Costs and Utilization of New-to-Market Neurologic Medications.

BACKGROUND AND OBJECTIVES: The objective of this study was to compare the utilization and costs (total and out-of-pocket) of new-to-market neurologic medications with existing guideline-supported neurologic medications over time. METHODS: We used a healthcare pharmaceutical claims database (from 2001 to 2019) to identify patients with both a diagnosis of 1 of 11 separate neurologic conditions and either a new-to-market medication or an existing guideline-supported medication for that condition. Neurologic conditions included orthostatic hypotension, spinal muscular atrophy, Duchenne disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, myasthenia gravis, Huntington disease, tardive dyskinesia, transthyretin amyloidosis, and migraine. New-to-market medications were defined as all neurologic medications approved by the US Food and Drug Administration (FDA) between 2014 and 2018. In each year, we determined the median out-of-pocket and standardized total costs for a 30-day supply of each medication. We also measured the proportion of patients receiving new-to-market medications compared with all medications specific for the relevant condition. RESULTS: We found that the utilization of most new-to-market medications was small (<20% in all but 1 condition), compared with existing, guideline-supported medications. The out-of-pocket and standardized total costs were substantially larger for new-to-market medications. The median (25th percentile, 75th percentile) out-of-pocket costs for a 30-day supply in 2019 were largest for edaravone ($712.8 [$59.8-$802.0]) and eculizumab ($91.1 [$3.0-$3,216.4]). For new-to-market medications, the distribution of out-of-pocket costs was highly variable and the trends over time were unpredictable compared with existing guideline-supported medications. DISCUSSION: Despite the increasing number of FDA-approved neurologic medications, utilization of newly approved medications in the privately insured population remains small. Given the high costs and similar efficacy for most of the new medications, limited utilization may be appropriate. However, for new medications with greater efficacy, future studies are needed to determine whether high costs are a barrier to utilization.

Effect of enterally administered sleep-promoting medication on the intravenous sedative dose and its safety and cost profile in mechanically ventilated patients: A retrospective cohort study.

BACKGROUND: The clinical effect of enteral administration of sleep-promoting medication (SPM) in mechanically ventilated patients remains unclear. This study aimed to investigate the relationship between enteral SPM administration and the intravenous sedative dose and examine the safety and cost of enteral SPM administration. METHODS: This single-center retrospective cohort study was conducted in a Japanese tertiary hospital intensive care unit (ICU). The exposure was enteral SPM administration during mechanical ventilation. The outcome was the average daily propofol dose per body weight administered as a continuous sedative during mechanical ventilation. Patients were divided into three groups based on the timing of SPM administration at ICU admission: "administration within 48 hours (early administration [EA])," "administration after 48 hours (late administration [LA])," and "no administration (NA)." We used multiple linear regression models. RESULTS: Of 123 included patients, 37, 50, and 36 patients were assigned to the EA, LA, and NA groups, respectively. The average daily propofol dose per body weight was significantly lower in the EA group than in the LA and NA groups (ß -5.13 [95% confidence interval (CI) -8.93 to -1.33] and ß -4.51 [95% CI -8.59 to -0.43], respectively). Regarding safety, enteral SPM administration did not increase adverse events, including self-extubation. The total cost of neuroactive drugs tended to be lower in the EA group than in the LA and NA groups. CONCLUSIONS: Early enteral SPM administration reduced the average daily propofol dose per body weight without increasing adverse events.

Specialist alcohol inpatient treatment admissions and non-specialist hospital admissions for alcohol withdrawal in England: an inverse relationship.

