The Evolving Role of Monomethyl Fumarate Treatment as Pharmacotherapy for Relapsing-Remitting Multiple Sclerosis.

Multiple sclerosis is the most common autoimmune disease affecting the central nervous system (CNS) worldwide. Multiple sclerosis involves inflammatory demyelination of nerve fibers in the CNS, often presenting with recurrent episodes of focal sensory or motor deficits associated with the region of the CNS affected. The prevalence of this disease has increased rapidly over the last decade. Despite the approval of many new pharmaceutical therapies in the past 20 years, there remains a growing need for alternative therapies to manage the course of this disease. Treatments are separated into two main categories: management of acute flare versus long-term prevention of flares via disease-modifying therapy. Primary drug therapies for acute flare include corticosteroids to limit inflammation and symptomatic management, depending on symptoms. Several different drugs have been recently approved for use in modifying the course of the disease, including a group of medications known as fumarates (e.g., dimethyl fumarate, diroximel fumarate, monomethyl fumarate) that have been shown to be efficacious and relatively safe. In the present investigation, we review available evidence focused on monomethyl fumarate, also known as Bafiertam®, along with bioequivalent fumarates for the long-term treatment of relapsing-remitting multiple sclerosis.

Alkindi Sprinkle for Pediatric Patients With Primary Adrenocortical Insufficiency: A Narrative Review.

Adrenocortical insufficiency, also known as adrenal insufficiency (AI), is an endocrine disorder characterized by inadequate production of adrenal hormones, including glucocorticoids and mineralocorticoids (MCs). The condition can be categorized as primary, secondary, or tertiary AI, depending on the location of the defect. Classical symptoms of AI include weakness, fatigue, abdominal pain, tachycardia, hypotension, electrolyte imbalances, and hyperpigmentation. In children, the most common cause of AI is classical congenital adrenal hyperplasia, which results from a deficiency in the 21-hydroxylase enzyme. The 21-hydroxylase enzyme produces all steroids, such as cortisol and aldosterone. AI management primarily involves hormone replacement therapy, typically with oral hydrocortisone and MC supplementation. However, the administration of hydrocortisone to pediatric patients presents challenges related to the lack of available dose-appropriate formulations. Historically, crushed or split adult tablets were used for the pediatric treatment of AI, although this poses an increased risk of under- or overtreatment. Inadequate dosing in the pediatric population can adversely affect growth, development, and metabolic health. Alkindi Sprinkle is a pediatric-specific hydrocortisone oral granule preparation that manages cortisol levels to help facilitate accurate therapeutic dosing. Alkindi offers several advantages, including accurate dosing, taste masking, and ease of administration. The present investigation describes AI, the management of AI, and the treatment of pediatric AI using Alkindi Sprinkle, including clinical efficacy.

Antibacterial effect of rose bengal against colistin-resistant gram-negative bacteria.

Increasing drug resistance in Gram-negative bacteria presents significant health problems worldwide. Despite notable advances in the development of a new generation of ß-lactams, aminoglycosides, and fluoroquinolones, it remains challenging to treat multi-drug resistant Gram-negative bacterial infections. Colistin (polymyxin E) is one of the most efficacious antibiotics for the treatment of multiple drug-resistant Gram-negative bacteria and has been used clinically as a last-resort option. However, the rapid spread of the transferable gene, mcr-1 which confers colistin resistance by encoding a phosphoethanolamine transferase that modifies lipid A of the bacterial membrane, threatens the efficacy of colistin for the treatment of drug-resistant bacterial infections. Colistin-resistant strains of Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae often reduce their susceptibility to other anti-Gram-negative bacterial agents. Thus, drugs effective against colistin-resistant strains or methods to prevent the acquisition of colistin-resistance during treatment are urgently needed. To perform cell-based screenings of the collected small molecules, we have generated colistin-resistant strains of E. coli, A. baumannii, K. pneumoniae, P. aeruginosa, and S. enterica Typhimurium. In-house MIC assay screenings, we have identified that rose bengal (4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein) is the only molecule that displays unique bactericidal activity against these strains at low concentrations under illumination conditions. This article reports the antibacterial activity of a pharmaceutical-grade rose bengal against colistin-resistant Gram-negative bacteria.

