Assessment of the adequacy of counselling regarding reproductive-related issues in women of childbearing age on anti-epileptic drugs.

BACKGROUND: The use of anti-epileptic drugs (AEDs) in women of childbearing age (WCBA) necessitates careful counselling regarding reproductive-related issues. AIM: (i) To compare documentation of appropriate counselling regarding reproductive-related issues in WCBA prescribed AEDs for non-epilepsy vs. epilepsy indications, and (ii) to examine whether the frequency of counselling improved after introduction of 'standardized typed advice'. DESIGN: Retrospective audit and quality assessment and improvement programme. METHODS: We analysed medical records of all WCBA prescribed gabapentin, pregabalin, topiramate, valproate or carbamazepine by a general neurology clinical service before (Study period A) and after (Study period B) introduction of standardized typed passages regarding potential teratogenicity ± interactions with hormonal contraception at a university teaching hospital. The χ2 test or the Fisher's exact test was employed, as appropriate. RESULTS: In WCBA prescribed AEDs for non-epilepsy indications, documentation of appropriate counselling regarding potential teratogenicity improved from 49% (17/35 patients) in Period A to 79% (27/34 patients) in Period B (P = 0.008). The frequency of counselling regarding teratogenicity was higher in patients prescribed AEDs for epilepsy compared with non-epilepsy indications in Study period A (100% vs. 49%, P = 0.002), but was no longer significantly different in Study period B (86% vs. 79%, P = 0.64). Documentation of counselling regarding potential interaction of enzyme-inducing AEDs with hormonal contraception did not significantly change between study periods. CONCLUSION: Significant improvements in documentation regarding potential teratogenicity of AEDs prescribed for non-epilepsy indications can be achieved by introducing standardized, typed passages copied to patients. Such a practice change is practical and widely applicable to neurological and non-neurological practice worldwide.

Relationship between 'on-treatment platelet reactivity', shear stress, and micro-embolic signals in asymptomatic and symptomatic carotid stenosis.

BACKGROUND: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy. METHODS: This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100® and 'low shear stress' with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve. RESULTS: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup. DISCUSSION: Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.

A group randomised trial of two methods for disseminating a smoking cessation programme to public antenatal clinics: effects on patient outcomes.

OBJECTIVE: To assess the differential effectiveness of two methods of disseminating a smoking cessation programme to public hospital antenatal clinics. DESIGN: Group randomised trial. SETTING: 22 antenatal clinics in New South Wales, Australia. INTERVENTION: Clinics were allocated to a simple dissemination (SD) condition (11 clinics) which received a mail-out of programme resources or to an intensive dissemination (ID) condition (11 clinics) which included the mail-out plus feedback, training, and ongoing support with midwife facilitator. MAIN OUTCOME MEASURES: Independent cross sectional surveys of women on a second or subsequent visit undertaken pre-dissemination and 18 months after dissemination. Outcomes were: (1) levels of smoking status assessment by clinic staff; (2) proportion of women identifying as having been smokers at their first visit who reported receiving cessation advice; (3) proportion of these women who had quit (self report and expired air carbon monoxide (CO)); and (4) smoking prevalence among all women (self report and CO). SUBJECTS: 5849 women pre-dissemination (2374 SD, 3475 ID) and weighted sample of 5145 women post-dissemination (2302 SD, 2843 ID). RESULTS: There were no significant differences between the groups on change on any outcome. Change in either group was minimal. In the post-dissemination survey, the cessation proportions were 6.4% (SD) and 10.5% (ID). CONCLUSIONS: Relatively modest strategies for encouraging incorporation of smoking cessation activities into antenatal care were not effective in the long term. Alternative strategies should be implemented and evaluated. The findings reinforce the importance of a whole population approach to tobacco control.

Direct telemarketing of smoking cessation interventions: will smokers take the call?

