Medicinal and illegal drugs among Danish car drivers.

PubMed

Behrensdorff, Inge; Steentoft, Anni

2003-11-01

The objective of this study was to get an insight into the prevalence of medicinal and illegal drugs among car drivers in a Danish rural area. The police randomly stopped about 1000 car drivers and asked them to deliver a saliva sample and gave them a questionnaire to fill in at home. Laboratory analyses by specific methods of samples, which a screening found positive, confirmed that 2% were positive for benzodiazepines or illegal drugs (amphetamine, cannabis, cocaine or opiates): 1.3% were positive for illegal drugs and 0.7% for benzodiazepines. Questionnaire statements from some of the drivers confirm that occasionally some of these drive despite a suspicion to be under the influence of an illegal drug (2.8%), an illegal drug including alcohol (4%), a hazardous medicinal drug including alcohol (8.5%), or alcohol alone above the legal limit (24.5%). These results are considered reliable for the survey area and may not reflect national conditions. The overall results indicate that in this study driving under the influence of illegal drugs or alcohol seems to be associated to especially men, aged 22-44 years. Driving under the influence of hazardous medicinal drugs seems to be associated to middle-aged/elderly drivers, both men and women.

Drugs given by a syringe driver: a prospective multicentre survey of palliative care services in the UK.

PubMed

Wilcock, Andrew; Jacob, Jayin K; Charlesworth, Sarah; Harris, Elayne; Gibbs, Margaret; Allsop, Helen

2006-10-01

The use of a syringe driver to administer drugs by continuous subcutaneous infusion is common practice in the UK. Over time, drug combinations used in a syringe driver are likely to change and the aim of this survey was to obtain a more recent snapshot of practice. On four separate days, at two-week intervals, a questionnaire was completed for every syringe driver in use by 15 palliative care services. Of 336 syringe drivers, the majority contained either two or three drugs, but one-fifth contained only one drug. The median (range) volume of the infusions was 15 (9.5-48) mL, and duration of infusion was generally 24 hours. Only one combination was reported as visually incompatible, and there were 13 site reactions (4% of total). Laboratory physical and chemical compatibility data are available for less than half of the most frequently used combinations.

Alcohol and drug use among young adults driving to a drinking location.

PubMed

Voas, Robert B; Johnson, Mark B; Miller, Brenda A

2013-09-01

Clubs that feature electronic music dance events (EMDEs) draw young adults aged 18-34 who are at high-risk for alcohol-related crashes to locations where alcohol sales are the principal source of revenue. Up to 30% of these attendees may also use drugs. This provides an important context in which to study driving arrangements that reflect concern with impaired driving. We explored whether drivers were using less alcohol and fewer drugs at exit than their passengers were and whether a driver for the group ever changed after consuming too much during the evening. Using biological measures of alcohol consumption (breath tests) and drug use (oral fluid tests), 175 drivers and 272 passengers were surveyed among young adults arriving at and departing from EMDEs in San Francisco. Upon exit from the drinking locations, only 20% of the drivers, compared to 47% of the passengers, had a high breath alcohol concentration (defined as a BrAC of .05 g/dL or greater). Further, there was evidence that drivers with high BrACs switched to passenger status on exit and former passengers with lower BrACs replaced those drivers. However, there were no differences in the prevalence of drug use among drivers and passengers. These findings suggest that the effort by young adult drivers to avoid alcohol-impaired driving appears to be reducing the number of drivers with high BrACs returning from drinking locations, such as EMDEs, by about one third. However, there is no similar pattern for drugged driving. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Alcohol and Drug Use Among Young Adults Driving to a Drinking Location

PubMed Central

Voas, Robert B.; Johnson, Mark B.; Miller, Brenda A.

2013-01-01

Background Clubs that feature electronic music dance events (EMDEs) draw young adults aged 18 to 34 who are at high-risk for alcohol-related crashes to locations where alcohol sales are the principal source of revenue. Up to 30% of these attendees may also use drugs. This provides an important context in which to study driving arrangements that reflect concern with impaired driving. We explored whether drivers were using less alcohol and fewer drugs at exit than their passengers were and whether a driver for the group ever changed after consuming too much during the evening. Methods Using biological measures of alcohol consumption (breath tests) and drug use (oral fluid tests), 175 drivers and 272 passengers were surveyed among young adults arriving at and departing from EMDEs in San Francisco. Results Upon exit from the drinking locations, only 20% of the drivers, compared to 47% of the passengers, had a high breath alcohol concentration (defined as a BrAC of .05 g/dL or greater). Further, there was evidence that drivers with high BrACs switched to passenger status on exit and former passengers with lower BrACs replaced those drivers. However, there were no differences in the prevalence of drug use among drivers and passengers. Conclusions These findings suggest that the effort by young adult drivers to avoid alcohol-impaired driving appears to be reducing the number of drivers with high BrACs returning from drinking locations, such as EMDEs, by about one third. However, there is no similar pattern for drugged driving. PMID:23415848

Patterns of drug use in fatal crashes.

PubMed

Romano, Eduardo; Pollini, Robin A

2013-08-01

To characterize drug prevalence among fatally injured drivers, identify significant associations (i.e. day of week, time of day, age, gender), and compare findings with those for alcohol. Descriptive and logistic mixed-model regression analyses of Fatality Analysis Reporting System data. US states with drug test results for >80% of fatally injured drivers, 1998-2010. Drivers killed in single-vehicle crashes on public roads who died at the scene of the crash (n = 16 942). Drug test results, blood alcohol concentration (BAC), gender, age and day and time of crash. Overall, 45.1% of fatally injured drivers tested positive for alcohol (39.9% BAC ≥ 0.08) and 25.9% for drugs. The most common drugs present were stimulants (7.2%) and cannabinols (7.1%), followed by 'other' drugs (4.1%), multiple drugs (4.1%), narcotics (2.1%) and depressants (1.5%). Drug-involved crashes occurred with relative uniformity throughout the day while alcohol-involved crashes were more common at night (P < 0.01). The odds of testing positive for drugs varied depending upon drug class, driver characteristics, time of day and the presence of alcohol. Fatal single-vehicle crashes involving drugs are less common than those involving alcohol and the characteristics of drug-involved crashes differ, depending upon drug class and whether alcohol is present. Concerns about drug-impaired driving should not detract from the current law enforcement focus on alcohol-impaired driving. © 2013 Society for the Study of Addiction.

Presence of psychoactive substances in oral fluid from randomly selected drivers in Denmark.

PubMed

Simonsen, K Wiese; Steentoft, A; Hels, T; Bernhoft, I M; Rasmussen, B S; Linnet, K

2012-09-10

This roadside study is the Danish part of the EU-project DRUID (Driving under the Influence of Drugs, Alcohol, and Medicines) and included three representative regions in Denmark. Oral fluid samples (n=3002) were collected randomly from drivers using a sampling scheme stratified by time, season, and road type. The oral fluid samples were screened for 29 illegal and legal psychoactive substances and metabolites as well as ethanol. Fourteen (0.5%) drivers were positive for ethanol (alone or in combination with drugs) at concentrations above 0.53g/l, which is the Danish legal limit. The percentage of drivers positive for medicinal drugs above the Danish legal concentration limit was 0.4%; while, 0.3% of the drivers tested positive for one or more illicit drug at concentrations exceeding the Danish legal limit. Tetrahydrocannabinol, cocaine, and amphetamine were the most frequent illicit drugs detected above the limit of quantitation (LOQ); while, codeine, tramadol, zopiclone, and benzodiazepines were the most frequent legal drugs. Middle aged men (median age 47.5 years) dominated the drunk driving group, while the drivers positive for illegal drugs consisted mainly of young men (median age 26 years). Middle aged women (median age 44.5 years) often tested positive for benzodiazepines at concentrations exceeding the legal limits. Interestingly, 0.6% of drivers tested positive for tramadol, at concentrations above the DRUID cut off; although, tramadol is not included in the Danish list of narcotic drugs. It can be concluded that driving under the influence of drugs is as serious a road safety problem as drunk driving. Copyright © 2012. Published by Elsevier Ireland Ltd.

Therapeutic modulation of epigenetic drivers of drug resistance in ovarian cancer

PubMed Central

Zeller, Constanze; Brown, Robert

2010-01-01

Epigenetic changes in tumours are associated not only with cancer development and progression, but also with resistance to chemotherapy. Aberrant DNA methylation at CpG islands and associated epigenetic silencing are observed during the acquisition of drug resistance. However, it remains unclear whether all of the observed changes are drivers of drug resistance, causally associated with response of tumours to chemotherapy, or are passenger events representing chance DNA methylation changes. Systematic approaches that link DNA methylation and expression with chemosensitivity will be required to identify key drivers. Such drivers will be important prognostic or predicitive biomarkers, both to existing chemotherapies, but also to epigenetic therapies used to modulate drug resistance. PMID:21789144

SAM survey on "drugs and fatal accidents": search of substances consumed and comparison between drivers involved under the influence of alcohol or cannabis.

PubMed

Biecheler, Marie-Berthe; Peytavin, Jean-François; Facy, Françoise; Martineau, Hélène

2008-03-01

A survey was conducted to produce reliable epidemiological data concerning the role played by alcohol and drugs in fatal road accidents in France. The aims are to describe the conduct of the survey, evaluate the overall quality of the findings, and analyze the substances consumed by the involved drivers. A comparison between drivers involved under the influence of alcohol only, cannabis only, or both substances is emphasized. By a June 1999 law, all drivers in France involved in an immediate fatality accident between October 2001 and 2003 had to undergo a urine test and, if that was not possible or the test proved positive, had a blood sample taken in order to test for drugs (cannabis, cocaine, heroin, amphetamines). The results were combined with the usual procedures of the police force, which include the results of tests for illegal alcohol levels. A unique and reliable set of accident data on the role of drugs was thus compiled for epidemiological purposes: 10,000 accident reports involving over 17,000 drivers were analyzed. The responsibility level of each driver involved in an accident was determined. Results were generated for a representative sample of about 11,000 drivers. Alcohol levels above the legal limit (0.5 g/L of blood) were found in 21% of all drivers involved in accidents (killed, injured, or unharmed). Cannabis headed the list of illicit drugs detected, with a prevalence of 6.8% (THC > or = 1 ng/mL); it was present in the under-35s and especially the under-25s. About 40% of drivers under the influence of cannabis also had an illegal alcohol level. The other drugs, whether alone or in association with cannabis, are relatively rare. Accident characteristics of drivers detected positive for cannabis only are markedly different from drivers under the influence of alcohol. The overrepresentation of drivers responsible, from 1.7 over the whole population, rises to 2.3 for cannabis alone (THC > or = 1 ng/mL), to 9.4 for alcohol alone (> or =0.5 mg/L), and to 14.1 for the alcohol-cannabis combination. The high incidence (26%) of alcohol or drugs among the population of drivers involved in fatal accidents highlights the importance for road safety of the consumption of these substances. Alcohol remains the major risk at any age. Young drivers consuming alcohol and cannabis represent a priority target for prevention.

Detection of illicit drugs in impaired driver saliva by a field-usable SERS analyzer

NASA Astrophysics Data System (ADS)

Shende, Chetan; Huang, Hermes; Farquharson, Stuart

2014-05-01

One of the greatest dangers of drug use is in combination with driving. According to the most recent National Highway Traffic Safety Administration (NHTSA) studies, more than 11% of drivers tested positive for illicit drugs, while 18% of drivers killed in accidents tested positive for illicit, prescription or over-the-counter drugs. Consequently, there is a need for a rapid, noninvasive, roadside drug testing device, similar to the breathalyzers used by law enforcement officials to estimate blood alcohol levels of impaired drivers. In an effort to satisfy this need we have been developing a sampling kit that allows extraction of drugs from 1 mL of saliva and detection by surfaceenhanced Raman spectroscopy using a portable Raman analyzer. Here we describe the development of the sampling kit and present measurements of diazepam at sub μg/mL concentrations measured in ~15 minutes.

The role of alcohol, marijuana, and other drugs in the accidents of injured drivers. Volume 1, Findings

DOT National Transportation Integrated Search

1982-01-01

Using samples of blood obtained from 497 injured drivers at a Rochester, NY hospital, this study determined the incidence rates of alcohol, THC (marijuana agent), and other drugs. Accident data (police reports, driver interviews) were also collected,...

The role of alcohol, marijuana, and other drugs in the accidents of injured drivers. Volume 2, Appendices

DOT National Transportation Integrated Search

1982-01-01

Using samples of blood obtained from 497 injured drivers at a Rochester, NY hospital, this study determined the incidence rates of alcohol, THC (marijuana agent), and other drugs. Accident data (police reports, driver interviews) were also collected,...

Drugs in injured drivers in Denmark.

