A change of heart: the new infective endocarditis prophylaxis guidelines.

New Australian guidelines for the prevention of infective endocarditis were published in July 2008. The guidelines were revised by a multidisciplinary group to reflect recent changes in international recommendations regarding antibiotic prophylaxis for infective endocarditis. The reasons for the changes are explored in this review and the implications for dental practice are discussed.

Intern Prescribing for Common Clinical Conditions.

To examine the ability of interns to prescribe appropriately for common clinical conditions at the commencement and completion of the intern year. Interns' perceptions of their ability to prescribe and the perceived influences on their practices were also assessed. The study was conducted at a teaching hospital in urban New South Wales, Australia. A self-complete questionnaire was administered to 56 interns at the beginning and end of internship. At the beginning of the year respondents were asked to identify how equipped they felt they were to perform specific functions related to prescribing practice. Interns were also asked to write hospital prescriptions for four common clinical cases scenarios: post-operative pain, urinary tract infection, asthma, and community-acquired pneumonia. At the end of the year interns were asked to prescribe for the same clinical scenarios and also asked to identify the main influences on their practice. At the beginning of the year 54% of interns felt equipped to choose an appropriate drug for common clinical conditions, however, few felt they were able to determine the appropriate dose (23% of respondents) or dose frequency (25%). A previously validated four-point rating scale was used by two assessors to judge appropriateness of prescribing [Kappa = 0.6]. At the beginning of the year at least two-thirds of interns were prescribing 'inappropriately' for all clinical conditions. By the end of the year 75% were prescribing 'appropriately' for all conditions. The main perceived influences on prescribing practices were registrars, consultants, books and pharmacists.The use of hypothetical clinical cases to explore prescribing ability has shown that doctors are ill-equipped to perform various aspects of prescribing on graduating from medical school. Although our findings may not translate into practice directly they highlight the existence of a potential problem that warrants further study, especially in the areas of actual practice and the influences on it in the early postgraduate years.

Intracellular Ca2+ and contractile responses to alpha 1-adrenoceptor subtype activation in rat aortic vascular smooth muscle.

To simultaneously and rapidly measure intracellular Ca2+ concentration ([Ca2+]i) and contraction in vascular smooth muscle, the Ca2+ fluorophore, fura-2/acetoxymethyl ester, was incorporated into an intact sample of rat aorta. Noradrenaline produced a biphasic [Ca2+]i response (phase-1 and phase-2) which was different to the monophasic contractile response. Phase-1 of the [Ca2+]i response was a large, fast, transient increase which usually clearly preceded contraction. Phase-2 of the [Ca2+]i response was slower, peaked between 20-40 s after addition of noradrenaline, and often subsequently declined whilst contraction continued to increase. Contraction followed phase-2 of the [Ca2+]i response to noradrenaline more closely than phase-1. WB 4101 (alpha 1A-adrenoceptor antagonist) produced a major reduction in phase-1 of the [Ca2+]i response to noradrenaline, a lesser reduction of phase-2 of the [Ca2+]i response to noradrenaline and least reduction of contraction. Chlorethylclonidine (alpha 1B-adrenoceptor antagonist) reduced phase-1 and phase-2 of the [Ca2+]i response and contraction to noradrenaline to a similar degree. We conclude that noradrenaline produces a biphasic [Ca2+]i increase and that neither alpha 1-adrenoceptor subtype is specifically linked to phase-1 or phase-2 of the [Ca2+]i response to noradrenaline in the rat aorta. However, selective alpha 1B-adrenoceptor activation shows a higher force/[Ca2+]i relationship in comparison to alpha 1A-adrenoceptor activation.

Hospitalisation for adverse events related to drug therapy: incidence, avoidability and costs.