AIMS: We assessed the relationship between specialist and non-specialist admissions for alcohol withdrawal since the introduction of the UK government Health and Social Care Act in 2012. METHODS: Using publicly available national data sets from 2009 to 2019, we compared the number of alcohol withdrawal admissions and estimated costs in specialist and non-specialist treatment settings. RESULTS: A significant negative correlation providing strong evidence of an association was observed between the fall in specialist and rise in non-specialist admissions. Significant cost reductions within specialist services were displaced to non-specialist settings. CONCLUSIONS: The shift in demand from specialist to non-specialist alcohol admissions due to policy changes in England should be reversed by specialist workforce investment to improve outcomes. In the meantime, non-specialist services and staff must be resourced and equipped to meet the complex needs of these service users.

The Effects of Melatonin Supplementation on Sleep Quality and Assessment of the Serum Melatonin in ICU Patients: A Randomized Controlled Trial.

OBJECTIVES: To evaluate whether the use of exogenous melatonin affects sleep, reduces the prevalence of delirium, and decreases the need for analgosedation and to assess whether serum melatonin indices correlate with exogenous administration in critically ill patients. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: Multicenter ICUs of two tertiary hospitals. PATIENTS: A total of 203 adult patients who were admitted to the ICU and administered with analgesics and/or sedatives. INTERVENTIONS: Oral melatonin (10 mg) or placebo for up to seven consecutive nights. MEASUREMENTS AND MAIN RESULTS: The number of observed sleeping hours at night was assessed by the bedside nurse. Sleep quality was evaluated using the Richards Campbell Questionnaire Sleep (RCSQ). The prevalence of delirium, pain, anxiety, adverse reactions, duration of mechanical ventilation, length of ICU and hospital stays, and doses of sedative and analgesic drugs administered were recorded. The use of analgesics and sedatives was assessed daily. Melatonin levels were determined by enzyme-linked immunosorbent assay. Based on the RCSQ results, sleep quality was assessed to be better in the melatonin group than that in the placebo group with a mean (SD) of 69.7 (21.2) and 60.7 (26.3), respectively (p = 0.029). About 45.8% and 34.4% of participants in the melatonin and placebo groups had very good sleep (risk ratio, 1.33; 95% CI, 0.94-1.89), whereas 3.1% and 14.6% had very poor sleep (risk ratio, 0.21; 95% CI, 0.06-0.71), respectively. No significant difference was observed regarding the days free of analgesics or sedatives, the duration of night sleep, and the occurrence of delirium, pain, and anxiety. Melatonin serum peak levels at 2 AM were 150 pg/mL (range, 125-2,125 pg/mL) in the melatonin group and 32.5 pg/mL (range, 18.5-35 pg/mL) in the placebo group (p < 0.001). CONCLUSIONS: Melatonin was associated with better sleep quality, which suggests its possible role in the routine care of critically ill patients in the future.

Prescription Benzodiazepine Use in Privately Insured U.S. Children and Adolescents.

INTRODUCTION: Benzodiazepines are commonly prescribed in the U.S. but entail safety concerns, including dependency. In pediatrics, many indications lack trial data. Authors aimed to describe youth initiating prescription benzodiazepine treatment, identify potential indications and prescribing concerns, estimate the duration of treatment by potential indication, and identify factors that predict long-term use. METHODS: The study cohort included children (aged 3-12 years) and adolescents (aged 13-17 years) initiating prescription benzodiazepine treatment (≥3 days' supply) from January 2010 to September 2015 in a U.S. commercial claims database. Potential indications included selected ICD-9-CM diagnoses (≤30 days prior). Long-term (≥6 months) benzodiazepine treatment was estimated with Kaplan-Meier estimation and modified Poisson regression identified independent predictors of long-term benzodiazepine treatment (analysis completed in 2018). RESULTS: Of 24,504 children and 61,046 adolescents initiating benzodiazepines, 62% of the children and 68% of the adolescents had a potential indication. Anxiety disorders were the most common indication, with mental health indications more common among adolescents (45%) than children (23%) and epilepsy and movement disorders higher in children. Recent opioid prescriptions were common before benzodiazepine initiation (children, 22%; adolescents, 21%). Six percent of the initiators became long-term benzodiazepine users. Potential indication, provider contact, psychotropic medication, and chronic conditions independently predicted long-term benzodiazepine treatment in adolescents and children. CONCLUSIONS: U.S. children and adolescents are prescribed benzodiazepines for various mental health and other medical conditions, many lacking evidence of pediatric efficacy. Long-term benzodiazepine treatment, concurrent opioid prescriptions, psychotropic use, and prior substance use disorder diagnoses suggest safety risks among some youth prescribed benzodiazepines.