PubMed

Bernhoft, I M; Steentoft, A; Johansen, S S; Klitgaard, N A; Larsen, L B; Hansen, L B

2005-06-10

As part of the project Impaired Motorists, Methods of Roadside Testing and Assessment for Licensing (IMMORTAL) under the European Commission's Transport RTD Programme of the 5th Framework Programme [I.M. Bernhoft, Drugs in accidents involved drivers in Denmark, D-R4.3 of the project Impaired Motorists, Methods Of Roadside Testing and Assessment for Licensing (IMMORTAL), , 2005], a study regarding drugs in accident-involved drivers was carried out in Denmark. The main objectives of this study were: (1) to collect and analyse samples from injured drivers for the presence of drugs; (2) to give an indication whether drugs may have contributed to traffic accidents; and (3) to get information on the drug-positive drivers and their drug use. This paper focuses on objective 1. Injured drivers who were treated in hospital were asked to give a saliva sample, a blood sample or both. The samples were screened for the following substances: opiates, amphetamines, methamphetamines, incl. MDMA (ecstasy), cannabinoids and metabolites, cocaine and metabolites and benzodiazepines. Screenings were carried out by means of Cozart Microplate EIA kit. Positive screenings were confirmation analysed by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography/tandem mass spectrometry (LC/MS/MS). In total, 26 out of 330 patients were confirmed positive for one or more of the six drug groups. However, three patients were excluded from the survey for various reasons. Of the remaining 23 drug-positive patients 15 were found positive for one drug group, and in five of these cases alcohol was present in a concentration over the legal limit in Denmark (0.05%). The other eight patients were found positive for two drug groups, and in four of these cases, alcohol was also present in a concentration over the legal limit. Alcohol was found both in combinations with medicinal drugs, with illegal drugs and with both. Based on the saliva or blood concentrations, we estimate that there is a strong suspicion of impairment in 9 out of 23 cases, and in another six cases it was likely that the drivers were impaired.

The Effect of Lowering the Legal Drink-Drive Limit on the Toxicological Findings in Driver Fatalities: A Comparison of Two Jurisdictions.

PubMed

Hamnett, Hilary J; Poulsen, Helen

2018-01-26

In December 2014, the legal blood alcohol limit for drivers in both Scotland and New Zealand was reduced from 80 to 50 mg/100 mL. This paper reports a retrospective study comparing changes in the toxicological findings in deceased drivers and motorcyclists before and after the limit change in both jurisdictions. A year of fatal motor vehicle crashes prior to and following the limit change is examined for both countries. In Scotland, there was an increase in drug prevalence among fatally injured drivers and motorcyclists, with the use of all drug groups increasing after the limit change, with the exception of cannabinoids. In New Zealand, there was a reduction in cases involving drugs only, but increases in the numbers of deceased drivers and motorcyclists positive for alcohol only and co-using alcohol and drugs. © 2018 American Academy of Forensic Sciences.

[Detection of zopiclone in many drivers--a sign of misuse or abuse].

PubMed

Bramness, J G; Skurtveit, S; Mørland, J

1999-08-20

In 1998 zopiclone had a 42% share of the prescribed hypnotic drug market in Norway. The National Institute of Forensic Toxicology analyses all blood samples from suspected drugged drivers. The rise in zopiclone prescription was partly reflected in an increase in the number of drivers with zopiclone detected in the blood. We looked closer at the test results from 101 drivers with zopiclone detected in their blood in the January 1994 to April 1999 period. 60% had blood concentrations of zopiclone above the concentration observed after intake of therapeutic doses; 80% had higher blood concentrations than those expected 8 hours after intake of therapeutic doses. The majority of the drivers also tested positive for illegal drugs, prescription drugs with abuse potential, or alcohol. This indicates that zopiclone is misused or abused. Therefore the same caution should be applied when prescribing zopiclone as is applied when prescribing e.g. benzodiazepines.

2013-2014 National Roadside Study of alcohol and drug use by drivers : alcohol results.

DOT National Transportation Integrated Search

2016-12-01

This report describes the alcohol results from the 20132014 National Roadside Survey (NRS), a national field study to : estimate the prevalence of alcohol-, drug-, and alcohol-plus-drug-involved driving, primarily among nighttime weekend : drivers...

2013–2014 national roadside study of alcohol and drug use by drivers : methodology.

DOT National Transportation Integrated Search

2016-07-01

This report describes the methodology for the National Roadside Study (NRS), a national field study to estimate the prevalence of alcohol-, drug-, and alcohol-plus-drug-involved driving primarily among nighttime weekend drivers, but also daytime Frid...

Implementation plan for combating the drug-impaired driver.

DOT National Transportation Integrated Search

1988-01-01

Beginning on April 1, 1988, the Commonwealth of Virginia's revised drug-impaired driving statute went into effect. It defines the drug-impaired driver as one who is under the influence to a degree that impairs his or her ability to drive safely. The ...

49 CFR 382.213 - Controlled substance use.

Code of Federal Regulations, 2013 CFR

2013-10-01

... drug or substance identified in 21 CFR 1308.11 Schedule I. (b) No driver shall report for duty or...-Schedule I drug or substance that is identified in the other Schedules in 21 CFR part 1308 except when the... is familiar with the driver's medical history and has advised the driver that the substance will not...

49 CFR 382.213 - Controlled substance use.

Code of Federal Regulations, 2014 CFR

2014-10-01

... drug or substance identified in 21 CFR 1308.11 Schedule I. (b) No driver shall report for duty or...-Schedule I drug or substance that is identified in the other Schedules in 21 CFR part 1308 except when the... is familiar with the driver's medical history and has advised the driver that the substance will not...

49 CFR 382.213 - Controlled substance use.

Code of Federal Regulations, 2012 CFR

2012-10-01

... drug or substance identified in 21 CFR 1308.11 Schedule I. (b) No driver shall report for duty or...-Schedule I drug or substance that is identified in the other Schedules in 21 CFR part 1308 except when the... is familiar with the driver's medical history and has advised the driver that the substance will not...

Prevalence of drugs in oral fluid from truck drivers in Brazilian highways.

PubMed

Bombana, Henrique Silva; Gjerde, Hallvard; Dos Santos, Marcelo Filonzi; Jamt, Ragnhild Elén Gjulem; Yonamine, Mauricio; Rohlfs, Waldo José Caram; Muñoz, Daniel Romero; Leyton, Vilma

2017-04-01

Traffic accidents are responsible for 1.25 million deaths worldwide and are the most common cause of death among those aged 15-29 years. In Brazil, traffic accidents caused more than 44,000 deaths in 2014. The use of psychoactive drugs is an important risk factor for being involved in traffic accidents. Previous studies have found that psychoactive substances are commonly used by truck drivers in Brazil to maintain their extensive work schedule and stay awake while driving during nighttime hours. The state of Sao Paulo is one of the most important states regarding goods transportation. Important highways cross through Sao Paulo to other regions from Brazil and to other countries in Latin America. This study aims to determine the prevalence of illicit drug use by truck drivers in the state of Sao Paulo through toxicological analyses of oral fluid. Truck drivers were randomly stopped by police officers on federal roads during morning hours. Oral fluid samples were collected using the Quantisal™ device. In addition, a questionnaire concerning sociodemographic characteristics and health information was administered. Oral fluid samples were screened for amphetamine, cocaine, and tetrahydrocannabinol (Δ9-THC) by ELISA and the confirmation was performed using ultra performance liquid chromatography with tandem mass spectrometry detection (UPLC-MS/MS). Of the 764 drivers stopped, 762 agreed to participate. The participants were driving an average of 614km and 9.4h a day. Of the total samples, 5.2% (n=40) tested positive for drugs. Cocaine was the most frequently found drug (n=21), followed by amphetamine (n=16) and Δ9-THC (n=8). All drivers were men with an average age of 42.5 years. With these results we were able to verify that many truck drivers were still consuming psychoactive drugs while driving, and cocaine was the most prevalent one. This reinforces the need for preventive measures aimed at controlling the use of illicit drugs by truck drivers in Brazil. Copyright © 2017 Elsevier B.V. All rights reserved.

Identifying types of drug intoxication : laboratory evaluation of a subject-examination procedure

DOT National Transportation Integrated Search

1985-05-01

The Los Angeles Police Department (LAPD) has developed a rating procedures for use in detecting drug-impaired drivers. The purpose of the rating procedures is to determine whether the driver is impaired and to identify the responsible drug class (e.g...

Alcohol and drugs use among drivers injured in road accidents in Campania (Italy): A 8-years retrospective analysis.

PubMed

Carfora, Anna; Campobasso, Carlo Pietro; Cassandro, Paola; Petrella, Raffaella; Borriello, Renata

2018-05-09

A recent update of the Italian Road Traffic Law (RTL 41/2016), established severe penal sanctions when drivers, driving under the influence of alcohol (DUI) or drugs (DUID), are involved in road accident that results in death or injuries. A study was carried out to assess the trends of consumption of alcohol, illicit drugs or pharmaceutical among injured drivers suspected for DUI or DUID from 2009 to 2016 in the region of Campania (Italy). Confirmation toxicological analyses were performed on 780 blood samples and 1017 urine samples collected from 1797 injured drivers. These drivers all tested positive for alcohol or drug use through immunoassay screening applied at hospital emergency units and their biological samples transferred to the Forensic Reference Laboratory (FRL) for confirmation analysis. The GC/HS-FID methodology was used to test Blood Alcohol Concentration (BAC). Qualitative and quantitative analyses for drugs were performed using the GC/MS or LC-MS/MS methodology. The BAC >0.5g/L was confirmed in 91.5% of drivers suspected for DUI cases and in 93% of DUID respectively. In DUI cases, results show an increasing incidence of road accidents involving drivers with BAC above 1.5g/L while at concentrations above 0.8g/L alcohol and drugs are both used. Among the suspected DUID cases, the intake of alcohol in association with drugs has consistently increased over time and positive results on blood samples was confirmed for multiple drugs (20%) or cannabis and cocaine alone (18%) followed by benzodiazepines (6%) and methadone (3.5%) respectively. The majority of injured drivers suspected for DUID (1017 cases) did not authorize blood sampling, therefore only urine was analyzed showing the prevalent use of cannabis, followed by multiple drug>cocaine>benzodiazepines>opiates. Among 1797 drivers, suspected at screening for DUI or DUID, 15.4% of cases (64 blood and 213 urine samples) were not confirmed by GC/HS, GC/MS or LC-MS/MS analysis. In forensic toxicological investigations, it is mandatory to satisfy the best quality standards, which is not achievable if immunochemical screening is only performed on urine. Therefore, only confirmed positive results of alcohol or drugs on blood samples can represent conclusive evidence to demonstrate the DUI or DUID related offences. An improvement of the protocols currently applied in Italy for the assessment of DUI or DUID crimes is needed and the confirmation analysis on blood should be considered mandatory. Copyright © 2018 Elsevier B.V. All rights reserved.

49 CFR 385.605 - New entrant registration driver's license and drug and alcohol testing requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... America-Domiciled Carriers § 385.605 New entrant registration driver's license and drug and alcohol testing requirements. (a) A non-North America-domiciled motor carrier must use only drivers who possess a... Federal de Conductor—to operate its vehicles in the United States. (b) A non-North America-domiciled motor...

49 CFR 385.605 - New entrant registration driver's license and drug and alcohol testing requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... America-Domiciled Carriers § 385.605 New entrant registration driver's license and drug and alcohol testing requirements. (a) A non-North America-domiciled motor carrier must use only drivers who possess a... Federal de Conductor—to operate its vehicles in the United States. (b) A non-North America-domiciled motor...

49 CFR 385.605 - New entrant registration driver's license and drug and alcohol testing requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... America-Domiciled Carriers § 385.605 New entrant registration driver's license and drug and alcohol testing requirements. (a) A non-North America-domiciled motor carrier must use only drivers who possess a... Federal de Conductor—to operate its vehicles in the United States. (b) A non-North America-domiciled motor...

49 CFR 385.605 - New entrant registration driver's license and drug and alcohol testing requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... America-Domiciled Carriers § 385.605 New entrant registration driver's license and drug and alcohol testing requirements. (a) A non-North America-domiciled motor carrier must use only drivers who possess a... Federal de Conductor—to operate its vehicles in the United States. (b) A non-North America-domiciled motor...

49 CFR 385.605 - New entrant registration driver's license and drug and alcohol testing requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... America-Domiciled Carriers § 385.605 New entrant registration driver's license and drug and alcohol testing requirements. (a) A non-North America-domiciled motor carrier must use only drivers who possess a... Federal de Conductor—to operate its vehicles in the United States. (b) A non-North America-domiciled motor...

Correlates of drug use and driving among undergraduate college students.

