of vaccines against tick infestations on cattle

Articles in International JournalsCattle ticks are responsible for great economic losses in cattle farming worldwide, and their main control method, chemicals, has been showing problems, whether resulting from the development of resistant strains of ticks or environmental contamination. Research studies directed toward developing vaccines against ticks are emerging. One way to evaluate those vaccines is to calculate the percentage of efficacy. The aim of this study was to analyze scientific publications archived in PubMed that used this method of assessment and discuss the main factors that may affect its calculation. Thus, 25 articles addressing this subject were selected. The percentage of efficacy was usually calculated in one of two ways, with one considering the reduced fertility of eggs and the other not. The latter method may underestimate the vaccine efficacy, and the most complete formula for calculating the efficacy reflects how much the vaccine actually affects the infestation. In our view, the use of the complete formula for calculating the percentage of efficacy is broader and more representative of the vaccine effect on the tick population.RESUMO - Carrapatos de bovinos são responsáveis por grandes perdas econômicas para a pecuária bovina mundial e seu principal método de controle, o químico, vem apresentando problemas, seja pelo desenvolvimento de amostras de carrapatos resistentes ou pela contaminação ambiental. Na tentativa de diminuir a utilização dos acaricidas, surgem pesquisas direcionadas ao desenvolvimento de vacinas contra carrapatos. Uma maneira de avaliar essas vacinas é pelo cálculo de percentagem de eficácia. O objetivo deste trabalho foi analisar as publicações científicas indexadas no PubMed que utilizaram este método de avaliação e discutir os principais fatores que podem interferir no seu cálculo. Dessa maneira, selecionaram-se 25 artigos que tratavam desse assunto. A percentagem de eficácia apareceu sendo calculada de duas formas, uma considerando a redução da fertilidade dos ovos e a outra não. Essa última pode subestimar a eficiência da vacina, e a fórmula de cálculo da eficácia mais completa representa o quanto da infestação a vacina realmente reduziu. Em nosso entendimento, a utilização da fórmula completa para o cálculo da percentagem de eficácia é mais abrangente e representativa do efeito da vacina na população de carrapatos

Efficacy and Tolerability of 6-Month Treatment with Tamsulosin Plus the Hexanic Extract of Serenoa repens versus Tamsulosin Plus 5-Alpha-Reductase Inhibitors for Moderate-to-Severe LUTS-BPH Patients: Results of a Paired Matched Clinical Study

The objective of this subset analysis was to evaluate and compare the efficacy and tolerability of two combination treatments for men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Data were from a real-world, open-label, prospective, and multicenter study performed in outpatient urology clinics. Men with moderate-to-severe LUTS/BPH received 6-month treatment with tamsulosin (TAM) in combination with either the hexanic extract of S. repens (HESr) or a 5-alpha-reductase inhibitor (5ARI). Changes in urinary symptoms and quality of life were measured using the IPSS and BII questionnaires, respectively. Treatment tolerability was assessed by recording adverse effects (AEs). Patients in the two study groups were matched using iterative and propensity score matching approaches. After iterative matching, data were available from 136 patients (n = 68 treated with TAM + 5ARI, n = 68 with TAM + HESr). After 6 months of treatment, mean (SD) IPSS total score improved by 7.7 (6.3) and 6.7 (5.0) points in the TAM + 5ARI and TAM + HESr groups, respectively (p = 0.272); mean BII total scores improved by 3.1 (2.9) and 2.9 (2.4) points (p = 0.751), respectively. AEs were reported by 26.5% and 10.3% of patients in the same groups, mostly affecting sexual function (p < 0.027). When used in a real-world setting to treat patients with moderate-severe LUTS/BPH, 6-month treatment with TAM + HESr was as effective as TAM + 5ARI, but with better tolerability. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Genetic variation in the tau protein phosphatase-2A pathway is not associated with Alzheimer's disease risk