Alcohol withdrawal is associated with poorer outcome in acute ischemic stroke.

OBJECTIVE: To determine the association between alcohol abuse (AA) and alcohol withdrawal (AW) with acute ischemic stroke (AIS) outcomes. METHODS: All adult AIS admissions in the United States from 2004 to 2014 were identified from the National Inpatient Sample (weighted n = 4,438,968). Multivariable-adjusted models were used to evaluate the association of AW with in-hospital medical complications, mortality, cost, and length of stay in patients with AIS. RESULTS: Of the AA admissions, 10.6% of patients, representing 0.4% of all AIS, developed AW. The prevalence of AA and AW in AIS increased by 45.2% and 40.0%, respectively, over time (p for trend <0.001). Patients with AA were predominantly men (80.2%), white (65.9%), and in the 40- to 59-year (44.6%) and 60- to 79-year (45.6%) age groups. After multivariable adjustment, AIS admissions with AW had >50% increased odds of urinary tract infection, pneumonia, sepsis, gastrointestinal bleeding, deep venous thrombosis, and acute renal failure compared to those without AW. Patients with AW were also 32% more likely to die during their AIS hospitalization compared to those without AW (odds ratio 1.32, 95% confidence interval 1.11-1.58). AW was associated with ≈15-day increase in length of stay and ≈$5,000 increase in hospitalization cost (p < 0.001). CONCLUSION: AW is associated with increased cost, longer hospitalizations, and higher odds of medical complications and in-hospital mortality after AIS. Proactive surveillance and management of AW may be important in improving outcomes in these patients.

Historical Persistence of Alcohol-Induced Mortality in the Russian Federations: Legacy of Early Industrialization.

AIMS: The study aims to investigate insofar regional differences in alcohol-induced mortality in Russia, which emerged during the early industrialization of the country, persisted over a prolonged period of time (from late nineteenth to early twenty-first century), surviving fundamental political and social changes Russia experienced. METHODS: Multivariate regression models with historical and contemporary data on alcohol-induced mortality in Russian regions were estimated to document the persistence of spatial patterns of mortality, as well as to identify the possible mediating variables. Numerous robustness checks were used to corroborate the results. RESULTS: Alcohol-induced male mortality in Russian regions in 1880s-1890s is significantly and strongly correlated with male mortality due to accidental alcohol poisoning in Russian regions in 2010-2012. For female mortality, no robust correlation was established. The results for male mortality do not change if one controls for a variety of other determinants of alcohol-induced mortality and are not driven by outlier regions. Consumption of strong alcohol (in particular vodka) appears to be the mediator variable explaining this persistence. CONCLUSIONS: Hazardous drinking behavioral patterns, once they emerge and crystalize during the periods of fragmentation of the traditional society and the early onsets of modernization and urbanization, can be extremely persistent. Even highly intrusive policy interventions at a later stage (like those of the Soviet government) may turn out to be insufficient to change the path-dependent outcomes.

Reward, Relief and Habit Drinking: Initial Validation of a Brief Assessment Tool.