PubMed

Kohn, Christine; Saleheen, Hassan; Borrup, Kevin; Rogers, Steve; Lapidus, Garry

2014-01-01

Drug use by drivers is a significant and growing highway safety problem. College students are an important population to understand drugged driving. The objective of this study was to examine correlates of drugged driving among undergraduate college students. We conducted an anonymous, confidential, 24-question survey at a large New England public university during the 2010-2011 academic year among undergraduates in courses that met a graduation requirement. Data include demographics; academics; housing status; lifestyle; personal values; high school/college drug use; and driving following alcohol use, drug use, or both; and as a passenger with a driver who used alcohol, drugs, or both. Descriptive statistics were calculated. Chi-square tests compared driver alcohol use, drug use, or both with demographic, academic, and lifestyle variables. Logistic regression analyses were performed with drugged driving as the dependent variable. Odds ratios and corresponding 95 percent confidence intervals were calculated for each of the potential explanatory variables in relation to the outcome. Four hundred forty-four of 675 students completed surveys (66% participation rate). Participants were representative of the student body with a mean age of 19.4 (±1.3 years), 51 percent male, 75 percent white, and 10 percent Hispanic. Seventy-eight percent lived on campus, 93 percent had a driver's license, and 37 percent had access to a car. Students disagreed that cannabinoids impair driving (18%) compared to other drugs (17%), stimulants (13%), depressants (11%), hallucinogens (8%), and alcohol (7%). Twenty-three percent drove after alcohol use and 22 percent drove after drug use. Forty-one percent reported having been a passenger with a driver who had been drinking and 37 percent with a driver using drugs. Drugged driving was more likely among males vs. females (30% vs. 14%, P < .01), those living off campus (34% vs. 19%, P < .01), those reporting that parties are important (33% vs. 14%, P < .01), those reporting that community service is not important (28% vs. 18%, P < .05), those reporting that religion is not important (28% vs. 14%, P < .01), and those reporting personal drug use in high school (75% vs. 14%, P < .01) and well as that their best friends used drugs in high school (42% vs. 12%, P < .01) and college (50% vs. 8%, P < .01). Those factors most associated with drugged driving included using drugs in high school (odds ratio [OR] = 9.5, 95% confidence interval [CI]: 4.6-19.6) and best friends in college used drugs regularly (OR = 6.2, 95% CI: 3.4-11.6). Self-reported drugged driving and riding as a passenger with a drugged driver is common among subgroups of college students. The identification of undergraduate subgroups at risk for drugged driving will guide the design and implementation of traffic safety activities.

Drug and alcohol crash risk : traffic safety facts : research note.

DOT National Transportation Integrated Search

2015-02-01

While the extent of use of alcohol by drivers and the risks posed by alcohol use have been well known for many decades, relatively little has been known about the use of other drugs by drivers and the associated risks. However, drug-impaired driving ...

Overview of drug and alcohol use among large truck and bus drivers, 2011–13.

DOT National Transportation Integrated Search

2016-12-01

This report provides a broad overview of drug and alcohol usage among large truck and bus drivers for 201113. Data sources for the overview are: testing results from motor carrier drug testing programs, roadside inspections on large trucks and bus...

Roadside drug testing: An evaluation of the Alere DDS® 2 mobile test system.

PubMed

Rohrig, Timothy P; Moore, Christine M; Stephens, Kimberly; Cooper, Kelsey; Coulter, Cynthia; Baird, Tyson; Garnier, Margaux; Miller, Samuel; Tuyay, James; Osawa, Kei; Chou, Joshua; Nuss, Carson; Collier, Jeff; Wittman, Karen Cudlin

2018-04-01

The number of drivers using drugs has increased over the last few years, and is likely to continue its upward trend. Testing drivers for alcohol use is routine and standardized, but the same is not true for the identification of driving under the influence of drugs (DUID). The Drug Evaluation and Classification Program (DECP) was developed to train police officers to recognize the signs and symptoms of recent drug use and remains an invaluable program; however, there are insufficient numbers of these highly trained drug recognition experts (DREs) available to attend every potential drug involved traffic incident. While blood and urine samples are used to test for drugs in a driver, both have disadvantages, particularly as they pertain to the length of time required after a traffic stop to sample collection. Therefore, the development of oral fluid testing devices which can be operated at the roadside and have the potential to assist officers in the identification of drug use is a major advancement in DUID cases. This project evaluated the performance of one instrumental oral fluid roadside testing device (Alere DDS®2) compared to DRE opinion, oral fluid laboratory-based analysis, and routine blood testing. The results showed that there was a good correlation with DRE observations and the device performance was >80% in all drug categories compared to laboratory-based analytical testing, both in oral fluid and blood, with few exceptions. The instrument can be considered a useful tool to assist law enforcement in identifying a drugged driver. Because the device does not test for all potentially impairing drugs, the opinion of the police officer regarding the condition of the driver should still be considered the most important aspect for arrest and further action. Copyright © 2017 John Wiley & Sons, Ltd.

The role alcohol, marijuana and other drugs in the accidents of injured drivers

DOT National Transportation Integrated Search

1982-03-01

A study was conducted of 497 drivers injured in a motor vehicle accident and treated at a hospital. The objectives were to determine the incidence of alcohol and other drugs in their blood systems at the time of the crash and the role these drugs may...

Sleep driving: sleepwalking variant or misuse of z-drugs?

PubMed

Pressman, Mark R

2011-10-01

Sleep driving is most often classified as a variant of sleepwalking, but should be distinguished from impaired driving due to misuse or abuse of sedative/hypnotic drugs. Z-drugs; zolpidem and zopiclone in particular, have been associated with the majority of reported cases of impaired driving. Numerous studies have found z-drugs in driving under influence (DUI) related police stops, arrests and accidents. Impaired drivers are reported to have 1) blood levels of z-drugs that exceed therapeutic ranges 2) failed to take the medication at the correct time or remain in bed for sufficient time and/or 3) combined z-drugs with other central nervous system (CNS) depressants and/or alcohol. Consistent with CNS depression, z-drug-impaired drivers may demonstrate cognitive function at low levels with drivers still able to understand and respond to questions while sleepwalkers are completely unable to understand or interact with police. Z-drug-impaired drivers are often severely physically impaired, unable to stand up or maintain balance while sleepwalkers are able to stand and walk unaided. Sleep driving and impaired driving due to z-drugs may overlap. Sleep driving and drug-impaired driving are statistically rare events, but due to the billions of doses prescribed each year may still result in numerous DUI related arrests and accidents. Copyright © 2010 Elsevier Ltd. All rights reserved.

Substance use and social, health and safety-related factors among fatally injured drivers.

PubMed

Karjalainen, Karoliina; Blencowe, Tom; Lillsunde, Pirjo

2012-03-01

The aim of this study was to examine different socio-demographic, health and safety-related factors, and psychoactive substance use among fatally injured drivers in road traffic accidents in Finland during 2006-2008. An accident information register maintained by the Traffic Safety Committee of Insurance Companies (VALT) of the Finnish Motor Insurers' Centre was used as basic data, and the basic data were complemented with further toxicological analytical information retrieved from autopsy reports from the Department of Forensic Medicine, Helsinki University. The data included all the drivers (n=556) who were driving a motor vehicle and who died in a road traffic accident in Finland during 2006-2008. Of all the 556 fatally injured drivers 43% (n=238) had psychoactive substance findings. 51% (n=121) of substance positive drivers had a finding for alcohol only, the rest had a finding for one or more illicit/medicinal drugs impairing driving ability, and possibly also alcohol. Fatally injured drivers with alcohol findings were significantly younger (mean age 34 years) than sober drivers (mean age 44 years) or drivers with findings for drugs (mean age 45 years). Socio-demographic background did not differ substantially among drunken/drugged and sober drivers, although drivers with alcohol findings had a slightly lower education and socioeconomic position. Previous substance abuse problems were highly prevalent among drivers with substance findings and mental or both mental and physical health problems were more common among drivers with drug findings. The non-use of safety equipment and driving at a high speed were more common among fatally injured drivers with substance findings. Substance abuse and mental health problems, as well as reckless driving behavior were more pronounced among fatally injured drivers with substance findings when compared to sober drivers. Thus, prevention and early intervention concerning substance abuse, mental health problems and DUI are essential. Improved traffic safety cannot be achieved by means of traffic policy only, but integration with other policies, such as health and social policy should be strengthened. Copyright © 2011 Elsevier Ltd. All rights reserved.

Drug use among drivers

DOT National Transportation Integrated Search

1975-02-01

Randomly selected drivers were stopped at times and places of previous fatal crashes in Lincoln, Nebraska, and Dade County (Miami), Florida. Breath, urnine, blood, and lip swab samples were requested, for later analysis for drugs and medications. A c...

Results of the 2013–2014 national roadside survey of alcohol and drug use by drivers : traffic safety facts : research note.

DOT National Transportation Integrated Search

2015-02-01

In 20132014, the National Highway Traffic Safety Administration conducted the most recent National Roadside Survey of Alcohol and Drug Use by Drivers.1 This voluntary and anonymous study is the second to collect data on drug use, presenting our fi...

The role of illicit, licit, and designer drugs in the traffic in Hungary.

PubMed

Institóris, László; Hidvégi, Előd; Dobos, Adrienn; Sija, Éva; Kereszty, Éva M; Tajti, László Balázs; Somogyi, Gábor Pál; Varga, Tibor

2017-06-01

The aim of this study was to investigate the prevalence and pattern of psychoactive substances among suspected DUID (Driving Under the Influence of Drugs) drivers in Hungary in 2014 and 2015. Blood and/or urine samples of 1252 suspected drivers (600 in 2014 and 652 in 2015) were analyzed for classical illicit and licit drugs, stimulant designer drugs (SDDs), and for synthetic cannabinoids, with 78.3% and 79.6% positive cases for at least one substance in 2014, and 2015, respectively. Impairment was proven in 39.2% (2014) and 35.7% (2015) of all drivers tested, based on the legal criteria of Hungary. Classical illicit drugs were found to be present in blood or urine of 89-61%, drivers tested. Drivers also tested positive for legal medications in 20-22%, SDDs in 21-28%, and synthetic cannabinoids in 15-19% of all cases. This indicates a drop in prevalence for classical illicit drugs and a slight but statistically non-significant increase for the other three substance groups. The distribution of drug types in each category were: [1] classical illicit drugs: cannabis (432), amphetamine (321), and cocaine (79); [2] medicines: alprazolam (94) and clonazepam (36); [3] SDDs: pentedrone (137) and α-PVP (33); [4] synthetic cannabinoids: AB-CHMINACA (46) and MDMB-CHMICA (30). The average age of illicit drug and SDD users was 30 years, while legal medications users were 36 years old on average, and the mean age of synthetic cannabinoid users was 26.5 years. The presence of both alcohol and at least one drug in samples was found in about 10% of the cases, both years. The ratio of multi-drug use was 33.0% in 2014 and 41.3% in 2015. Compared to former years the number of drivers who tested positive for drugs doubled in Hungary, but it is still low compared to alcohol positive cases. The relatively low detected rate of DUID can be explained by (1) combined alcohol consumption masking drug symptoms, (2) the absence of road-side tests for illicit and designer drugs and, (3) police officers not adequately trained to recognize milder symptoms of impairment. Targeted education of police officers, prompt medical examination and the use of a symptom-focused on-site survey, could improve the efficacy of DUID investigations. Our findings are not comparable with drug consumption habits of the general driving population. The last roadside survey (DRUID EU-6 Project) was performed in Hungary in 2008-2009, prior to the mass spreading of designer drugs. As their appearance has drastically changed the pattern of drug consumption of the population, a new roadside survey, targeting general drivers, would be necessary. Copyright © 2017 Elsevier B.V. All rights reserved.

A novel algorithm for finding optimal driver nodes to target control complex networks and its applications for drug targets identification.

PubMed

Guo, Wei-Feng; Zhang, Shao-Wu; Shi, Qian-Qian; Zhang, Cheng-Ming; Zeng, Tao; Chen, Luonan

2018-01-19

The advances in target control of complex networks not only can offer new insights into the general control dynamics of complex systems, but also be useful for the practical application in systems biology, such as discovering new therapeutic targets for disease intervention. In many cases, e.g. drug target identification in biological networks, we usually require a target control on a subset of nodes (i.e., disease-associated genes) with minimum cost, and we further expect that more driver nodes consistent with a certain well-selected network nodes (i.e., prior-known drug-target genes). Therefore, motivated by this fact, we pose and address a new and practical problem called as target control problem with objectives-guided optimization (TCO): how could we control the interested variables (or targets) of a system with the optional driver nodes by minimizing the total quantity of drivers and meantime maximizing the quantity of constrained nodes among those drivers. Here, we design an efficient algorithm (TCOA) to find the optional driver nodes for controlling targets in complex networks. We apply our TCOA to several real-world networks, and the results support that our TCOA can identify more precise driver nodes than the existing control-fucus approaches. Furthermore, we have applied TCOA to two bimolecular expert-curate networks. Source code for our TCOA is freely available from http://sysbio.sibcb.ac.cn/cb/chenlab/software.htm or https://github.com/WilfongGuo/guoweifeng . In the previous theoretical research for the full control, there exists an observation and conclusion that the driver nodes tend to be low-degree nodes. However, for target control the biological networks, we find interestingly that the driver nodes tend to be high-degree nodes, which is more consistent with the biological experimental observations. Furthermore, our results supply the novel insights into how we can efficiently target control a complex system, and especially many evidences on the practical strategic utility of TCOA to incorporate prior drug information into potential drug-target forecasts. Thus applicably, our method paves a novel and efficient way to identify the drug targets for leading the phenotype transitions of underlying biological networks.

Results from the 2013 drug and alcohol testing survey.

DOT National Transportation Integrated Search

2015-12-01

This report summarizes the results of the 2013 Federal Motor Carrier Safety Administration (FMCSA) Drug and Alcohol Testing Survey. This annual survey measures the percentage of drivers with commercial drivers licenses (CDLs) that test positive fo...

Results from the 2008 Drug and Alcohol Testing Survey

DOT National Transportation Integrated Search

2010-01-01

This report summarizes the results of the 2008 Federal Motor Carrier Safety Administration Drug and Alcohol Testing Survey. This annual survey measures the percentage of drivers with commercial drivers licenses who test positive for controlled sub...