Antibacterial Activity of Pharmaceutical-Grade Rose Bengal: An Application of a Synthetic Dye in Antibacterial Therapies.

Rose bengal has been used in the diagnosis of ophthalmic disorders and liver function, and has been studied for the treatment of solid tumor cancers. To date, the antibacterial activity of rose bengal has been sporadically reported; however, these data have been generated with a commercial grade of rose bengal, which contains major uncontrolled impurities generated by the manufacturing process (80-95% dye content). A high-purity form of rose bengal formulation (HP-RBf, >99.5% dye content) kills a battery of Gram-positive bacteria, including drug-resistant strains at low concentrations (0.01-3.13 µg/mL) under fluorescent, LED, and natural light in a few minutes. Significantly, HP-RBf effectively eradicates Gram-positive bacterial biofilms. The frequency that Gram-positive bacteria spontaneously developed resistance to HP-RB is extremely low (less than 1 × 10-13). Toxicity data obtained through our research programs indicate that HP-RB is feasible as an anti-infective drug for the treatment of skin and soft tissue infections (SSTIs) involving multidrug-resistant (MDR) microbial invasion of the skin, and for eradicating biofilms. This article summarizes the antibacterial activity of pharmaceutical-grade rose bengal, HP-RB, against Gram-positive bacteria, its cytotoxicity against skin cells under illumination conditions, and mechanistic insights into rose bengal's bactericidal activity under dark conditions.

Methods for investigating crash risk: Comparing case-control with responsibility analysis.

OBJECTIVE: There are 2 primary methods for establishing relative risk: case-control studies, in which crash and matched control data are collected separately, and responsibility analysis, which exploits a single existing crash database by using nonresponsible drivers as an "induced exposure" control group (which is less expensive and therefore more feasible for examining the large number of substances that can impact driving behavior). Though both approaches are scientifically sound and methodologically valid, each approach has its own inherent obstacles to overcome. In this article, we examine in detail how different criteria for the development of control cases influence the accuracy of crash risk estimates for drivers with positive blood alcohol concentrations (BACs). METHODS: We applied responsibility analysis to crash-involved drivers in a recent crash case-control study, thereby providing 2 sets of control cases: Those from responsibility analysis and those from the case control study. RESULTS: Case-control and responsibility analysis crash risk curves did not differ significantly, indicating that both systems generate valid estimates of the relative crash risk of drivers on the road. CONCLUSIONS: The results suggest that when researchers are faced with finance or time constraints that make case-control studies infeasible, responsibility analysis should be considered a viable alternate methodological approach.

Drivers with alcohol use disorders and their risks of crash involvement.

BACKGROUND: The relationship between driver blood alcohol concentration (BAC) and crash involvement is well understood. However, the role of alcohol use disorders (AUDs) (i.e., dependence or abuse) in crash occurrence, as distinguished from non-clinical heavy alcohol consumption, has not been adequately explored. METHODS: Data from the 2010-2011 Crash Risk Study conducted in Virginia Beach, VA, were used in this study. Drivers involved in crashes were compared with control drivers, and four drinker groups were examined: alcohol dependent, alcohol abusers, heavy drinkers, and all other current (i.e., normative) drinkers. Logistic regression analyses were conducted on two outcomes: having a moderate BAC (≥0.05 g/dl), and crash involvement. RESULTS: Overall, 2411 crash-involved and 5514 control drivers provided useable data, 52.4% of which were men and 70.8% Whites. The prevalence of drivers with AUDs was lower for the crash-involved drivers (8.7%) than for the control drivers (12.7%). Only heavy drinkers, but not abusive or dependent drinkers, were over four times more likely to drive with moderate BACs at nighttime. More important, at nighttime, the odds of crash involvement for dependent drinkers were only one third of those for normative drinkers. Daytime crashes, however, were more likely to involve normative drinkers than any of the other three drinker types. CONCLUSIONS: Drivers with AUDs are not more likely than normative drinkers to drive with moderate BACs at night. After accounting for the influence of BAC, dependent drinkers have a lower risk of being involved in a crash, at any time of the day.