AIMS: Few smokers currently make use of available and effective cessation strategies, despite their expressed desire to quit and reported interest in cessation support. This study aimed to explore the feasibility of a telephone-based direct-marketing approach to delivering cessation strategies. DESIGN, SETTING, MEASUREMENTS AND PARTICIPANTS: A community survey was conducted to explore the views of current adult smokers regarding the acceptability, likely uptake and barriers to uptake of smoking cessation services offered by direct telephone marketing. FINDINGS: Three quarters (73.8%) of smokers contacted agreed to be surveyed. Of the 194 study participants, 75.3% reported that they would utilize vouchers for discount nicotine replacement therapy (NRT), 66.5% would use a mailed self-help booklet, 57.2% would take up the offer of regular mailings of personalized letters and self-help materials and 46.4% would utilize a 'we-call-you' telephone counselling service. The characteristics of those indicating likely uptake of these services were also explored. The two major barriers to uptake of services were preferring to quit without help and a belief that a particular service would not help the participant. CONCLUSIONS: The data suggest strong support for the direct marketing of smoking cessation strategies; they also highlight the need for further study of the cost-effectiveness of telephone-based direct marketing of smoking cessation strategies as a population-based strategy for reducing the prevalence of smoking in the community.

Src family kinase and adenosine differentially regulate multiple MAP kinases in ischemic myocardium: modulation of MAP kinases activation by ischemic preconditioning.

Recent studies suggest that ischemia activates Src and members of the mitogen-activated protein (MAP) kinase superfamily and their downstream effectors, including big MAP kinase 1 (BMK1) and p90 ribosomal S6 kinase (p90RSK). It has also been reported that adenosine is released during ischemia and involved in triggering the protective mechanism of ischemic preconditioning. To assess the roles of Src and adenosine in ischemia-induced MAP kinases activation, we utilized the Src inhibitor PP2 (4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) and the adenosine receptor antagonist 8-(p-sulfophenyl) theophylline (SPT) in perfused guinea pig hearts. PP2 (1 microm) inhibited ischemia-induced Src, BMK1 and JNK activation but not JAK2 and p38 activation. SPT inhibited ischemia-mediated p38 and JNK activation. These results demonstrate that Src family kinase and adenosine regulate MAP kinases by parallel pathways. Preconditioning significantly improved both recovery of developed pressure and dp/dt in isolated guinea pig hearts. Since the protective effect of preconditioning was blocked by PP2 (1 microm) and SPT (50 microm), we next investigated the regulation of Src, MAP kinases and p90RSK during preconditioning. The activity and time course of ERK1/2 was not changed, but p90RSK activation by reperfusion was completely inhibited by preconditioning. In contrast, the activation by ischemia of Src, BMK1, p38 and JNK was significantly faster in preconditioned hearts. Maximal BMK1 activation by ischemia was also significantly enhanced by preconditioning. These data suggest important roles for Src family kinases and adenosine in mediating preconditioning, and suggest specific roles for individual MAP kinases in preconditioning.

Cardiac hypertrophy and failure: lessons learned from genetically engineered mice.

Congestive heart failure is a major and growing public health problem. Because of improved survival of myocardial infarction patients produced by thrombolytic therapy or per-cutaneous revascularization it represents the only form of cardiovascular disease with significantly increased incidence and prevalence. Clinicians view this clinical syndrome as the final common pathway of diverse pathologies such as myocardial infarction and haemodynamic overload. Insights into mechanisms for heart failure historically derived from physiological and biochemical studies which identified compensatory adaptations for the haemodynamic burden associated with the pathological condition including utilization of the Frank Starling mechanism, augmentation of muscle mass, and neurohormonal activation to increase contractility. Therapy has largely been phenomenological and designed to prevent or limit the deleterious effects of these compensatory processes. More recently insights from molecular and cell biology have contributed to a more mechanistic understanding of potential causes of cardiac hypertrophy and failure. Many different analytical approaches have been employed for this purpose. These include the use of conventional animal models which permit serial observation of the onset and progression of heart failure and a sequential analysis of underlying biochemical and molecular events. Neonatal murine cardiomyocytes have been a powerful tool to examine in vitro subcellular mechanisms devoid of the confounding functional effects of multicellular preparations and heterogeneity of cell type. Finally, significant progress has been made by utilizing tissue from human cardiomyopathic hearts explanted at the time of orthotopic transplantation. Each of these methods has significant advantages and disadvantages. Arguably the greatest advance in our understanding of cardiac hypertrophy and failure over the past decade has been the exploitation of genetically engineered mice as biological reagents to study in vivo the effects of alterations in the murine genome. The power of this approach, in principle, derives from the ability to precisely overexpress or ablate a gene of interest and examine the phenotypic consequences in a cardiac specific post-natal manner. In contrast to conventional animal models of human disease which employ some form of environmental stress, genetic engineering involves a signal known molecular perturbation which produces the phenotype.

Quitting smoking in pregnancy.