Detecting alcohol and illicit drugs in oral fluid samples collected from truck drivers in the state of São Paulo, Brazil.

PubMed

Yonamine, Mauricio; Sanches, Livia Rentas; Paranhos, Beatriz Aparecida Passos Bismara; de Almeida, Rafael Menck; Andreuccetti, Gabriel; Leyton, Vilma

2013-01-01

Alcohol and drug use by truck drivers is a current problem in Brazil. Though there is evidence that alcohol consumption is occurring in higher proportions, the use of stimulant drugs to avoid fatigue and to maintain the work schedule has also been reported. The purpose of this study was to estimate the incidence of alcohol and illicit drug use among truck drivers on São Paulo state roads. São Paulo is the most populous state in Brazil and has the largest industrial park and economic production in the country. Data were assessed not only using a questionnaire but also, and more reliably, through toxicological analysis of oral fluid samples. Between the years 2002 and 2008, 1250 oral fluid samples were collected from truck drivers on the roads during morning hours. The samples were tested for the presence of alcohol, cocaine, tetrahydrocannabinol (THC), and amphetamine/methamphetamine. A previously published, validated gas chromatographic (gas chromatography-flame ionization detection and gas chromatography-mass spectrometry) method was applied to the samples for alcohol and drug detection. Of the total analyzed samples, 3.1 percent (n = 39) were positive: 1.44 percent (n = 18) were positive for alcohol, 0.64 percent (n = 8) for amphetamines, 0.56 percent (n = 7) for cocaine, and 0.40 percent (n = 5) for THC. In one case, cocaine and THC were detected. The results are indicative of the extent of alcohol and drug use by truck drivers in the state of São Paulo, Brazil. This research provides evidence that not only alcohol but also illicit drug use is a real problem among professional drivers. The use of these substances should be controlled to better promote safe driving conditions on Brazilian roads.

Results from the 2014 drug and alcohol testing survey : analysis brief.

DOT National Transportation Integrated Search

2016-10-01

This report summarizes the results of the 2014 Federal Motor Carrier Safety Administration (FMCSA) Drug and Alcohol Testing Survey. This annual survey measures the percentage of commercial drivers license (CDL) drivers who test positive for contro...

Results from the 2016 Drug and Alcohol Testing Survey : Analysis Brief

DOT National Transportation Integrated Search

2018-01-01

This report summarizes the results of the 2016 Federal Motor Carrier Safety Administration (FMCSA) Drug and Alcohol Testing Survey. This annual survey measures the percentage of commercial drivers license (CDL) drivers who test positive for contro...

Results from the 2012 drug and alcohol testing survey : [analysis brief].

DOT National Transportation Integrated Search

2014-12-01

This report summarizes the results of the 2012 Federal Motor Carrier Safety Administration (FMCSA) Drug and Alcohol Testing Survey. This annual survey measures the percentage of drivers with commercial drivers licenses (CDLs) who test positive for...

Results from the 2015 Drug and Alcohol Testing Survey : analysis brief.

DOT National Transportation Integrated Search

2017-06-01

This report summarizes the results of the 2015 Federal Motor Carrier Safety Administration (FMCSA) Drug and Alcohol Testing Survey. This annual survey measures the percentage of commercial drivers license (CDL) drivers who test positive for contro...

Drug involvement of fatally injured drivers

DOT National Transportation Integrated Search

2010-11-01

While data focusing on the danger of driving under the influence : of alcohol is readily available and often cited, less is : known or discussed about drivers under the influence of : other drugs. The Fatality Analysis Reporting System (FARS), : a ce...

A Practical Methodology for Disaggregating the Drivers of Drug Costs Using Administrative Data.

PubMed

Lungu, Elena R; Manti, Orlando J; Levine, Mitchell A H; Clark, Douglas A; Potashnik, Tanya M; McKinley, Carol I

2017-09-01

Prescription drug expenditures represent a significant component of health care costs in Canada, with estimates of $28.8 billion spent in 2014. Identifying the major cost drivers and the effect they have on prescription drug expenditures allows policy makers and researchers to interpret current cost pressures and anticipate future expenditure levels. To identify the major drivers of prescription drug costs and to develop a methodology to disaggregate the impact of each of the individual drivers. The methodology proposed in this study uses the Laspeyres approach for cost decomposition. This approach isolates the effect of the change in a specific factor (e.g., price) by holding the other factor(s) (e.g., quantity) constant at the base-period value. The Laspeyres approach is expanded to a multi-factorial framework to isolate and quantify several factors that drive prescription drug cost. Three broad categories of effects are considered: volume, price and drug-mix effects. For each category, important sub-effects are quantified. This study presents a new and comprehensive methodology for decomposing the change in prescription drug costs over time including step-by-step demonstrations of how the formulas were derived. This methodology has practical applications for health policy decision makers and can aid researchers in conducting cost driver analyses. The methodology can be adjusted depending on the purpose and analytical depth of the research and data availability. © 2017 Journal of Population Therapeutics and Clinical Pharmacology. All rights reserved.

Drug use among drivers who drank on alcohol outlets from Porto Alegre, Brazil.

PubMed

De Boni, Raquel B; Bastos, Francisco Inacio; de Vasconcellos, Mauricio; Oliveira, Fernanda; Limberger, Renata P; Pechansky, Flavio

2014-01-01

Driving under the influence of multiple substances is a public health concern, but there is little epidemiological data about their combined use and putative impact on driving in low and middle-income countries where traffic crashes have been clustering in recent years. The aim of this study is to estimate the prevalence of alcohol and drug use - as well as their associated factors - among drivers in the context of alcohol outlets (AOs). A probability three-stage sample survey was conducted in Porto Alegre, Brazil. Individuals who were leaving AO were screened, with the selection of 683 drivers who met the inclusion criteria. Drivers answered a structured interview, were breathalyzed, and had their saliva collected for drug screening. Prevalences were assessed using domain estimation and logistic regression models assessed covariates associated with substance use. Benzodiazepines 3.9% (SE 2.13) and cocaine 3.8% (SE 1.3) were the most frequently detected drugs in saliva. Among drivers who were going to drive, 11% had at least one drug identified by the saliva drug screening, 0.4% two, and 0.1% three drugs in addition to alcohol. In multivariable analyses, having a blood alcohol concentration (BAC)>0.06% was found to be associated with a 3.64 times (CI 95% 1.79-7.39) higher chance of drug detection, compared with interviewees with lower BACs. To drive under the influence of multiple substances is likely to be found in this setting, highlighting an association between harmful patterns of consume of alcohol and the misuse of other substances. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Professional drivers and psychoactive substances consumption: results from medical surveillance at the workplace in Piedmont region].

PubMed

Rosso, G L; Feola, M; Rubinetto, Maria Paola; Petti, N; Rubinetto, L

2011-01-01

The use of psychoactive substances has been shown to be a risk factor for accidents in professional drivers. According to an approved Italian law, in order to detect dependency at the workplace the occupational health physician is called to assess the use of illicit drugs among professional drivers. The main purpose of this study was to investigate the use of psychoactive substances among professional drivers. From July to December 2008, rapid urine screening test was carried out on 198 professional drivers. All positive results from the screening stage were verified by specialized laboratories. We found 4 workers with a positive rapid urine screening test (7.1%), one of which was positive only for benzodiazepines and another positive test was not confirmed by specialized laboratory. By only considering illegal substances detected, 6.1% of the drivers tested positive. In this study, the high number of consumers among professional drivers ranged from 31 to 35 years old. Cannabis (THC) was the most frequently detected substance (seen in 10 over 12 cases,), after that was methadone (2/12 cases) and cocaine (1/12 case). We only had one case where more than one substance was found in the same subject (THC and cocaine). Five (41.7%) were former drug-addicts and public Pathological Addiction Services (Ser.T.) had previously followed them. Our results highlight the problem of drug consumption among professional drivers in Piedmont region. Health education and medical surveillance in workplace drug-testing may improve worker and third parties safety.

Marijuana, other drugs, and alcohol use by drivers in Washington state : appendices.

DOT National Transportation Integrated Search

2016-07-01

In Washington State legal sales of marijuana began July 8, 2014. A voluntary, anonymous roadside study was conducted to assess the prevalence of drivers testing positive for alcohol and other drugs, including marijuana, on Washingtons roads. Data ...

Marijuana, other drugs, and alcohol use by drivers in Washington State.

DOT National Transportation Integrated Search

2016-07-01

In Washington State legal sales of marijuana began July 8, 2014. A voluntary, anonymous roadside study was conducted to assess the prevalence of drivers testing positive for alcohol and other drugs, including marijuana, on Washingtons roads. Data ...

2007 national roadside survey of alcohol and drug use by drivers : alcohol results

DOT National Transportation Integrated Search

2009-12-01

This report presents the prevalence estimates for alcohol-involved driving derived from the recently completed U.S. : national field survey of alcohol- and drug-involved driving (primarily of nighttime weekend drivers, but also daytime : Friday drive...

Determination of different recreational drugs in sweat by headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME GC/MS): Application to drugged drivers.

PubMed

Gentili, Stefano; Mortali, Claudia; Mastrobattista, Luisa; Berretta, Paolo; Zaami, Simona

2016-09-10

A procedure based on headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography/mass spectrometry (GC/MS) has been developed for the determination of most commonly used drugs of abuse in sweat of drivers stopped during roadside controls. DrugWipe 5A sweat screening device was used to collect sweat by a specific pad rubbed gently over forehead skin surface. The procedure involved an acid hydrolysis, a HS-SPME extraction for drugs of abuse but Δ(9)-tetrahydrocannabinol, which was directly extracted in alkaline medium HS-SPME conditions, a GC separation of analytes by a capillary column and MS detection by electron impact ionisation. The method was linear from the limit of quantification (LOQ) to 50ng drug per pad (r(2)≥0.99), with an intra- and inter-assay precision and accuracy always less than 15% and an analytical recovery between 95.1% and 102.8%, depending on the considered analyte. Using the validated method, sweat from 60 apparently intoxicated drivers were found positive to one or more drugs of abuse, showing sweat patches testing as a viable economic and simple alternative to conventional (blood and/or urine) and non conventional (oral fluid) testing of drugs of abuse in drugged drivers. Copyright © 2016 Elsevier B.V. All rights reserved.

A comparison of drug use in driver fatalities and similarly exposed drivers

DOT National Transportation Integrated Search

1977-07-01

Author's abstract: Crash information, urine, blood and bile samples from 900 fatally injured drivers were collected by medical examiners in 22 areas of the country. Randomly selected living drivers were interviewed at times and places of recent fatal...

Examining the impact of opioid analgesics on crash responsibility in truck drivers involved in fatal crashes.

PubMed

Reguly, Paula; Dubois, Sacha; Bédard, Michel

2014-01-01

Commercial motor vehicle (CMV) drivers, particularly drivers of large trucks continue to be a population of concern regarding traffic safety despite the reduction in large truck crash rates over the past decade. Medication and drug use while driving is one important risk factor for large truck crashes. Work-related exposures, such as vibration, manual handling and poor ergonomics contribute to an increased risk for injuries and chronic conditions and are common reasons for opioid analgesic (OA) use by CMV truck drivers. The objectives of this study were to examine the role of OA use in CMV truck drivers involved in fatal crashes by: (a) generating prevalence estimates of OA use; (b) documenting the relationship between OA use and crash responsibility. Case-control study using logistic regression to compare Fatality Analysis Reporting System (1993-2008) record of one or more crash-related unsafe driver actions (UDAs--a proxy measure of responsibility) between drivers with a positive drug test and drivers with a negative drug test for OA, controlling for age, other drug use, and driving history. The annual prevalence of OA use among all CMV drivers of large trucks involved in fatal crashes did not exceed 0.46% for any year in the study period and mostly ranged between 0.1 and 0.2%. Male truck drivers using OA had greater odds of committing an UDA (OR: 2.80; 95% CI: 1.64; 4.81). Middle-aged users had greater odds than younger or older users. The results of our study indicate that the presence of OAs is associated with greater odds of committing an UDA. This association may have implications for the commercial transport industry and traffic safety. However, the limited prevalence of OA use is encouraging and further research is needed to address the limitations of the study. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Results of the 2007 national roadside survey of alcohol and drug use by drivers

DOT National Transportation Integrated Search

2009-07-01

The 2007 NRS included, for the first time, measures to estimate the use of other potentially impairing drugs by drivers. Prior roadside surveys had collected breath samples to determine blood alcohol concentration (BAC). Due to developments in analyt...

Predominance of alcohol and illicit drugs among traffic accidents fatalities in an urban area of Brazil.

