Epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge in Japan: An exploratory descriptive study using a nationwide claims database.

BACKGROUND: Little is known about the nationwide epidemiology of the annual rate, causative substance, and clinical course of overdose-related admission. We aimed to describe the epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge to home. METHODS: We assessed all cases of admission due to overdose (21,663 episodes) in Japan from October 2012 through September 2013 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. RESULTS: The annual rate of overdose admission was 17.0 per 100,000 population. Women exhibited two peaks in admission rates at 19-34 years (40.9 per 100,000) and ≥75 years (27.8 per 100,000). Men exhibited one peak in the admission rate at ≥75 years (23.7 per 100,000). Within 90 days prior to overdose, ≥60% and ≥9% of patients aged 19-49 years received a prescription for benzodiazepines and barbiturates, respectively. In addition, 59% of patients aged ≥75 years received a prescription for benzodiazepines prior to overdose, 47% had a history of congestive heart failure, and 24% had a diagnosis of poisoning by cardiovascular drugs. The proportion of patients with recent psychiatric treatments decreased with age (65.1% in those aged 35-49 years and 13.9% in those aged ≥75 years). CONCLUSIONS: The findings emphasize the need for overdose prevention programs that focus on psychiatric patients aged 19-49 years who are prescribed benzodiazepines or barbiturates and on non-psychiatric patients aged ≥75 years who are prescribed benzodiazepines or digitalis.

Neonatal abstinence syndrome: Pharmacologic strategies for the mother and infant.

Opioid use in pregnancy has increased dramatically over the past decade. Since prenatal opioid use is associated with numerous obstetrical and neonatal complications, this now has become a major public health problem. In particular, in utero opioid exposure can result in neonatal abstinence syndrome (NAS) which is a serious condition characterized by central nervous system hyperirritability and autonomic nervous system dysfunction. The present review seeks to define current practices regarding the approach to the pregnant mother and neonate with prenatal opiate exposure. Although the cornerstone of prenatal management of opioid dependence is opioid maintenance therapy, the ideal agent has yet to be definitively established. Pharmacologic management of NAS is also highly variable and may include an opioid, barbiturate, and/or α-agonist. Genetic factors appear to be associated with the incidence and severity of NAS. Establishing pharmacogenetic risk factors for the development of NAS has the potential for creating opportunities for "personalized genomic medicine" and novel, individualized therapeutic interventions.

Hypothermia for Intracranial Hypertension after Traumatic Brain Injury.

BACKGROUND: In patients with traumatic brain injury, hypothermia can reduce intracranial hypertension. The benefit of hypothermia on functional outcome is unclear. METHODS: We randomly assigned adults with an intracranial pressure of more than 20 mm Hg despite stage 1 treatments (including mechanical ventilation and sedation management) to standard care (control group) or hypothermia (32 to 35°C) plus standard care. In the control group, stage 2 treatments (e.g., osmotherapy) were added as needed to control intracranial pressure. In the hypothermia group, stage 2 treatments were added only if hypothermia failed to control intracranial pressure. In both groups, stage 3 treatments (barbiturates and decompressive craniectomy) were used if all stage 2 treatments failed to control intracranial pressure. The primary outcome was the score on the Extended Glasgow Outcome Scale (GOS-E; range, 1 to 8, with lower scores indicating a worse functional outcome) at 6 months. The treatment effect was estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common odds ratio (with an odds ratio <1.0 favoring hypothermia). RESULTS: We enrolled 387 patients at 47 centers in 18 countries from November 2009 through October 2014, at which time recruitment was suspended owing to safety concerns. Stage 3 treatments were required to control intracranial pressure in 54% of the patients in the control group and in 44% of the patients in the hypothermia group. The adjusted common odds ratio for the GOS-E score was 1.53 (95% confidence interval, 1.02 to 2.30; P=0.04), indicating a worse outcome in the hypothermia group than in the control group. A favorable outcome (GOS-E score of 5 to 8, indicating moderate disability or good recovery) occurred in 26% of the patients in the hypothermia group and in 37% of the patients in the control group (P=0.03). CONCLUSIONS: In patients with an intracranial pressure of more than 20 mm Hg after traumatic brain injury, therapeutic hypothermia plus standard care to reduce intracranial pressure did not result in outcomes better than those with standard care alone. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN34555414.).

