Community pharmacists-Leaders for antibiotic stewardship in respiratory tract infection.

WHAT IS KNOWN AND OBJECTIVE: Hospital-based pharmacists are established antibiotic stewards, but the potential for community pharmacists is largely untapped. This commentary explores the potential leadership role of the community pharmacist in antibiotic stewardship using upper respiratory tract infection (URTI) as an example. COMMENT: Community pharmacists are well placed for antibiotic stewardship, possessing the capability (knowledge of medicines), opportunity (contact with prescribers and patients) and inherent commitment. Providing further motivation with information on patient education has great potential to change patient behaviour with respect to consulting a healthcare professional for an antibiotic prescription. A Global Respiratory Infection Partnership pharmacy-led educational initiative was shown to have a positive impact and can promote appropriate self-management of URTI and reduce levels of inappropriate antibiotic use. WHAT IS NEW AND CONCLUSION: Community pharmacists are ideally placed as antibiotic stewards to lead the quest to contain the threat of antibiotic resistance.

Randomised, double-blind, placebo-controlled studies on flurbiprofen 8.75 mg lozenges in patients with/without group A or C streptococcal throat infection, with an assessment of clinicians' prediction of 'strep throat'.

BACKGROUND: Diagnosing group A streptococcus (Strep A) throat infection by clinical examination is difficult, and misdiagnosis may lead to inappropriate antibiotic use. Most patients with sore throat seek symptom relief rather than antibiotics, therefore, therapies that relieve symptoms should be recommended to patients. We report two clinical trials on the efficacy and safety of flurbiprofen 8.75 mg lozenge in patients with and without streptococcal sore throat. METHODS: The studies enrolled adults with moderate-to-severe throat symptoms (sore throat pain, difficulty swallowing and swollen throat) and a diagnosis of pharyngitis. The practitioner assessed the likelihood of Strep A infection based on historical and clinical findings. Patients were randomised to flurbiprofen 8.75 mg or placebo lozenges under double-blind conditions and reported the three throat symptoms at baseline and at regular intervals over 24 h. RESULTS: A total of 402 patients received study medication (n = 203 flurbiprofen, n = 199 placebo). Throat culture identified Strep A in 10.0% of patients and group C streptococcus (Strep C) in a further 14.0%. The practitioners' assessments correctly diagnosed Strep A in 11/40 cases (sensitivity 27.5%, and specificity 79.7%). A single flurbiprofen lozenge provided significantly greater relief than placebo for all three throat symptoms, lasting 3-4 h for patients with and without Strep A/C. Multiple doses of flurbiprofen lozenges over 24 h also led to symptom relief, although not statistically significant in the Strep A/C group. There were no serious adverse events. CONCLUSIONS: The results highlight the challenge of identifying Strep A based on clinical features. With the growing problem of antibiotic resistance, non-antibiotic treatments should be considered. As demonstrated here, flurbiprofen 8.75 mg lozenges are an effective therapeutic option, providing immediate and long-lasting symptom relief in patients with and without Strep A/C infection.

Corticosterone Contributes to Diet-Induced Reprogramming of Post-Metamorphic Behavior in Spadefoot Toads.

Stressful experiences in early life can have phenotypic effects that persist into, or manifest during, adulthood. In vertebrates, such carryover effects can be driven by stress-induced secretion of glucocorticoid hormones, such as corticosterone, which can lead to developmental reprogramming of hypothalamic-pituitary-adrenal/interrenal axis activity and behavior. Nutritional stress in the form of early life nutrient restriction is well known to modify later life behaviors and stress activity through corticosterone-related mechanisms. However, it is not known whether corticosterone is also mechanistically involved in carryover effects induced by a different form of nutritional variation: the use of alternate or entirely novel types of dietary resources. The plains spadefoot (Spea bombifrons) presents an excellent system for testing this question, since larvae of this species have evolved to use 2 alternate diet types: an ancestral detritus-based diet and a more novel diet of live shrimp. While previous work has shown that feeding on the novel shrimp diet influences juvenile (i.e., post-metamorphic) behavior and corticosterone levels, it is unclear whether these diet-induced carryover effects are mediated by diet-induced corticosterone itself. To test for the mechanistic role of corticosterone in diet-induced carryover effects, we experimentally treated S. bombifrons larvae with exogenous corticosterone and measured subsequent effects on juvenile behavior and corticosterone levels. We found that while shrimp-fed larvae had elevated corticosterone levels, treatment of larvae with corticosterone itself had effects on juvenile behavior that partially resembled those carryover effects induced by the shrimp diet, such as altered food seeking and higher locomotor activity. However, unlike carryover effects caused by the shrimp diet, larval corticosterone exposure did not affect juvenile corticosterone levels. Overall, our study shows that corticosterone-related mechanisms are likely involved in carryover effects induced by a novel diet, yet such diet-induced carryover effects are not driven by corticosterone alone.