AIMS: Alcohol use disorder is highly heterogeneous. One approach to understanding this heterogeneity is the identification of drinker subtypes. A candidate classification consists of reward and relief subtypes. The current study examines a novel self-report measure of reward, relief, and habit drinking for its clinical correlates and subjective response (SR) to alcohol administration. METHODS: Non-treatment-seeking heavy drinkers (n = 140) completed the brief reward, relief, habit drinking scale (RRHDS). A subset of this sample (n = 67) completed an intravenous alcohol administration. Individuals were classified into drinker subtypes. A crowdsourced sample of heavy drinkers (n = 187) completed the RRHDS and a validated reward relief drinking scale to compare drinking classification results. RESULTS: The majority of the sample was classified as reward drinkers (n = 100), with fewer classified as relief (n = 19) and habit (n = 21) drinkers. Relief and habit drinkers reported greater tonic alcohol craving compared to reward drinkers. Reward drinkers endorsed drinking for enhancement, while relief drinkers endorsed drinking for coping. Regarding the alcohol administration, the groups differed in negative mood, such that relief/habit drinkers reported a decrease in negative mood during alcohol administration, compared to reward drinkers. The follow-up crowdsourcing study found a 62% agreement in reward drinker classification between measures and replicated the tonic craving findings. CONCLUSIONS: Our findings suggest that reward drinkers are dissociable from relief/habit drinkers using the brief measure. However, relief and habit drinkers were not successfully differentiated, which suggests that these constructs may overlap phenotypically. Notably, measures of dysphoric mood were better at detecting group differences than measures capturing alcohol's rewarding effects.

Price of Four Loko in Large U.S. Cities, 2018.

BACKGROUND: Supersized alcopops are flavored alcoholic beverages that contain up to 5.5 standard alcoholic drinks in a single can. Limited research suggests Four Loko-the most commonly consumed supersized alcopop by underage drinkers-is among the least expensive ready-to-drink alcohol products on the U.S. market. This is a public health concern because alcohol prices are inversely associated with consumption and related harms, particularly among youth. This study investigated Four Loko's retail price per volume of alcohol in large U.S. cities. METHODS: This study used multistage random sampling to collect data in the largest city of each state and Washington, DC. A simple random sample of 5 ZIP codes from each city was selected and entered into Four Loko's website product locator. Within ZIP codes, up to 4 stores were randomly selected and contacted by telephone. Retailers were interviewed about Four Loko in regard to: availability, volume, alcohol by volume (abv), price for 1 can, and discounts for purchasing more than 1 can. RESULTS: The sample included 344 retail stores with Four Loko in stock. Average price per standard alcoholic drink (i.e., 14 g of absolute alcohol) was $0.54 for Four Loko products. Taking into account volume, price, and discounts, an average of 17 standard alcoholic drinks could be purchased via Four Loko with $10. Adjusted analysis using linear regression showed that availability of bulk price discounts and higher abv (14% vs. 12%) were associated with lower price per drink. CONCLUSION: This study verifies that Four Loko is among the least expensive ready-to-drink alcohol available for purchase in the United States. Given that consuming a single supersized alcopop constitutes binge drinking and is therefore unsafe, regulatory agencies should consider a variety of steps to reduce the availability and abv of these products and increase their retail price in order to reduce and prevent unsafe alcohol consumption.

Trends in Prescribed Central Nervous System Depressant Medications Among Adults Who Regularly Consume Alcohol: United States 1999 to 2014.

