Implementing a fracture liaison service open model of care utilizing a cloud-based tool.

PURPOSE: Although half of women and one-quarter of men aged 50 and older will sustain an acute low-trauma fracture, less than a quarter receive appropriate secondary fracture prevention. The goal of this quality improvement demonstration project was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in three open health care systems aided by a cloud-based tool. METHODS: The pre-post study design examined the proportion of men and women over age 50 who received appropriate assessment (bone mineral density, vitamin D levels) and treatment (calcium/vitamin D, pharmacologic therapy) in the six months following a recently diagnosed fracture. The pre-study (Pre FLS) included a retrospective chart review for baseline data (N = 344 patients) within each health care system. In the post-evaluation (Post FLS, N = 148 patients), the FLS coordinator from each health care system examined these parameters following enrollment and for 6 months following the recently diagnosed fracture. Data were managed in the cloud-based FLS application tool. RESULTS: Ninety-three participants completed the program. The FLS program increased the percentage of patients receiving bone mineral density testing from 21% at baseline to 93% (p < 0.001) Post FLS implementation. Assessments of vitamin D levels increased from 25 to 84% (p < 0.001). Patients prescribed calcium/vitamin D increased from 36% at baseline to 93% (p < 0.001) and those prescribed pharmacologic treatment for osteoporosis increased on average from 20 to 54% (p < 0.001) Post FLS. CONCLUSIONS: We conclude that the FLS model of care in an open health care system, assisted by a cloud-based tool, significantly improved assessment and/or treatment of patients with a recently diagnosed osteoporotic fracture. Future studies are necessary to determine if this model of care is scalable and if such programs result in prevention of fractures. Mini-Abstract: The goal was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in open health care systems aided by a cloud-based tool. This model significantly improved assessment and/or treatment of patients with a recently diagnosed fracture.

Growth performance and digestion of growing lambs fed diets supplemented with glycerol.

Two experiments were conducted to evaluate the effects of replacing corn with an increasing concentration of high-purity glycerol (>99%) on growth performance, economical efficiency, blood constituents and nutrient digestibility of growing lambs. In experiment one, 24 male lambs (initial BW=33.6±6.0 kg; age=6.75±0.75 months) were randomly assigned to one of the three experimental treatments containing 0%, 5% or 10% glycerol to replace corn in concentrate. In experiment two, nine lambs (initial BW=44.7±2.2 kg, age=8.84±0.32 months) were used in a digestion trial with three treatments (three lambs per treatment) with glycerol replacing corn at 0%, 5% or 10% in the concentrate. Total dry matter (DM) intake decreased quadratically (P=0.003) with increasing concentration of glycerol in the diet. Lambs fed glycerol diets had greater average daily gain (P=0.005) and better feed efficiency (P=0.002) compared with the control. Feed costs were also reduced with glycerol inclusion. Glycerol supplementation did not affect serum concentrations of total protein, albumin, globulin, total lipid, cholesterol and glucose concentrations. Glycerol supplementation had no effect (P>0.05) on organic matter and CP digestion, but improved DM (P=0.0003), crude fiber (P=0.10), ether extract (P=0.0002) and nitrogen-free extract (P=0.05) digestion. In conclusion, glycerol can replace corn up to 10% of DM in the diets of growing lambs.

Bromelain-based enzymatic debridement and minimal invasive modality (mim) care of deeply burned hands.

The objective was to critically review the data and assess the implications of NexoBrid [NexoBrid-NXB formerly Debrase Gel Dressing-DGD]a in the special field of deep hand burns. Detailed analysis of endpoints in the treatment of hand burn patients was conducted as part of a multi-center, open label, randomized, controlled two-arm study to evaluate the safety and efficacy of NXB enzymatic debridement, comparing it to the current standard of care (SOC). These results were compared to a large cohort of patients treated with NXB in a previous, single arm study. Thirty-one burned hands were treated with NXB and 41 hand burns were in the SOC group. In the NXB group, 4 out of 31 hand burns (12.9%) required some excisional debridement compared to 29 out of the 41 (70.7%) in the SOC group (p<0.0001). Mean percentage of burn wound area excised in the NXB group was 4.4 ± 13.1% compared to 52.0 ± 41.4% in the SOC group (p<0.0001). None of the NXB-treated hands required escharotomy compared to 4 out of the 41 (9.7%) in the SOC group. NXB enzymatic debridement demonstrated a statistically significant reduction in burn wound excision and auto-grafting compared to SOC, and seems to prevent the need for emergency escharotomy. a DGD is produced by MediWound and distributed under the name NexoBrid®.

