Antiplatelet Effect Durability of a Novel, 24-Hour, Extended-Release Prescription Formulation of Acetylsalicylic Acid in Patients With Type 2 Diabetes Mellitus.

High platelet reactivity and high platelet turnover have been implicated in incomplete platelet inhibition during immediate-release acetylsalicylic acid therapy in patients with type 2 diabetes mellitus (DM). An extended-release acetylsalicylic acid (ER-ASA; Durlaza) formulation was developed to provide 24-hour antithrombotic effects with once-daily dosing. The objective of the study was to evaluate the antiplatelet effects of ER-ASA in patients with DM. In this open-label, single-center study, patients with DM (n = 40) and multiple cardiovascular risk factors received ER-ASA 162.5 mg/day for 14 ± 4 days. Multiple platelet function tests, serum and urinary thromboxane B2 metabolites, prostacyclin metabolite, and high-sensitive C-reactive protein levels were assessed at 1, 12, 16, and 24 hours post-dose. Patients with high platelet turnover and/or high platelet reactivity were treated with ER-ASA 325 mg/day for 14 ± 4 days, and laboratory analyses were repeated. All patients responded to ER-ASA 162.5 mg/day as measured by arachidonic acid-induced aggregation, and there was no loss of the platelet inhibitory effect of ER-ASA 162.5 mg/day over 24 hours post-dose (p = not significant). The antiplatelet effect was sustained over 24 hours for all platelet function measurements. Mean 1- to 24-hour serum thromboxane B2 levels were low with both doses and were lower with ER-ASA 325 mg/day compared with 162.5 mg/day therapy (p = 0.002). In conclusion, ER-ASA 162.5 mg daily dose provided sustained antiplatelet effects over 24 hours in patients with type 2 DM and multiple cardiovascular risk factors and had a favorable tolerability profile.

Safety and tolerability of extended-release acetylsalicylic acid capsules: a summary of double-blind comparative studies.

AIM: To evaluate tolerability of a new extended-release acetylsalicylic acid (ER-ASA). MATERIALS & METHODS: Daily ER-ASA (162.5-1300 mg) for up to 6 weeks was evaluated (four studies; n = 565). Safety of ER-ASA, immediate-release (IR; 150-1200 mg) ASA and enteric-coated ASA (75 mg) was assessed. RESULTS: Forty-three out of 184 (23.4%) patients with atherosclerosis (ER-ASA 162.5 mg group) experienced adverse events versus 51/195 (26.2%) patients receiving IR-ASA 150 mg. Overall, 48.7 and 51.3% of patients in the ER-ASA group experienced no gastrointestinal discomfort or any gastrointestinal symptoms, respectively, versus 42.1 and 57.9% of patients in the IR-ASA group, respectively. In healthy volunteers, adverse event incidence was comparable between ER-ASA and IR-ASA and between ER-ASA and enteric-coated ASA. CONCLUSION: Safety of the new ER-ASA formulation was consistent with other ASA formulations.

Drug delivery and therapeutic impact of extended-release acetylsalicylic acid.

Current treatment guidelines recommend once-daily, low-dose acetylsalicylic acid (ASA; aspirin) for secondary prevention of cardiovascular events. However, the anti-thrombotic benefits of traditional ASA formulations may not extend over a 24-h period, especially in patients at high risk for a recurrent cardiovascular event. A next-generation, extended-release ASA formulation (ER-ASA) has been developed to provide 24-h anti-thrombotic coverage with once-daily dosing. The pharmacokinetics of ER-ASA indicates slower absorption and prolonged ASA release versus immediate-release ASA, with a favorable safety profile. ER-ASA minimizes systemic ASA absorption and provides sustained antiplatelet effects over a 24-h period.

A randomized trial to assess the pharmacodynamics and pharmacokinetics of a single dose of an extended-release aspirin formulation.

AIMS: Low-dose acetylsalicylic acid (ASA; aspirin) for secondary prevention reduces cardiovascular disease mortality risk. ASA acetylates cyclooxygenase in the portal circulation and is rapidly (half-life, 20 min) hydrolyzed. Certain patients with cardiovascular disease may exhibit high on-therapy platelet reactivity as a result of high platelet turnover, a process whereby platelets are produced and are active beyond the duration of antiplatelet coverage provided by once-daily immediate-release (IR) ASA. A once-daily, extended-release (ER) ASA formulation using ER microcapsule technology was developed to release ASA over the 24-h dosing interval and reduce maximal plasma concentrations to spare peripheral endogenous endothelial prostacyclin production. METHODS: Healthy adults (n = 50) were randomized in a crossover study to receive two different ER-ASA single doses (up to 325 mg) and two different IR-ASA single doses (up to 81 mg) in four periods, each separated by ≥14 days. Pharmacodynamics was assessed by measuring serum thromboxane B2 (TXB2), urine 11-dehydro-TXB2, and arachidonic acid-induced platelet aggregation. Pharmacokinetics was determined for ASA and salicylic acid (SA). RESULTS: Both formulations produced dose-dependent inhibition on all pharmacodynamic parameters. Marked inhibition of TXB2 and 11-dehydro-TXB2 was maintained over the 24-h dosing interval after a dose of ≥81 mg ER-ASA or ≥40 mg IR-ASA. The dose required to achieve 50% of maximum TXB2 inhibition with ER-ASA was 49.9 mg versus 29.6 mg for IR-ASA, for a similar maximum pharmacodynamic effect (98.9% TXB2 inhibition). This suggests that an approximately twofold greater ER-ASA dose (162.5 mg) is necessary to obtain the same response as that of IR-ASA 81 mg. Peak ASA concentrations were lower and Tmax was longer with ER-ASA versus IR-ASA. Administration of IR-ASA resulted in a dose-normalized mean Cmax of ASA that was approximately sixfold higher than that for ER-ASA and a Cmax of SA approximately two- to threefold higher than that for ER-ASA. CONCLUSION: Both ASA formulations showed dose-dependent antiplatelet activity. Compared with the IR-ASA, ER-ASA released active drug more slowly, resulting in prolonged absorption and lower systemic drug concentrations, which is expected for an ER (24-h) formulation.