BACKGROUND: Although the risks of using central nervous system depressant (CNS-D) medications with alcohol are well documented, little is known about trends in prescribed use of these medications among individuals who regularly consume alcohol (i.e., trends in "concurrent use"). We examined changes in the prevalence of prescribed CNS-D medications among individuals who drank alcohol on 52 or more occasions in the past year ("regular drinking"). CNS-D medications included sedative-hypnotics (subclassified as anxiolytics or sleep medications) and opioids. METHODS: We used 8 cross-sectional cycles of the National Health and Nutrition Examination Survey (1999-2000 to 2013-2014) from participants aged 20 and older (n = 37,709). We used log-binomial regression to examine (i) prevalence trends of prescribed CNS-D medication use, (ii) trend differences by drinking status, and (iii) correlates of CNS-D medication use. RESULTS: Among those who drink regularly, the relative annual increase in prevalence of sedative-hypnotic use was 5.3% (95% CI: 2.7 to 7.9): Anxiolytic and sleep medication use increased annually by 3.7% (95% CI: 0.8 to 6.7) and 11.2% (95% CI: 6.5 to 16.0), respectively. Opioid use trends among those who drink regularly were not statistically significant but were nonlinear. Differences in CNS-D medication trends between those who drink regularly and those who drink infrequently/abstain were not statistically significant. Those who drink regularly were less likely than those who drink infrequently/abstain to use opioids (adjusted relative risk [ARR]: 0.69, 95% CI: 0.60 to 0.78) and anxiolytics (ARR: 0.71, 95% CI: 0.61 to 0.81), but not sleep medications (ARR: 1.04, 95% CI: 0.80 to 1.35). Those aged 40 and older were 2 to 5 times as likely as those aged 20 to 29 to use sedative-hypnotics. CONCLUSIONS: Among those who drink regularly, the prevalence of prescribed sedative-hypnotic use increased and prescribed opioid use remained common. These trends indicate that a substantial portion of the population is at risk of alcohol-related adverse drug reactions-particularly those aged 40 and older.

Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial.

BACKGROUND: ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation. METHODS: This was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12% (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality. RESULTS: There were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8% (74.1-100), intravenous 94.4% (78-100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6%) vs 7 (4.2%), p < 0.01; more self-extubations: n = 14 (8.1%) vs 4 (2.4%), p = 0.03; a lighter sedative target (RASS = 0): 93% (71-100) vs 83% (61-100), p < 0.01; and lower total drug costs: 2.39 (0.75-9.78) vs 4.15 (1.20-20.19) €/day with mechanical ventilation (p = 0.01). CONCLUSIONS: Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01360346 . Registered on 25 March 2011.

Effect of Alcohol Sensitivity in Healthy Young Adults on Breath Pharmacokinetics of Acetaldehyde After Mouth Washing with Alcohol.

BACKGROUND: Acetaldehyde is causally related to head and neck cancer. Individuals with aldehyde dehydrogenase 2 deficiency experience alcohol sensitivity and are referred to as "flushers" because of their skin-flushing response to high blood acetaldehyde levels after alcohol consumption. Acetaldehyde is produced in the oral cavity after local alcohol exposure without alcohol ingestion. However, the relationship between the oral acetaldehyde level after local alcohol exposure and alcohol sensitivity is unclear. Herein, sampling the exhaled breath, we evaluated the effect of alcohol sensitivity on the pharmacokinetics of ethanol (EtOH) and acetaldehyde in breath after mouth washing with alcohol. METHODS: Twenty-eight healthy young adults were divided into flusher and nonflusher groups based on an EtOH patch test. The subjects washed their mouths for 30 seconds with 40 ml of 5% v/v alcohol, and their breath samples were collected 12 times over 20 minutes after mouth washing and rinsing with water. EtOH and acetaldehyde concentrations in all breath samples were measured using sensor gas chromatography. RESULTS: Breath EtOH concentrations exponentially decreased in both groups after mouth washing with alcohol. Breath acetaldehyde concentrations showed an immediate increase, followed by an almost exponential decrease in both groups, but concentrations in the flusher group remained higher than those in the nonflusher group throughout the 20-minute measurement period. This was reflected in a peak concentration (Cmax ) of 808 ± 70 parts-per-billion (ppb) versus 1,715 ± 223 ppb, respectively (p = 0.001), and area under the curve values of 3,528 ± 1,399 ppb minutes versus 8,637 ± 1,293 ppb minutes, respectively (p = 0.002). CONCLUSIONS: This study revealed high concentrations of acetaldehyde in breath after local alcohol exposure in the oral cavity among flushers even without alcohol ingestion. This contributes to an increased risk among flushers of mutagenic DNA lesions in the mucosa of the upper digestive tract and cancer.

Chemical characterization and safety assessment of dokha: An emerging alternative tobacco product.