Marijuana and the Risk of Fatal Car Crashes: What Can We Learn from FARS and NRS Data?

Lab studies have shown that marijuana can severely impair driving skills. Epidemiological studies, however, have been inconclusive regarding the contribution of marijuana use to crash risk. In the United States, case-control studies based on the merging of comparable crash Fatality Analysis Reporting System (FARS) and non-crash National Roadside Survey (NRS) data have been applied to assess the contribution of drugs to crash risk, but these studies have yielded confusing, even contradictory results. We hypothesize that such a divergence of results emanates from limitations in the databases used in these studies, in particular that of the FARS. The goal of this effort is to examine this hypothesis, and in doing so, illuminate the pros and cons of using these databases for drugged-driving research efforts. We took advantage of two relatively recent cannabis crash risk studies that, despite using similar databases (the FARS and the NRS) and following similar overall approaches, yielded opposite results (Li, Brady, & Chen, 2013; Romano, Torres-Saavedra, Voas, & Lacey, 2014). By identifying methodological similarities and differences between these efforts, we assessed how the limitations of the FARS and NRS databases contributed to contradictory and biased results. Because of its limitations, we suggest that the FARS database should neither be used to examine trends in drug use nor to obtain precise risk estimates. However, under certain conditions (e.g., based on data from jurisdictions that routinely test for drugs, with as little variation in testing procedures as possible), the FARS database could be used to assess the contribution of drugs to fatal crash risk relative to other sources of risk such as alcohol.

Drinking and driving and perceptions of arrest risk among California drivers: Relationships with DUI arrests in their city of residence.

OBJECTIVE: Addressing drinking and driving remains a challenge in the United States. The present study aims to provide feedback on driving under the influence (DUI) in California by assessing whether drinking and driving behavior is associated with the DUI arrest rates in the city in which the driver lives; whether this is due to perceptions that one can get arrested for this behavior; and whether this differed by those drivers who would be most affected by deterrence efforts (those most likely to drink outside the home). METHODS: This study consisted of a 2012 roadside survey of 1,147 weekend nighttime drivers in California. City DUI arrest rates for 2009-2011 were used as an indicator of local enforcement efforts. Population average logistic modeling was conducted modeling the odds of perceived high arrest likelihood for DUI and drinking and driving behavior within the past year. RESULTS: As the DUI arrest rates for the city in which the driver lives increased, perceived high risk of DUI arrest increased. There was no significant relationship between either city DUI arrest rates or perceived high risk of DUI arrest with self-reported drinking and driving behavior in the full sample. Among a much smaller sample of those most likely to drink outside the home, self-reported drinking and driving behavior was negatively associated with DUI arrests rates in their city of residence but this was not mediated by perceptions. CONCLUSION: The results of the present study suggest that perceptions are correlated with one aspect of DUI efforts in one's community. Those who were more likely to drink outside the home could be behaviorally influenced by these efforts.

Acceptance of drinking and driving and alcohol-involved driving crashes in California.

BACKGROUND: Alcohol-impaired driving accounts for substantial proportion of traffic-related fatalities in the U.S. Risk perceptions for drinking and driving have been associated with various measures of drinking and driving behavior. In an effort to understand how to intervene and to better understand how risk perceptions may be shaped, this study explored whether an objective environmental-level measure (proportion of alcohol-involved driving crashes in one's residential city) were related to individual-level perceptions and behavior. METHODS: Using data from a 2012 cross-sectional roadside survey of 1147 weekend nighttime drivers in California, individual-level self-reported acceptance of drinking and driving and past-year drinking and driving were merged with traffic crash data using respondent ZIP codes. Population average logistic regression modeling was conducted for the odds of acceptance of drinking and driving and self-reported, past-year drinking and driving. RESULTS: A non-linear relationship between city-level alcohol-involved traffic crashes and individual-level acceptance of drinking and driving was found. Acceptance of drinking and driving did not mediate the relationship between the proportion of alcohol-involved traffic crashes and self-reported drinking and driving behavior. However, it was directly related to behavior among those most likely to drink outside the home. DISCUSSION: The present study surveys a particularly relevant population and is one of few drinking and driving studies to evaluate the relationship between an objective environmental-level crash risk measure and individual-level risk perceptions. In communities with both low and high proportions of alcohol-involved traffic crashes there was low acceptance of drinking and driving. This may mean that in communities with low proportions of crashes, citizens have less permissive norms around drinking and driving, whereas in communities with a high proportion of crashes, the incidence of these crashes may serve as an environmental cue which informs drinking and driving perceptions. Perceptual information on traffic safety can be used to identify places where people may be at greater risk for drinking and driving. Community-level traffic fatalities may be a salient cue for tailoring risk communication.