Le but était de réaliser une révision attentive des données et d'évaluer la place de Nexobrid (Nexobrid-NXB, précédemment Debrase Gel Dressing-DGD) dans l'indication particulière des brûlures profondes de la main. Une analyse détaillée des objectifs dans le traitement des brûlures de la main a été conduite en partie par une étude multicentrique, ouverte, randomisée, contrôlée avec 2 groupes pour évaluer la sécurité et l'efficacité de ce débridement enzymatique par rapport aux soins habituels (Standard of Care ou SOC). Ces résultats ont été comparés à une vaste cohorte de patients traités par NXB dans une étude précédente sur un seul groupe. 31 mains brûlées furent traitées par NXB et 41 dans le groupe SOC. Dans le groupe NXB, 4 sur 31 mains brûlées soit 12,9 % nécessitèrent une excision partielle, alors que 29 sur 41 dans le groupe SOC (70,7 %) (p < 0,0001). La moyenne des zones brûlées excisées dans le groupe NXB était de 4,4 (+ ou - 13,1 %) comparée aux 52,0 (+ ou - 41,4 % du groupe SOC) (p <0,0001). Aucune des mains traitées par NXB ont nécessité une excision totale, comparée à 4 sur 41 du groupe SOC (9,7 % du groupe). Le débridement enzymatique NXB montre une réduction statistiquement significative de l'indication d'excision avec autogreffe par rapport au groupe traité classiquement et semble prévenir la nécessité d'une escarrotomie en urgence.

Minimally invasive burn care: a review of seven clinical studies of rapid and selective debridement using a bromelain-based debriding enzyme (Nexobrid®).

Current surgical and non-surgical eschar removal-debridement techniques are invasive or ineffective. A bromelainbased rapid and selective enzymatic debriding agent was developed to overcome these disadvantages and compared with the standard of care (SOC). The safety and efficacy of a novel Debriding Gel Dressing (DGD) was determined in patients with deep partial and full thickness burns covering up to 67% total body surface area (TBSA). This review summarizes data from seven studies, four of which were randomized clinical trials that included a SOC or control vehicle. DGD eschar debridement efficacy was >90% in all studies, comparable to the SOC and significantly greater than the control vehicle. The total area excised was less in patients treated with DGD compared with the control vehicle (22.9% vs. 73.2%, P<0.001) or the surgical/non-surgical SOC (50.5%, P=0.006). The incidence of surgical debridement in patients treated with DGD was lower than the SOC (40/163 [24.5%] vs. 119/170 [70.0%], P0.001). Less autografting was used in all studies. Long-term scar quality and function were similar in DGD- and SOCtreated. DGD is a safe and effective method of burn debridement that offers an alternative to surgical and non-surgical SOC.

Les protocoles actuels de détersion d'une brûlure, chirurgicaux et non chirurgicaux, sont soit invasifs soit inefficaces. Un enzyme détersif rapide et spécifique, dérivé de la bromélaïne, a été développé dans le but de palier à ces 2 inconvénients. Il a été comparé aux techniques usuelles (TU). L'efficacité et l'innocuité d'un Gel Topique Détersif (GTD) ont été évaluées chez des patients souffrant de brûlures intermédiaires et profondes atteignant jusqu'à 67% de la Surface Corporelle Totale (SCT). Cette revue compile les données de 7 études cliniques, dont 4, randomisées, faisaient appel aux TU ou à un groupe contrôle. La détersion obtenue avec GTD était toujours > 90%, comparable aux TU et meilleure que dans le groupe contrôle. La surface relative excisée totale était moindre après GTD que chez les contrôles (22.9% VS 73.2%, p<0,001) ou les patients sous TU (50.5%, p=0,006). Le nombre de patients ayant eu besoin de chirurgie a été inférieur dans le groupe GTD que dans le groupe TU (40/163 [24.5%] VS 119/170 [70%], p<0,001). Le recours aux greffes était moins fréquent dans toutes les études. Les qualités cicatricielle et fonctionnelle à distance étaient comparables après TU et GTD. GTD est une technique de détersion efficace et sûre qui offre une alternative au TU, chirurgical ou non.