Economic evaluation of decompressive craniectomy versus barbiturate coma for refractory intracranial hypertension following traumatic brain injury.

OBJECTIVES: Decompressive craniectomy and barbiturate coma are often used as second-tier strategies when intracranial hypertension following severe traumatic brain injury is refractory to first-line treatments. Uncertainty surrounds the decision to choose either treatment option. We investigated which strategy is more economically attractive in this context. DESIGN: We performed a cost-utility analysis. A Markov Monte Carlo microsimulation model with a life-long time horizon was created to compare quality-adjusted survival and cost of the two treatment strategies, from the perspective of healthcare payer. Model parameters were estimated from the literature. Two-dimensional simulation was used to incorporate parameter uncertainty into the model. Value of information analysis was conducted to identify major drivers of decision uncertainty and focus future research. SETTING: Trauma centers in the United States. SUBJECTS: Base case was a population of patients (mean age = 25 yr) who developed refractory intracranial hypertension following traumatic brain injury. INTERVENTIONS: We compared two treatment strategies: decompressive craniectomy and barbiturate coma. MEASUREMENTS AND MAIN RESULTS: Decompressive craniectomy was associated with an average gain of 1.5 quality-adjusted life years relative to barbiturate coma, with an incremental cost-effectiveness ratio of $9,565/quality-adjusted life year gained. Decompressive craniectomy resulted in a greater quality-adjusted life expectancy 86% of the time and was more cost-effective than barbiturate coma in 78% of cases if our willingness-to-pay threshold is $50,000/quality-adjusted life year and 82% of cases at a threshold of $100,000/quality-adjusted life year. At older age, decompressive craniectomy continued to increase survival but at higher cost (incremental cost-effectiveness ratio = $197,906/quality-adjusted life year at mean age = 85 yr). CONCLUSIONS: Based on available evidence, decompressive craniectomy for the treatment of refractory intracranial hypertension following traumatic brain injury provides better value in terms of costs and health gains than barbiturate coma. However, decompressive craniectomy might be less economically attractive for older patients. Further research, particularly on natural history of severe traumatic brain injury patients, is needed to make more informed treatment decisions.

Early drug discovery and the rise of pharmaceutical chemistry.

Studies in the field of forensic pharmacology and toxicology would not be complete without some knowledge of the history of drug discovery, the various personalities involved, and the events leading to the development and introduction of new therapeutic agents. The first medicinal drugs came from natural sources and existed in the form of herbs, plants, roots, vines and fungi. Until the mid-nineteenth century nature's pharmaceuticals were all that were available to relieve man's pain and suffering. The first synthetic drug, chloral hydrate, was discovered in 1869 and introduced as a sedative-hypnotic; it is still available today in some countries. The first pharmaceutical companies were spin-offs from the textiles and synthetic dye industry and owe much to the rich source of organic chemicals derived from the distillation of coal (coal-tar). The first analgesics and antipyretics, exemplified by phenacetin and acetanilide, were simple chemical derivatives of aniline and p-nitrophenol, both of which were byproducts from coal-tar. An extract from the bark of the white willow tree had been used for centuries to treat various fevers and inflammation. The active principle in white willow, salicin or salicylic acid, had a bitter taste and irritated the gastric mucosa, but a simple chemical modification was much more palatable. This was acetylsalicylic acid, better known as Aspirin®, the first blockbuster drug. At the start of the twentieth century, the first of the barbiturate family of drugs entered the pharmacopoeia and the rest, as they say, is history.

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.

