Assessment of the Availability, Cost, and Motivations for Use over Time of the New Psychoactive Substances-Benzodiazepines Diclazepam, Flubromazepam, and Pyrazolam-in the UK.

INTRODUCTION: There has been increasing interest in the availability of non-prescription benzodiazepines and their sale as new psychoactive substances. We wanted to determine UK availability from Internet suppliers and motivations for use of three benzodiazepines (diclazepam, flubromazepam, and pyrazolam). METHODS: In November 2014 and March 2016, using the European Monitoring Centre for Drugs and Drug Addiction Snapshot Methodology, Internet search engines ( google.co.uk , uk. yahoo.com and ask.com.uk ) were searched using the terms 'buy diclazepam', 'buy flubromazepam' and 'buy pyrazolam'. Threads from drug-user forums ( bluelight.org , drugs-forum.com , erowid.org , legalhighsforum.com ) were analysed using a general inductive approach. Data were converted into price per gram/pellet to allow cost comparisons and to determine motivations for use. RESULTS: There was an increase in websites selling these benzodiazepines between 2014 and 2016: diclazepam (49 in 2014 to 55 in 2016), pyrazolam (33 to 35), and flubromazepam (39 to 45). Thirty-eight (63.3%) sites were based in the UK/Europe. Drugs were sold as pellets (49 websites, 81.7%), powder (19, 31.7%), and blotters (1, 1.7%). Pill forms were not available, and one (1.7%) website sold diclazepam/flubromazepam in liquid form. The cost reduced with increasing purchase quantities. Main motivations for use included anxiolysis, management of benzodiazepine withdrawal, sedation/sleep aid, and management of stimulant withdrawal. CONCLUSIONS: These three benzodiazepines are widely available online, most commonly as pellets, and are (mis)used for a number of reasons. This study could be used to support triangulation of data from other sources to inform harm minimisation strategies.

Pre-hospital ambulance care of patients following a suspected seizure: A cross sectional study.

PURPOSE: We aimed to investigate the characteristics of patients presenting to the ambulance service with suspected seizures, the costs of managing these patients and the factors which predicted transport to hospital. METHODS: We employed a cross-sectional design using routine clinical data from a UK regional ambulance service. Logistic regression was used to identify predictors of transport to hospital from ambulance response times, demographics, clinical (physiological) findings and treatments. RESULTS: There were 177,715 emergency incidents recorded in 2011/12 of which 2.9% (5139/177,715) were classified as seizures by ambulance call handlers and 2.7% (4884/177,715) by paramedics on the scene. Suspected seizures were the seventh most common call type. The annual cost of managing these incidents was £890,148. Clinical and physiological variables were normal for most patients. 59.3% (2894/4884) of patients were transported to hospital. 1/4884 (0.02%) patient died. Administration of diazepam, insertion of an airway and pyrexia perfectly predicted transport to hospital, tachycardia had a modest association, but other variables were only weak predictors of transport to hospital. CONCLUSIONS: This study shows that most patients after a suspected seizure are not acutely unwell but nevertheless most patients are transported to hospital. Further research is required to determine which factors are important in decisions to transport to hospital and to create evidence-based tools to help paramedics identify patients who could be safely managed without transport to hospital.

Midazolam vs diazepam in prolonged seizures in children: A pharmacoeconomic approach.