[Comprehensive dental treatment under general anaesthesia: implementation among patients with mouth opening limitation].

Patients unable to tolerate routine dental treatment in an ordinary dental setting may undergo a wide range of dental procedures under general anaesthesia. This report describes a practical protocol for providing comprehensive dental treatment under general anaesthesia. The importance and uniqueness of planning, treating and adopting safety measures is illustrated through the presentation of clinical cases of patients with mouth opening limitation. Complete treatment can thus be achieved in a single visit, thereby eliminating repetition of coping with anxiety associated with repeated treatment sessions.

British Dietetic Association evidence-based guidelines for the dietary management of irritable bowel syndrome in adults.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic debilitating functional gastrointestinal disorder. Diet and lifestyle changes are important management strategies. The aim of these guidelines is to systematically review key aspects of the dietary management of IBS, with the aim of providing evidence-based guidelines for use by registered dietitians. METHODS: Questions relating to diet and IBS symptom management were developed by a guideline development group. These included the role of milk and lactose, nonstarch polysaccharides (NSP), fermentable carbohydrates in abdominal bloating, probiotics and empirical or elimination diets. A comprehensive literature search was conducted and relevant studies from January 1985 to November 2009 were identified using the electronic database search engines: Cinahl, Cochrane Library, Embase, Medline, Scopus and Web of Science. Evidence statements, recommendations, good practice points and research recommendations were developed. RESULTS: Thirty studies were critically appraised. A dietetic care pathway was produced following a logical sequence of treatment and formed the basis of these guidelines. Three lines of dietary management were identified. first line: Clinical and dietary assessment, healthy eating and lifestyle management with some general advice on lactose and NSP. Second line: Advanced dietary interventions to improve symptoms based on NSP, fermentable carbohydrates and probiotics. Third line: Elimination and empirical diets. Research recommendations were also identified relating to the need for adequately powered and well designed randomised controlled trials. CONCLUSIONS: These guidelines provide evidence-based details of how to achieve the successful dietary management of IBS.

Nutrient and light limitation of periphyton in the River Thames: implications for catchment management.

Soluble reactive phosphorus (SRP) concentrations in the River Thames, south east England, have significantly decreased from an annual maximum of 2100 µg l(-1) in 1997 to 344 in 2010, primarily due to the introduction of phosphorus (P) removal at sewage treatment works within the catchment. However, despite this improvement in water quality, phytoplankton biomass in the River Thames has greatly increased in recent years, with peak chlorophyll concentrations increasing from 87 µg l(-1) in the period 1997 to 2002, to 328 µg l(-1) in 2009. A series of within-river flume mesocosm experiments were performed to determine the effect of changing nutrient concentrations and light levels on periphyton biomass accrual. Nutrient enrichment experiments showed that phosphorus, nitrogen and silicon were not limiting or co-limiting periphyton growth in the Thames at the time of the experiment (August-September 2010). Decreasing ambient SRP concentration from 225 µg l(-1) to 173 µg l(-1) had no effect on periphyton biomass accrual rate or diatom assemblage. Phosphorus limitation became apparent at 83 µg SRP l(-1), at which point a 25% reduction in periphyton biomass was observed. Diatom assemblage significantly changed when the SRP concentration was reduced to 30 µg l(-1). Such stringent phosphorus targets are costly and difficult to achieve for the River Thames, due to the high population density and intensive agriculture within the Thames basin. Reducing light levels by shading reduced the periphyton accrual rate by 50%. Providing shading along the River Thames by planting riparian tree cover could be an effective measure to reduce the risk of excessive algal growth. If the ecology of the Thames is to reach the WFD's "good ecological status", then both SRP concentration reductions (probably to below 100 µg l(-1)) and increased shading will be required.

Duration of response after treatment of mild to moderate depression with Hypericum extract STW 3-VI, citalopram and placebo: a reanalysis of data from a controlled clinical trial.