Patterns of medical diagnosis and treatment of migraine and probable migraine in a health plan.

The objectives of this study were to assess the proportion of subjects with strict migraine (SM, migraine with and without aura), probable migraine (PM), and all migraine (AM, SM and PM pooled together), who receive a medical diagnosis or a specific treatment within a health plan. Eligible participants were 18-55-year participants of a non-profit health maintenance organization (HMO) who had received out-patient, emergency department, or in-patient care from a physician within the past year. We used a validated computer-assisted telephone interview (CATI) survey to identify SM, PM and controls (received out-patient, emergency department, or in-patient care from a physician for any reason within the past year, but did not have SM or PM). Medical and prescription drug claims for the 24-month period were linked to participant files. Among 8579 respondents, we identified 1265 SM sufferers and 1252 PM sufferers, which were compared with 960 randomly selected controls. Just 194 (15.3%) SM, 21 (1.7%) PM, and 215 (8.5%) AM sufferers received an in-patient or out-patient primary migraine claim in the previous 24 months, compared with six (0.5%) controls; 240 (18.9%) SM, 39 (3.1%) PM, 279 (11.1%) AM sufferers, and eight controls (0.6%) received any migraine claim. There were claims for migraine drugs (ICD-9 code for triptans or ergot compounds) for just 140 (11.1%) SM and 34 (2.7%) PM sufferers, and migraine analgesics (butalbital and isomethepthene compounds), for 6.3% SM and 2.2% PM sufferers (0.7% of the controls). Migraine preventives were used for a larger number of SM and PM sufferers (19.6% and 13.1%), but also for controls (10.5%), indicating that they were probably used for other medical reasons. Both SM and PM are underdiagnosed and undertreated within a health plan. Educational strategies should focus on physician education addressing diagnosing the full spectrum of migraine and physician management of migraine with specific migraine therapy in appropriate patients.

Butalbital-containing agents: should they be banned? No.

Butalbital compounds are of proven efficacy in the treatment of tension headache. Decades of experience have established their value in the treatment of other mild-to-moderate headaches. Untold numbers of people rely on these medications as their drug of choice or use them when vasoconstrictors, opioids, or nonsteroidal anti-inflammatory agents are contraindicated. The medications are cost-effective with only occasional and minor immediate adverse effects. Their overuse may cause the evolution of episodic primary headaches to chronic daily headaches; however, removal of these agents from the market would reduce the chronic daily headache in the general population by a small fraction of 1%.

Should butalbital-containing analgesics be banned? Yes.

In the United States analgesic-overuse headache is often caused by butalbital-containing analgesics. These agents can cause physical and psychological dependency, and dangerous withdrawal syndromes. Butalbital-containing analgesics have already been banned in several European countries. They are proven effective in tension-type headache, but not in migraine; there are many alternative treatments for migraine and tension-type headache. In the 20 years since analgesic overuse headache was widely recognized, butalbital overuse has remained distressingly common. It is time to ban these agents.

[Value of early acoustic and somatosensory evoked potentials in monitoring and prognostic assessment of coma in barbiturate therapy--comparison with clinical aspects and EEG]. / Zum Stellenwert früher akustischer und somatosensorisch evozierter Potentiale in der Uberwachung und prognostischen Beurteilung des Komas unter Barbiturattherapie--vergleichende Untersuchungen mit Klinik und EEG.