The impact of marijuana decriminalization on California drivers.

BACKGROUND: The liberalization of marijuana laws has led to concerns that such changes will increase "drugged driving" and crash-related mortality. California decriminalized marijuana effective January 1, 2011; we examine the impact of this change on marijuana-involved driving. METHODS: We used laboratory testing from roadside surveys and the Fatality Analysis Reporting System (FARS) to assess impacts on weekend nighttime drivers and fatally injured drivers, respectively. We calculated marijuana prevalence (measured by laboratory-confirmed delta-9-tetrahydrocannabinol [THC] in roadside surveys and cannabinoids in FARS) and compared corresponding 95% confidence intervals (CI) to identify statistically significant changes post-decriminalization. We also conducted multiple logistic regression analyses to determine whether the odds of marijuana-involved driving increased significantly after controlling for potential confounders. RESULTS: There was no statistically significant change in the prevalence of THC-positive driving among weekend nighttime drivers (n=894) in 2012 (9.2%; 95% CI: 6.3, 12.2) compared to 2010 (11.3%; 95% CI: 8.5, 14.0) or in the adjusted odds of testing positive for THC (adjusted odds ratio [AOR]=0.96; 95% CI: 0.57, 1.60). In contrast, we found a statistically significant increase in the prevalence of cannabinoids among fatally injured drivers in 2012 (17.8%; 95% CI: 14.6, 20.9) compared to the pre-decriminalization period 2008-2010 (11.8%; 95% CI: 10.3, 13.3). The adjusted odds of testing positive for cannabinoids were also significantly higher in 2012 (AOR=1.67; 95% CI: 1.28, 2.18). CONCLUSIONS: Our study generated discrepant findings regarding the impact of decriminalization on marijuana-involved driving in California. Factors that may have contributed to these findings, particularly methodological factors, are discussed.

The relative risk of involvement in fatal crashes as a function of race/ethnicity and blood alcohol concentration.

INTRODUCTION: The literature presents a puzzling picture of Latinos being overrepresented in alcohol-related crashes, but not in noncrash drinking and driving. This report examines if, like other demographic variables in which some groups are at a higher crash risk than others (e.g., young drivers), different racial/ethnic groups face different crash risks. METHOD: This study compares blood-alcohol information from the 2006-2007 U.S. Fatality Analysis Reporting System (FARS) with control data from the 2007 U.S. National Roadside Survey. Logistic regression, including a dual interaction between BAC and race/ethnicity, was used to estimate crash risk at different BAC levels. RESULTS: It was found that, although Hispanic and African-American drivers were less likely to be involved in single-vehicle crashes than their White counterparts, all drivers face similar BAC relative crash risk regardless of their group membership. The overrepresentation of Latino drivers in alcohol-related crashes could be explained by differences in patterns of consumption, driving exposure, lack of awareness of driving rules, and/or socioeconomics.

Drugs and alcohol: their relative crash risk.