St. John's Wort (Hypericum perforatum L.) is a useful medication in the treatment of mild to moderate depression. By reanalysis of the data obtained from a total of 154 patients, who responded in a randomised, multicentric, double-blind, placebo-controlled study, to 6 weeks of treatment for an episode of moderate depression with either 20 mg citalopram or 900 mg Hypericum extract STW 3-VI, the duration of response and occurrence of relapse/recurrence were evaluated. Duration of response and occurrence of relapse/recurrence was measured by re-evaluating the responders in a controlled-clinical trial (final score of ≤10 according to HAMD at the end of the clinical trial) according to the Hamilton Rating Scale for Depression (HAMD). In total, 30 (19.5%) of the 154 responders were diagnosed with a relapse. The numbers of patients with relapses were highest in the citalopram group (14 of 54), whereas patients who were treated with Hypericum extract STW 3-VI showed the lowest relapse rate (8/54); patients from the placebo group showed a relapse rate of 8/46. No difference in the severity of relapse could be observed. The duration of response was longest for the Hypericum group (1817 days), intermediate for the citalopram group (1755 days) and shortest for the placebo group (802 days). Hypericum extract STW 3-VI is more efficient in lowering the relapse and recurrence rates of responders, when compared to citalopram and placebo. In addition, duration of response was increased in the group treated with Hypericum extract STW 3-VI.

Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study.

OBJECTIVE: The objective of this double-blind, randomised, placebo-controlled, multicentre clinical study was to demonstrate the non-inferiority and safety of the hypericum extract STW3-VI in a once-daily dosage regime in the treatment of moderate depression. During the 6-week treatment phase, the course of depression was documented by use of HAMD (items 1-17), the von Zerssen's Adjective Mood Scale (BfS) and the CGI scales. The primary objective of this 3-arm design study was to demonstrate the non-inferiority of hypericum extract STW3-VI (900 mg) to the SSRI citalopram (20 mg) and superiority of hypericum over placebo. METHODS: Outpatients (N = 388) suffering from moderate depression were enrolled. The safety and tolerability of hypericum extract in comparison to citalopram and placebo was investigated on the basis of CGI, the occurrence of adverse events and the investigation of laboratory parameters and vital signs. RESULTS: From almost identical baseline values of 21.9 +/- 1.2 points (hypericum extract), 21.8 +/- 1.2 points (citalopram) and 22.0 +/- 1.2 points (placebo), the HAMD score was reduced to 10.3 +/- 6.4 (hypericum extract), 10.3 +/- 6.4 (citalopram) and 13.0 +/- 6.9 (placebo), respectively. Based on this data, the statistical significant therapeutic equivalence of hypericum extract STW3-VI to citalopram (p < 0.0001) and the superiority of this hypericum extract over placebo (p < 0.0001) was demonstrated. At the end of treatment 54.2 % (hypericum extract), 55.9 % (citalopram) and 39.2 % (placebo) of the patients were assessed as therapy responders. The secondary efficacy parameters, change in BfS, CGI and amount of therapy responders showed that the hypericum group was not statistically different from the citalopram group, and significantly superior to the placebo group. Significantly more adverse events with "certain", "probable" or "possible" relation to study medication were documented in the citalopram group (hypericum: 17.2 %, citalopram: 53.2 %, placebo: 30 %). In most cases, the investigators assessed the tolerability of hypericum extract, citalopram and placebo as "good" or "very good". CONCLUSION: The non-inferiority of hypericum extract as compared to citalopram and the superiority of both active compounds to placebo were demonstrated, as well as a better safety and tolerability of hypericum extract in comparison to citalopram. These results revealed that hypericum extract STW3-VI is a good alternative to chemically defined antidepressants in the treatment of outpatients with moderate depression.

Efficacy and tolerability of hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertraline.