Smoking doubles the risk of having a low-birthweight baby and significantly increases the rate of perinatal mortality and several other adverse pregnancy outcomes. The mean reduction in birthweight for babies of smoking mothers is 200 g. High quality interventions to help pregnant women quit smoking produce an absolute difference of 8.1% in validated late-pregnancy quit rates. If abstinence is not achievable, it is likely that a 50% reduction in smoking would be the minimum necessary to benefit the health of mother and baby. Healthcare providers perform poorly in antenatal interventions to stop women smoking. Midwives deliver interventions at a higher rate than doctors. The efficacy of nicotine replacement therapy has not been established in pregnancy. Currently, its use should only be considered in women smoking more than 10 cigarettes per day who have made a recent, unsuccessful attempt to quit and who are motivated to quit. Relapse prevention programs have shown little success in the postpartum period.

Src and multiple MAP kinase activation in cardiac hypertrophy and congestive heart failure under chronic pressure-overload: comparison with acute mechanical stretch.

Activation of members of the mitogen-activated protein (MAP) kinase family and their downstream effectors has been proposed to play a key role in the pathogenesis of cell survival, ischaemic preconditioning, cardiac hypertrophy and heart failure. This study investigated the responses of Src kinase and multiple MAP kinases during the transition from compensated pressure-overload hypertrophy to decompensated congestive heart failure. Extracellular signal-regulated protein kinase (ERK) 1/2, p38, and Src were activated by chronic pressure-overload and their activity was sustained for 8 weeks after aortic banding. In contrast, while p90 ribosomal S6 kinase (90RSK) and big MAP kinase 1 (BMK1) were activated in compensated hypertrophy, their activities were significantly decreased in hearts with heart failure. No changes were found in C-Jun NH2 terminal kinase (JNK) activity after aortic banding. These data suggest that differential activation of MAP kinase family members may contribute to the transition from compensated to decompensated hypertrophy. We also examined acute effects of mechanical stretch on the activation of these kinases in normal and hypertrophied hearts. In the isolated coronary-perfused heart, a balloon in the left ventricle was inflated to achieve minimum end-diastolic pressure of 25 mmHg for 10-20 min. In normal guinea pig hearts, stretch activated ERK1/2, p90RSK, p38, Src, and BMK1 but not JNK. However in hypertrophied hearts, further activation of these kinases was not observed by acute mechanical stretch. Mechanical stretch-induced activation of ERK1/2 and p38 kinase in normal hearts was attenuated significantly by a protein kinase C inhibitor, chelerythrine. We demonstrate that ERK1/2, p90RSK, p38, Src, and BMK1 are activated by chronic pressure-overload and by acute mechanical stretch. These data suggest that Src, BMK1 and p90RSK play a role as novel signal transduction pathways leading to cardiac hypertrophy. In addition, the differential inhibition of p90RSK and BMK1 in hearts with congestive heart failure suggests the specific role of these two kinases to maintain cardiac function under chronic pressure-overload.

Sarcoplasmic reticulum Ca(2+) atpase (SERCA) 1a structurally substitutes for SERCA2a in the cardiac sarcoplasmic reticulum and increases cardiac Ca(2+) handling capacity.

Ectopic expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) 1a pump in the mouse heart results in a 2.5-fold increase in total SERCA pump level. SERCA1a hearts show increased rates of contraction/relaxation and enhanced Ca(2+) transients; however, the cellular mechanisms underlying altered Ca(2+) handling in SERCA1a transgenic (TG) hearts are unknown. In this study, using confocal microscopy, we demonstrate that SERCA1a protein traffics to the cardiac SR and structurally substitutes for the endogenous SERCA2a isoform. SR Ca(2+) load measurements revealed that TG myocytes have significantly enhanced SR Ca(2+) load. Confocal line-scan images of field-stimulated SR Ca(2+) release showed an increased rate of Ca(2+) removal in TG myocytes. On the other hand, ryanodine receptor binding activity was decreased by approximately 30%. However, TG myocytes had a greater rate of spontaneous ryanodine receptor opening as measured by spark frequency. Whole-cell L-type Ca(2+) current density was reduced by approximately 50%, whereas the time course of inactivation was unchanged in TG myocytes. These studies provide important evidence that SERCA1a can substitute both structurally and functionally for SERCA2a in the heart and that SERCA1a overexpression can be used to enhance SR Ca(2+) transport and cardiac contractility.

Differential uptake of a smoking cessation programme disseminated to doctors and midwives in antenatal clinics.