OBJECTIVE: A previous European cost-utility study reported that use of buccal midazolam in the community setting for the treatment of prolonged seizures (ie, seizures lasting ≥5 minutes) in children was associated with an overall €12 507 399 reduction in annual costs charged to the Italian national health service compared with rectal diazepam. We re-evaluated these findings by applying a more conservative approach. METHODS: The Italian Delphi panel reconvened to apply a more conservative assessment of available reports. A decision-tree model was used, allowing for different treatment pathways depending on whether or not a caregiver administers treatment, an ambulance is required for transport of the child to hospital, and an inpatient stay is required. Direct medical costs were derived from Italian healthcare system data. Estimates of the annual number of prolonged tonic-clonic seizures expected in the country were based on studies which assessed seizure duration using video-EEG recordings and medical records. RESULTS: Although drug acquisition costs were greater for buccal midazolam than for rectal diazepam, the acquisition cost difference was outweighed by larger cost savings resulting mostly from a reduction in hospital admissions. Assuming that 1.2% of tonic and/or clonic seizures occurring in children and adolescents over a 12-month period are prolonged, the annual nationwide reduction in costs from preferring buccal midazolam to rectal diazepam was estimated at €3 577 587.9. CONCLUSIONS: In this more conservative revised analysis, the high cost of buccal midazolam is still counteracted by greater cost savings compared with rectal diazepam, but cost reduction was less than previously estimated.

Healthcare Utilization Characteristics for Intranasal Midazolam Versus Rectal Diazepam.

To investigate connections between patient demographics, health care utilization, prescription use, and refills for patients using intranasal midazolam, per rectum diazepam, or both. A retrospective cohort contained patients with epilepsy prescribed intranasal midazolam, per rectum diazepam, or both. We analyzed number of emergency department visits, ambulance services, urgent care visits, and unplanned hospitalizations. A total of 5458 patients were identified. Patients on intranasal midazolam had on average 1.53 fewer emergency department visits (95% confidence interval 1.16-1.89, P < .0001), 0.29 fewer uses of ambulance services (95% confidence interval 0.17-0.41, P < .0001), and 0.60 fewer urgent care visits (95% confidence interval 0.36-0.83, P < .0001) compared to patients in the per rectum diazepam group. Patients with commercial insurance were more likely to have intranasal midazolam prescription (odds ratio = 1.73, 95% confidence interval 1.42-2.11, P < .0001). The results substantiate the cost-effective benefits of prescribing intranasal midazolam compared to per rectum diazepam because several aspects of health care utilization were decreased in those using intranasal midazolam.

Diazepam or midazolam for orotracheal intubation in the ICU?

OBJECTIVE: to compare clinical and cost effectiveness of midazolam and diazepam for urgent intubation. METHODS: patients admitted to the Central ICU of the Santa Casa Hospital Complex in Porto Alegre, over the age of 18 years, undergoing urgent intubation during 6 months were eligible. Patients were randomized in a single-blinded manner to either intravenous diazepam or midazolam. Diazepam was given as a 5 mg intravenous bolus followed by aliquots of 5 mg each minute. Midazolam was given as an intravenous bolus of 5 mg with further aliquots of 2.5 mg each minute. Ramsay sedation scale 5-6 was considered adequate sedation. We recorded time and required doses to reach adequate sedation and duration of sedation. RESULTS: thirty four patients were randomized, but one patient in the diazepam group was excluded because data were lost. Both groups were similar in terms of illness severity and demographics. Time for adequate sedation was shorter (132 ± 87 sec vs. 224 ± 117 sec, p = 0.016) but duration of sedation was similar (86 ± 67 min vs. 88 ± 50 min, p = 0.936) for diazepam in comparison to midazolam. Total drug dose to reach adequate sedation after either drugs was similar (10.0 [10.0-12.5] mg vs. 15.0 [10.0-17.5] mg, p = 0.248). Arterial pressure and sedation intensity reduced similarly overtime with both drugs. Cost of sedation was lower for diazepam than for midazolam (1.4[1.4-1.8] vs. 13.9[9.4-16.2] reais, p <0.001). CONCLUSIONS: intubation using intravenous diazepam and midazolam is effective and well tolerated. Sedation with diazepam is associated to a quicker sedation time and to lower costs.

Diazepam or midazolam for orotracheal intubation in the ICU? / Diazepam ou midazolam para entubação orotraqueal na UTI?