PubMed

Pelição, Fabrício Souza; Peres, Mariana Dadalto; Pissinate, Jauber Fornaciari; de Paula, Daniela Mendes Louzada; de Faria, Maria das Graças Corrêa; Nakamura-Palacios, Ester Miyuki; De Martinis, Bruno Spinosa

2016-10-02

The objective of this study was to determine the prevalence of alcohol and illicit drug use among victims of fatal traffic accidents in the Metropolitan Region of Vitória, Brazil, during the period 2011-2012. Blood samples were collected and analyzed for the presence of drugs from 391 deceased victims of traffic crashes that occurred in the Metropolitan Region of Vitória, Brazil. The victims included drivers, passengers, and pedestrians. Sociodemographic variables such as age, gender, day of the week, and period of the year in which the accidents occurred were recorded. The analyses were performed by a gas chromatography-flame ionization method for alcohol and by a gas chromatography-mass spectrometry for amphetamines, cocaine, and cannabis. The results showed that 44.8% (n = 175) of all cases were positive for alcohol and/or illicit drugs. The detection of alcohol and/or drugs was more frequent in young males, aged 17 to 34, whose samples were positive in 46.8% of cases. Small differences among drivers, passengers, and pedestrians were observed (drivers = 45.9%, passengers = 46.4%, and pedestrians = 45.6%). In general, the most prevalent drug was alcohol, with 141 positive cases (36.1%), followed by cocaine, with 47 positive cases (12%). Amphetamines and cannabis had positivity rates of 4.1 and 4.3%, with 16 and 17 positive cases, respectively. The combined use of alcohol and other drugs was found in 36 cases (9.2%). Crack cocaine use was observed in 27.7% of the positive cases for cocaine. For the effective reduction of traffic accidents related to driving under influence of drugs (DUID), we suggest the intensification of enforcement actions against the use of alcohol by drivers, the definition of which illicit drugs should be surveyed, as well the cutoff values, the promotion of changing legislation to oblige drivers to provide samples for toxicological testing, and the establishment of public information programs and specific actions aimed at young drivers to promote behavioral changes.

Medication use and the risk of motor vehicle collision in West Virginia drivers 65 years of age and older: a case-crossover study.

PubMed

Rudisill, Toni M; Zhu, Motao; Davidov, Danielle; Leann Long, D; Sambamoorthi, Usha; Abate, Marie; Delagarza, Vincent

2016-03-15

The current generation of older adults reports a higher lifetime prevalence of prescription, over-the-counter, and recreational drug use. The purpose of this analysis is to characterize the drug usage and determine the risk of motor vehicle collision associated with individual medications in a population of drivers ≥ 65 years. A case-crossover study was conducted at West Virginia University Healthcare's facilities using data obtained from the electronic health records (n = 611) of drivers ≥ 65 years admitted for medical treatment following a motor vehicle collision which occurred between Jan. 1, 2009 and June 30, 2014. Patients' medication usage 14 days before collision were matched and compared to their medication usage during four control periods prior to collision. Odds ratios were then calculated for the most prevalent individual medications and pharmaceutical sub-classes using conditional logistic regression. Analgesic, cardiovascular and gastrointestinal medicines were common. Few drivers tested positive for either licit or illicit drugs. Of those testing positive for drugs, benzodiazepines and opiates were prevalent. Drivers consuming Tramadol (adjusted OR 11.41; 95% CI 1.27, 102.15) were at a significantly increased risk of motor vehicle collision. Older adult drivers who have a prescription for this medication may need to be aware of the potential risk. Further research is necessary in a larger, more nationally representative population.

Which drugs are associated with highest risk for being arrested for driving under the influence? A case-control study.

PubMed

Bogstrand, Stig Tore; Gjerde, Hallvard

2014-07-01

The aim of this study was to determine the association between drug type and arrest for driving under the influence of drugs (DUID) by calculating odds ratios (ORs) using a case-control design. A DUID arrest is in most cases related to aberrant or risky driving and might therefore be regarded as a proxy for a drug related traffic crash. The 'cases' were 2738 drivers arrested on suspicion of drugged driving from April 2008 to March 2009 with blood alcohol concentrations below the legal limit of 0.2g/L; 794 were arrested due to involvement in road traffic crashes, whereas 1944 were arrested for other reasons, mainly dangerous driving, suspected impairment when stopped in traffic controls, or because of phone calls to the police from other road users or observers. The 'controls' were 9375 random drivers in normal traffic, also with alcohol concentrations below this limit. Blood samples from 'cases' and oral fluid samples from 'controls' were analyzed for 15 drugs that have legislative concentration limits in Norway, in addition to two other commonly detected psychoactive drugs. The most prevalent illicit drug in the control group was tetrahydrocannabinol (THC; 0.58%), which was also commonly found in samples from drivers arrested due to road crash (15.6%) or arrested for other reasons (21.8%). Amphetamine/methamphetamine was most prevalent among arrested drivers involved in crashes (30.6%) and drivers arrested for other reasons (56.9%), whereas only 0.18% of the control group was positive for amphetamine/methamphetamine. The single-use substances which gave highest OR for police arrest were amphetamine/methamphetamine, alprazolam, clonazepam and oxazepam. The majority of the alprazolam and clonazepam findings were probably due to non-therapeutic use of medicinal drugs purchased on the illegal market. Combinations of two or more drugs yielded higher ORs than the use of single substances; combinations of amphetamine/methamphetamine and benzodiazepines gave the highest risk. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

High prevalence of previous arrests for illicit drug use and/or impaired driving among drivers killed in motor vehicle crashes in Sweden with amphetamine in blood at autopsy.

PubMed

Jones, Alan Wayne; Holmgren, Anita; Ahlner, Johan

2015-08-01

Amphetamine, and to a lesser extent the secondary amine methamphetamine, are major recreational drugs of abuse in Sweden. These central stimulant amines are identified in blood from roughly 50% of people arrested for driving under the influence of drugs (DUID). However, much less information is available about the presence of amphetamine in blood of drivers killed in road-traffic crashes. This retrospective 10-year study (2001-2010) used a forensic toxicology database (TOXBASE) to retrieve information about road-traffic crashes when the driver had amphetamine and/or methamphetamine in autopsy blood. Forensic toxicology results were available from over 95% of all drivers killed on Swedish roads during this 10-year period. Amphetamine was present in the blood of 106 drivers (3.9%) either alone or together with other psychoactive substances (e.g. alcohol, cannabis, diazepam, alprazolam, etc.). The vast majority of fatalities were male (95%) with a mean age (±standard deviation) of 37±11.4 years (range 16-67 years). The mean (median) and highest concentrations of amphetamine in femoral blood were 1.36 mg/L (1.0mg/L) and 6.74 mg/L, respectively. Many of the victims (75%) had been arrested previously for use of illicit drugs or DUID. The median number of previous arrests was 4 (range 0-83) and amphetamine or methamphetamine were among the drugs identified in blood samples from 89% of cases (0-100%). The high prevalence of repeat DUID offending and/or use of illicit drugs among the drivers killed in road-traffic crashes suggests that an early intervention and treatment for stimulant abuse might have been more beneficial than conventional punishments for such drug-related crimes. Copyright © 2015 Elsevier B.V. All rights reserved.

Putting Drivers to the Test: Transportation Drug and Alcohol Testing.

ERIC Educational Resources Information Center

Baker, John G.

1994-01-01

Outlines what is required of school districts for compliance with new regulations that require employers to test drivers with a commercial driver's license for the illegal use of alcohol and controlled substances. (MLF)

The incidence of drugs in fatally injured drivers

DOT National Transportation Integrated Search

1974-02-01

Methods for the collection of blood, urine, bile and alcohol washes of face and fingers from fatally injured drivers have been developed. Specimens were supplied by coroners and medical examiners from fatally injured drivers. Seven hundred and ten we...

THE PREVALENCE OF CANNABIS-INVOLVED DRIVING IN CALIFORNIA

PubMed Central

Johnson, Mark B.; Kelley-Baker, Tara; Voas, Robert B.; Lacey, John H.

2013-01-01

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. PMID:22101027

Alcohol and illicit drugs in drivers involved in road traffic crashes in the Milan area. A comparison with normal traffic reveals the possible inadequacy of current cut-off limits.

PubMed

Ferrari, Davide; Manca, Monica; Banfi, Giuseppe; Locatelli, Massimo

2018-01-01

Driving under the influence of alcohol and/or illicit drugs in Italy is regulated by the articles 186 and 187 of the National Street Code. Epidemiological studies on drivers involved in road traffic crashes (RTC) provide useful information about the use/abuse of these substances in the general population. Comparison with case control studies may reveal important information like the cut-off limits adequacy. Data from 1587 blood tests for alcohol and 1258 blood tests for illicit drugs on drivers involved in RTC around Milan between 2012 and 2016, were analyzed and compared with a published random survey (DRUID) from the European Community. Our data from RTC-involved drivers show that alcohol abuse is not age-related whereas illicit drugs are more common in young people. Cannabinoids are frequent among younger drivers (median age 27) whereas cocaine is more often detected in adults (median age 34). The calculated odds ratio after comparison with the DRUID survey shows that a blood alcohol concentration below the legal limit does not represent a risk factor in having a car accident whereas concentrations of cocaine and cannabinoids within the legal limits are associated with being involved in a car accident. Despite authority efforts, the abuse of alcohol and illicit drugs is still common in young drivers. We suspect that the cut-off limits for cannabinoids and cocaine and/or the pre-analytical procedures for these substances are inadequate. We suggest a better standardization of the procedure by shortening the time interval between the request for investigation and blood collection and propose the adoption of more stringent cut-off limits. Copyright © 2017 Elsevier B.V. All rights reserved.

Oregon Driver Education. Alcohol/Drugs and Driving.

ERIC Educational Resources Information Center

Oregon State Dept. of Education, Salem. Div. of Curriculum and School Improvement.

This curriculum unit contains 10 modules, to be used in 10 driver education class sessions, on driving under the influence of alcohol and/or other drugs (DUI). The unit aims to combat the Oregon DUI problem, especially among 15- to 24-year-olds, with values clarification, awareness of risk factors and personal boundaries, refusal skills, social…

Frequency and irregularity of heart rate in drivers suspected of driving under the influence of cannabis.

PubMed

Khiabani, Hassan Z; Mørland, Jørg; Bramness, Jørgen G

2008-12-01

Delta 9-tetrahydrocannabinol (THC) is the major active component of cannabis. Cardiovascular effects of THC have previously been reported: tachycardia after intake, but also bradycardia at higher doses. The purpose of this study was, firstly, to investigate the frequency and irregularity of heart rate in a group of cannabis users in their natural surroundings. We also compared THC-positive drivers with a regular pulse with THC-positive drivers with an irregular pulse. The division of Forensic Toxicology and Drug Abuse (DFTDA) at the Norwegian Institute of Public Heath analyzes blood samples from all drivers suspected of driving under the influence of drugs. We studied pulse rate and regularity in 502 THC-positive drivers who tested negative for other substances. As a control group, we randomly selected 125 drug-negative cases from the database of the DFTDA; no alcohol, narcotics, or medicinal drugs of abuse were detected. The Delta9-THC-positive drivers had a higher mean pulse rate than the control group [82.8 beats/min (SD 16.3) versus 75.6 beats/min (SD 9.2)] and more cases with tachycardia were detected in the Delta9-THC-positive group (19.4% versus 1.6%). There was only one driver with an irregular heart beat in the control group, while there were nine among the Delta9-THC-positive drivers. The drivers with an irregular pulse were over-represented amongst those with the lowest blood Delta9-THC concentrations. This report represents a large study of subjects in a real-life situation and includes observations on pulse frequency, regularity, and blood Delta9-THC concentration. A substantial fraction of Delta9-THC-positive drivers had tachycardia, but there was no correlation between blood Delta9-THC concentration and pulse rate in the present study. We had no further diagnostic information on the cause of the pulse irregularities, but our results indicate that occasional users of cannabis tend to have irregular heart rates at low THC concentrations and at low pulse rates.

The need for drugged driving per se laws: a commentary.

PubMed

DuPont, Robert L; Voas, Robert B; Walsh, J Michael; Shea, Corinne; Talpins, Stephen K; Neil, Mark M

2012-01-01

Triggered by the new federal commitment announced by the Office of National Drug Control Policy (ONCDP) to encourage states to enact drugged driving per se laws, this article reviews the reasons to establish such laws and the issues that may arise when trying to enforce them. A review of the state of drunk driving per se laws and their implications for drugged driving is presented, with a review of impaired driving enforcement procedures and drug testing technology. Currently, enforcement of drugged driving laws is an adjunct to the enforcement of laws regarding alcohol impairment. Drivers are apprehended when showing signs of alcohol intoxication and only in the relatively few cases where the blood alcohol concentration of the arrested driver does not account for the observed behavior is the possibility of drug impairment pursued. In most states, the term impaired driving covers both alcohol and drug impairment; thus, driver conviction records may not distinguish between the two different sources of impairment. As a result, enforcement statistics do not reflect the prevalence of drugged driving. Based on the analysis presented, this article recommends a number of steps that can be taken to evaluate current drugged driving enforcement procedures and to move toward the enactment of drug per se laws.

Factors associated with drug use among male motorbike taxi drivers in urban Vietnam.

PubMed

Nguyen, Huy Van; Vu, Thinh Toan; Pham, Ha Nguyen

2014-08-01

A cross-sectional study was conducted on a sample of 291 male motorbike taxi drivers (MMTDs) recruited through social mapping technique in Hanoi, Vietnam, for face-to-face interviews to examine factors associated with drug use among MMTDs using Information-Motivation-Behavioral skills (IMB) model. Among 291 MMTDs, 17.18% reported drug use sometime in their lives, 96% of whom were drug injectors. Being depressed, being originally borne in urban cities, currently residing in rural areas, having a longer time living apart from their wives/lovers, using alcohol, following Buddhism, and reporting lower motivation of HIV prevention predict significantly higher odds of uptaking drugs.

