The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Periodontal debridement with povidone-iodine in periodontal treatment: Short-term clinical and biochemical observations

Background: The aim of the present study was to evaluate the clinical effects of one-stage periodontal debridement with an ultrasonic instrument, associated with 0.5% povidone (pvp)-iodine irrigation in patients with chronic periodontitis. Methods: Forty-five patients were randomly assigned into three groups: the control group (CG) received quadrant root planing at I-week intervals over four consecutive sessions; the periodontal debridement plus pvp-iodine group (PD-PIG) received a 45-minute full-mouth debridement with an ultrasonic instrument, associated with 0.5% pvp-iodine irrigation; and the periodontal debridement group (PDG) received a 45-minute full-mouth periodontal debridement with an ultrasonic instrument, associated with NaCl irrigation. Results: At the 3-month evaluation, the mean probing depth (PD) reduction in CG was 2.51 +/- 0.52 mm, 2.53 +/- 0.50 mm in PD-PIG, and 2.58 +/- 0.60 mm in PDG (P 0.05). The N-benzoyl-L-arginine-p-nitroanilide (BAPNA) test showed a significant reduction in trypsin activity only during the first month (P < 0.05); at 3 months there were no differences compared to baseline (P= 0.80). Conclusion: This study provides no evidence that pvp-iodine is effective as an adjunct for one-stage periodontal debridement.77349850

Prevalência do HPV em mulheres rastreadas para o câncer cervical

To assess the prevalence of high-risk genital human papillomavirus (HPV) infection by age group and risk factors associated. OBJETIVO: Analisar a prevalência da infecção genital por papilomavírus humano (HPV) de alto risco por faixa etária e fatores associados. MÉTODOS: Estudo transversal com amostra de 2.300 mulheres (15–65 anos) que buscaram rastreamento para o câncer cervical entre fevereiro de 2002 e março de 2003 em São Paulo e Campinas, estado de São Paulo. Aplicou-se questionário epidemiológico e realizou-se coleta cervical para citologia oncológica e teste de captura híbrida II. As análises estatísticas empregadas foram teste de qui-quadrado de Pearson e análise multivariada pelo método forward likelihood ratio. RESULTADOS: A prevalência total da infecção genital por HPV de alto risco foi de 17,8%, distribuída nas faixas etárias: 27,1% (<25 anos), 21,3% (25–34 anos), 12,1% (35-44 anos), 12,0% (45–54 anos) e de 13,9% (55–65 anos). Participantes com maior número de parceiros sexuais durante a vida apresentaram maior freqüência da infecção. Relacionamento estável, idade de 35 a 44 anos e ex-fumantes foram associados à proteção da infecção. A infecção genital por HPV de alto risco ocorreu em 14,3% das citologias normais, em 77,8% das lesões escamosas de alto grau e nos dois (100%) casos de carcinoma. CONCLUSÕES: A prevalência da infecção genital por HPV de alto risco na amostra estudada foi alta. Houve predomínio de casos abaixo dos 25 anos e tendência a um novo aumento após os 55 anos, com maior freqüência naqueles com maior número de parceiros sexuais durante a vidaOBJECTIVE: To assess the prevalence of high-risk genital human papil- lomavirus (HPV) infection by age group and risk factors associated. METHODS: Cross-sectional study in a sample of 2,300 women (15-65 years old) who self-referred to cervical cancer screening in Sao Paulo and Campinas, Southeastern Brazil, between February 2002 and March 2003. An epidemiological questionnaire was applied and cervical specimens were obtained for cytology and hybrid capture II test (HCII) for HPV detection. Statistical analysis included Pearson Chi-square and unconditional multiple logistic regression model (forward likelihood ratio). RESULTS: High-risk genital HPV infection prevalence in this sample was 17.8% and age distribution was as follows: 27.1% (<25 years), 21.3% (25-34 years), 12.1% (35-44 years), 12.0% (45-54 years) and 13.9% (55-65 years). Subjects with the highest number of lifetime sexual partners had the highest rates of genital HPV infection. To be living with a partner, aged 35 to 44 years, and former smokers were protective factors. High-risk genital HPV infection was 14.3% in normal cytology, 77.8% in high grade squamous intraepithelial lesions and in the two cases (100%) of cervical cancer. CONCLUSIONS: High-risk HPV prevalence was high in the sample studied. The highest prevalence of HPV infection was seen in women under 25 years old and then a new increase was seen over the age of 55 and the highest rates were found among those with many sexual partners during their lifetimeComitê Europeu de Pesquisa da Comunidade Econômica Européia (CEE–INCO DEV 4-CT-2001-10013

Dopamine D3 receptor antagonist reveals a cryptic pocket in aminergic GPCRs

The recent increase in the number of X-ray crystal structures of G-protein coupled receptors (GPCRs) has been enabling for structure-based drug design (SBDD) efforts. These structures have revealed that GPCRs are highly dynamic macromolecules whose function is dependent on their intrinsic flexibility. Unfortunately, the use of static structures to understand ligand binding can potentially be misleading, especially in systems with an inherently high degree of conformational flexibility. Here, we show that docking a set of dopamine D3 receptor compounds into the existing eticlopride-bound dopamine D3 receptor (D3R) X-ray crystal structure resulted in poses that were not consistent with results obtained from site-directed mutagenesis experiments. We overcame the limitations of static docking by using large-scale high-throughput molecular dynamics (MD) simulations and Markov state models (MSMs) to determine an alternative pose consistent with the mutation data. The new pose maintains critical interactions observed in the D3R/eticlopride X-ray crystal structure and suggests that a cryptic pocket forms due to the shift of a highly conserved residue, F6.52. Our study highlights the importance of GPCR dynamics to understand ligand binding and provides new opportunities for drug discovery.N.F. acknowledges support from Generalitat de Catalunya (FI-Agaur). GDF acknowledges support from MINECO (BIO2014-53095-P) and FEDER. We also thank all the volunteers of GPUGRID who donated GPU computing time to the project