Dokha is known to be one of the most rapidly spreading alternative tobacco products (ATPs) in the Middle East and North Africa (MENA) region. It is smoked using a pipe known as Midwakh. There is no scientific research published on the chemical composition of dokha and only very little was done to investigate its impact on human health. Three different types of dokha were included in this study. The trace metals content in the dokha samples were analyzed using inductively-coupled plasma-optical emission spectroscopy and energy-dispersive X-ray spectroscopy-scanning electron microscope. Dokha smoke was generated using a device that simulates human smoking/puffing. The smoke samples were collected on Tenax and activated carbon adsorbent tubes followed by chemical analysis using thermal desorption-gas chromatography-mass spectrometry. The results showed the presence of toxic metals in dokha samples such as cobalt, cadmium, chromium, and lead in amounts classified as harmful to human health. In addition, the presence of several potentially harmful and even toxic organic compounds in dokha smoke was identified based on the available clinical data. These included 22 irritants, 3 known carcinogens, and 5 central nervous system (CNS) depressants in addition to several other compounds with miscellaneous effects. The findings of this work demonstrate evidence for the presence of potentially harmful and toxic metals and compounds in dokha tobacco as well as dokha smoke. More research is required to further investigate the clinical impact of dokha on human health.

Esophageal Cooling Device Versus Other Temperature Modulation Devices for Therapeutic Normothermia in Subarachnoid and Intracranial Hemorrhage.

Achieving and maintaining normothermia (NT) after subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) often require temperature modulating devices (TMD). Shivering is a common adverse effect of TMDs that can lead to further costs and complications. We evaluated an esophageal TMD, the EnsoETM (Attune Medical, Chicago, IL), to compare NT performance, shiver burden, and cost of shivering interventions with existing TMDs. Patients with SAH or ICH and refractory fever were treated with the EnsoETM. Patient demographics, temperature data, shiver severity, and amounts and costs of medications used for shiver management were prospectively collected. Controls who received other TMDs were matched for age, gender, and body surface area to EnsoETM recipients, and similar retrospective data were collected. All patients were mechanically ventilated. Fever burden was calculated as areas of curves of time spent above 37.5°C or 38°C. Demographics, temperature data, and costs of EnsoETM recipients were compared with recipients of other TMDs. Eight EnsoETM recipients and 24 controls between October 2015 and November 2016 were analyzed. There were no differences between the two groups in demographics or patient characteristics. No difference was found in temperature at initiation (38.7°C vs. 38.5°C, p = 0.4) and fever burden above 38°C (-0.44°C × hours vs. -0.53°C × hours, p = 0.47). EnsoETM recipients showed a nonsignificant trend in taking longer to achieve NT than other TMDs (5.4 hours vs. 2.9 hours, p = 0.07). EnsoETM recipients required fewer shiver interventions than controls (14 vs. 30, p = 0.02). EnsoETM recipients incurred fewer daily costs than controls ($124.27 vs. $232.76, p = 0.001). The EnsoETM achieved and maintained NT in SAH and ICH patients and was associated with less shivering and lower pharmaceutical costs than other TMDs. Further studies in larger populations are needed to determine the EnsoETM's efficacy in comparison to other TMDs.

Population Level Effects of a Mass Media Alcohol and Breast Cancer Campaign: A Cross-Sectional Pre-Intervention and Post-Intervention Evaluation.