Objective: to compare clinical and cost effectiveness of midazolam and diazepam for urgent intubation. Methods: patients admitted to the Central ICU of the Santa Casa Hospital Complex in Porto Alegre, over the age of 18 years, undergoing urgent intubation during 6 months were eligible. Patients were randomized in a single-blinded manner to either intravenous diazepam or midazolam. Diazepam was given as a 5 mg intravenous bolus followed by aliquots of 5 mg each minute. Midazolam was given as an intravenous bolus of 5 mg with further aliquots of 2.5 mg each minute. Ramsay sedation scale 5-6 was considered adequate sedation. We recorded time and required doses to reach adequate sedation and duration of sedation. Results: thirty four patients were randomized, but one patient in the diazepam group was excluded because data were lost. Both groups were similar in terms of illness severity and demographics. Time for adequate sedation was shorter (132 ± 87 sec vs. 224 ± 117 sec, p = 0.016) but duration of sedation was similar (86 ± 67 min vs. 88 ± 50 min, p = 0.936) for diazepam in comparison to midazolam. Total drug dose to reach adequate sedation after either drugs was similar (10.0 [10.0-12.5] mg vs. 15.0 [10.0-17.5] mg, p = 0.248). Arterial pressure and sedation intensity reduced similarly overtime with both drugs. Cost of sedation was lower for diazepam than for midazolam (1.4[1.4-1.8] vs. 13.9[9.4-16.2] reais, p <0.001). Conclusions: intubation using intravenous diazepam and midazolam is effective and well tolerated. Sedation with diazepam is associated to a quicker sedation time and to lower costs. .

Objetivo: comparar eficácia clínica e custo de midazolam e diazepam para intubação urgente. Métodos: pacientes internados na UTI Central do Complexo Hospitalar Santa Casa de Porto Alegre, >18 anos de idade e submetidos a entubação urgente durante seis meses eram elegíveis. Pacientes foram randomizados para receber diazepam ou midazolam intravenoso. Diazepam foi dado como bolus IV de 5 mg seguido por alíquotas de 5 mg a cada minuto. Midazolam foi dado como um bolus IV de 5 mg, com alíquotas adicionais de 2,5 mg a cada minuto. Escala de sedação de Ramsay 5-6 foi considerada sedação adequada. Registramos tempo e doses necessárias para atingir sedação adequada e sua duração. Resultados: trinta e quatro pacientes foram randomizados; um paciente no grupo diazepam foi excluído por perda dos dados. Grupos foram semelhantes para gravidade da doença e demografia. Tempo de sedação adequada foi mais curto (132 ± 87 vs. 224 ± 117 segundos, p = 0,016), mas a duração da sedação foi similar (86 ± 67 vs. 88 ± 50 min., p = 0,936) para o diazepam em comparação com o midazolam. Dose total da droga para atingir a sedação adequada foi semelhante para ambas as drogas (10,0 [10,0-12,5] vs. 15,0 [10,0-17,5] mg, p = 0,248). Pressão arterial e intensidade da sedação reduziram da mesma forma para ambas as drogas ao longo do tempo. O custo da sedação foi menor para diazepam do que para midazolam (1,4[1,4-1,8] vs. 13,9[9,4-16,2] reais, p < 0,001). Conclusões: entubação usando diazepam e midazolam intravenosos é eficaz e bem tolerada. Sedação com diazepam está associada a sedação mais rápida e menores custos. .

[Cost-effectiveness of buccal midazolam in the treatment of prolonged convulsive seizures in the outpatient setting in Spain]. / Coste-efectividad de una solucion bucal de midazolam en el tratamiento de las crisis convulsivas prolongadas en el entorno ambulatorio en España.