OBJECTIVE: The objective of this double-blind, multi-center clinical study was to demonstrate the non-inferiority of hypericum extract versus sertraline in the treatment of moderate depression. METHODS: A total of 241 patients with a diagnosis of moderate depressive disorder (according to ICD-10 criteria) were randomized with either 50 mg sertraline or 612 mg hypericum extract (hypericum group n = 123; sertraline group n = 118). According to the study protocol, 200 patients were treated for at least 12 weeks ( n = 102 hypericum extract; n = 98 sertraline); 81 patients in the hypericum group and 80 in the sertraline group were treated after week 12 for an additional 12 weeks. Thus, most patients were treated for a period of 6 months. The primary efficacy variable was the 17-item HAMD total score at the end of the first 12-week double-blind treatment period. RESULTS: After the first 12-week treatment period, the HAMD score decreased from almost identical initial values (22.0 +/- 1.1 for hypericum and 22.1 +/- 1.1 points for sertraline) to 8.3 +/- 5.5 points (hypericum) and 8.1 +/- 5.6 points (sertraline) (mean +/- SD) in the patients treated per-protocol (PP) population. The statistical test for non-inferiority (boundary delta = 3) revealed that hypericum extract is not inferior to sertraline ( P < 0.0001). The mean difference between the treatments was 0.1995 points, with a corresponding one-sided 97.5 % confidence interval (-infinity, 1.3772). In patients who continued treatment in the follow-up phase, the HAMD score at the end of the study was 5.7 +/- 4.8 points (hypericum group) and 7.1 +/- 6.3 points (sertraline group). Comparable improvement was also found for the von Zerssen's Adjective Mood Scale (BfS) and CGI during the first and second 12-week treatment period in both treatment groups. With 68.6 % of patients in the hypericum group and 70.4 % in the sertraline group, the percentage of patients rated as responders did not differ significantly between treatment groups (12 weeks). The adverse events of 12 patients in the hypericum group (9.8 %) and of 16 patients in the sertraline group (13.6 %) were possibly related to study medication. No basic differences in the treatment groups were observed and no interaction with concomitant medication was documented. In most cases , the investigators assessed the tolerability of hypericum extract and sertraline as "good" or "very good." CONCLUSIONS: The results indicate that hypericum extract STW 3 is not inferior to sertraline and that it is a well-tolerated drug for the treatment of moderate depression. These favorable effects were achieved with a once-daily dose of 612 mg of hypericum extract given for up to 24 weeks.

Percutaneous regional compared with local anaesthesia for facial lacerations: a randomised controlled trial.

OBJECTIVE: Facial lacerations are usually repaired after local infiltration of an anaesthetic agent. Regional nerve blocks of the face offer several theoretical advantages over local infiltration. This study compared the pain of injection and anaesthetic efficacy of percutaneous regional and local anaesthesia for facial lacerations. STUDY DESIGN: Randomised clinical trial. PARTICIPANTS: Convenience sample of emergency department patients with facial lacerations requiring suturing in anatomical areas innervated by a regional nerve (supraorbital, infraorbital, or mental). INTERVENTIONS: Facial lacerations treated using standard wound care. Lacerations were randomised to local or regional infiltration of lidocaine (lignocaine) 1% with adrenaline (epinephrine) 1:100 000 using a number 27 needle. OUTCOMES: Pain of injection on 100 mm visual analogue scale (VAS) and need for rescue anaesthetic infiltration before suturing. DATA ANALYSIS: Group comparisons were with Student's t test and chi(2) test. This study had 80% power to detect a 20 mm difference in pain of injection (two tailed, alpha = 0.05). RESULTS: 36 patients were randomised to local (18) and regional (18) anaesthesia. Mean (SD) age was 20 (14); 19% were female. Groups were similar in baseline characteristics. Patients in the regional anaesthesia group experienced more pain during infiltration than patients in the local anaesthesia group (42.4 mm v 24.8 mm, mean difference 17.6 mm (95% CI 0.3 to 35.6 mm) and were more likely to require additional infiltration of a local anaesthetic (28% v 0%, (95% CI 6% to 50%)) than patients in the local anaesthetic group. CONCLUSIONS: Local infiltration of anaesthetics for facial lacerations is less painful and results in more effective anaesthesia than percutaneous regional infiltration.

Evaluation of synaptosomal uptake inhibition of most relevant constituents of St. John's wort.