Rapid relief of acute sore throat with AMC/DCBA throat lozenges: randomised controlled trial.

AIM: As antibiotics are generally not recommended for the treatment of acute sore throat, the availability of clinically efficacious, over-the-counter (OTC) treatment alternatives is becoming increasingly important. This study was designed to determine the analgesic properties of amylmetacresol and 2,4-dichlorobenzyl alcohol (AMC/DCBA) throat lozenges (Strepsils) in the relief of acute sore throat caused by upper respiratory tract infections. METHODS: Patients (n = 310) were randomly assigned to receive AMC/DCBA throat lozenges (n = 155) or non-medicated placebo lozenges (n = 155). After baseline assessments, patients completed three rating assessments at 10 timepoints from 5 to 20 min after first dose. Subsequent lozenges were taken as required, and assessments were made at the end of Day 1, 24 h after first dose, and at the end of Days 2 and 3. Analgesic properties were assessed by comparing severity of throat soreness and sore throat relief ratings. Difficulty in swallowing and functional impairment scores were also assessed. RESULTS: Amylmetacresol/DCBA throat lozenges reduced throat soreness at 5 min after first dose, which persisted for 2 h and was significantly different vs. non-medicated lozenges at all assessment timepoints for the duration of the 3-day study. Similar significant effects were observed with sore throat relief, easing of difficulty with swallowing and functional impairment scores. There were no differences in adverse events reported between treatment groups. CONCLUSION: Amylmetacresol/DCBA throat lozenges provide rapid analgesic effects that last for 2 h, providing ongoing relief long after the lozenge has dissolved. The superior analgesic effects and improvements in functional impairment scores observed with AMC/DCBA throat lozenges translate into pain relief benefits that are clinically meaningful and are thus a suitable OTC treatment option for patients in the self-management of acute sore throat.

Scintigraphy can be used to compare delivery of sore throat formulations.

AIMS: Sore throat (pharyngitis) is commonly treated with over-the-counter lozenges, tablets, sprays and gargles. While the efficacy of the active ingredients has been examined, less is known about the comparative efficacy of the different delivery formats. METHODS: A pilot study was initially performed, followed by an open-label, four-way crossover study in healthy volunteers to quantitatively assess the delivery efficacy of a lozenge, tablet, spray and gargle, using technetium-99m and scintigraphy as a marker of deposition and clearance of the active ingredients. RESULTS: Initial deposition in the mouth and throat combined was significantly greater for the solid dose forms (lozenge and tablet) than for the spray or gargle. Rates of clearance were initially similar for the tablet and lozenge with low levels of radioactivity present at up to 2 h. At 10 and 20 min, significantly more of the dose remained for the lozenge than for the tablet. The mouth appeared to act as a reservoir for continued clearance to the throat. DISCUSSION AND CONCLUSION: Scintigraphy is an effective means of quantifying the delivery efficiency, and hence availability, of sore throat medications. The results presented here suggest that both lozenges and tablets offer considerable advantages over sprays or gargles, both in terms of proportion of the dose delivered to the mouth and throat, combined, and clearance from these regions. These delivery formats provide fast, effective and prolonged delivery of active ingredients, highlighting their potential benefits for sore throat medication.

Field testing of decision coaching with a decision aid for parents facing extreme prematurity.

OBJECTIVE: The objective of this study is to assess and modify an existing decision aid and field-test decision coaching with the modified aid during consultations with parents facing potential delivery at 23 to 24 weeks gestation. STUDY DESIGN: International Patient Decision Aid Standards instrument (IPDASi) scoring deficits, multi-stakeholder group feedback and α-testing guided modifications. Feasibility/acceptability were assessed. The Decisional Conflict Scale was used to measure participants' decisional conflict before (T1) and immediately after (T2) the consultation. RESULTS: IPDASi assessment of the existing aid (score 11/35) indicated it required updated data, more information and a palliative care description. Following modification, IPDASi score increased to 26/35. Twenty subjects (12 pregnancies) participated in field-testing; 15 completed all questionnaires. Most participants (89%) would definitely recommend this form of consultation. Decisional conflict scores decreased (P<0.001) between T1 (52±25) and T2 (10±16). CONCLUSION: Field testing demonstrated that consultations using the aid with decision coaching were feasible, reduced decisional conflict and may facilitate shared decision-making.

Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension.

Two multicenter, double-blind, placebo-controlled, parallel group studies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist irbesartan. The effect of irbesartan withdrawal and the effect of adding hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) orally once daily. Irbesartan reduced blood pressure in a dose-related manner. Reductions from baseline in trough seated diastolic blood pressure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg irbesartan. At week 8, statistically significant reductions over placebo were observed in trough seated blood pressure with all irbesartan doses > or = 50 mg. These reductions reached statistical significance versus placebo within 2 weeks with 100, 200, and 300 mg irbesartan. Plasma irbesartan concentrations correlated with dose. Angiotensin II and aldosterone levels generally showed dose-related changes, consistent with AT1 receptor blockade. In patients not controlled at 8 weeks, the addition of 12.5 mg HCTZ resulted in further dose-related reductions in blood pressure. Irbesartan demonstrated a placebo-like safety profile and no dose-related toxicity. Irbesartan, administered alone or in combination with HCTZ, was well tolerated. Withdrawal of irbesartan did not result in rebound hypertension or adverse events. Thus, once-daily irbesartan is both an effective and safe antihypertensive agent for the treatment of mild-to-moderate hypertension.

Moisture induced solid phase degradation of l-ascorbic acid Part 1: a kinetic study using tristimulus colorimetry and a quantitative HPLC assay.

l-Ascorbic acid was found to degrade in the solid phase with discoloration under the influence of moisture in proportion to the moisture content. This degradation pattern was different to that in solution and followed zero order kinetics. The exclusion of air reduced the rate of reaction suggesting the degradation may proceed via an oxidative route but no evidence was found for the presence of dehydroascorbic acid. A method was developed for the determination of dehydroascorbic acid using an automated precolumn reduction reaction with dl-dithiothreitol. The degradation was found to be zero order and activation energy was been measured at 37.57 kJ mol(-1) by high performance liquid chromotography (HPLC) assay and 33.30 kJ mol(-1) by tristimulus colorimetry, resulting in a 12.8% difference between the two methods. Tristimulus colorimetry was more sensitive to the onset of degradation than HPLC assay, but it is non-specific. The purpose of this study was to obtain kinetic data on the rate of degradation of l-ascorbic acid alone under the influence of moisture and air and to identify whether tristimulus colorimetry could be used as a rapid and non-destructive means of monitoring for the degradation of l-ascorbic acid in the solid phase. Further studies to determine the degradation pathway and to identify the degradation products are to be reported in subsequent papers.

Moisture induced solid phase degradation of l-ascorbic acid part 2, separation and characterization of the major degradation products.

The influence of moisture in the presence and absence of air on the solid state degradation of l-ascorbic acid has been investigated previously [1]. Reaction kinetics were studied using tristimulus colorimetry and a quantitative high performance liquid chromatographic assay for both total l-ascorbic acid and dehydroascorbic acid. The degradation gave rise to a discolouration of the samples, the most severely degraded samples were almost black in appearance although over 68% w/w of the l-ascorbic acid remained. The samples were analyzed for the presence of carbonyl compounds, furan related compounds, compounds responsible for the discolouration and evolution of carbon dioxide. No 2,4-dinitrophenylhydrazine (2,4-DNP) derivatives of carbonyl compounds or furan related compounds were detected by HPLC. An HPLC screening procedure was developed which was used to monitor for compounds responsible for the discolouration, at least eight unknown compounds were resolved and a relative response factor of 5.47 was assigned to them with respect to l-ascorbic acid at 280 nm. One mole of carbon dioxide was evolved per mole of l-ascorbic acid. This paper describes the investigation into the identity of the degradation products.

Moisture induced solid phase degradation of l-ascorbic acid part 3, structural characterisation of the degradation products.