INTRODUCTION: To be able to treat prolonged epileptic crises practical, safe and effective rescue medication is needed. Today, the standard treatment in community healthcare is rectal diazepam. The introduction of a buccal solution of midazolam opens up a new perspective in their treatment. AIMS: To evaluate the cost-effectiveness of buccal midazolam with respect to rectal diazepam for children diagnosed with epilepsy who present prolonged convulsive seizures in the community setting in Spain. MATERIALS AND METHODS: The study produces a model of its cost-effectiveness from the perspective of the Spanish National Health System (SNS), with the outcomes presented in terms of cost-quality adjusted life years. Data were collected from different sources, including estimations regarding the clinical effectiveness from a clinical trial, from a Delphi panel in Spain and from a national survey carried out on parents of children with epilepsy in order to determine the current practices. RESULTS: Treatment with buccal midazolam produces a saving in costs in comparison to rectal diazepam. The amount saved by the Spanish SNS comes to 5,484 euros per patient per year. Treatment with buccal midazolam offers an improved health-related quality of life. This, together with the savings in costs, means that there is a dominance of buccal midazolam over rectal diazepam in all the settings that have been examined. CONCLUSIONS: The results obtained with the model show that buccal midazolam is more cost-effective than rectal diazepam due to a reduction in the need to call out ambulances and for stays in hospital, as well as an improved health-related quality of life.

TITLE: Coste-efectividad de una solucion bucal de midazolam en el tratamiento de las crisis convulsivas prolongadas en el entorno ambulatorio en España.Introduccion. El tratamiento de las crisis epilepticas prolongadas requiere disponer de una medicacion de rescate comoda, segura y efectiva. Actualmente, el tratamiento estandar en la comunidad es el diacepam rectal. La introduccion de una solucion bucal de midazolam abre una perspectiva nueva en el tratamiento. Objetivo. Evaluar el coste-efectividad del midazolam bucal respecto al diacepam rectal para los niños con un diagnostico de epilepsia que presentan crisis convulsivas prolongadas en la comunidad en España. Materiales y metodos. Modelo coste-efectividad desde la perspectiva del Sistema Nacional de Salud (SNS) español, con resultados presentados en terminos de costes y años de vida ajustados por calidad. Los datos se obtuvieron de varias fuentes, incluidas las estimaciones de efectividad clinica de un ensayo clinico, de un panel Delphi en España y de una encuesta nacional a padres de niños con epilepsia para determinar las practicas actuales. Resultados. El tratamiento con midazolam bucal produce un ahorro de costes en comparacion con el diacepam rectal. El ahorro para el SNS español es de 5.484 euros por paciente al año. El tratamiento con midazolam bucal ofrece una mejora en la calidad de vida relacionada con la salud. Esto, unido al ahorro de costes, hace que el midazolam bucal sea dominante frente al diacepam rectal en todos los escenarios examinados. Conclusion. Los resultados del modelo muestran que el midazolam bucal es mas coste-efectivo que el diacepam rectal debido a una reduccion en la necesidad de llamadas a la ambulancia y estancias en el hospital, asi como a una mejora en la calidad de vida relacionada con la salud.

The cost effectiveness of licensed oromucosal midazolam (Buccolam(®)) for the treatment of children experiencing acute epileptic seizures: an approach when trial evidence is limited.