OBJECTIVES: To determine the incidence of hospital admissions for adverse events related to drug therapy, and to assess whether these drug-related admissions (DRAs) could have been reasonably prevented. SETTING: A tertiary teaching hospital. DESIGN AND PATIENTS: Prospective assessment of all admissions through the emergency department and resulting in a stay of more than 24 hours during 30 consecutive days in November and December 1994 to determine if the admission was related to drug therapy. Cases of intentional overdose were excluded. MAIN OUTCOME MEASURES: The number, type, causality and avoidability of drug-related admissions. RESULTS: Of 965 admissions, 55 (5.7%) were assessed as being drug-related. Drug-related admissions (DRAs) were designated possibly (38%), probably (46%) or definitely (16%) drug-related; caused by prescribing factors (26%), patient noncompliance (27%) and adverse drug reactions (47%); and classified as definitely (5.5%), possibly (60.0%) and not (34.5%) avoidable. The estimated annual cost to the hospital for all DRAs was $3,496,956 and for unavoidable DRAs was $1,629,494. CONCLUSION: The DRA rate we found lies around the middle of the range of other published rates. Few DRAs were judged definitely avoidable and over one-third were unavoidable. Nevertheless, the largest proportion were judged possibly avoidable. As the drugs identified in this study are clearly needed in the community, efforts to reduce DRAs must concentrate on education, counselling and monitoring of drug therapy.

Relationship between nifedipine sensitivity of aortae and blood pressure of stroke-prone spontaneously hypertensive rats.

1. We have previously described an increased sensitivity to inhibition by nifedipine of noradrenaline-induced contractures of blood vessels in hypertension. In this study we have investigated whether changes in blood pressure (BP) change the sensitivity to nifedipine and K+ of aortic rings from normotensive (Wistar-Kyoto rats, WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). 2. SHRSP were treated with: hydralazine plus hydrochlorothiazide; captopril plus hydrochlorothiazide; hydralazine plus guanethidine; or captopril alone. WKY rats were treated with deoxycorticosterone acetate (DOCA) and NaCl. Treatment commenced from 5 weeks of age and continued until 13-15 weeks. 3. The SHRSP treatments produced similar reductions in BP, and the BP of all the treated groups were significantly lower than the mean BP of untreated SHRSP (201.0 +/- 7.7 mmHg). The mean BP of the treated WKY rats (134.2 +/- 7.6 mmHg) was significantly higher than the mean BP of the untreated WKY rats (86.8 +/- 7.4 mmHg). 4. An area-under-curve (AUC) analysis of the inhibitory effects of nifedipine on responses of aortae to noradrenaline showed no differences between treated and untreated SHRSP groups (overall mean 40.6 +/- 1.9% and 43.4 +/- 3.4% inhibition of control AUC, respectively), or between DOCA-salt treated WKY and untreated WKY groups (58.8 +/- 5.9 and 64.8 +/- 2.3, respectively). Noradrenaline-induced contractures of aortae from all SHRSP groups were significantly more sensitive to inhibition by nifedipine than aortae from both WKY groups. 5. The molar concentration of agonist required to evoke 50% of the maximum response (EC50) values for potassium chloride (KCl) were significantly increased in the aortae of all treated SHRSP groups in comparison to those from untreated SHRSP (treated SHRSP groups, 15.53 +/- 0.68 mmol/L vs untreated SHRSP group, 11.36 +/- 1.10 mmol/L). The EC50 values for KCl for the aortae from the DOCA-treated WKY rats were significantly less than those from aortae of the untreated WKY (11.80 +/- 0.80 and 17.08 +/- 1.50 mmol/L, respectively). 6. We conclude that reduction (in SHRSP) or increase (in WKY) of the BP has no effect on the sensitivity of aortic smooth muscle to the inhibitory effects of nifedipine on responses to noradrenaline, suggesting that alterations in voltage-dependent Ca2+ mechanisms may be a primary phenomenon in the SHRSP. In contrast, the fact that sensitivity to KCl changes in the treated SHRSP and WKY aortae suggests such sensitivity is secondary to the BP and thus a separate phenomenon from voltage-dependent Ca2+ mechanisms.

Increased sensitivity to inhibition by nifedipine of responses of the mesenteric artery bed of the SHRSP to noradrenaline is not dependent on alpha 1-adrenoceptor subtypes.