OBJECTIVE: The purpose of this study was to determine (a) whether among sober (blood alcohol concentration [BAC] = .00%) drivers, being drug positive increases the drivers' risk of being killed in a fatal crash; (b) whether among drinking (BAC > .00%) drivers, being drug positive increases the drivers' risk of being killed in a fatal crash; and (c) whether alcohol and other drugs interact in increasing crash risk. METHOD: We compared BACs for the 2006, 2007, and 2008 crash cases drawn from the U.S. Fatality Analysis Reporting System (FARS) with control drug and blood alcohol data from participants in the 2007 U.S. National Roadside Survey. Only FARS drivers from states with drug information on 80% or more of the drivers who also participated in the 2007 National Roadside Survey were selected. RESULTS: For both sober and drinking drivers, being positive for a drug was found to increase the risk of being fatally injured. When the drug-positive variable was separated into marijuana and other drugs, only the latter was found to contribute significantly to crash risk. In all cases, the contribution of drugs other than alcohol to crash risk was significantly lower than that produced by alcohol. CONCLUSIONS: Although overall, drugs contribute to crash risk regardless of the presence of alcohol, such a contribution is much lower than that by alcohol. The lower contribution of drugs other than alcohol to crash risk relative to that of alcohol suggests caution in focusing too much on drugged driving, potentially diverting scarce resources from curbing drunk driving.

Characteristics of designated drivers and their passengers from the 2007 National Roadside Survey in the United States.

OBJECTIVE: The objectives of this study were to estimate the prevalence of designated driving in the United States, compare these results with those from the 1996 National Roadside Survey, and explore the demographic, drinking, and trip characteristics of both designated drivers and their passengers. METHODS: The data used were from the 2007 National Roadside Survey, which randomly stopped drivers, administered breath tests for alcohol, and administered a questionnaire to drivers and front seat passengers. RESULTS: Almost a third (30%) of nighttime drivers reported being designated drivers, with 84 percent of them having a blood alcohol concentration of zero. Drivers who were more likely to be designated drivers were those with a blood alcohol concentration that was over zero but still legal; who were under 35 years of age; who were African American, Hispanic, or Asian; and whose driving trip originated at a bar, tavern, or club. Over a third of passengers of designated drivers reported consuming an alcoholic drink the day of the survey compared to a fifth of passengers of nondesignated drivers. One fifth of passengers of designated drivers who reported drinking consumed 5 or more drinks that day. CONCLUSIONS: Designated driving is widely used in the United States, with the majority of designated drivers abstaining from drinking alcohol. However, because designated driving separates drinking from driving for passengers in a group traveling together, this may encourage passengers to binge drink, which is associated with many adverse health consequences in addition to those arising from alcohol-impaired driving. Designated driving programs and campaigns, although not proven to be effective when used alone, can complement proven effective interventions to help reduce excessive drinking and alcohol-impaired driving.

Field testing of the Alere DDS2 Mobile Test System for drugs in oral fluid.

A preliminary field evaluation of a second-generation handheld oral fluid testing device, the Alere DDS2 Mobile Test System (DDS2), is described. As part of a larger study, drivers were randomly stopped at various locations across California (in 2012) and asked to submit voluntarily to a questionnaire regarding their drug and alcohol use, a breath alcohol test and collection of oral fluid with the Quantisal device. The Quantisal-collected oral fluid samples were sent for laboratory-based analyses. At one location, 50 drivers were asked to submit an additional oral fluid sample using the DDS2 collection device; these samples were analyzed by using the DDS2 mobile test system. Thirty-eight donors (76%) provided specimens that were successfully run on the mobile system; in 12 cases (24%), the device failed to provide a valid result. Thirty-two of the 38 collected samples were negative for all drugs; five were positive for tetrahydrocannabinol and one was positive for methamphetamine using the mobile device. These results corresponded exactly with the laboratory-based results from the Quantisal oral fluid collection.

Drinking and driving in the United States: comparing results from the 2007 and 1996 National Roadside Surveys.