BACKGROUND: In the UK, two treatment options are used for acute epileptic seizures in the community-rectal diazepam and unlicensed buccal midazolam. In practice, the former is rarely used, with unlicensed buccal midazolam being widely recommended and prescribed by physicians. In September 2011, Buccolam(®) (licensed midazolam oromucosal solution) became the first medicine to receive a Paediatric-Use Marketing Authorization (PUMA) and it is indicated for the treatment of prolonged, acute, convulsive seizures by caregivers in the community for children (aged 6 months to <18 years) diagnosed with epilepsy. The approval process for a PUMA product differs from other marketing authorization processes and may be based upon small population subsets and may not, in some cases, require new safety or efficacy data to be generated; a similar situation to that seen for orphan drugs. This can lead to challenges when conducting economic evaluations. OBJECTIVE: The aim of this study was to assess the cost effectiveness of Buccolam(®) for children with a diagnosis of epilepsy suffering prolonged, acute, convulsive seizures occurring in the UK community setting. DESIGN AND PERSPECTIVE: A hybrid model was developed according to a UK payer perspective. The model included a time-to-event simulation for the frequency and location of occurrence of seizures, along with a decision-tree model that assessed the treatment pathway when a seizure occured. The model compared treatment with Buccolam(®) with standard care in the community (95 % unlicensed buccal midazolam and 5 % rectal diazepam) or either treatment alone. The model was informed by data from a variety of sources, including clinical effectiveness estimates, and costs based on published UK data, using 2012-13 prices, where possible. To determine current practice and real-world effectiveness, a Delphi panel and a survey of parents of children with epilepsy were conducted. RESULTS: Buccolam(®) showed a reduction in costs of £2,939 compared with standard care, £14,269 compared with rectal diazepam alone and £886 compared with unlicensed buccal midazolam alone. Increases of 0.025, 0.082 and 0.013 quality-adjusted life-years, respectively, were also seen. Buccolam(®) remained dominant across a range of scenario analyses. CONCLUSION: This model demonstrates the possibility of constructing a thorough economic case when trial or real-world data are not available. The results of the model show Buccolam(®) to be cost saving compared with rectal diazepam due to a reduction in the need for ambulance callouts and hospital stays, and compared with unlicensed buccal midazolam, through reduced drug costs and wastage.

Benefits of using magnesium sulphate (MgSO4) for eclampsia management and maternal mortality reduction: lessons from Kano State in Northern Nigeria.

BACKGROUND: Despite clear emphasis through the Millennium Development Goals, the problem of high maternal mortality persists especially within low and middle income countries. Various studies report remarkably high maternal mortality rates in northern Nigeria, where maternal mortality rates exceed 1,000 deaths per 100,000 live births and eclampsia contributes approximately 40% of maternal deaths. Across Nigeria, diazepam is routinely used for the management of eclampsia. Prior to February 2008, diazepam was widely used for the management of eclampsia in Kano State (within northern Nigeria) with case fatality rate being over 20%. While magnesium sulphate (MgSO4) is recognized as the most effective drug for the management of eclampsia; this study aims to compare MgSO4 therapy with diazepam therapy in terms of case fatality rates and costs. FINDINGS: This retrospective study, including 1045 patients with eclampsia and pre-eclampsia during the years 2008 and 2009, reports a drop in case fatality rates from 20.9% (95% CI: 18.7, 23.2) to 2.3% (95% CI: 1.4, 3.2) among eclampsia patients following the MgSO4 intervention. The study observed no significant difference in the cost of using MgSO4 therapy compared to diazepam therapy. CONCLUSIONS: The study found a remarkable reduction in case fatality rate due to eclampsia in those who received MgSO4 therapy with minimal increase in costs when compared to diazepam therapy. Concerted efforts should be focused on properly introducing MgSO4 into emergency obstetric protocols especially within developing countries to reduce maternal mortality and also impact on health system performance.

Treatment gap for people living with epilepsy in Madagascar.

Using an indirect assessment technique we assessed the epilepsy treatment gap (ETG) in Madagascar. We estimate the ETG in Madagascar to be 92%. However, given the sociological, economic and sanitary conditions of the country, it is likely that the true ETG is even higher than our estimate. Our study also documents the lack of access to treatment for patients in this developing country. The indirect method could be used to assess the treatment gaps of other chronic medical conditions.

Cost-effectiveness of venlafaxine XL compared with diazepam in the treatment of generalised anxiety disorder in the United Kingdom.