32 CFR 634.36 - Detection, apprehension, and testing of intoxicated drivers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MOTOR VEHICLE TRAFFIC SUPERVISION Traffic Supervision § 634.36 Detection, apprehension, and testing of intoxicated drivers. (a) Law enforcement personnel usually detect drivers under the influence of alcohol or other drugs by observing...

32 CFR 634.36 - Detection, apprehension, and testing of intoxicated drivers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MOTOR VEHICLE TRAFFIC SUPERVISION Traffic Supervision § 634.36 Detection, apprehension, and testing of intoxicated drivers. (a) Law enforcement personnel usually detect drivers under the influence of alcohol or other drugs by observing...

Driver injury severity outcome analysis in rural interstate highway crashes: a two-level Bayesian logistic regression interpretation.

PubMed

Chen, Cong; Zhang, Guohui; Liu, Xiaoyue Cathy; Ci, Yusheng; Huang, Helai; Ma, Jianming; Chen, Yanyan; Guan, Hongzhi

2016-12-01

There is a high potential of severe injury outcomes in traffic crashes on rural interstate highways due to the significant amount of high speed traffic on these corridors. Hierarchical Bayesian models are capable of incorporating between-crash variance and within-crash correlations into traffic crash data analysis and are increasingly utilized in traffic crash severity analysis. This paper applies a hierarchical Bayesian logistic model to examine the significant factors at crash and vehicle/driver levels and their heterogeneous impacts on driver injury severity in rural interstate highway crashes. Analysis results indicate that the majority of the total variance is induced by the between-crash variance, showing the appropriateness of the utilized hierarchical modeling approach. Three crash-level variables and six vehicle/driver-level variables are found significant in predicting driver injury severities: road curve, maximum vehicle damage in a crash, number of vehicles in a crash, wet road surface, vehicle type, driver age, driver gender, driver seatbelt use and driver alcohol or drug involvement. Among these variables, road curve, functional and disabled vehicle damage in crash, single-vehicle crashes, female drivers, senior drivers, motorcycles and driver alcohol or drug involvement tend to increase the odds of drivers being incapably injured or killed in rural interstate crashes, while wet road surface, male drivers and driver seatbelt use are more likely to decrease the probability of severe driver injuries. The developed methodology and estimation results provide insightful understanding of the internal mechanism of rural interstate crashes and beneficial references for developing effective countermeasures for rural interstate crash prevention. Copyright © 2016 Elsevier Ltd. All rights reserved.

Subcutaneous drug infusions: a review of problems and solutions.

PubMed

Mitten, T

2001-02-01

Subcutaneous drug infusion using a portable syringe driver has had a significant impact on patient comfort in palliative care. It permits the continuous delivery of a range of drug therapies, so bypassing problems of dysphagia, weakness and the inability of many patients in the terminal phase to take oral medication. The devices are not problem-free, however. Mechanical problems, reactions at the infusion site and difficulties with the mixing of drugs in the syringe are all widely recognized. This article reviews some general issues with the operation of portable syringe drivers, and discusses a range of potential problems and their solutions.

Graduated driver license compliant teens involved in fatal motor vehicle crashes.

PubMed

Pressley, Joyce C; Addison, Diane; Dawson, Patrick; Nelson, Sharifa S

2015-09-01

Significant reductions in motor vehicle injury mortality have been reported for teen drivers after passage of graduated driver licensing (GDL), seat belt, and no tolerance alcohol and drug laws. Despite this, teen drivers remain a vulnerable population with elevated fatal crash involvement. This study examines driver, vehicle, and crash characteristics of GDL-compliant, belted, and unimpaired teen drivers with the goal of identifying areas where further improvements might be realized. The Fatality Analysis Reporting System (FARS) for 2007 to 2009 was used to examine and classify driver violations/errors in compliant teen drivers (n = 1,571) of passenger vehicles involved in a fatal collision. Teens driving unbelted, non-GDL compliant, or impaired by alcohol or drugs were excluded. Statistical analysis used χ, Fisher's exact and multivariable logistic regression. Odds ratios are reported with 95% confidence intervals. Significance was defined as p < 0.05. Nearly one third (n = 1,571) of teen drivers involved in a fatal motor vehicle crash were GDL compliant, unimpaired, and belted. The majority held an intermediate GDL license (90.6%). Crash-related factors were identified for 63.1% of fatal crashes. Age- and sex-adjusted odds identified overcorrecting, speeding, lane errors, school morning crashes, distractions, and driving on slippery surfaces as having increased odds of fatality for the teen driver as well as newer vehicle models and heavier vehicle weight as protective. Among compliant drivers, weekday crashes before and after school and committing a driving violation at the time of crash were associated with increased risk of driver death and higher incidence of incapacitating injury in surviving drivers. Therapeutic study, level V.

23 CFR 192.4 - Adoption of drug offender's driver's license suspension.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Adoption of drug offender's driver's license suspension... State under each of sections 104(b)(1), 104(b)(3), and 104(b)(5) of title 23 of the United States Code... apportioned to any State under each of sections 104(b)(1), 104(b)(3), and 104(b)(5) of title 23 of the United...

23 CFR 192.4 - Adoption of drug offender's driver's license suspension.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Adoption of drug offender's driver's license suspension... State under each of sections 104(b)(1), 104(b)(3), and 104(b)(5) of title 23 of the United States Code... apportioned to any State under each of sections 104(b)(1), 104(b)(3), and 104(b)(5) of title 23 of the United...

23 CFR 192.4 - Adoption of drug offender's driver's license suspension.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Adoption of drug offender's driver's license suspension... State under each of sections 104(b)(1), 104(b)(3), and 104(b)(5) of title 23 of the United States Code... apportioned to any State under each of sections 104(b)(1), 104(b)(3), and 104(b)(5) of title 23 of the United...

23 CFR 192.4 - Adoption of drug offender's driver's license suspension.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Adoption of drug offender's driver's license suspension... State under each of sections 104(b)(1), 104(b)(3), and 104(b)(5) of title 23 of the United States Code... apportioned to any State under each of sections 104(b)(1), 104(b)(3), and 104(b)(5) of title 23 of the United...

Prevalence of psychoactive substances, alcohol and illicit drugs, in Spanish drivers: A roadside study in 2015.

PubMed

Domingo-Salvany, Antonia; Herrero, M Jesús; Fernandez, Beatriz; Perez, Julio; Del Real, Pilar; González-Luque, Juan Carlos; de la Torre, Rafael

2017-09-01

A survey was conducted during 2015 to monitor psychoactive substance use in a sample of drivers in Spanish roads and cities. Traffic police officers recruited drivers at sites carefully chosen to achieve representativeness of the driver population. A brief questionnaire included the date, time, and personal and driving patterns data. Alcohol use was ascertained through ethanol breath test at the roadside and considered positive if concentrations >0.05mg alcohol/L were detected. Four drug classes were assessed on-site through an oral fluid screening test that, if positive, was confirmed through a second oral fluid sample at a reference laboratory. Laboratory confirmation analyses screened for 26 psychoactive substances. To evaluate the association between drug findings and age, sex, road type (urban/interurban), and period of the week (weekdays, weeknights, weekend days, weekend nights), logistic regression analyses were done (overall, and separately for alcohol, cannabis and cocaine). A total of 2744 drivers, mean age of 37.5 years, 77.8% men, were included. Overall, 11.6% of the drivers had at least one positive finding to the substances assessed. Substances more frequently testing positive were cannabis (7.5%), cocaine (4.7%) and alcohol (2.6%). More than one substance was detected in 4% of the subjects. The proportion of positive results decreased with age, and was more likely among men and on urban roads. The pattern for alcohol use was similar but did not change with age and increased among drivers recruited at night. Cannabis was more likely to be detected at younger ages and cocaine was associated with night driving. Alcohol use before driving has decreased over the last decade; however, the consumption of other illegal drugs seems to have increased. The pattern of illegal psychoactive substance observed is similar to that declared in surveys of the general population of adults. Copyright © 2017. Published by Elsevier B.V.

Should a psychiatrist report a bus driver's alcohol and drug abuse? An ethical dilemma.

PubMed

Leeman, C P; Cohen, M A; Parkas, V

2001-01-01

Denial of alcohol or drug abuse, and of its possible consequences, can complicate medical and psychiatric care. We present the case of an HIV-positive bus driver with substance abuse who initially denied ongoing use of alcohol and of other drugs, but later admitted to both. The psychiatrist's duty to protect the patient's confidentiality, coupled with concerns about public safety, created an ethical dilemma. In discussing this dilemma we stress the importance of preserving confidentiality, both to facilitate treatment and also to further the safety of others.

An evaluation of immediate roadside prohibitions for drinking drivers in British Columbia: findings from roadside surveys.

PubMed

Beirness, Douglas J; Beasley, Erin E

2014-01-01

The purpose was to determine the impact of new immediate roadside prohibitions (IRPs) for drinking drivers introduced in British Columbia in September 2010 as assessed by random roadside surveys of alcohol and drug use among nighttime drivers. Two roadside surveys were conducted prior to and following the introduction of IRPs. Drivers were randomly selected from the traffic stream in 5 cities and asked to provide a breath sample to determine alcohol content and a sample of oral fluid to be tested for the presence of psychoactive drugs. The survey was conducted between the hours of 9:00 p.m. and 3:00 a.m. on Wednesday through Saturday nights in June 2010 and again in June 2012. Driving after drinking decreased significantly following the introduction of IRPs. In particular, the percentage of drivers with blood alcohol concentrations (BACs) over 80 mg/dL decreased by 59 percent; drivers with BACs of at least 50 mg/dL decreased by 44 percent. The decreases in drinking and driving were not restricted to specific subgroups of drivers but were universal across age groups, sex, and communities. The results also revealed a changing pattern of drinking of driving. For example, the typical pattern of increased drinking and driving on weekend nights was not observed and the prevalence of drinking drivers on the road during late night hours was less than half that found in 2010. The prevalence of drug use by drivers in 2012 did not change from the levels reported in 2010. The IRP program combined immediate short-term roadside suspensions with vehicle impoundment and monetary penalties to enhance the swiftness, certainty, and perceived severity of sanctions for drinking and driving. The introduction of these measures was associated with a substantial reduction in the prevalence of driving with a BAC over 50 mg/dL and driving with a BAC over 80 mg/dL.

49 CFR 40.331 - To what additional parties must employers and service agents release information?

Code of Federal Regulations, 2014 CFR

2014-10-01

... employer of Commercial Motor Vehicle (CMV) drivers holding commercial driving licenses (CDLs) or as a third party administrator for owner-operator CMV drivers with CDLs, you are authorized to comply with State... DOT drug and alcohol testing rules (including positive tests and refusals) by any CMV driver holding a...

49 CFR 40.331 - To what additional parties must employers and service agents release information?

Code of Federal Regulations, 2011 CFR

2011-10-01

... employer of Commercial Motor Vehicle (CMV) drivers holding commercial driving licenses (CDLs) or as a third party administrator for owner-operator CMV drivers with CDLs, you are authorized to comply with State... DOT drug and alcohol testing rules (including positive tests and refusals) by any CMV driver holding a...

A systematic study on drug-response associated genes using baseline gene expressions of the Cancer Cell Line Encyclopedia

NASA Astrophysics Data System (ADS)

Liu, Xiaoming; Yang, Jiasheng; Zhang, Yi; Fang, Yun; Wang, Fayou; Wang, Jun; Zheng, Xiaoqi; Yang, Jialiang

2016-03-01

We have studied drug-response associated (DRA) gene expressions by applying a systems biology framework to the Cancer Cell Line Encyclopedia data. More than 4,000 genes are inferred to be DRA for at least one drug, while the number of DRA genes for each drug varies dramatically from almost 0 to 1,226. Functional enrichment analysis shows that the DRA genes are significantly enriched in genes associated with cell cycle and plasma membrane. Moreover, there might be two patterns of DRA genes between genders. There are significantly shared DRA genes between male and female for most drugs, while very little DRA genes tend to be shared between the two genders for a few drugs targeting sex-specific cancers (e.g., PD-0332991 for breast cancer and ovarian cancer). Our analyses also show substantial difference for DRA genes between young and old samples, suggesting the necessity of considering the age effects for personalized medicine in cancers. Lastly, differential module and key driver analyses confirm cell cycle related modules as top differential ones for drug sensitivity. The analyses also reveal the role of TSPO, TP53, and many other immune or cell cycle related genes as important key drivers for DRA network modules. These key drivers provide new drug targets to improve the sensitivity of cancer therapy.

Use of drugs of abuse in less than 30-year-old drivers killed in a road crash in France: a spectacular increase for cannabis, cocaine and amphetamines.