In our previous investigations, we could demonstrate that extract preparations of Hypericum perforatum (St. John's wort, SJW) inhibit the uptake of several neurotransmitters (serotonin, norepinephrine, dopamine, GABA, L-glutamate) in synaptosomal preparations of rodent brain. Hyperforin, the lipophilic constituent, was identified as the main component responsible for these effects. The properties seen for hyperforin in these and other pharmacological models present a plausible and logical explanation for the well documented antidepressive effects of SJW extract preparations in clinical studies. However, evidence for other active principles in SJW extract have been reported (See also communications by Misane & Ogren and Philippu in this issue). Accordingly, we tested various SJW extract preparations and all relevant constituents as possible inhibitors of synaptosomal uptake of neurotransmitters. Two further components were found to be active in those models. Adhyperforin, like hyperforin, showed a strong inhibiting profile in all uptake systems investigated. Moreover, we could observe a weak to moderate inhibiting profile for the oligomeric procyanidins fraction (OPC). Further investigations would have to clarify any possible contribution of these two constituents to the antidepressive effects of SJW extract seen in animal experiments and clinical trials.

Hyperforin--antidepressant activity by a novel mechanism of action.

Hyperforin represents a major antidepressive constituent of St. John's wort (SJW) extract. It not only inhibits the neuronal uptake of serotonin, norepinephrine and dopamine like many other antidepressants, but also inhibits GABA and L-glutamate uptake. This broad-spectrum effect is obtained by an elevation of the intracellular Na+ concentration, probably due to activation of sodium conductive pathways not yet finally identified but most likely ionic channels. This makes hyperforin the first member of a new class of compounds with a preclinical antidepressant profile due to a completely novel mechanism of action.

PRAM-1 is a novel adaptor protein regulated by retinoic acid (RA) and promyelocytic leukemia (PML)-RA receptor alpha in acute promyelocytic leukemia cells.

The t(15;17) translocation, found in 95% of acute promyelocytic leukemia, encodes a promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARalpha) fusion protein. Complete remission of acute promyelocytic leukemia can be obtained by treating patients with all-trans retinoic acid, and PML-RARalpha plays a major role in mediating retinoic acid effects in leukemia cells. A main model proposed for acute promyelocytic leukemia is that PML-RARalpha exerts its oncogenic effects by repressing the expression of retinoic acid-inducible genes critical to myeloid differentiation. By applying subtraction cloning to acute promyelocytic leukemia cells, we identified a retinoic acid-induced gene, PRAM-1 (PML-RARalpha target gene encoding an Adaptor Molecule-1), which encodes a novel adaptor protein sharing structural homologies with the SLAP-130/fyb adaptor. PRAM-1 is expressed and regulated during normal human myelopoiesis. In U937 myeloid precursor cells, PRAM-1 expression is inhibited by expression of PML-RARalpha in the absence of ligand and de novo superinduced by retinoic acid. PRAM-1 associates with other adaptors, SLP-76 and SKAP-55HOM, in myeloid cell lines and with protein tyrosine kinase lyn. By providing the first evidence that PML-RARalpha dysregulates expression of an adaptor protein, our data open new insights into signaling events that are disrupted during transformation by PML-RARalpha and induced by retinoic acid during de novo differentiation of acute promyelocytic leukemia cells.

The ups and downs of medical school applicants.

The number of students applying to medical schools is shrinking after rising steadily during the 1990s. The decline is the latest turn in the behavior of the applicant pool, which historically has gone through many cycles. Although government policies have strongly influenced the past behavior of the applicant pool, the more recent cycles appear to be related to changes in the Medical College Admission Test (MCAT) and labor market conditions. This article first reviews the cyclical nature of the pool and outlines some of the important factors that have influenced its patterns. Then it focuses on more recent data covering 1990-2000, showing how changes made in 1991 to the MCAT have affected the applicant pool. Data are presented to document the close relationship between the number of students taking the MCAT and the number of medical school applicants in subsequent years. Using this relationship, a projection model has been developed for making projections of the number of applicants for the entering class in osteopathic medical schools in future years. Actual data are compared to the model's projections.

Pretreatment of lacerations with lidocaine, epinephrine, and tetracaine at triage: a randomized double-blind trial.