AIMS: To examine the relationship between a TV-led breast cancer mass-media campaign in the North East of England (conducted in two waves: Jul/2015 and Nov/2015), awareness of the link between alcohol and cancer, intention to reduce alcohol consumption and support for alcohol related policies. METHODS: Three cross-sectional surveys were conducted; one over the 2 weeks pre-campaign (n = 572); one immediately following campaign wave 1 (n = 576); and another immediately following campaign wave 2 (n = 552). Survey questions assessed; campaign exposure; awareness of the links between alcohol and related cancers; intention to change alcohol consumption; and support for alcohol related policies. RESULTS: The proportion of respondents indicating awareness of alcohol as a cancer risk factor was larger post-campaign compared to pre-campaign. The largest increase was seen for breast cancer with 45% aware of the links post-campaign wave 2 compared to 33% pre-campaign. The proportion of respondents indicating 'strong support' of the seven alcohol related policies significantly increased between surveys. The proportion of respondents both aware of alcohol as a cancer risk factor and supportive of the seven alcohol related policies significantly increased between surveys. There was no significant change in self-reported intention to reduce alcohol consumption amongst increasing/higher risk drinkers. CONCLUSION: These findings indicate that a mass-media campaign raising awareness of the links between alcohol and breast cancer is associated with increased awareness and alcohol related policy support at a population level. However, there was no association found with a change in short-term drinking intentions. SHORT SUMMARY: A mass-media campaign raising awareness of the links between alcohol and breast cancer is associated with increased awareness and alcohol policy support at a population level but does not appear to be associated with a change in short term drinking intentions.

Improving uncertainty in Widmark equation calculations: Alcohol volume, strength and density.

The Widmark equation is probably the most commonly used calculation for medicolegal purposes. Recently the National Research Council (USA) and the Forensic Science Regulator (UK) have called for the uncertainty of all results to be given with all forensic measurements and calculations. To improve the uncertainty of measurement of results from Widmark calculations we have concentrated on the uncertainties of measurement involved in the calculation of amount of alcohol, that of the volume of alcohol, the concentration of alcohol and the density of alcohol as previous studies have investigated some of the other factors involved. Using experimental studies, the scientific literature and legal statutes, we have determined revised and improved uncertainties of the concentration of ethanol for Widmark calculations for both the USA and UK. Based on the calculations that we have performed we recommend the use of Monte Carlo Simulation for the determination of uncertainty of measurement for Widmark Calculations.

Adolescent binge alcohol exposure increases risk assessment behaviors in male Wistar rats after exposure to an acute psychological stressor in adulthood.

Teenage binge drinking is a common practice that has been shown to increase the risk for developing mood disorders in adulthood. The hypothalamo-pituitary-adrenal (HPA) axis is often dysfunctional in mood disorder patients, and animal models of adolescent binge alcohol exposure similarly show disordered HPA axis function, even after long periods of alcohol abstinence. Here, we sought to investigate the anxiety-like behavioral consequences of binge alcohol exposure in a Wistar rat model. Male rats were administered alcohol in a binge pattern during peri-puberty, and one month later, anxiety-like behaviors were measured using the elevated plus maze. A subset of the rats then underwent 30min of restraint stress, and the anxiety-like behaviors were measured again. We observed an increase in risk assessment behaviors due to both adolescent binge alcohol exposure and restraint stress, but no differences in canonical anxiety-like behaviors. We also repeated the observation that adolescent binge alcohol induces long-term changes in HPA axis sensitivity. Therefore, we concluded that a history of peri-pubertal binge alcohol exposure subtly alters the behavioral response to subsequent acute psychological stress during adulthood, which may over time contribute to the development of mood disorders. This relatively pragmatic animal model represents a more clinically relevant tool in understanding the molecular mechanisms underlying the long-term effects of adolescent binge drinking.

Alcohol exposure in utero is associated with decreased gray matter volume in neonates.

