ACE gene polymorphisms influence t-PA-induced brain vessel reopening following ischemic stroke

Angiotensin converting enzyme (ACE) influences vessels tone and the coagulation/fibrinolysis system. The ACE gene I/D polymorphism has been linked with PAI-1 and fibrinogen levels and with Factors VII and X activities. Therefore, we aimed to test whether I/D polymorphism could be related to thrombolysis safety and efficacy. We studied strokes involving the middle cerebral artery (MCA) territory of patients who received t-PA <3 h of stroke onset. Blood samples were obtained before t-PA administration to measure fibrinogen, PAI-1, Factors VII and X. I/D polymorphism was determined by polymerase chain reaction and agarose electrophoresis. Recanalization rates were serially evaluated by Transcranial Doppler. Among 96 included patients the genotype frequency was: DD = 33.3%, ID = 57.3% and II = 9.4%. A strong association was found between DD homozygous and successful recanalization rates (DD = 69.2%, ID + II = 31.6%, p = 0.002 at 1 h; DD = 91.3%, ID + II = 51%, p = 0.001 at 6 h; DD = 100%, ID + II = 72.3%, p = 0.003 at 24 h post-t-PA administration). In fact, DD genotype was an independent predictor of recanalization (OR = 4.3 95% CI 1.35–13.49, p = 0.013). No relation was found between I/D polymorphism and symptomatic hemorrhagic complications (p = 0.237). No association between ACE genotypes and Factor VII or Factor X activities, neither with fibrinogen or PAI-1 levels was observed. DD homozygous is strongly associated with MCA recanalization following t-PA treatment. Mechanisms of benefit remain unknown since I/D polymorphism had similar FVII and X activities and PAI-1 and fibrinogen levels in our stroke population.     

Epidemiologic genotyping of methicillin-resistant Staphylococcus aureus by pulsed-field gel electrophoresis at a university hospital and comparison with antibiotyping and protein A and coagulase gene polymorphisms

A total of 124 methicillin-resistant Staphylococcus aureus (MRSA) isolates were ascertained at the University Hospital of the Canary Islands between January 1997 and April 2000. Genotyping included pulsed-field gel electrophoresis (PFGE) (SmaI digestion) and PCR-restriction fragment length polymorphism (PCR-RFLP) analysis for the coagulase (coa) and protein A (spa) genes. Antibiotic resistance was the main phenotypic marker correlated with genotyping results. Three main PFGE types were detected: A (with 12 subtypes), B (with 2 subtypes), and C. PFGE type A1 was the most commonly found (61% of isolates) and the one responsible for all the epidemic outbreaks. Other genetics markers used (coa and spa RFLPs) were significantly correlated with the PFGE types detected (P < 0.001). These PCR-RFLP assays were useful as molecular markers for a quick, preliminary study of MRSA outbreaks.     

Rapid diagnosis of Mycobacterium tuberculosis bacteremia by PCR.

A method based on DNA amplification and hybridization has been used for the rapid detection of Mycobacterium tuberculosis in blood samples from 38 hospitalized patients (15 human immunodeficiency virus [HIV] positive and 23 HIV negative) in whom localized or disseminated forms of tuberculosis were suspected. In 32 of these patients, the diagnosis of tuberculosis was eventually confirmed by conventional bacteriological or histological procedures. M. tuberculosis DNA was detected with the PCR technique in the peripheral blood mononuclear cells from 9 of 11 (82%) HIV-infected patients and in 7 of 21 (33%) HIV-negative patients (P < 0.01), while M. tuberculosis blood cultures were positive in 1 of 8 (12.5%) and 1 of 18 (5.5%) patients, respectively. PCR was positive in all cases with disseminated disease in both HIV-negative and HIV-positive patients and also in the HIV-positive patients with extrapulmonary tuberculosis. Seven samples from patients with documented illness other than tuberculosis and 12 specimens from healthy volunteers, including seven volunteers with a recent positive purified protein derivative test, were used as controls and had a negative PCR. These results suggest that detection of M. tuberculosis DNA in peripheral blood mononuclear cells may be a useful tool for rapid diagnosis of disseminated and extrapulmonary forms of tuberculosis, especially in an HIV-positive population.     

Continuing Medical Education: an international reality

We are all aware today of the growing interest in continuing medical education (CME) programmes in many European Countries and it is important to understand why and how CME could become an international reality. It is obvious that patients need a good doctor--the best possible--as far as medical knowledge, attention to the patient's quality of life and cost-control is concerned. All European health care systems have to take into consideration everything that causes patient dissatisfaction, risk management and unjustified expenses. An example is the increase of claims and complaints against doctors and the strong attention of patients to medical procedures. In other words, medicine worldwide is becoming a service industry and has to consider quality and quantity of performances as well as to pay attention to personal responsibility. The object of our work is to evaluate the CME systems present in Europe, to show the work done on CME by the CME Committee of the European Academy of Allergology and Clinical Immunology and to highlight the Consensus Report on CME approved by an international panel of CME experts.     

Pharmacokinetics and pharmacodynamics of 25-mg estradiol implants in postmenopausal Mexican women

OBJECTIVE: To assess the serum concentrations of estradiol (E2), estrone (E1), gonadotrophins, sex hormone-binding globulin, and lipids, and to determine degree of symptom relief after subcutaneous implantation of 25 mg estradiol in postmenopausal Mexican women. DESIGN: Fifteen postmenopausal, hysterectomized women participated in an open, observational study. Blood samples were obtained before implantation and at regular intervals during a study period of 24 weeks. Climacteric symptoms were evaluated by means of the Greene climacteric scale. Wilcoxon's test was performed on the paired results of pre-and postimplantation values. RESULTS: Serum concentrations of E2 obtained after implantation were fairly constant, remaining within the early follicular range for the entire study period of 24 weeks, and were associated with significant symptom relief. A physiological, premenopausal E2:E1 ratio was achieved. No significant metabolic changes occurred. Side effects were estrogenic in nature and no removal of implant was required. CONCLUSIONS: Subcutaneous implantation of 25 mg estradiol results in physiological, premenopausal estrogen concentrations in most women and is associated with considerable symptom relief without inducing significant adverse metabolic effects.     