<p>Abstract</p> <p>Background</p> <p>Tau abnormal hyperphosphorylation and the formation of neurofibrillary tangles in AD brain is the result of upregulation of tau kinases and downregulation of tau phosphatases.</p> <p>Methods</p> <p>In a group of 729 Spanish late-onset Alzheimer's disease (AD) patients and 670 healthy controls, we examined variations into a set of candidate genes (PPP2CA, PPP2R2A, ANP32A, LCMT1, PPME1 and PIN1) in the tau protein phosphatase-2A (PP2A) pathway, to address hypotheses of genetic variation that might influence AD risk.</p> <p>Results</p> <p>There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by age, gender or APOE ε4 allele.</p> <p>Conclusion</p> <p>Our negative findings in the Spanish population argue against the hypothesis that genetic variation in the tau protein phosphatase-2A (PP2A) pathway is causally related to AD risk</p

Identification and characterization of Rhipicephalus (Boophilus) microplus candidate protective antigens for the control of cattle tick infestations

The cattle ticks, Rhipicephalus (Boophilus) spp., affect cattle production in tropical and subtropical regions of the world. Tick vaccines constitute a cost-effective and environmentally friendly alternative to tick control. The recombinant Rhipicephalus microplus Bm86 antigen has been shown to protect cattle against tick infestations. However, variable efficacy of Bm86-based vaccines against geographic tick strains has encouraged the research for additional tick-protective antigens. Herein, we describe the analysis of R. microplus glutathione-S transferase, ubiquitin (UBQ), selenoprotein W, elongation factor-1 alpha, and subolesin (SUB) complementary DNAs (cDNAs) by RNA interference (RNAi) in R. microplus and Rhipicephalus annulatus. Candidate protective antigens were selected for vaccination experiments based on the effect of gene knockdown on tick mortality, feeding, and fertility. Two cDNA clones encoding for UBQ and SUB were used for cattle vaccination and infestation with R. microplus and R. annulatus. Control groups were immunized with recombinant Bm86 or adjuvant/saline. The highest vaccine efficacy for the control of tick infestations was obtained for Bm86. Although with low immunogenic response, the results with the SUB vaccine encourage further investigations on the use of recombinant subolesin alone or in combination with other antigens for the control of cattle tick infestations. The UBQ peptide showed low immunogenicity, and the results of the vaccination trial were inconclusive to assess the protective efficacy of this antigen. These experiments showed that RNAi could be used for the selection of candidate tick-protective antigens. However, vaccination trials are necessary to evaluate the effect of recombinant antigens in the control of tick infestations, a process that requires efficient recombinant protein production and formulation systems

Multiple Local and Recent Founder Effects of TGM1 in Spanish Families

<div><h3>Background</h3><p>Mutations in the <em>TGM1</em> gene encoding transglutaminase 1 are a major cause of autosomal recessive congenital ichthyosis. In the Galician (NW Spain) population, three mutations, c.2278C>T, c.1223_1227delACAC and c.984+1G>A, were observed at high frequency, representing ∼46%, ∼21% and ∼13% of all <em>TGM1</em> gene mutations, respectively. Moreover, these mutations were reported only once outside of Galicia, pointing to the existence of historical episodes of local severe genetic drift in this region.</p> <h3>Methodology/Principal Findings</h3><p>In order to determine whether these mutations were inherited from a common ancestor in the Galician population, and to estimate the number of generations since their initial appearance, we carried out a haplotype-based analysis by way of genotyping 21 SNPs within and flanking the <em>TGM1</em> gene and 10 flanking polymorphic microsatellite markers spanning a region of 12 Mb. Two linkage disequilibrium based methods were used to estimate the time to the most recent common ancestor (TMRCA), while a Bayesian-based procedure was used to estimate the age of the two mutations. Haplotype reconstruction from unphased genotypes of all members of the affected pedigrees indicated that all carriers for each of the two mutations harbored the same haplotypes, indicating common ancestry.</p> <h3>Conclusions/Significance</h3><p>In good agreement with the documentation record and the census, both mutations arose between 2,800–2,900 years ago (y.a.), but their TMRCA was in the range 600–1,290 y.a., pointing to the existence of historical bottlenecks in the region followed by population growth. This demographic scenario finds further support on a Bayesian Coalescent Analysis based on <em>TGM1</em> haplotypes that allowed estimating the occurrence of a dramatic reduction of effective population size around 900–4,500 y.a. (95% highest posterior density) followed by exponential growth.</p> </div