The effects of noradrenaline (NA) on the perfusion pressure of mesenteric vascular bed preparations from stroke-prone spontaneously hypertensive rats (SHRSP) or weight-matched normotensive Wistar-Kyoto (WKY) rats in the presence of chloroethylclonidine (CEC, alpha 1B-adrenoceptor antagonist) or WB4101 (WB, alpha 1A-adrenoceptor antagonist), with or without the addition of nifedipine, were studied. NA caused a greater maximum increase in the perfusion pressure of the SHRSP mesenteric bed than that of the WKY, and the EC50 for NA was lower in the SHRSP. There was no difference between the normotensive or hypertensive beds in the reduction of responses to NA produced by WB or CEC. Nifedipine, in the presence of either CEC or WB, further reduced responses to NA, but to a significantly greater extent in the SHRSP than in the WKY. There was no difference within either group between the additional inhibitory effect of nifedipine in combination with CEC or WB. These results confirm that following alpha 1-adrenoceptor subtype blockade, the response to NA by the mesenteric bed of the SHRSP is more sensitive to inhibition by nifedipine than its WKY counterpart. However, the increased sensitivity to the inhibitory effects of nifedipine on responses to NA is not a result of preferential linkage of Ca2+ entry mechanisms to one or other of the alpha 1-adrenoceptor subtypes.

The difference in nifedipine sensitivity between hypertensive and normotensive rat aortae is dependent on age.

1. In order to investigate further whether the increased sensitivity to inhibition by nifedipine of the responses to noradrenaline of aortae from spontaneously hypertensive stroke-prone (SHRSP) rats is related to the development of the hypertension, we have compared the sensitivity to noradrenaline, potassium chloride (KCl) and nifedipine of aortae from SHRSP and control (Wistar-Kyoto) WKY rats of different age groups (young: 3-5 weeks, and adult: 13-16 weeks). 2. The sensitivity to KCl was found to be less in the aortae from the adult WKY group than in any of the other three groups. Responses to noradrenaline of the adult WKY aortae were also less sensitive to inhibition by nifedipine in comparison to each of the other three groups. 3. The changes in sensitivity were not due to the changes in the populations of alpha 1-adrenoceptor subtypes as responses of the adult SHRSP aortae to noradrenaline were more sensitive to nifedipine in the presence of either the alpha 1-adrenoceptor subtype antagonists chloroethylclonidine or WB4101 than were those of the adult WKY aortae, but aortae from the young SHRSP were not. 4. These results suggest that, rather than the SHRSP aorta becoming more sensitive to nifedipine and potassium depolarization as hypertension develops, it is the WKY aorta that becomes more resistant as it matures.

Prescriber guidelines improve initiation of anticoagulation.

OBJECTIVES: To improve the initiation of anticoagulation in patients with thrombotic disorders. DESIGN AND SETTING: We carried out a preliminary audit in 1991, developed and implemented strategies to address identified problems, and followed up with another audit in 1993. Medical records of inpatients at The Royal Melbourne Hospital whose anticoagulation therapy was initiated with heparin (intravenous) in therapeutic doses and subsequently converted to warfarin were prospectively assessed over 19-day periods. INTERVENTION: Pocket-sized laminated prescriber guidelines for initiating anticoagulation were disseminated after publishing the results of the first audit, together with a single prominent display of two posters in series advocating the use of the guidelines. RESULTS: The audits identified 25 eligible patients in 1991 and 27 in 1993. The mean duration of intravenous heparin therapy was reduced from 150 hours in 1991 to 97 hours in 1993 (P < 0.002). The mean delay before initiating warfarin therapy after starting heparin therapy was reduced from 69 hours in 1991 to 21 hours in 1993 (P < 0.002). The mean percentage of time the activated partial thromboplastin time was within the therapeutic range increased from 30% in 1991 to 44% in 1993 (P < 0.05) and was above the therapeutic range increased from 13% in 1991 to 24% in 1993 (P < 0.01). Although the number of adverse events was too small to draw definitive conclusions, no difference in adverse haemorrhagic effects was noted between the 1991 and 1993 groups. CONCLUSION: There was an improvement in the initiation of anticoagulation and we hypothesise that this was most likely due to a broad acceptance of the guidelines into clinical practice.