Neuroimaging studies have indicated that prenatal alcohol exposure is associated with alterations in the structure of specific brain regions. However, the temporal specificity of such changes and their behavioral consequences are less known. Here we explore the brain structure of infants with in utero exposure to alcohol shortly after birth. T2 structural MRI images were acquired from 28 alcohol-exposed infants and 45 demographically matched healthy controls at 2-4 weeks of age on a 3T Siemens Allegra system as part of large birth cohort study, the Drakenstein Child Health Study (DCHS). Neonatal neurobehavior was assessed at this visit; early developmental outcome assessed on the Bayley Scales of Infant Development III at 6 months of age. Volumes of gray matter regions were estimated based on the segmentations of the University of North Carolina neonatal atlas. Significantly decreased total gray matter volume was demonstrated for the alcohol-exposed cohort compared to healthy control infants (p < 0.001). Subcortical gray matter regions that were significantly different between groups after correcting for overall gray matter volume included left hippocampus, bilateral amygdala and left thalamus (p < 0.01). These findings persisted even when correcting for infant age, gender, ethnicity and maternal smoking status. Both early neurobehavioral and developmental adverse outcomes at 6 months across multiple domains were significantly associated with regional volumes primarily in the temporal and frontal lobes in infants with prenatal alcohol exposure. Alcohol exposure during the prenatal period has potentially enduring neurobiological consequences for exposed children. These findings suggest the effects of prenatal alcohol exposure on brain growth is present very early in the first year of life, a period during which the most rapid growth and maturation occurs.

Assessment of the Role Played by N-propanol Found in Postmortem Blood in the Discrimination Between Antemortem Consumption and Postmortem Formation of Ethanol Using Rats.

This study disproves the reliability of n-propanol as a biomarker to establish whether the ethanol found in postmortem blood is derived from antemortem ingestion or postmortem putrefactive processes. Two groups of rats were given ethanol or normal saline solution, respectively, and sacrificed 1.5 h later. After putrefaction, blood and, in a few cases, urine samples from the rats were analyzed for ethanol and n-propanol by head-space gas chromatography equipped with flame ionization detection. Although the concentration ratios of ethanol/n-propanol in the postmortem blood collected from the bodies without prior alcohol consumption were expected to be <20 (as per limited case reports and previous in vitro studies), in samples from several rats that were on saline solution, this ratio was found to exceed 20. In conclusion, the concentration ratio of ethanol/n-propanol in postmortem blood does not allow for the discernment between antemortem ingestion and the postmortem synthesis of ethanol.

Computed tomography assessment of peripubertal craniofacial morphology in a sheep model of binge alcohol drinking in the first trimester.

Identification of facial dysmorphology is essential for the diagnosis of fetal alcohol syndrome (FAS); however, most children with fetal alcohol spectrum disorders (FASD) do not meet the dysmorphology criterion. Additional objective indicators are needed to help identify the broader spectrum of children affected by prenatal alcohol exposure. Computed tomography (CT) was used in a sheep model of prenatal binge alcohol exposure to test the hypothesis that quantitative measures of craniofacial bone volumes and linear distances could identify alcohol-exposed lambs. Pregnant sheep were randomly assigned to four groups: heavy binge alcohol, 2.5 g/kg/day (HBA); binge alcohol, 1.75 g/kg/day (BA); saline control (SC); and normal control (NC). Intravenous alcohol (BA; HBA) or saline (SC) infusions were given three consecutive days per week from gestation day 4-41, and a CT scan was performed on postnatal day 182. The volumes of eight skull bones, cranial circumference, and 19 linear measures of the face and skull were compared among treatment groups. Lambs from both alcohol groups showed significant reduction in seven of the eight skull bones and total skull bone volume, as well as cranial circumference. Alcohol exposure also decreased four of the 19 craniofacial measures. Discriminant analysis showed that alcohol-exposed and control lambs could be classified with high accuracy based on total skull bone volume, frontal, parietal, or mandibular bone volumes, cranial circumference, or interorbital distance. Total skull volume was significantly more sensitive than cranial circumference in identifying the alcohol-exposed lambs when alcohol-exposed lambs were classified using the typical FAS diagnostic cutoff of ≤10th percentile. This first demonstration of the usefulness of CT-derived craniofacial measures in a sheep model of FASD following binge-like alcohol exposure during the first trimester suggests that volumetric measurement of cranial bones may be a novel biomarker for binge alcohol exposure during the first trimester to help identify non-dysmorphic children with FASD.