This study used decision modelling to compare the cost-effectiveness of venlafaxine XL (Efexor XL) to that of diazepam to treat non-depressed patients suffering from generalised anxiety disorder (GAD), from the perspective of the United Kingdom's National Health Service (NHS). Starting treatment with venlafaxine XL instead of diazepam significantly increased the expected probability of being in remission by 83% at 6 months (from 16.8% to 30.7%), and the expected probability of relapsing at 6 months was decreased by 79% (from 16.9% to 3.5%). The expected 6-month NHS cost of using venlafaxine XL to treat GAD was estimated to be pounds sterling 353 compared to pounds sterling 311 with diazepam. Hence starting GAD treatment with venlafaxine XL (75 mg per day) instead of diazepam (5 mg three times per day) is clinically more effective and the cost-effective strategy for managing non-depressed patients suffering from GAD in the UK.

Diazepam or midazolam for external DC cardioversion (the DORM Study).

AIMS: To compare the clinical efficacy and tolerability of two intravenous sedatives for physician-led DC cardioversion of atrial arrhythmias. METHODS AND RESULTS: One hundred and forty-one patients attending for elective DC cardioversion of atrial arrhythmias were randomized to intravenous midazolam or diazepam. Sedation was administered using titration protocols. Procedure times, operator satisfaction scores and adverse events were documented. The patients immediate, 24- and 48-h recall and awareness of after-effects were obtained from questionnaires. Seventy-one patients received midazolam (mean 12.5 mg) and 70 patients received diazepam (mean 28.1 mg). There were 16 minor adverse events with midazolam (20% hypotension, 3% oxygen desaturation) and nine with diazepam (7% hypotension, 6% required additional analgesia), P = 0.14. There were no major adverse events. Sedation time was 5.0 +/- 3.4 min for midazolam and 6.5 +/- 3.4 min for diazepam (P = 0.0016). Patients awoke 77 +/- 46 min post-sedation with midazolam and 39 +/- 24 min with diazepam (P < 0.0001). There was no recall of the procedure at 48 h and no difference in awareness of after-effects between the two groups at 24 or 48 h, P = ns. CONCLUSION: Physician-led cardioversion of atrial arrhythmias using intravenous sedation is effective and well tolerated. Sedation with diazepam was associated with fewer minor adverse events and a quicker recovery time than midazolam.

A comparison of lorazepam and diazepam as initial therapy in convulsive status epilepticus.

BACKGROUND: Previous trials have suggested lorazepam may be superior to diazepam as first-line treatment of convulsive status epilepticus (CSE), with improved seizure outcome, and a lower incidence of side-effects. Many published guidelines however still recommend diazepam. AIM: To compare the efficacy, safety and cost of lorazepam compared to diazepam, in adults with CSE. DESIGN: Retrospective case note audit. METHODS: Cases of CSE were retrospectively identified over two 18-month periods either side of the introduction of a new management protocol in May 1997, in which lorazepam 4 mg i.v. was substituted for diazepam 10 mg i.v. as first-line treatment for CSE. Diagnostic codes for all admissions and casualty presentations of patients over 16 years of age were examined for primary or secondary codes including 'epilepsy', 'fits' or 'status epilepticus'. Medical records and casualty notes were reviewed to identify CSE cases. Treatment groups were compared using ANOVA and a Tukey post hoc analysis. Treatment success was defined as cessation of seizures without recurrence in the subsequent 12 h. RESULTS: In both premonitory and established CSE, both drugs were equally effective at terminating seizures, but significantly fewer seizure recurrences followed lorazepam, and fewer repeat doses were needed. There were no differences in reported adverse events or in drug costs. DISCUSSION: We recommend that lorazepam be the first-line therapy in preference to diazepam in adults with CSE.

Treatment of febrile seizures: the influence of treatment efficacy and side-effect profile on value to parents.

