Prospective observational study of the effect of dual antiplatelet therapy with tranexamic acid treatment on platelet function and bleeding after cardiac surgery.

BACKGROUND: The bleeding impact of dual antiplatelet therapy (DAPT), aspirin and clopidogrel, maintained until coronary artery bypass graft surgery (CABG), is still a matter of debate. The lack of preoperative antiplatelet activity measurement and heterogeneity of antifibrinolytic protocols in prior studies make the conclusions questionable. The aim of this prospective study was to determine, after preoperative antiplatelet activity measurement, if the maintenance of DAPT until CABG increases bleeding in patients treated with tranexamic acid (TA). METHODS: This observational study included 150 consecutive patients, 89 treated with aspirin and 61 treated with DAPT, undergoing a first-time planned on-pump CABG with TA treatment. Antiplatelet activity was measured with platelet aggregation tests and quantification of VASP phosphorylation. Postoperative bleeding at 24 h was recorded and propensity score analysis was performed. RESULTS: Based on VASP assay, 54% of patients showed high on-clopidogrel platelet activity inhibition. Postoperative bleeding at 24 h increased by 22% in the DAPT group, compared with the aspirin group (680 [95% CI: 360-1670] vs 558 [95%CI: 267-1270] ml, P < 0.01), consistent with increased blood transfusion (21% vs 7%, P = 0.01); a higher incidence of mediastinitis did not reach statistical significance (15% vs 4%, P = 0.05). Bleeding correlated with the extent of clopidogrel antiplatelet effect, with the best correlation for the VASP assay. CONCLUSIONS: Maintenance of DAPT until the day of CABG in patients treated with TA, increased postoperative bleeding at 24 h in parallel with preoperative antiplatelet activity induced by clopidogrel.

Increase in both angiogenic and angiostatic mediators in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with a marked pulmonary vascular remodeling. The aim of this study was to investigate a potential imbalance between angiogenic and angiostatic factors in this disease. METHODS AND RESULTS: Sixty-four subjects with IPF and 10 healthy control subjects (60-70 years old) were prospectively included in this multicenter study. Plasma levels of vascular endothelial growth factor A (VEGF-A), thrombospondin-1 (TSP-1) and stem cell factor (SCF) were determined by Elisa. Comparisons between IPF and controls were made using the Mann-Whitney U test. We also analyzed these soluble mediators in relation with IPF severity (DLCO<40% or>40%) predicted or total lung capacity (TLC) and forced vital capacity (FVC) (both<55% or>55% predicted) using the same test. VEGF-A plasma levels were increased in IPF vs. controls (P=0.0008) as well as those of TSP-1 (P=0.008), irrespective of the severity of the disease as reflected by DLCO, TLC or FVC values. In contrast, SCF levels were similar in IPF and controls. CONCLUSIONS: Factors modulating angiogenic responses are dysregulated in patients with IPF with increases in VEGF-A and TSP-1. The serial assessment of VEGF-A and TSP-1 during the follow-up and the search for potential relationships with the outcome of the disease might give us hints to the clinical implication of these results.

Innovative Method for the Analysis of Dexpanthenol in Hair Care Products.

Background: Dexpanthenol is a widely used humectant in hair care products, especially anti-hairfall products. The hair care industry is highly regulated in East Asia and treats products containing the combination of dexpanthenol, zinc pyrithione, and nicotinamide (vitamin B3) as quasi-drugs. Objective: Because dexpanthenol lacks a UV chromophore, existing methodologies for analysis in finished products include pretreatments and/or HPLC-UV analysis at low wavelengths at which poor signal-to-noise is observed. These time-consuming methods lack the robustness needed for routine use in quality laboratories. This has resulted in the need for a simple, fast, accurate, and robust UHPLC-MS method to quantify dexpanthenol in hair care products that could be easily adapted in quality laboratories. Methods: The MS detection was performed in positive ion mode with data acquired in single-ion recording for dexpanthenol (206.14 m/z), dexpanthenol-d6 (212.29 m/z), and Leucine Enkephalin acetate salt (556.28 m/z). Quantitation was performed using peak area ratio of dexpanthenol to the internal standard. Results: The resulting linear curve R² was 0.9998 with sample precision RSDs <2.5%. The accuracy recoveries were within 2% and the robustness results were within 3% of the nominal conditions. Conclusions: The resulting method for the quantitation of dexpanthenol is fast, accurate, and robust in the range of 170.24-1024.5 ng/mL in shampoo and conditioner, which is easily adaptable in quality laboratories. Highlights: This study determined optimal sample preparation and UHPLC-MS conditions to quantify dexpanthenol in finished hair care products.

Incidence of shoulder and neck pain in a working population: effect modification between mechanical and psychosocial exposures at work? Results from a one year follow up of the Malmö shoulder and neck study cohort.