OBJECTIVES: The objectives of this study were to (a) use data from the 2007 National Roadside Survey (NRS) to determine the characteristics of weekend nighttime drivers with positive blood alcohol concentrations (BACs) on U.S. roads in 2007; (b) determine the relationship of the driving environment and trip characteristics associated with drinking drivers; and (c) compare the findings for the 2007 NRS with those for the 1996 NRS. METHODS: Like the 1996 NRS, the 2007 NRS used a stratified random national roadside survey sample of the contiguous 48 states and collected nighttime data on Fridays and Saturdays between 10 p.m. and 3 a.m. Officers directed 8384 drivers into off-road parking areas where our research team asked them to participate in the survey. RESULTS: Of those approached, 7159 (85.4%) provided a breath test. Results revealed that 12 percent of the nighttime drivers had positive BACs, and of those, 2 percent were higher than the 0.08 BAC illegal limit in the United States. Since the 1996 NRS, we found significant reductions in the percentage of BAC-positive drivers across different demographic groups. Age was among the most significant factors associated with a weekend driver having a positive BAC. The probability that a driver would be drinking peaked in the 21- to 25-year-old age group. Male drivers were more likely than female drivers to be drinking, and Asian and Hispanic drivers were less likely than white drivers to be drinking. Drinking drivers were more likely to be driving short distances (5 or fewer miles) late at night (between 1 and 3 a.m.) and to be coming from a bar or restaurant. Finally, 26 percent of the drivers who reported that they would drive less than 5 miles on the night of the survey had positive BACs, compared to only 16 percent who indicated that they would drive between 6 and 20 miles and 10 percent who planned to drive more than 20 miles. CONCLUSIONS: The 2007 NRS provides another benchmark in the 4-decade record of drinking drivers on American roads and provides a basis for measuring progress in combating driving under the influence during the coming decade.

Drinking drivers and drug use on weekend nights in the United States.

BACKGROUND: Studies of drinking drivers in alcohol-related crashes have shown that high breath-alcohol concentrations (BrACs) are associated with illegal drug use. Until the 2007 National Roadside Survey (NRS), the prevalence of drugs among drinking drivers on U.S. roads was unknown. Using NRS data, we explore how many drivers with positive BrACs may also be using drugs and their significance to current drinking-driving enforcement procedures. METHODS: Based on a stratified, random sample covering the 48 U.S. contiguous states, we conducted surveys on weekend nights from July-November 2007. Of the 8384 eligible motorists contacted, 85.4% provided a breath sample; 70.0%, an oral fluid sample; and 39.1%, a blood sample. We conducted regression analyses on 5912 participants with a breath test and an oral fluid or blood test. The dependent variables of interest were illegal drugs (cocaine, cannabinoids, street drugs, street amphetamines, and opiates) and medicinal drugs (prescription and over-the-counter). RESULTS: 10.5% of nondrinking drivers were using illegal drugs, and 26 to 33% of drivers with illegal BrACs (≥ 0.08 g/dL) were using illegal drugs. Medicinal drug use was more common among nondrinking drivers (4.0%) than among drivers with illegal BrACs (2.4%). CONCLUSIONS: The significant relationship between an illegal BrAC and the prevalence of an illegal drug suggests as many as 350,000 illegal drug-using drivers are arrested each year for DWI by U.S. alcohol-impaired driving enforcement. These drug-using drivers need to be identified and appropriate sanctions/treatment programs implemented for them in efforts to extend per se laws to unapprehended drug users.

Passengers of impaired drivers.

INTRODUCTION: The aims of this study are: (a) to estimate the prevalence of passengers riding with alcohol-impaired drivers; (b) to investigate the role of demographic factors (age, gender, race/ethnicity, educational status) and relevant driving conditions (time of the day, trip origin, vehicle ownership) on shaping the likelihood of alcohol-impaired driving; (c) to identify and estimate the prevalence of passengers as alternative drivers (PADs); and (d) to examine the role that vehicle ownership plays in shaping the occurrence of PADs. METHOD: Data came from a unique convenience sample of passengers obtained from the 2007 National Roadside Survey, a random sample of drivers from the 48 contiguous states. RESULTS: The prevalence of PADs in the targeted population (mostly weekend night vehicles) was higher with drivers at .00

Interpretation of oxycodone concentrations in oral fluid.