Prospective associations between a priori dietary patterns adherence and kidney function in an elderly Mediterranean population at high cardiovascular risk.

PURPOSE: To assess the association between three different a priori dietary patterns adherence (17-item energy reduced-Mediterranean Diet (MedDiet), Trichopoulou-MedDiet and Dietary Approach to Stop Hypertension (DASH)), as well as the Protein Diet Score and kidney function decline after one year of follow-up in elderly individuals with overweight/obesity and metabolic syndrome (MetS). METHODS: We prospectively analyzed 5675 participants (55-75 years) from the PREDIMED-Plus study. At baseline and at one year, we evaluated the creatinine-based estimated glomerular filtration rate (eGFR) and food-frequency questionnaires-derived dietary scores. Associations between four categories (decrease/maintenance and tertiles of increase) of each dietary pattern and changes in eGFR (ml/min/1.73m2) or ≥ 10% eGFR decline were assessed by fitting multivariable linear or logistic regression models, as appropriate. RESULTS: Participants in the highest tertile of increase in 17-item erMedDiet Score showed higher upward changes in eGFR (β: 1.87 ml/min/1.73m2; 95% CI: 1.00-2.73) and had lower odds of ≥ 10% eGFR decline (OR: 0.62; 95% CI: 0.47-0.82) compared to individuals in the decrease/maintenance category, while Trichopoulou-MedDiet and DASH Scores were not associated with any renal outcomes. Those in the highest tertile of increase in Protein Diet Score had greater downward changes in eGFR (β: - 0.87 ml/min/1.73m2; 95% CI: - 1.73 to - 0.01) and 32% higher odds of eGFR decline (OR: 1.32; 95% CI: 1.00-1.75). CONCLUSIONS: Among elderly individuals with overweight/obesity and MetS, only higher upward change in the 17-item erMedDiet score adherence was associated with better kidney function after one year. However, increasing Protein Diet Score appeared to have an adverse impact on kidney health. TRIAL REGISTRATION NUMBER: ISRCTN89898870 (Data of registration: 2014)

Prevalence of emergency contraceptive pill use among Spanish adolescent girls and their family and psychological profiles

The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background:Adolescent girls’ family context and psychological characteristics play important roles in their sexual behavior, including the use of the emergency contraceptive pill (ECP). This study aims to (1) determine the prevalence of ECP use among girls who have had sexual intercourse and (2) comparatively analyze their family and psychological profiles according to whether they have used ECPs. Methods:The sample of 1735 Spanish girls aged 15 to 18 came from a representative sample of the 2014 edition of the Health Behaviour in School-aged Children (HBSC) study. Of this sample, 398 girls had sexual intercourse and reported their ECP use. Data collection for the HBSC study was performed through an online questionnaire to which adolescents responded anonymously in school. Data analyses were descriptive and bivariate and were performed with the statistical program IBM SPSS Statistics 23.Results:The results demonstrated that 30.65% of girls who had sexual intercourse used ECPs. Noticeable differences in paternal knowledge and communication with the father were observed between girls who used the ECP at least once and those who did not use it. In contrast, differences between girls who used the ECP once and those who used it twice or more were pronounced with regard to parental knowledge, communication with parents, maternal affection,life satisfaction, sense of coherence and depression. Conclusions:This work demonstrates a high prevalence of ECP use and a more positive family and psychological profile for girls who used ECP once compared with those who used it twice or more.Peer reviewedFinal Published versio