The influence of moisture on the solid phase degradation of l-ascorbic acid and the chemical characteristics of the degradation products have been investigated previously [Shephard et al. (1998) (in press)]. Moisture induced degradation in the solid phase leads to severe discolouration. This paper describes the isolation of the compounds responsible for the discolouration and their partial chemical identification. Eight different degradation compounds were found to be present in a severely discoloured sample [Shepherd et al. (1998) (in press)]. Three of the compounds were present at levels above 1% of the total chromatography peak area with the major degradation peak present at 29% in a sample with 5% v/w moisture present when stored at 60 degrees C for 42 days. The major impurity was isolated and was found to exhibit a lambda(max) at 280 nm with further absorbance to 600 nm. This material was pyrolysed at 300, 500, and 600 degrees C. Amongst the volatile pyrolysates tentatively identified were furfural, 2-furancarboxylic acid, 1-(2-furanyl)-ethanone, tetrahydrofuran and 1-(2-furanyl)-1-propanone along with some aromatic compounds such as benzene and phenol. The periodate consumption of the major impurity was examined and the products of the reaction investigated. Estimation of hydroxyl and carbonyl group content by acetyl group determination of the acetate and reduced acetate showed that for every five repeating units there was one hydroxyl group and for every four repeating units there was one carbonyl group. Elemental analysis gave 46.26% carbon, 5.42% hydrogen and 48.32% oxygen giving an empirical formula of CH(2)O.

Audit on complicated diverticular disease.

Seventy-three patients were seen between 1970 and 1983 with complicated diverticular disease. There were only six hospital deaths (8%). Two out of 7 patients with faecal peritonitis died, 2 of 27 patients with purulent peritonitis died and there was one death each associated with an inflammatory mass and a peridiverticular abscess. Five of the six hospital deaths were from cardiorespiratory disease and only one was from sepsis. Three of the early deaths were in patients who were receiving steroid therapy. There were three late deaths: one from uncontrolled sepsis, one an anaesthetic death from coronary occlusion during revision of a Hartmann operation and the third was an incidental myocardial infarction. A very conservative surgical policy was adopted, primary resection only being used for an inflammatory mass and selectively for fistula and local purulent disease. Despite our apparent low hospital mortality there was a high incidence of complication; wound sepsis 29%, fistula after colostomy closure 12% and anastomotic dehiscence after primary or secondary reconstruction 12%. These findings indicate the need for a prospective audit which is now in progress.

Contributions to the history of psychology: LVII. Terman-Binet communication.

An attempt is made to reconcile some views on possible communication between Alfred Binet and Lewis M. Terman on the basis of a letter from Terman's papers.

The effects of cryopreservation and transfer on embryonic development in the common marmoset monkey, Callithrix jacchus.

Embryos were collected at the 4-10-cell stage from the oviducts (Day 4; Day 1 = ovulation) or as morulae (Day 7) from the uterus of marmosets and frozen in 1.5 M-DMSO (Days 4 and 7) or 1.0 M-glycerol (Day 4 only), using a slow freezing and thawing technique. Of 22 Day-4 embryos frozen in DMSO, 18 were recovered and 16 of these were transferred to 10 synchronized recipients; 7 recipients became pregnant compared with all 7 control recipients receiving 10 unfrozen embryos. Fifteen frozen-thawed morulae were transferred to 9 Day-6 recipients; the pregnancy rate (55.6%) was lower than for control embryos (85.7%). Embryos frozen in glycerol suffered severe osmotic stress during glycerol addition and removal. Of 8 recipients, 3 (37.5%) became pregnant but only one fetus was carried to term. These results on embryo collection, freezing and transfer in the marmoset have important implications for developing improved methods for freezing human embryos and the breeding of endangered primates.

Successful transfer of the embryos of Przewalski's horses (Equus przewalskii) and Grant's zebra (E. burchelli) to domestic mares (E. caballus).

Blastocysts were collected non-surgically from 2 Przewalski's horse and 2 Grant's zebra mares and transferred extra-specifically to domestic horse and donkey recipients. Nine Przewalski's horse embryos were transferred surgically, and 2 non-surgically, to domestic Welsh-type pony mares. After surgical transfer, 7 (77.8%) pregnancies were established and 4 foals were born. Twelve Grant's zebra embryos were transferred surgically to 5 pony and 7 domestic donkey recipients respectively and 1 non-surgically to a donkey; 3 (60%) zebra-in-horse pregnancies were established and 2 went to term. Only 2 (28.6%) zebra-in-donkey pregnancies were established but neither went to term, although one zebra foal was aborted alive at Day 292 but failed to survive. No pregnancies resulted from the non-surgical transfers. Measurement of chorionic gonadotrophin concentrations and parental-specific lymphocytotoxic antibodies in the serum of the recipient animals indicated a pronounced maternal immunological response to the extra-specific embryo, but this could not be correlated with success or failure of pregnancy. The results indicate that extra-specific embryo transfer may be a useful aid to breeding exotic equids in captivity.