STUDY OBJECTIVE: To assess the impact of mechanical exposure and work related psychosocial factors on shoulder and neck pain. DESIGN: A prospective cohort study. PARTICIPANTS: 4919 randomly chosen, vocationally active men and women ages 45-65 residing in a Swedish city. Neck and shoulder pain were determined by the standardised Nordic questionnaire. Mechanical exposure was assessed by an index based on 11 items designed and evaluated for shoulder and neck disorders. Work related psychosocial factors were measured by the Karasek and Theorell demand-control instrument. MAIN RESULTS: High mechanical exposure was associated with heightened risk for shoulder and neck pain among men and women during follow up. Age adjusted odds ratios (OR) were 2.17 (95% confidence intervals (CI): 1.65, 2.85) and 1.59 (95% CI: 1.22, 2.06), respectively. In women, job strain (high psychological job demands and low job decision latitude) correlated with heightened risk (OR = 1.73, 95% CI: 1.29, 2.31). These risk estimates remained statistically significant when controlled for high mechanical exposure regarding job strain (and vice versa), and for sociodemographic factors. Testing for effect modification between high mechanical exposure and job strain showed them acting synergistically only in women. CONCLUSION: Job related mechanical exposure in both sexes, and psychosocial factors in women, seem independently of each other to play a part for development of shoulder and neck pain in vocationally active people. The effect of psychosocial factors was more prominent in women, which could be the result of biological factors as well as gender issues. These results suggest that interventions aiming at reducing the occurrence of shoulder and neck pain should include both mechanical and psychosocial factors.

Summary workshop report: bioequivalence, biopharmaceutics classification system, and beyond.

The workshop "Bioequivalence, Biopharmaceutics Classification System, and Beyond" was held May 21-23, 2007 in North Bethesda, MD, USA. This workshop provided an opportunity for pharmaceutical scientists to discuss the FDA guidance on the Biopharmaceutics Classification System (BCS), bioequivalence of oral products, and related FDA initiatives such as the FDA Critical Path Initiative. The objective of this Summary Workshop Report is to document the main points from this workshop. Key highlights of the workshop were (a) the described granting of over a dozen BCS-based biowaivers by the FDA for Class I drugs whose formulations exhibit rapid dissolution, (b) continued scientific support for biowaivers for Class III compounds whose formulations exhibit very rapid dissolution, (c) scientific support for a number of permeability methodologies to assess BCS permeability class, (d) utilization of BCS in pharmaceutical research and development, and (e) scientific progress in in vitro dissolution methods to predict dosage form performance.

Parental economic stress: evidence of an overlooked public health risk among Swedish families.

BACKGROUND: Studies have demonstrated that when parents shoulder considerable financial responsibilities, adverse health outcomes may occur. The present study assesses the association between economic stress and self-rated health in a sample of Swedish parents, and especially how this relation is affected by foreign origin and employment status. METHODS: A questionnaire was sent to a random sample of 5,600 individuals between the ages of 21 and 81 in Malmö, Sweden. The total response rate was 69%. Among the respondents, 824 were parents having at least one child living at home. The main exposures were such sociodemographic variables as country of origin and employment status, and economic stress. The outcome variable was self-rated health. RESULTS: Of the parents in the study, the 34.7% coded as exposed to economic stress showed a significantly increased odds ratio for poor self-rated health (OR=3.12, 95% CI: 2.01-4.84) adjusted for age and sex. After controlling for foreign origin and unemployment, the odds ratio remained statistically significant regarding exposure to economic stress (OR=1.94; 1.16-3.23). In the multivariate model, foreign origin and unemployment were also strongly associated with poor self-rated health (OR=1.78, 95% CI: 1.12-2.88; OR=1.67, 95% CI: 1.01-2.75, respectively). The adjusted population-attributable risk for poor self-rated health was estimated to be 27.4% for economic stress, 26.6% for foreign origin, and 16.7% for unemployment. CONCLUSIONS: Parental economic stress was associated with low self-rated health to a statistically significant degree, even when accounting for employment status and foreign origin. It, therefore, deserves to be seriously considered as an potential public health risk factor among Swedish families.

Social network, social support and the rate of decline of CD4 lymphocytes in asymptomatic HIV-positive homosexual men.

AIMS: To test a stress-disease hypothesis by investigating the influence of social network and social support factors on the course over time of the CD4 lymphocytes in an HIV-positive population of gay men. METHODS: The study is a prospective cohort study of a representative population of HIV-positive gay men, undertaken at the Department of Infectious Diseases, Malmö University Hospital. This is the only clinic providing care for HIV-positive individuals in the city of Malmö in southern Sweden (population 248,000). A total of 115 HIV-positive homosexual men, who had not received an AIDS diagnosis, were invited to take part in the study. Seventy-five men (65%) accepted to be interviewed and 64 men (56%) fulfilled the inclusion criteria for the statistical analysis. RESULTS: In a multivariate analysis adjustments were made for age, level of the first CD4 count and time since first contact with the clinic. Men with high family contact frequency had a longer half-life (20.3 years) of the CD4 lymphocyte count than men with a low family contact frequency (7.4 years) (p = 0.03). Men with high social participation also had a longer half-life of CD4 lymphocyte count (14.7 years), compared with men with low social participation (6.3 years, p = 0.10). CONCLUSIONS: The findings of this study imply the importance of social support and social network factors as modifiers of the rate of decline of the CD4 lymphocyte level, which is an important prognostic marker of survival in HIV-positive homosexual men.