25 comatose patients suffering from severe cerebral lesions of different etiology were examined during barbiturate-therapy by Glasgow-Pittsburg-Coma-Scoring-System (GPCS), EEG, somatosensory and brainstem acoustic evoked potentials. The findings were correlated in view of prognostic prediction and importance for monitoring. A modified form of the Glasgow-Outcome-Score (GOS; independent-survival, dependent-survival, dead) was used for evaluating the outcome. In case of an initial GPCS less than 10 points none of the patients survived, in case of GPCS greater than 10 points 11 out of 19 patients survived. The latter relation of survival was also found in patients with improving or impairing scores during the observation period. In case of initial burst-suppression pattern in the EEG 7 out of 11 patients survived, in case of diffuse abnormalities with or with-out additional focal signs - 4 out of 10 patients survived, but in the latter there was none with an outcome of independent survival. All patients with an isoelectric EEG died. In case of bilateral recording of scalp- SEP 7 out of 11 patients survived, in case of unilateral loss of scalp-EP 4 out of 8 patients survived, but in the latter cases none with an outcome of independence. All patients with initial bilateral failure of scalp-SSEP or loss during the observation period died. In case of bilateral registrable BAEP (wave I to V) 11 out of 17 patients survived. All patients with initial uni- or bilateral failure of those potentials or loss during the observation period died.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of Fiorinal with Codeine in the treatment of tension headache.

A randomized, double-blind, placebo-controlled, multicenter study was conducted to ascertain the contribution of Fiorinal and codeine phosphate to the efficacy of Fiorinal with Codeine in relieving the pain, tension, and muscle stiffness associated with tension headache. Patients were given Fiorinal with Codeine, Fiorinal alone, codeine alone, or placebo for use during two separate headache attacks at least 24 hours apart and were asked to rate the effectiveness of the assigned medication on each occasion. The various symptoms of tension headache were evaluated by the patient 0.5, 1, 2, 3, and 4 hours after ingestion of the study medication. At the final patient visit, the investigator assessed the effect of treatment on the three chief components of tension headache, head pain, psychic tension, and muscle contraction. Fiorinal with Codeine was generally significantly more effective than placebo or Fiorinal alone in improving all patient-evaluated items between the second and the fourth hours after administration. The combination was also generally significantly better than codeine alone with respect to pain severity, pain relief, the ability to perform daily activities, and average pathology. The three variables rated by the physician also were generally reduced significantly more with the combination than with placebo or Fiorinal alone. Side effects occurred in only one patient treated with Fiorinal with Codeine.

Energy expenditure in acute trauma to the head with and without barbiturate therapy.

The increased energy expenditure associated with severe trauma to the head appears genuine but exhibits wide variation in its magnitude. Patients with severe acute trauma to the head without barbiturate treatment are hypermetabolic with an average energy expenditure 26 per cent over predicted. Barbiturate therapy abolishes this hypermetabolism and decreases energy expenditure to 14 per cent below predicted. In the individual patient, there appears to be a close relationship between the degree of suppression of energy expenditure and the serum barbiturate level. However, this relationship would appear to be different in each patient, and therefore, for this group, a significant correlation between energy expenditure and serum barbiturate level does not exist. The wide variability of energy expenditure in individual patients makes the estimation of energy expenditure by population predictive formulas imprecise. This may lead to incorrect estimates of caloric requirements and inappropriate provision of exogenous energy substrates. Although for those patients receiving energy expenditure and serum barbiturate levels in the individual may further aid in estimating the caloric expenditure for each individual, in order to provide appropriate amounts of calories to the patient with trauma to the head, energy expenditure should be measured in each instance.

Evaluation and management of the violent patient in emergency settings.

The evaluation and management of the violent patient in emergency settings is a complicated task for emergency psychiatric specialists. Etiologic considerations must be carefully weighed. The interplay of biologic, psychologic, and social factors has to be clearly recognized. Psychiatrists and physicians staffing emergency departments must be facile with the application of psychopharmacologic treatment. In addition, a familiarity and comfort with physical restraint must be developed. Interview styles and stances that diverge from traditional psychiatric "examining" should be employed. There is no sure-fire way to prevent violence, but adhering to the above principles should help to minimize violence as well as allow staff to comfort this most difficult aspect of emergency psychiatry.

Barbiturate prescribing: psychiatrists' views.

When questioned by post most of a one-in five sample of consultant psychiatrists replied that they did not favour the use of barbiturates as hypnotics or a sedatives.