AIMS: Two methods of dissemination (simple and intensive) were used to disseminate a smoking cessation programme to doctors and midwives working in antenatal clinics. This paper describes the differential uptake of the smoking cessation programme by doctors and midwives. It investigates whether the number of smoking cessation interventions used differ due to the type of dissemination. It also examines the frequency with which doctors and midwives provide smoking cessation interventions after dissemination. DESIGN: Clinics were randomized to the method of dissemination (simple or intensive). Pre-post test design was used to examine the relationship between dissemination method and professional status at baseline and follow-up. A baseline survey collected data on the use of smoking cessation intervention in the clinics prior to dissemination. A follow-up survey was conducted 18 months after the dissemination. SETTING: Twenty-three public hospital antenatal clinics in NSW. PARTICIPANTS: All clinical staff (midwives and doctors) working in the clinic during the 1-2-week survey period prior to dissemination and 18 months after the dissemination were asked to participate. The response rate was 63% (223) at baseline and 64% (182) at follow-up. Only 48% of midwives and doctors at follow-up were working in the original clinic. MEASURES: The proportion of clinicians who initially adopted the programme; the proportion of clinicians who had used one or more programme components in the last week); the number of types of smoking cessation intervention provided (maximum = 13), and the estimated proportion of clients offered smoking cessation intervention. FINDINGS: More midwives than doctors "ever used" the programme (76% vs. 25%) and continued to implement (58% vs. 22%) the programme 18 months after dissemination. Both midwives and doctors increased the number of types of smoking cessation intervention offered at follow-up compared to baseline (mean difference 2.8). Midwives provided more smoking cessation interventions than doctors at baseline (mean difference 0.9) and at follow-up (1.6), regardless of method used to disseminate the programme. Midwives' mean estimates of the proportion of clients offered interventions were greater than doctors' (midwives' 59% vs. doctors' 35%) at follow-up. CONCLUSION: The dissemination of a smoking cessation programme increased the level of smoking cessation interventions used by doctors and midwives. Doctors and midwives differ in their uptake of smoking cessation programmes. This information can be used to plan programme dissemination strategies in the future.

Interactional skills of students from traditional and non-traditional medical schools before and after alcohol education.

OBJECTIVE: To compare alcohol-related intervention and general interactional skills performance of medical students from a traditional (Sydney) and a non-traditional (Newcastle) medical school, before and after participation in an alcohol education programme about brief intervention. DESIGN: In two controlled trials, students received either a didactic alcohol education programme or didactic input plus skills-based training. Prior to and after training, all students completed videotaped interviews with simulated patients. SETTING: The Faculties of Medicine at the University of Newcastle and the University of Sydney, Australia. SUBJECTS: Fifth-year medical students (n=154). RESULTS: Both alcohol-related intervention and general interactional skills scores of the Newcastle students were significantly higher than those of the Sydney students at pre-test but not after training. Although alcohol-related interactional skills scores improved after training at both universities, they did not reach a satisfactory level. The educational approach used had no effect on post-test scores at either university. CONCLUSIONS: Significant baseline differences in interactional skills scores favouring non-traditional over traditional students were no longer evident after both groups had been involved in an alcohol education programme. Further research is required to develop more effective alcohol intervention training methods.

Preventive and other interactional skills of general practitioners, surgeons, and physicians: perceived competence and endorsement of postgraduate training.

BACKGROUND: Perceived competencies and support for formal postgraduate training across a range of preventive and other interactional skills were examined in three medical groups. METHODS: All eligible final year students and recent graduates of the three major Australian medical colleges (n = 767) were mailed a questionnaire examining communication skills in four domains: preventive, educational, therapeutic, and general. RESULTS: Overall consent rate was 45%. For most items, at least one-third of each group reported low competence. On preventive items, low competence ratings ranged from 5 to 39% in general practice, 38 to 67% in surgery, and 33 to 51% in the speciality physician group. Significant intergroup differences occurred on eight competence items. Agreement with training on preventive topics ranged from 80 to 91% in general practice, 48 to 69% in surgery, and 72 to 82% in the specialty physician group. On all 11 training items where significant differences occurred, the general practice group reported the highest level and the surgeon group the lowest level of endorsement for formal training and assessment. CONCLUSIONS: Substantial proportions in the general practice, surgery, and the physician specialty report lack of competence in common interactional skills. There were high levels of support for formal training in preventive and other interactional skills. The strong endorsement supports the development of effective, tailored interactional skills training programs.