OBJECTIVE: The purpose of this retrospective study was to compare oxycodone concentrations in saliva and whole blood with a view to propose therapeutic concentrations in oral fluid. Oral fluid is an easy specimen to collect with several advantages over urine, including ease of collection and difficulty of adulteration. As oral fluid is a reflection of free drug circulating in the blood, drug concentrations in saliva are more closely related to blood levels than urine concentrations. The number of testing laboratories offering the analysis of prescription pain medications in urine has increased significantly over the last few years, along with the overuse and abuse of pain killing drugs, specifically oxycodone. Hence, the utility of oral fluid analysis in this field was assessed. DESIGN: Paired specimens of blood and oral fluid were retrospectively studied in an attempt to establish a range for oxycodone concentrations in oral fluid reflective of therapeutic intake. Twenty-three paired oral fluid-blood specimens were studied. Oral fluid samples had been collected with the Quantisal™ oral fluid device, stored cold and shipped overnight to the laboratory prior to testing. Blood specimens were collected simultaneously in gray top tubes. RESULTS: From 23 pairs of samples, the median concentration in oral fluid was 524 µg/L and blood was 53 µg/L. The whole blood to plasma ratio for oxycodone was 1.3, so the median plasma concentration was 41 µg/L projecting a saliva to plasma ratio (S:P ratio) of 12. The comparison of oral fluid-blood concentrations allowed the projection of a S:P ratio for oxycodone and the development of a potential therapeutic range for oxycodone in oral fluid. CONCLUSION: Saliva drug concentrations in pain management are more closely related to blood levels than urine so can be more easily interpreted. These data provide a foundation for interpretative advances; however, further research surrounding other pain medications and controlled studies are necessary.

Alcohol-related risk of driver fatalities: an update using 2007 data.

OBJECTIVE: The purpose of this study was to determine whether the relative risk of being involved in an alcohol-related crash has changed over the decade from 1996 to 2007, a period during which there has been little evidence of a reduction in the percentage of all fatal crashes involving alcohol. METHOD: We compared blood-alcohol information for the 2006 and 2007 crash cases (N = 6,863, 22.8% of them women) drawn from the U.S. Fatality Analysis Reporting System (FARS) with control blood-alcohol data from participants in the 2007 U.S. National Roadside Survey (N = 6,823). Risk estimates were computed and compared with those previously obtained from the 1996 FARS and roadside survey data. RESULTS: Although the adult relative risk of being involved in a fatal alcohol-related crash apparently did not change from 1996 to 2007, the risk for involvement in an alcohol-related crash for underage women has increased to the point where it has become the same as that for underage men. Further, the risk that sober underage men will become involved in a fatal crash has doubled over the 1996-2007 period. CONCLUSIONS: Compared with estimates obtained from a decade earlier, young women in this study are at an increased risk of involvement in alcohol-related crashes. Similarly, underage sober drivers in this study are more at risk of involvement in a crash than they were a decade earlier.

The prevalence of cannabis-involved driving in California.

BACKGROUND: Various national surveys suggest that cannabis use is rising nationally and many States have passed legislation that has potential to increase usage even further. This presents a problem for public roadways, as research suggests that cannabis impairs driving ability. METHODS: Anonymous oral fluid samples and breath tests were obtained from more than 900 weekend nighttime drivers randomly sampled from six jurisdictions in California. Oral fluid samples were assayed for the presence of Schedule I drugs. Drivers also completed information on self-reported drug use and possession of a medical cannabis permit. Data from the 2007 National Roadside Survey (collected using comparable methods) were used as a comparison. RESULTS: Using the 2010 data, a total of 14.4% of weekend nighttime drivers tested positive for illegal drugs, with 8.5% testing positive for delta-9-tetrahydrocannabinol (THC). THC-positive rates varied considerably among jurisdictions, from a low of 4.3% in Fresno to a high of 18.3% in Eureka. A comparison with the 2007 NRS data found an increase in THC-positive drivers in 2010, but no increase in illegal drugs other than cannabis. Drivers who reported having a medical cannabis permit were significantly more likely to test positive for THC. CONCLUSIONS: Cannabis-involved driving has increased in California since 2007. Nearly 1-in-10 weekend, nighttime drivers tested positive for THC, and in some jurisdictions, the rate was nearly 1-in-5. The possible contribution of cannabis legislation, such as decriminalization and medical cannabis usage, is discussed.