OBJECTIVES: We examined parents' perception of the value of treatments designed to reduce the risk of febrile seizure recurrence. STUDY DESIGN: The families of 42 children with febrile seizures were recruited after pediatric or neuropediatric consultation. A mail questionnaire addressed the family's willingness to pay for a hypothetical treatment for febrile seizures with risk reductions for future febrile seizures of 25%, 50%, 75%, and 100%. The hypothetical clinical scenario was then modified to include the side- effect profiles of either daily phenobarbital or valproic acid, or intermittent diazepam prophylaxis. Covariates included the nature of the child's febrile seizure(s), parents' familiarity with febrile seizures, experiences at the time of febrile seizures or with medication side effects, education and income, and mastery and trait anxiety. RESULTS: Thirty-eight parents, representing 22 of 42 families, completed questionnaires. There was a dramatic inflection in parents' willingness to pay for 100% risk reduction as opposed to 75% or lower risk reductions. Introduction of side effects dramatically reduced the value attached to each level of treatment benefit. Nevertheless, a few parents (3/38) would pay "as much as it takes" to be rid of their child's recurrence risk. CONCLUSIONS: Given the range of value assigned to prophylactic medication for febrile seizures, management strategies for children with febrile seizures must be responsive to the needs and values of individual families.

A behavioral economic analysis of polydrug abuse in alcoholics: asymmetrical substitution of alcohol and cocaine.

Economic concepts can be used to assess how drug prices affect consumption patterns. Increases in price for a commodity typically result in reductions in consumption. Demand is considered elastic if decreases in consumption are proportionally greater than increases in price, and inelastic if they are proportionally smaller than rises in price. The price of one commodity can also affect consumption of others. Commodities can function as substitutes, complements or independents, and these concepts refer to increases, decreases, or no change in the consumption of one item as the price of another increases. This study evaluated the effects of drug prices on hypothetical drug-purchasing decisions in 53 alcohol abusers. Experiments 1, 2, and 3 examined how alcohol, cocaine, and Valium prices, respectively, influenced purchases of alcohol, cocaine, Valium, heroin, marijuana and nicotine. As price of alcohol rose in Experiment 1, alcohol purchases decreased and demand for alcohol was inelastic. Cocaine was a complement to alcohol, but other drugs purchases were independent of alcohol prices. In Experiment 2, demand for cocaine was elastic as its price increased. Alcohol was a substitute for cocaine, but other drug purchases did not change significantly. In Experiment 3, demand for Valium was elastic as its price rose, and all other drug purchases were independent of Valium prices. Hypothetical choices were reliable between and within subjects and associated with urinalysis results and lifetime histories of drug abuse. These results suggest that, among alcohol abusers, cocaine is a complement to alcohol, but alcohol is a substitute for cocaine.

Pharmacoeconomic considerations in treatment options for acute seizures.

Two pharmacoeconomic studies on the treatment of acute seizures have been conducted. In 1991, Kriel and colleagues surveyed parents of children with a history of cluster seizures, prolonged seizures, or status epilepticus who had been instructed in the use of rectal diazepam. A comparison of data before instruction with data after instruction showed a reduced need for emergency department visits with rectal diazepam. Instruction thus provided a pharmacoeconomic benefit, despite the cost of the product. In 1996, Marchetti and coworkers found that intravenous fosphenytoin was associated with fewer adverse events than intravenous phenytoin. Fosphenytoin thus reduced the need for adverse event management and provided a substantial pharmacoeconomic benefit, despite its higher cost, compared with phenytoin. This study had a number of limitations, however, and hospital pharmacists remain resistant to the use of fosphenytoin. Additional studies may provide more pharmacoeconomic data to support the greater use of fosphenytoin in the treatment of acute pediatric seizures.

Polydrug abuse in heroin addicts: a behavioral economic analysis.