Predicting posttraumatic stress disorder after childbirth.

OBJECTIVE: around 50% of women report symptoms that indicate some aspect of their childbirth experience was 'traumatic', and at least 3.1% meet diagnosis for PTSD six months post partum. Here we aimed to conduct a prospective longitudinal study and examine predictors of birth-related trauma - predictors that included a range of pre-event factors - as a first step in the creation of a screening questionnaire. METHOD: of the 933 women who completed an assessment in their third trimester, 866 were followed-up at four to six week post partum. Two canonical discriminant function analyses were conducted to ascertain factors associated with experiencing birth as traumatic and, of the women who found the birth traumatic, which factors were associated with those who developed PTSD. FINDINGS: a mix of 16 pre-birth predictor variables and event-specific predictor variables distinguished women who reported symptoms consistent with trauma from those who did not. Fourteen predictor variables distinguished women who went on to develop PTSD from those who did not. CONCLUSIONS: anxiety sensitivity to possible birthing problems, breached birthing expectations, and severity of any actual birth problem, predicted those who found the birth traumatic. Prior trauma was the single most important predictive factor of PTSD. Evaluating the utility of brief, cost-effective, and accurate screening for women at risk of developing birth-related PTSD is suggested.

The validity of psychiatric diagnoses: the case of 'specific' developmental disorders.

We tested whether developmental coordination disorder (DCD) and mixed receptive expressive language disorder (RELD) are valid diagnoses by assessing whether they are separated from each other, from other childhood disorders, and from normality by natural boundaries termed zones of rarity. Standardized measures of intelligence, language, motor skills, social cognition, and executive functioning were administered to children with DCD (n = 22), RELD (n = 30), autistic disorder (n = 30), mental retardation (n = 24), attention deficit/hyperactivity disorder (n = 53) and to a representative sample of children (n = 449). Discriminant function scores were used to test whether there were zones of rarity between the DCD, RELD, and other groups. DCD and RELD were reliably distinguishable only from the mental retardation group. Cluster and latent class analyses both resulted in only two clusters or classes being identified, one consisting mainly of typical children and the other of children with a disorder. Fifty percent of children in the DCD group and 20% in the RELD group were clustered with typical children. There was no evidence of zones of rarity between disorders. Rather, with the exception of mental retardation, the results imply there are no natural boundaries between disorders or between disorders and normality.

Depression Anxiety Stress Scale: is it valid for children and adolescents?

The Depression Anxiety Stress Scale (Lovibond & Lovibond, 1995) is used to assess the severity of symptoms in child and adolescent samples although its validity in these populations has not been demonstrated. The authors assessed the latent structure of the 21-item version of the scale in samples of 425 and 285 children and adolescents on two occasions, one year apart. On each occasion, parallel analyses suggested that only one component should be extracted, indicating that the test does not differentiate depression, anxiety, and stress in children and adolescents. The results provide additional evidence that adult models of depression do not describe the experience of depression in children and adolescents.

Predicting absenteeism and turnover intentions in the health professions.

OBJECTIVES: The study examined the mediating influence of individual psychological reactions to work on the relationship between organisational climate and job withdrawal behaviours (viz, intention to leave and absenteeism). METHODS: 1097 hospital employees were surveyed using the Queensland Public Agency Staff Survey (QPASS) to obtain measures of organisational climate, psychological reactions to work, job satisfaction, and self-reported levels of intention to leave. Group-level absenteeism data were provided from the Health Service District files. RESULTS: Two psychological states, quality of work life and job satisfaction, were found to fully mediate the relationship between the organisational climate variable, role clarity, and intention to leave, while individual distress was found to partially mediate the same relationship. However, the hypothesised mediation effect of psychological states on the relationship between organisational climate and absenteeism did not emerge. CONCLUSION: Skills shortages and increasing demands for health services make retention of staff in the health service industry vitally important. As a means of addressing this issue, this study presents an emergent mediating model defining relationships among individual psychological factors, aspects of organisational climate and intention to leave. Identification of the processes associated with staff withdrawal behaviours or intentions will assist in devising interventions to improve retention.

Rural adolescents experiencing an urban transition.

OBJECTIVE: To determine the distress levels of adolescents leaving rural Queensland towns for urban boarding schools. DESIGN: A questionnaire study and focus groups were used to collect data from students who made the transition and those who did not. PARTICIPANTS: Two hundred and fifty-five rural students completed the questionnaire and of these 36 left home to attend an urban boarding school. Twenty-eight students participated in one of five focus groups. MEASURES: Self-report scales administered were Life Events Scale and the Depression, Anxiety, Stress Scale. A semistructured set of prompts was used in the focus groups. RESULTS: Both methodologies revealed adolescents reported coping well with the transition from rural and remote family homes and schools to boarding school in the city. Reported distress levels of those who moved were no higher than those who did not and homesickness, while common, was rarely high or enduring. Adolescents who moved offered useful insights in the focus groups into the best and worst aspects of the transition; how best to cope, and how families and schools can ease their path. CONCLUSIONS: In general, adolescents who leave isolated homes and schools to board in the city manage the transition surprisingly well and regard the transition as having a number of advantages. Being prepared for the move emerged as important.