PubMed

Mura, P; Chatelain, C; Dumestre, V; Gaulier, J M; Ghysel, M H; Lacroix, C; Kergueris, M F; Lhermitte, M; Moulsma, M; Pépin, G; Vincent, F; Kintz, P

2006-07-13

A collaborative study was conducted in France in order to determine the prevalence of cannabinoids, opiates, cocaine metabolites and amphetamines in blood samples from drivers killed in road accidents in 2003 and 2004 and to compare these values with those of a previous study performed during the period 2000-2001 involving 900 drivers. Blood samples were provided from 2003 under 30-year-old drivers, killed in a traffic accident. Drugs of abuse were determined by gas chromatography-mass spectrometry using the same analytical procedures in all the 12 laboratories. The most frequently observed compounds were by far cannabinoids, that tested positive in 39.6% of the total number of samples. Delta9 tetrahydrocannabinol (THC), the most active of the principle constituents in marijuana (cannabis sativa), was detected in the blood of 28.9% drivers and was the single drug of abuse in 80.2% of the positive cases. It was associated with amphetamines in 7.4% and with opiates and cocaine in 1.9 and 4.8%, respectively. Amphetamines were present in 3.1% of the total number of samples, cocaine metabolites in 3.0% and opiates in 3.5%. When comparing these results with those of a previous study performed 3 years before, a significant increase is observed for THC (28.9% versus 16.9%), cocaine metabolites (3.0% versus 0.2%) and amphetamines (3.1% versus 1.4%). This study demonstrates the critical necessity of implementing in France as soon as possible systematical roadside testing for drugs of abuse.

Field evaluation of the Los Angeles Police Department drug detection procedure.

DOT National Transportation Integrated Search

1986-12-01

The Los Angeles Police Department (LAPD) has developed a drug recognition program designed to provide trained officers the ability to detect drug-impaired drivers and to identify the responsible drug class (e.g., stimulant, depressant, etc. ). As par...

78 FR 3077 - Qualification of Drivers; Exemption Applications; Epilepsy and Seizure Disorders

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-15

... consciousness that resulted from a known medical condition (e.g., drug reaction, high temperature, acute... truck driving school and drive tractor trailer with his wife, as she is a long haul driver. Victor...

Field test of on-site drug detection devices

DOT National Transportation Integrated Search

2000-10-01

This NHTSA-sponsored study reports the findings of a field evaluation of five on-site drug screening devices used by law enforcement to screen for illicit drugs among drivers suspected of driving under the influence (DUI) of alcohol or other drugs. I...

2007 national roadside survey of alcohol and drug use by drivers : drug results.

DOT National Transportation Integrated Search

2009-12-01

This report presents the first national prevalence estimates for drug-involved driving derived from the recently : completed 2007 National Roadside Survey (NRS). The NRS is a national field survey of alcohol- and drug-involved : driving conducted pri...

The economics of personalized medicine: commercialization as a driver of return on investment.

PubMed

Keeling, Peter; Roth, Mollie; Zietlow, Tom

2012-09-15

Optimizing commercialization of drugs is the sine qua non of the pharmaceutical industry and intensive work has been done to characterize fully the drivers of drug adoption and understand the resources required to optimize those drivers for full adoption of drugs. Conversely, while the pharmaceutical industry is actively embracing the new personalized medicine (PM) paradigm, much work remains to be done to understand fully what drives adoption of targeted therapies and how to resource those drivers appropriately. While the industry is slowly learning from its early missteps, progress is still inhibited by a lack of understanding of the specific hurdles that individual development teams face in developing and commercializing targeted therapies and the requirement for budgets specifically aimed at driving test adoption. This article considers the benefits of optimizing commercial planning in the PM space and the potential negative impact in potentially failing to optimize that planning. Real world insights are used to illustrate that a far broader commercial lens is required in the PM space and will touch on functional areas not usually included in the context of 'commercial' decisions. Copyright © 2012 Elsevier B.V. All rights reserved.

Drugs and highway safety 1980

DOT National Transportation Integrated Search

1980-05-01

This report presents findings of a study to describe (1) present knowledge about the relationship between drug use by drivers and highway safety, and (2) efforts to detect and prevent drug-impaired driving. Past, ongoing, and planned activities at fe...

Mutant onco-proteins as drug targets: successes, failures, and future prospects.

PubMed

McCormick, Frank

2011-02-01

Mutant onco-proteins play a direct, causal role in cancer and are therefore considered attractive drug targets. Clinical experience has supported this view, with some exceptions. However, clinical benefit has often been restricted by rapid emergence of drug-resistant clones through several distinct mechanisms. This problem can, in principle, be addressed through cocktails containing several drugs. However, the number of tumors whose survival is dependent on a single, druggable mutant onco-protein is currently unknown. The majority of tumors may be driven either by single drivers that are un-druggable, or by combinations of drivers. In both cases, new approaches will be necessary. Development of systemic RNA interference may be a solution to these problems. Copyright © 2010 Elsevier Ltd. All rights reserved.

Combating the drug-impaired driver : a prescription for safer highways.

DOT National Transportation Integrated Search

1985-01-01

In recent years, the Commonwealth of Virginia has increased its efforts to improve highway safety by combating the problems created by drunken drivers. However, law enforcement officials still face major obstacles in their efforts to detect and prose...

Drivers license display system

NASA Astrophysics Data System (ADS)

Prokoski, Francine J.

1997-01-01

Carjackings are only one of a growing class of law enforcement problems associated with increasingly violent crimes and accidents involving automobiles plays weapons, drugs and alcohol. Police traffic stops have become increasingly dangerous, with an officer having no information about a vehicle's potentially armed driver until approaching him. There are 15 million alcoholics in the US and 90 percent of them have drivers licenses. Many of them continue driving even after their licenses have ben revoked or suspended. There are thousands of unlicensed truck drivers in the country, and also thousands who routinely exceed safe operating periods without rest; often using drugs in an attempt to stay alert. MIKOS has developed the Drivers License Display Systems to reduce these and other related risks. Although every state requires the continuous display of vehicle registration information on every vehicle using public roads, no state yet requires the display of driver license information. The technology exists to provide that feature as an add-on to current vehicles for nominal cost. An initial voluntary market is expected to include: municipal, rental, and high value vehicles which are most likely to be mis-appropriated. It is anticipated that state regulations will eventually require such systems in the future, beginning with commercial vehicles, and then extending to high risk drivers and eventually all vehicles. The MIKOS system offers a dual-display approach which can be deployed now, and which will utilize all existing state licenses without requiring standardization.

A comparison of alcohol and drug use by random motor vehicle drivers in Brazil and Norway.

PubMed

Gjerde, Hallvard; Sousa, Tanara R; De Boni, Raquel; Christophersen, Asbjørg S; Limberger, Renata P; Zancanaro, Ivomar; Oiestad, Elisabeth L; Normann, Per T; Mørland, Jørg; Pechansky, Flavio

2014-05-01

A large proportion of road traffic crashes are related to driving under the influence (DUI) of alcohol or drugs. The aim of this study was to compare the use of alcohol, illegal drugs and psychoactive medicinal drugs among random drivers in Brazil and Norway, two countries with the same legal limit for drunk driving, but with marked differences in legislation history, enforcement and penalties for DUI, and to discuss any differences found. Roadside surveys were conducted on Fridays and Saturdays between noon and midnight. Samples of oral fluid were collected for analysis of drugs, whereas alcohol was determined by breath testing or by analysis of oral fluid. High participation rates of 94-97% were obtained in both countries. The weighted prevalence of driving with alcohol concentrations in breath or oral fluid equivalent to blood alcohol concentrations (BAC) above 0.2g/L was 2.7% (95% CI 2.2-3.3) in Brazil and 0.2% (95% CI 0.0-0.5) in Norway. Stimulants (amphetamines or cocaine) were found in samples from 1.0% (95% CI 0.7-1.4) of drivers in Brazil and 0.3% (95% CI 0.1-0.7) in Norway. The prevalence of amphetamines was highest among Brazilian truck drivers (3.6%; 95% CI 2.0-6.4). Tetrahydrocannabinol was found in samples from 0.5% (95% CI 0.3-0.8) of drivers in Brazil and 1.0% (95% CI 0.6-1.5) in Norway, whereas benzodiazepines or zopiclone were found in 1.0% (95% CI 0.7-1.4) and 1.7% (95% CI 1.2-2.4) of the samples from Brazil and Norway, respectively. The difference in the prevalence of alcohol may be related to the fact that Norway has implemented steps to reduce drunk driving since 1936, whereas Brazil has attempted to do the same for only a few years. Differences for drugs may be related to different patterns in the use of stimulants, cannabis and medicines. Copyright © 2014 Elsevier B.V. All rights reserved.

77 FR 4479 - Harmonizing Schedule I Drug Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-30

... [Docket No. FMCSA-2011-0073] RIN 2126-AB35 Harmonizing Schedule I Drug Requirements AGENCY: Federal Motor... examination report to clarify that drivers may not use Schedule I drugs and be qualified to drive commercial... DEA Drug Enforcement Administration FMCSA Federal Motor Carrier Safety Administration FR Federal...

77 FR 10391 - Harmonizing Schedule I Drug Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... [Docket No. FMCSA-2011-0073] RIN 2126-AB35 Harmonizing Schedule I Drug Requirements AGENCY: Federal Motor... the medical examination report to clarify that drivers may not use Schedule I drugs and be qualified...; email: [email protected] . SUPPLEMENTARY INFORMATION: FMCSA's recent rule harmonizing Schedule I drug...

Drug research methodology. Volume 4, Epidemiology in drugs and highway safety : the study of drug use among drivers and its role in traffic crashes

DOT National Transportation Integrated Search

1980-06-01

This report presents the findings of a workshop on epidemiology in drugs and highway safety. A cross-disciplinary panel of experts (1) identified methodological issues and constraints present in research to define the nature and magnitude of the drug...

Alcohol & drug use among drivers : British Columbia roadside survey 2008

DOT National Transportation Integrated Search

2009-01-01

Following two decades of progress dealing with alcoholimpaired : driving, greater attention is now being : directed toward the issue of driving while impaired by : drugs. Currently, there is far less information related to drug-impaired : driving tha...

Hair analysis in order to evaluate drug abuse in driver's license regranting procedures.

PubMed

Tassoni, G; Mirtella, D; Zampi, M; Ferrante, L; Cippitelli, M; Cognigni, E; Froldi, R; Cingolani, M

2014-11-01

In Italy, driving under the influence of drugs determines the suspension of the offender's driver's license. To regain the license the person must be drug free during an observation period. People whose license has been revoked or suspended can obtain, or re-obtain their driver's license subject to the judgment of a medical commission. The exclusion of illicit drug use is determined by means of toxicological analysis, mainly on urine or hair matrices. We reported the results of several years of experience of the forensic toxicology laboratory of the University of Macerata in the use of hair analysis for the assessment of past exposure to drugs in people suspected of driving under the influence of drugs. From 2004 to 2013, 8612 hair samples, were analyzed for opiates, cocaine and delta-9-tetrahydrocannabinol (Δ(9)-THC) using gas chromatography/mass spectrometry (GC/MS) method. We used a cutoff (SoHT or national guidelines) to determine the positive data, regardless of the hair sample concentrations. 1213 samples resulted positive, 71.7% were positive for cocaine and metabolites, 19.8% for morphine and metabolites, 8.5% for Δ(9)-THC. We also studied the timeframe of the abuse, as well as gender and age distribution of positive subjects. Moreover, we analyzed the possible deterrent effect of the hair analysis on driving under the influence of psychoactive substances. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Impairment related to blood amphetamine and/or methamphetamine concentrations in suspected drugged drivers.

PubMed

Gustavsen, Ingebjørg; Mørland, Jørg; Bramness, Jørgen G

2006-05-01

Experimental studies have investigated effects of low oral doses of amphetamine and methamphetamine on psychomotor functions, while less work has been done on effects of high doses taken by abusers in real-life settings. There are indications that intake of high doses may impair traffic related skills, and that abuse of amphetamines may cause hypersomnolence at the end-of-binge. The present study aimed at investigating the concentration-effect relationship between blood amphetamines concentrations and impairment in a population of real-life users. Eight hundred and seventy-eight cases with amphetamine or methamphetamine as the only drugs present in the blood samples were selected from the impaired driver registry at The Norwegian Institute of Public Health. In each case the police physician had concluded on whether the driver was impaired or not. 27% of the drivers were judged as not impaired, while 73% were judged as impaired. There was a positive relationship between blood amphetamines concentrations and impairment. The relationship reached a ceiling at blood amphetamines concentrations of 0.27-0.53 mg/l. Younger drivers were more often judged impaired than older drivers at similar concentrations. Despite the performance enhancing qualities of amphetamines demonstrated in some low dose laboratory experiments; this study revealed a positive relationship between blood amphetamines concentration and traffic related impairment.

76 FR 40306 - Harmonizing Schedule I Drug Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

... [Docket No. FMCSA-2011-0073] RIN 2126-AB35 Harmonizing Schedule I Drug Requirements AGENCY: Federal Motor... instructions for the medical examination report to clarify that drivers may not use Schedule I drugs and be.... Abbreviations CAA Clean Air Act. CFR Code of Federal Regulations. CMV Commercial Motor Vehicle. DEA Drug...