OBJECTIVE: Pretreatment of lacerations with topical anesthetics reduces the pain of subsequent anesthetic injection yet requires time. This study was conducted to determine the ability of triage nurses to identify lacerations necessitating closure and pretreat them with a topical anesthetic and to compare the pain levels of lidocaine injection in lacerations pretreated with LET (lidocaine 2%, epinephrine 1:1,000, tetracaine 2%) vs a placebo. METHODS: This was a double-blind, randomized clinical trial that included consecutive emergency department patients aged > or = 1 year with clean, non-bite lacerations < or = 6 hours old. At triage the lacerations were randomized to LET solution or a placebo containing epinephrine 1:1,000. At examination an emergency practitioner assessed the laceration edges for the presence of blanching and adequacy of anesthesia to a 27-gauge needlestick. At the practitioner's discretion, supplemental lidocaine was infiltrated through the wound and the patient (or guardian) recorded the pain of infiltration on a 100-mm visual analog scale marked "most pain" at the high end. The mean levels of pain of lidocaine infiltration were compared between groups with a t-test and the proportions of adequately anesthetized wounds were compared with a chi2 test. A sample of 40 patients had 80% power to detect a 20-mm between-group difference in the pain of injection (alpha = 0.05). RESULTS: Of 43 patients enrolled (mostly children and males), 22 received LET and 21 placebo. The groups were similar for baseline characteristics. Lacerations in the LET group were more frequently adequately anesthetized (46% vs 14%, p = 0.03), and LET patients experienced less pain from injection than controls (22 mm vs 42 mm, p = 0.02). CONCLUSIONS: Application of LET by triage nurses is more effective than placebo in adequately anesthetizing simple lacerations in normal hosts and decreases the pain of local anesthetic infiltration.

Inhibition of synaptosomal uptake of 3H-L-glutamate and 3H-GABA by hyperforin, a major constituent of St. John's Wort: the role of amiloride sensitive sodium conductive pathways.

Extracts of St. John's Wort are widely used for the treatment of depressive disorders. The active principles have not yet been finally elucidated. We have recently shown that hyperforin, a major active constituent of St. John's Wort, not only inhibits the neuronal uptake of serotonin, norepinephrine and dopamine, but also that of L-glutamate and GABA. No other antidepressant compound exhibits a similar broad uptake inhibiting profile. To investigate this unique kind of property, kinetic analyses were performed regarding the uptake of 3H-L-glutamate and 3H-GABA into synaptosomal preparations of mouse brain. Michaelis-Menten kinetics revealed a reduction of Vmax (8.27 to 1.80 pmol/mg/min for 3H-L-glutamate, 2.76 to 0.77 pmol/mg/min for 3H-GABA) while Km was nearly unchanged in both cases, suggesting non-competitive inhibition. The unselective uptake inhibition by hyperforin could be mimicked by the Na+-ionophore monensin and by the Na+-K+-ATPase inhibitor ouabain. However, both mechanisms can be discarded for hyperforin. Several amiloride derivatives known to affect sodium conductance significantly enhance 3H-GABA and 3H-L-glutamate uptake and inhibit the uptake inhibition by hyperforin, while monensin or ouabain inhibition were not influenced. Selective concentrations of benzamil for amiloride sensitive Na+-channels and selective concentrations of 5'-ethylisopropylamiloride (EIPA) for the Na+-H+-exchangers both had an attenuating effect on the hyperforin inhibition of L-glutamate uptake, suggesting a possible role of amiloride sensitive Na+-channels and Na+-H+-exchangers in the mechanism of action of hyperforin.

Use of alternative therapies among emergency department patients.

STUDY OBJECTIVE: To assess emergency department patients' use of alternative therapies. METHODS: This study used a cross-sectional observational survey of a convenience sample of ED patients. A trained research assistant administered a written questionnaire asking patients about alternative therapies. RESULTS: Of the 139 patients surveyed, 78 (56%) had tried alternative therapies in the past, 68 (87%) of whom believed that they were effective. The most frequently tried alternative therapies were massage therapy (31%), chiropractic (30%), herbs (24%), meditation (19%), and acupuncture (15%). Most patients (70%) who tried alternative therapies did not inform their physicians of such practice. CONCLUSION: Most ED patients in our sample had tried alternative therapies and among these patients, most did not inform their physicians. Herbal therapy in particular had been tried by about 1 in 4 patients. Emergency physicians should routinely question their patients regarding the use of alternative therapies, particularly herbal preparations, which may cause adverse effects.