A randomised controlled trial of clinical outreach education to rationalise antibiotic prescribing for acute dental pain in the primary care setting.

OBJECTIVE: To assess the effect of educational outreach visits on antibiotic prescribing for acute dental pain in primary care. STUDY DESIGN: RCT. SETTING: General dental practices in four health authority areas in Wales. SUBJECTS AND METHODS: General dental practitioners were recruited to the study and randomly allocated to one of the three study groups (control group, guideline group or intervention group). Following the intervention, practitioners completed a standardised questionnaire for each patient that presented with acute dental pain. INTERVENTIONS: The control group received no intervention. The guideline group received educational material by post. The intervention group received educational material by post and an academic detailing visit by a trained pharmacist. The educational material included evidence-based guidelines on prescribing for acute dental pain and patient information leaflets. MAIN OUTCOME MEASURES: The number of antibiotic prescriptions issued to patients presenting with dental pain and the number of 'inappropriate' antibiotic prescriptions. Antibiotics were considered to be inappropriate if the patient did not have symptoms indicative of spreading infection. RESULTS: A total of 1,497 completed questionnaires were received from 23, 20 and 27 general dental practitioners in the control, guideline and intervention group respectively. Patients in the intervention group received significantly fewer antibiotic prescriptions than patients in the control group (OR (95% CI) 0.63 (0.41, 0.95)) and significantly fewer inappropriate antibiotic prescriptions (OR (95% CI) 0.33 (0.21, 0.54)). However, antibiotic and inappropriate antibiotic prescribing were not significantly different in the guideline group compared to the control group (OR (95% CI) 0.83 (0.55, 1.21) and OR (95% CI) 0.82 (0.53, 1.29) respectively). CONCLUSIONS: Strategies based upon educational outreach visits may be successfully employed to rationalise antibiotic prescribing by dental practitioners.

Ibuprofen versus other non-steroidal anti-inflammatory drugs: use in general practice and patient perception.

OBJECTIVE: To investigate whether ibuprofen was as well-regarded by patients as other non-steroidal anti-inflammatory drugs (NSAIDs). DESIGN: Questionnaire sent to 1137 consecutive recipients of an NSAID prescription from 21 doctors in six general practices with computerized records. Patient responses were subsequently linked to data held on the practice records. SETTING: General practices in and around Nottingham, selected to reflect local variations in number of partners, list size, geographical location, deprivation, prescribing burden and prescribing rate. SUBJECTS: Unselected patients receiving NSAIDs prescribed for all indications for use. MAIN OUTCOME MEASURES: Effectiveness of ibuprofen and other NSAIDs, possible drug related adverse events, patients' overall satisfaction with ibuprofen and other NSAIDs, factors associated with choice of ibuprofen, drug costs of ibuprofen and other NSAIDs. RESULTS: The main NSAIDs used were ibuprofen, diclofenac and naproxen. Ibuprofen use ranged from 1.0% of prescriptions in one practice to 69.1% in another. Although ibuprofen was generally prescribed in low doses, it was perceived by patients as being as effective as the other NSAIDs used, even after allowing for severity of the pre-treatment condition. Overall, 50.5% of patients rated their NSAID the best treatment they had received for their condition with no differences between individual drugs. CONCLUSIONS: Ibuprofen is as highly regarded as other NSAIDs when used in similar circumstances. Switching patients to ibuprofen may be a realistic way of reducing financial and medical costs associated with NSAIDs.

Pharmacoepidemiology of non-steroidal anti-inflammatory drug use in Nottingham general practices.

AIM: To investigate the pharmacoepidemiology of NSAID usage in Nottingham general practices. DESIGN: Questionnaire sent to 1137 consecutive recipients of an NSAID prescription from 21 doctors in six general practices with computerized records. Patient responses were subsequently linked to data held on the practice records. SETTING: General practices in and around Nottingham, selected to reflect local variations in number of partners, list size, geographical location, deprivation, prescribing burden and prescribing rate. SUBJECTS: Unselected patients receiving NSAIDs prescribed for all indications. MAIN OUTCOME MEASURES: Indication for treatment, differences in prescribing to different age groups, compliance and overall scheme drug exposure, drug effectiveness and tolerability, possible drug-related adverse events, patients' overall satisfaction with treatment and estimated costs of care. RESULTS: NSAIDs were used for a wide range of conditions and only a small number of patients had rheumatoid arthritis. The main drugs used were ibuprofen, diclofenac and naproxen. Patients making short-term use of NSAIDs had low compliance if they experienced adverse drug effects, whilst conversely in long-term users, those with high compliance reported more adverse drug effects. Calculated compliance did not vary with age although older patients (over 65 years) claimed in their questionnaires to be more compliant than younger patients. Half the patients reported good or complete symptom relief. Half of those questions (and two thirds of those with good or complete symptom relief) rated their NSAID as the best treatment they had received for their current condition. The frequency of gastrointestinal adverse events was higher in the young and the old, which correlated with the use of anti-ulcer drugs, and increased with the total number of medications used. CONCLUSIONS: NSAIDs are used for a wide-range of conditions. They give symptom relief to, and are perceived as effective by, most patients taking them.