AIM: To assess how price and income affect hypothetical drug-purchasing decisions of polydrug abusers undergoing treatment for heroin addiction. PARTICIPANTS, DESIGN AND SETTING: Forty subjects participated in experiments in which they hypothetically "purchased" drugs as price or income varied. INTERVENTION: Experiment 1 examined effects of heroin price on purchases of heroin, valium, cocaine, marijuana and alcohol. Experiment 2 examined the effects of both heroin and valium prices on purchases of these drugs. In both these experiments, income remained constant. Experiment 3 examined the effects of increasing income on drug choices, with drug prices constant. FINDINGS: As price of heroin rose in Experiment 1, heroin purchases decreased. Reductions in heroin purchases were proportionally less than price increases, demonstrating inelastic demand for heroin. Valium and cocaine purchases increased as heroin price rose, and cross-price elasticity coefficients indicated that these drugs substituted for heroin. In Experiment 2, demand for both heroin and valium was inelastic. Valium substituted for heroin, but heroin purchases were independent of valium prices, suggesting an asymmetrical substitution effect. Marijuana and alcohol purchases were independent of valium price, but both these drugs substituted for heroin. In Experiment 3 demand for heroin and cocaine was income elastic, with purchases rising in greater proportion than income. Marijuana, alcohol and valium purchases did not vary with income, demonstrating that demand for these drugs was income inelastic. Hypothetical choices were reliable both between and within subjects. Moreover, drug choices in this hypothetical situation were correlated with urinalysis results, demonstrating initial validity of this methodology. CONCLUSIONS: This methodology may be useful for understanding the phenomenon of polydrug abuse.

Trends in the management of alcohol withdrawal syndrome.

Alcohol use among head and neck cancer patients is common. Alcohol withdrawal (especially delirium tremens) poses significant potential morbidity to postsurgical patients. Treatment with newer benzodiazepines (BZDs) such as lorazepam and midazolam has become more widespread, and mortality rates from severe alcohol withdrawal have decreased in recent years. The authors retrospectively studied 102 patients with a diagnosis of alcohol withdrawal, including 20 patients undergoing surgery for cancer of the head and neck. There were 81 men and 21 women, with a mean (+/- standard deviation [SD]) age of 52.3 (+/- 16.1) years. Many of these patients (46%) were treated with more than one BZD or other neuroleptic, while 49% received single agent therapy of either chlordiazepoxide (26%) or lorazepam (23%). Delirium tremens occurred in 12% of all patients undergoing withdrawal and in 10% of head and neck cancer patients, with a mortality rate of 9% and 0%, respectively. Single agent use was successful in greater than 95% when either lorazepam or chlordiazepoxide was used. Instances of combination treatment where older BZDs were used yielded a 69% success rate. The higher complication rate and lower treatment success with combination treatment was multifactorial. Optimal management of the alcohol withdrawal syndrome requires an understanding of its pathophysiology and the principles of its prevention along with a familiarity of BZD pharmacokinetic drug profiles. The authors present a treatment plan which is cost-effective, keeps morbidity low, and should allow a continued decreasing trend in mortality rates from delirium tremens.

Cost of ICU sedation: comparison of empirical and controlled sedation methods.

A randomised crossover study was undertaken to compare the quality and cost of controlled versus empirical sedation with midazolam in critically ill patients. Patients (n = 40) entering the ICU were enrolled provided they satisfied the strict entry criteria. During 90 hours of midazolam sedation, patients received randomly allocated 10-hour periods of controlled or empirical sedation. With empirical sedation, the mean dose of midazolam and the cost of sedation were almost double those with controlled sedation. The quality of sedation was superior with the controlled method. In a separate study on 352 patients, a cost-benefit analysis of controlled sedation with midazolam or propofol infusion or bolus injections of morphine plus diazepam showed that the quality of sedation achieved with propofol was superior to the other two regimens and that, with morphine plus diazepam, the quality of sedation was unacceptably poor. Although the direct purchase price of propofol was higher than that of other agents, the total cost of sedation with propofol was lower than that for midazolam for short-term intensive care (less than 24 hours) and comparable to midazolam for longer-term use. However, indirect benefits of sedation with propofol include a much shorter ICU stay with the attendant reduced nursing costs and greater throughout the patients, and this more than compensates for the higher purchase price of the agent.