Effect of angiotensin type I-receptor blockade on left ventricular remodeling in pressure overload hypertrophy.

BACKGROUND: The renin-angiotensin system is involved in cardiac remodeling. In contrast to the well-recognized salutary effects of angiotensin-converting enzyme inhibition, the value of angiotensin II type I (AT(1))-receptor blockade on left ventricular (LV) hypertrophy and dysfunction is controversial. METHODS AND RESULTS: Descending thoracic aorta-banded and sham-operated guinea pigs were given either losartan (30 mg x kg(-1) x day(-1) intraperitoneally) or vehicle for 8 weeks (n = 7 in each group). LV end-diastolic and end-systolic dimensions and wall thicknesses were measured echocardiographically, and LV fractional shortening, relative wall thickness, and LV mass normalized by body weight were calculated. Isolated heart function (Langendorff perfusion) was studied 8 weeks after surgery, and LV performance was assessed by maximum LV pressure and +/-dP/dt normalized by LV mass. Eight weeks after banding guinea pigs developed concentric LV hypertrophy and had decreased maximum LV pressure and +/-dP/dt normalized by LV mass; LV end-diastolic dimension and LV fractional shortening were unchanged. In band-operated guinea pigs treatment with losartan had no significant effects on any of these measurements. CONCLUSIONS: In guinea pigs with descending aortic banding, treatment with losartan for 8 weeks neither attenuates progression of pressure overload hypertrophy nor significantly improves impaired mass-normalized pressure-derived indices of LV contraction and relaxation.

Process measures in an antenatal smoking cessation trial: another part of the picture.

Data on provider and patient compliance can be crucial in understanding the degree of a health education program's effectiveness, as well as in identifying areas where the program requires modification. However, such data are rarely systematically reported in randomized trials. This report assesses the degree to which doctors and midwives complied with intervention protocols in a hospital antenatal smoking cessation trial, and also examines the program's acceptability to patients. Provider compliance was assessed principally via consultation audiotapes and provider-completed checklists. The audiotape analysis identified substantial compliance problems. For example, in relation to six specific smoking-related pregnancy risks, the proportions of Experimental Women informed about each individual risk ranged from 26 to 38% and the proportions receiving counselling items ranged from 52 to 79%. Doctors only informed a minority of Experimental Women of the increased risk of Sudden Infant Death Syndrome (28%) and of the presence of toxic chemicals in tobacco (21%). Comparison of compliance data from audiotapes and provider checklists revealed there was no significant agreement in three of four cases tested. Experimental Patients completed questionnaires to assess recall of smoking advice and to rate 12 program features. Of specific Experimental Program elements, the videotape (85%) received the highest level of positive patient ratings and the lottery (42%) the lowest. The process evaluation indicated that the Experimental Program needed some modification to increase its suitability for routine application. The findings also support the value of including an objective measure of provider compliance.

Disruption of a single copy of the SERCA2 gene results in altered Ca2+ homeostasis and cardiomyocyte function.

A mouse model carrying a null mutation in one copy of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase isoform 2 (SERCA2) gene, in which SERCA2 protein levels are reduced by approximately 35%, was used to investigate the effects of decreased SERCA2 level on intracellular Ca(2+) homeostasis and contractile properties in isolated cardiomyocytes. When compared with wild-type controls, SR Ca(2+) stores and Ca(2+) release in myocytes of SERCA2 heterozygous mice were decreased by approximately 40-60% and approximately 30-40%, respectively, and the rate of myocyte shortening and relengthening were each decreased by approximately 40%. However, the rate of Ca(2+) transient decline (tau) was not altered significantly, suggesting that compensation was occurring in the removal of Ca(2+) from the cytosol. Phospholamban, which inhibits SERCA2, was decreased by approximately 40% in heterozygous hearts, and basal phosphorylation of Ser-16 and Thr-17, which relieves the inhibition, was increased approximately 2- and 2.1-fold. These results indicate that reduced expression and increased phosphorylation of phospholamban provides compensation for decreased SERCA2 protein levels in heterozygous heart. Furthermore, both expression and current density of the sarcolemmal Na(+)-Ca(2+) exchanger were up-regulated. These results demonstrate that a decrease in SERCA2 levels can directly modify intracellular Ca(2+) homeostasis and myocyte contractility. However, the resulting deficit is partially compensated by alterations in phospholamban/SERCA2 interactions and by up-regulation of the Na(+)-Ca(2+) exchanger.