Assessment of general practitioners' management of hyperlipidaemia. A study using personal visits and a scenario-based questionnaire.

In summary our study has looked at the current management practices of hyperlipidaemia by general practitioners in an innovative way. Our results suggest that most GPs are managing this condition appropriately. Where their management differs from current guidelines is mainly in introducing medication early. We obtained significantly lower participation rates in the metropolitan as compared with the regional and rural areas, but we found no significant differences in the overall assessment of appropriate management between the different geographical regions of Victoria.

Improving the quality of antibiotic prescription patterns in general practice. The role of educational intervention.

OBJECTIVE: To assess the quality of antibiotic prescribing by Victorian general practitioners, and the effectiveness of educational intervention techniques in improving prescribing. DESIGN: A randomised, controlled, parallel group trial. SETTING AND PARTICIPANTS: In rural and metropolitan Victoria, 182 general practitioners (78 control, 104 intervention) began and 103 (41 control, 62 intervention) completed the study. INTERVENTION: Participants recorded their antibiotic prescribing for tonsillitis. The intervention group received an educational mailing campaign. A project pharmacist visited each doctor to discuss campaign messages. MAIN OUTCOME MEASURE: The percentages of prescriptions of antibiotics for tonsillitis complying with those recommended in Antibiotic guidelines. RESULTS: In the intervention group, prescriptions consistent with recommendations in the guidelines increased from 60.5% before the campaign to 87.7% afterwards. Improvement also occurred in the control group, from 52.9% to 71.7% of prescriptions. The improvement within the intervention group was significantly greater than that within the control group. CONCLUSIONS: The educational campaign significantly improved the prescribing of appropriate antibiotics for tonsillitis by general practitioners.

Effects of fentanyl on the rat aorta are mediated by alpha-adrenoceptors rather than by the endothelium.

We have assessed if fentanyl interacts with the endothelium to affect vessel tone. In the presence or absence of endothelium, fentanyl in concentrations greater than 10(-7) mol litre-1 decreased the sensitivity of the rat aortic rings to phenylephrine, but fentanyl in smaller concentrations had no significant effect. Rings, with or without endothelium, and pre-contracted by phenylephrine were relaxed by fentanyl, and this relaxation was not inhibited by the opioid receptor antagonist, naloxone. Pretreatment of the rings with either fentanyl or phentolamine protected alpha-adrenoceptors from block by the alpha-adrenoceptor antagonist, phenoxybenzamine. We conclude that, in the rat aorta, fentanyl-induced relaxation was mediated by alpha-adrenergic receptors, and that the endothelium modulated, but did not mediate, this relaxation.

Sufentanil and alfentanil cause vasorelaxation by mechanisms independent of the endothelium.

1. The aim of these experiments was to determine if the vasorelaxation of the rat isolated aorta induced by sufentanil or alfentanil is mediated by the endothelium, and, if not, by alpha-adrenoceptor blockade, or a direct effect on the smooth muscle. 2. Both sufentanil (from 10(-7) mol/L to 10(-4) mol/L) and alfentanil (from 10(-7) mol/L to 3 x 10(-4) mol/L) relaxed rings, where endothelium was intact and precontracted with 40 mmol/L KCl, in a concentration-related manner. Similarly, sufentanil and alfentanil relaxed rings, in the presence or absence of endothelium, which had been precontracted with phenylephrine. 3. Naloxone (10(-4) mol/L) had no significant effect on the relaxation induced by either sufentanil or alfentanil. 4. In a similar manner as phentolamine, pretreatment with sufentanil protected alpha-adrenoceptors from blockade by phenoxybenzamine (PBZ) in both endothelium intact and denuded rings, but the estimated potency of sufentanil was approximately 100-fold less than that of phentolamine in alpha-adrenoceptor protection. Treatment with alfentanil did not produce any receptor protection. 5. We concluded that, in the rat aorta, vascular relaxation induced by sufentanil is mediated by both alpha-adrenoceptor blockade and a direct effect on smooth muscle, whilst the relaxant effect of alfentanil is caused by direct effects alone. We also concluded that the endothelium has little role in relaxation produced by either drug.