Importance of inositol (1,4,5)-trisphosphate, intracellular Ca2+ release and myofilament Ca2+ sensitization in 5-hydroxytryptamine-evoked contraction of rabbit mesenteric artery.

1. Small strips from third-order branches of rabbit mesenteric artery (approximately 150-200 microM wide) contracted in response to noradrenaline (10 microM) or 5-hydroxytryptamine (5-HT; 10 microM) in oxygenated Krebs solution containing 2.5 mM Ca2+. In a Ca(2+)-free mock intracellular solution (0 Ca2+ plus 0.2 mM EGTA), noradrenaline (10 microM) and caffeine (10 mM) induced only a single, transient contraction in artery strips, while 5-HT (10 microM) failed to induce any response. 2. In strips of mesenteric artery which had been permeabilized with Staphylococcus alpha-toxin and bathed in Ca(2+)-free mock intracellular solution, noradrenaline (10 microM), caffeine (10 mM) and D-myo-inositol (1,4,5)-trisphosphate (IP3, 100 microM), but not 5-HT (10 or 100 microM) induced a transient contraction. In contrast to the non-permeabilized strips, contractions to noradrenaline, caffeine and IP3 were restored by prior incubation (10 min) in solution containing 0.08 microM Ca2+. The contractions to noradrenaline and IP3 in permeabilized muscle strips required the presence of 100 microM guanosine 5'-triphosphate (GTP), although in the absence of Ca2+. GTP alone did not induce contraction. 3. Exposure of permeabilized mesenteric artery strips to IP3 significantly reduced the subsequent contractile responses to caffeine. Contractile responses to caffeine and IP3 were abolished by the Ca(2+)-ATPase inhibitor, thapsigargin (1 microM). 4. Ca2+ (0.1-10 microM) induced concentration-dependent contraction in permeabilized artery strips. In strips which were submaximally contracted with 0.5 microM Ca2+/100 microM GTP, the subsequent addition of 5-HT (10 microM) stimulated further contraction. The protein kinase C inhibitor, H-7 (1 microM) abolished the 5-HT/GTP-induced contraction, but did not alter the contraction to Ca2+. 5. In non-permeabilized, endothelium-denuded segments of rabbit mesenteric artery bathed in Ca2+-replete Krebs solution, noradrenaline (10 microM) stimulated a rapid, transient accumulation of IP3. 5-HT(100 microM) failed to stimulate IP3 accumulation during exposure periods of up to 5 min. 5-HT (100 microM)did stimulate IP3 accumulation if the external K+ concentration was raised (to around 25 mM). This concentration of K+ alone did not stimulate IP3 production and the 5-HT-stimulated IP3 accumulation in the presence of elevated extracellular [K+] was abolished by the alpha l-adrenoceptor antagonist, prazosin(O.1 microM).6. These results suggest that intracellular Ca2+ release does not play an important role in 5-HT-induced smooth muscle contraction in the rabbit mesenteric artery. This is despite the fact that a significant intracellular Ca2+ pool is present in these cells, which can be discharged by either noradrenaline or IP3.However, 5-HT did stimulate smooth muscle contraction in the presence of raised intracellular calcium,suggesting that a component of the contraction to 5-HT will reflect an increase in myofilament Ca2+sensitivity, possibly due to the activation of protein kinase C.

Endothelium-dependent contractile responses to 5-hydroxytryptamine in the rabbit basilar artery.

1 5-Hydroxytryptamine (5-HT) and 5-carboxamidotryptamine (5-CT) stimulated additional, endothelium-dependent contractions in rabbit isolated basilar arteries which had been submaximally contracted with either histamine or potassium chloride. 2 The additional contractions to 5-HT were not altered by the 5-HT2 antagonist, ketanserin (1 microM), but were abolished in the presence of the cyclo-oxygenase inhibitor indomethacin (3 microM). 3 The additional smooth muscle contraction stimulated by 5-HT was increased in the presence of the competitive substrate inhibitor for nitric oxide synthase, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). 4 Neither of the selective 5-HT agonists, 8-hydroxy-dipropylaminotetralin (8-OH DPAT) or alpha-methyl 5-HT stimulated endothelium-dependent contraction, but these agonists did reduce the rate at which histamine-induced tension spontaneously declined. This effect represented a direct action on the smooth muscle cells, as it was independent of the presence of endothelial cells. 5 Smooth muscle relaxation was not obtained in response to 5-HT, whether or not indomethacin was present to block endothelium-dependent contraction. None of the other selective 5-HT agonists, 5-CT, 8-OH DPAT or alpha-methyl 5-HT produced endothelium-dependent smooth muscle relaxation, when applied against a background of contraction. 6 These data show that endothelium-dependent smooth muscle contraction can be produced by stimulating 5-HT receptors in the partially contracted rabbit basilar artery. Similar contraction to 5-CT indicates an involvement by 5-HT1 receptors. The susceptibility of the contractions to indomethacin suggest they are mediated by a metabolite of arachidonic acid.