Independent Effects of Neighborhood Poverty and Psychosocial Stress on Obesity Over Time

The objective of the study was to examine the independent effects of neighborhood poverty and psychosocial stress on increases in central adiposity over time. Data are from a community sample of 157 Non-Hispanic Black, Non-Hispanic White, and Hispanic adults collected in 2002–2003 and 2007–2008, and from the 2000 Decennial Census. The dependent variable was waist circumference. Independent variables included neighborhood poverty, perceived neighborhood physical environment, family stress, safety stress, everyday unfair treatment, and a cumulative stress index. Weighted 3-level hierarchical linear regression models for a continuous outcome were used to assess the effects of neighborhood poverty and psychosocial stress on central adiposity over time. We also assessed whether psychosocial stress mediated the association between neighborhood poverty and central adiposity. Neighborhood poverty and everyday unfair treatment at baseline were independently associated with increases in central adiposity over time, accounting for the other indicators of stress. Perceptions of the neighborhood physical environment and cumulative stress mediated associations between neighborhood poverty and central adiposity. Results suggest that residing in neighborhoods with higher concentrations of poverty and exposure to everyday unfair treatment independently heighten risk of increased central adiposity over time. Associations between neighborhood poverty and central adiposity were mediated by perceptions of the neighborhood physical environment and by the cumulative stress index. Public health strategies to reduce obesity should consider neighborhood poverty and exposure to multiple sources of psychosocial stress, including everyday unfair treatment.     

A Comparative View of Reported Adverse Effects of Statins in Social Media,Regulatory Data,Drug Information Databases and Systematic Reviews

Introduction

There are few studies assessing how data on adverse drug events from consumers on social media compare with other sources.

Aim

The aim of this study was to assess the consistency of adverse event data of statin medications from social media as compared with other sources.

Methods

We collected data on the adverse events of statins from Twitter, the US FDA Adverse Event Reporting System (FAERS), the UK Medicines and Healthcare products Regulatory Agency (MHRA), drug information databases (DIDs) and systematic reviews. We manually annotated 12,649 tweets collected between June 2013 and August 2018. We collected 45,447 reports from FAERS, 10,415 from MHRA, identified 17 systematic reviews with relevant data and extracted data from Facts and Comparisons^® and Clinical Pharmacology^®. We compared the proportion, relative frequencies and rank of each category of adverse event from each source using MedDRA^® primary System Organ Class codes.

Results

Compared with other sources, patients on social media are proportionally far more likely to complain about musculoskeletal symptoms than other adverse events. Most adverse events showed a high level of agreement between Twitter and regulatory data. DIDs tend to demonstrate similar patterns but not as strongly. Systematic reviews tend to examine pre-specified adverse events or those reported by trial investigators.

Conclusions

Combining the data from multiple sources, albeit challenging, may provide a broader safety profile of any medication. Systematically collected social media reports may be able to contribute information on the most pertinent adverse effects to patients.

     

Mortality in adolescents and young adults with chronic diseases during 16 years: a study in a Latin American tertiary hospital

ObjectivesTo evaluate mortality in adolescents and young adult patients with chronic diseases followed in a Latin American tertiary hospital.MethodsA cross-sectional retrospective study was performed in a tertiary/academic hospital in the state of São Paulo, Brazil. Death occurred in 529/2850 (18.5%) adolescents and young adult patients with chronic diseases, and 25/529 (4.7%) were excluded due to incomplete medical charts. Therefore, 504 deaths were evaluated.ResultsDeaths occurred in 316/504 (63%) of early adolescent patients and in 188/504 (37%) of late adolescent/young adult patients. Further comparisons between early adolescents (n = 316) and late adolescent/young adult patients (n = 188) with pediatric chronic diseases at the last hospitalization showed that the median disease duration (22.0 [0–173] vs. 43.0 [0–227] months, p < 0.001) was significantly lower in early adolescents vs. late adolescent/young adult patients. The median number of previous hospitalizations was significantly lower in the former group (4.0 [1–45] vs. 6.0 [1–52], p < 0.001), whereas the last hospitalization in intensive care unit was significantly higher (60% vs. 47%, p = 0.003). Regarding supportive measures, palliative care was significantly lower in the younger group compared to the older group (33% vs. 43%, p = 0.02). The frequencies of renal replacement therapy (22% vs. 13%, p = 0.02), vasoactive agents (65% vs. 54%, p = 0.01), and transfusion of blood products (75% vs. 66%, p = 0.03) were significantly higher in the younger group. The five most important etiologies of pediatric chronic diseases were: neoplasias (54.2%), hepatic diseases/transplantation (10%), human immunodeficiency virus (5.9%), and childhood-onset systemic lupus erythematosus and juvenile idiopathic arthritis (4.9%). Autopsy was performed in 58/504 (11%), and discordance between clinical and postmortem diagnoses was evidenced in 24/58 (41.3%).ConclusionsAlmost 20% of deaths occurred in adolescents and young adults with distinct supportive care and severe disease patterns. Discordance between clinical diagnosis and autopsy was frequently observed.