Responsibility Study: Main Illicit Psychoactive Substances Among Car Drivers Involved in Fatal Road Crashes

PubMed Central

Gadegbeku, Blandine; Amoros, Emmanuelle; Laumon, Bernard

2011-01-01

In 1999, in France, before considering modifications in drug legislation, the government requested a study of the effect of illicit drugs on the risk of road crashes. It implemented a systematic screening of illicit drugs for all drivers involved in fatal crashes between October 2001 and September 2003. Within the European DRUID project, the study was restricted to car drivers. The project reported here is a responsibility analysis and, as such, it belongs to the framework of case-control studies; the outcome of interest is “being responsible for a fatal crash”. It was assessed with a method adapted from Robertson and Drummer. Cases are the 4,946 car drivers who are responsible for the crash; controls are the 1,986 car drivers selected from the non-responsible car drivers, in a way that makes the control group similar to the general driving population. The effect of cannabis on fatal crash responsibility is significant after adjustment for age, sex and alcohol: adjusted odds ratio is 1.89 [1.43–2.51]. The dose-response effect is significant (p=0.0001). For alcohol (≥0.1 g/l), the adjusted odds ratio for responsibility is 8.39 [6.95–10.11]. No interaction was found between alcohol and cannabis. For amphetamine, cocaine and opiates, adjusted odds ratios were not significantly different from 1. However the statistical power is low. The study finds similar odds ratios for alcohol as previously published. For cannabis, the significant odds ratio together with the significant dose-response effect indicates a causal relationship between cannabis and road crashes. A multiplicative effect between cannabis and alcohol was noted. PMID:22105404

49 CFR 384.217 - Drug offenses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 5 2011-10-01 2011-10-01 false Drug offenses. 384.217 Section 384.217 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY... COMMERCIAL DRIVER'S LICENSE PROGRAM Minimum Standards for Substantial Compliance by States § 384.217 Drug...

49 CFR 384.217 - Drug offenses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Drug offenses. 384.217 Section 384.217 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY... COMMERCIAL DRIVER'S LICENSE PROGRAM Minimum Standards for Substantial Compliance by States § 384.217 Drug...

49 CFR 384.217 - Drug offenses.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 5 2013-10-01 2013-10-01 false Drug offenses. 384.217 Section 384.217 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY... COMMERCIAL DRIVER'S LICENSE PROGRAM Minimum Standards for Substantial Compliance by States § 384.217 Drug...

49 CFR 384.217 - Drug offenses.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 5 2012-10-01 2012-10-01 false Drug offenses. 384.217 Section 384.217 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY... COMMERCIAL DRIVER'S LICENSE PROGRAM Minimum Standards for Substantial Compliance by States § 384.217 Drug...

49 CFR 384.217 - Drug offenses.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 5 2014-10-01 2014-10-01 false Drug offenses. 384.217 Section 384.217 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY... COMMERCIAL DRIVER'S LICENSE PROGRAM Minimum Standards for Substantial Compliance by States § 384.217 Drug...

High risk for obstructive sleep apnea in truck drivers estimated by the Berlin questionnaire: prevalence and associated factors.

PubMed

Moreno, C R C; Carvalho, F A; Lorenzi, C; Matuzaki, L S; Prezotti, S; Bighetti, P; Louzada, F M; Lorenzi-Filho, G

2004-01-01

The health issues that attract our attention when analyzing the truck driver population are the high prevalence of sedentary habits, inadequate diet, obesity, and proportion of hypertensive. All these are either considered risk factors for or a consequence of Obstructive Sleep Apnea (OSA). The objective of this study was to investigate the risk for OSA among 10,101 truck drivers and to correlate it with potentially related factors, such as serum glucose and cholesterol levels, smoking habits, alcohol and drug consumption, and self-reported physical activity. The drivers were invited to participate in the campaign "Saúde na Boléia" (Health Behind the Wheel) promoted by a Brazilian company responsible for the maintenance of approximately 360km of roads in the country. Drivers who spontaneously stopped at the campaign booths placed along the roads were invited to answer a questionnaire covering sociodemographic data such as age, alcohol, and drug consumption. All participants completed a Berlin Questionnaire and were classified as low- or high-risk subjects for OSA based on questions about snoring, tiredness during the day, and the presence of hypertension or obesity. Blood collection was accomplished at the same site by nurses and/or nursing students collaborating with the campaign for subsequent laboratory studies. Approximately 26% of the truck drivers were found to be at high-risk group for OSA. An adjusted multiple logistic model found the independent risk factors of smoking (OR=1.16; p=0.014) and drug use (OR= 1.32; p < 0.0001) were associated with high risk for OSA. The presence of self-reported occasional (OR=0.62; p<0.0001) and regular (OR=0.53; p < 0.0001) physical activity was found to be an independent factor protective of OSA. Educational programs, including ones aimed at improving one's health habits, such as engagement in physical exercise, should be considered in the development of initiatives to reduce the risk for OSA among the truck driver population.

Opioids in oral fluid of Spanish drivers.

PubMed

Herrera-Gómez, Francisco; García-Mingo, Mercedes; Colás, Mónica; González-Luque, Juan Carlos; Álvarez, F Javier

2018-06-01

Driving under the influence of certain drugs is not allowed, and roadside drug testing is being considered an important tool for deterring driving under the influence of them. This study aimed to assess the presence and concentration of opioids, as well as their combined use with other drugs (laboratory confirmation after the on-road screening) in Spanish drivers between 2011 and 2016. In Spain, mandatory roadside breath alcohol and oral fluid drug testing (screening) are carried out by the Traffic Police using Dräger Alcotest ® 6810 device, and Dräger DrugTest ® 5000, DrugWipe ® , or Alere™ DDS ® 2 Mobile Test System. For positive cases in the period covered, 65,244, confirmation analysis and quantification using chromatographic techniques were performed. Opioids were confirmed in 8.6% of positive cases, being 7.2% positives to 6-acetylmorphine (6-AM), 6.5% to morphine, 5.4% to codeine, and 4.1% to methadone. The majority of the confirmed tests for morphine (96.5%), codeine (88.4%) and methadone (81.9) were also positive for 6-AM. The presence of other drugs, particularly cocaine and cannabis, was very common. Concentration values reached important levels. Positive results for morphine (0.1%), codeine (0.6%) or methadone (0.4%) alone were very infrequent. Drivers with a confirmed positive roadside test for morphine, codeine, and methadone had also consumed heroin and/or other illicit drugs, such as cocaine and/or THC, and at relevant concentrations. Improving interventions to combat the problem of driving under the influence of driving-impairing substances is a priority. Copyright © 2018 Elsevier B.V. All rights reserved.

The incidence and role of drugs in fatally injured drivers

DOT National Transportation Integrated Search

1992-10-30

Blood specimens were collected from a sample of 1882 drivers from 7 States, during 14 months in the years 1990 and 1991. The sample comprised operators of passenger cars, trucks, and motorcycles who died within 4 hours of their crash. Alcohol and 43 ...

Status report on Virginia's program to combat drug-impaired driving.

DOT National Transportation Integrated Search

1989-01-01

Beginning on April 1, 1988, police officers in the Commonwealth of Virginia were given the statutory authority to require that drivers suspected of driving under the influence of drugs (DUID) submit a blood sample to be tested for drug content. Altho...

Latent Classes of Polydrug Users as a Predictor of Crash Involvement and Alcohol Consumption.

PubMed

Scherer, Michael; Romano, Eduardo; Voas, Robert; Taylor, Eileen

2018-05-01

Polydrug users have been shown to be at higher risk for alcohol consumption and crash involvement. However, research has shown that polydrug groups differ in some important ways. It is currently unknown how polydrug-using groups differ in terms of crash involvement and alcohol consumption. The current study used latent class analysis to examine subgroups of polydrug users (n = 384) among a sample of drivers in Virginia Beach, Virginia (N = 10,512). A series of logistic regression analyses were conducted to determine the relationship between polydrug use categories and crash involvement and alcohol consumption. Four distinct subclasses of users were identified among polydrug-using drivers: Class 1 is the "marijuana-amphetamines class" and accounts for 21.6% of polydrug users. Class 2 is the "benzo-antidepressant class" and accounts for 39.0% of polydrug users. Class 3 is the "opioid-benzo class" and accounts for 32.7% of polydrug users. Finally, Class 4 is the "marijuana-cocaine class" and accounts for 6.7% of the study sample. Drivers in the opioid-benzo class were significantly more likely than those in any other class as well as non-drug users and single-drug users to be involved in a crash and were more likely than those in most other conditions to consume alcohol. No significant difference was found between marijuana-amphetamine users or benzo-antidepressant users and non-drug users on crash risk. Some polydrug users are indeed at greater risk for crash involvement and alcohol consumption; however, not all polydrug users are significantly worse than single-drug users and/or non-drug users, and the practice of lumping polydrug users together when predicting crash risk runs the risk of inaccurately attributing crash involvement to certain drivers.

Cannabis findings in drivers suspected of driving under the influence of drugs in Finland from 2006 to 2008.

PubMed

Blencowe, Tom; Pehrsson, Anna; Mykkänen, Sirpa; Gunnar, Teemu; Lillsunde, Pirjo

2012-04-10

The authors examined driving under the influence of drugs (DUID) cases which were found to be positive in whole blood for cannabis in Finland from 2006 to 2008. Factors studied were the number of cases positive for any combination of Δ(9)-tetrahydrocannabinol (THC) and the metabolites 11-hydroxy-Δ(9)-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol (THC-COOH). Concurrent use of amphetamines, benzodiazepines and/or alcohol was also recorded, as well as the drivers' age and gender. Altogether 2957 cannabis positive cases were retrieved from the database of the Alcohol and Drug Analytics Unit, National Institute for Health and Welfare. Drug findings were examined in relation to the zero-tolerance policy operated towards DUID in Finland. The number of cannabis positive cases in each year was approximately 1000 and the main demographic of cases was males aged 20-30 years. In the majority of cases (51.6%) the inactive metabolite THC-COOH was the only indication of cannabis use, however, associated use of amphetamines (58.8% of all cases) and/or benzodiazepines (63.9%) in cannabis positive drivers was very common. Detections for amphetamines and/or benzodiazepines were especially common in drivers with THC-COOH only (92.8% of these cases). Combined use of alcohol (25.7%) was also prevalent. Suspect DUID cases generally arise from suspicion on behalf of the police and the zero-tolerance policy offers an expedient means to deal with the challenges presented in DUID, particularly in view of the high incidence of multiple drug use - the legislation is not unduly punitive when enforced in this manner. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Driver Education Curriculum Guide. Alcohol and Other Drugs.

ERIC Educational Resources Information Center

Ohio State Dept. of Education, Columbus.

Designed to provide instructors and students with reliable and scientifically validated information about alcohol and other drugs, this curriculum guide presents lessons in six major areas: (1) drugs and traffic safety; (2) alcohol: what it is and how it works; (3) alcohol: use, abuse, and moderation; (4) drugs other than alcohol: types, uses, and…

Drug research methodology. Volume 3, The detection and quantitation of drugs of interest in body fluids from drivers

DOT National Transportation Integrated Search

1980-03-01

This report presents the findings of a workshop on the chemical analysis of human body fluids for drugs of interest in highway safety. A cross-disciplinary panel of experts reviewed the list of drugs of interest developed in a previous workshop and d...

Usefulness of hair analysis and psychological tests for identification of alcohol and drugs of abuse consumption in driving license regranting.

PubMed

Lendoiro, Elena; de Castro, Ana; Jiménez-Morigosa, Cristian; Gomez-Fraguela, Xosé A; López-Rivadulla, Manuel; Cruz, Angelines

2018-05-01

The implementation of the points-based driving license helps to change the drivers' behavior and is related to a reduction of traffic accidents and fatalities. In Spain, when a driver loses all points, the driving license is revoked, so the driver must enroll on a Driver Awareness and Re-education (DARE) course. However, at the moment offenders are not submitted to any test to confirm absence of alcohol or drugs of abuse consumption, even when 9% of Spanish drivers lose their driving license for driving under the influence (DUI). The objective of this pilot study was the comparison of the usefulness of psychological tests and hair analysis to identify those individuals with a chronic consumption of alcohol and drugs of abuse among drivers performing DARE courses. Volunteers were submitted to the AUDIT and DAST-10 tests. Also a hair sample was collected and analyzed for ethylglucuronide (EtG) (LOQ 5pg/mg) and 35 licit and illicit drugs (LOQ 5-50pg/mg) by LC-MS/MS. Sixty-one participants with a mean age of 37.2±11.6years, and mainly men (90.2%), were recruited and performed AUDIT and DAST-10 tests. All hair samples were analyzed for EtG and 17 samples for licit and illicit drugs. Mean AUDIT score was 9.6 (SD=7.5), showing a value ≥8 (indicator of hazardous and harmful alcohol use) in 52.4% of cases. Mean DAST-10 score was 2.9 (SD=3.3), but a score ≥6 was detected in 21.3% of cases (indicating drug abuse or dependence). Twenty-two samples were positive for EtG, 8 for drugs of abuse (8 cocaine, 2 opioids, 1 amphetamines, 1 cannabis), and 3 for medicines. EtG concentration (20.7-1254.1pg/mg) was higher than the Society of Hair Testing (SoHT) cut-off for chronic alcohol consumption (≥30pg/mg) in 21 cases. All positive cases for methadone and cannabis, and half of positive cases for opioids and cocaine presented higher concentrations than SoHT cut-offs for chronic consumption. Higher AUDIT score and higher EtG concentration in hair were statistically associated with declaration of alcohol consumption ≥4 times/month and with previous fine for DUI of alcohol. In addition, AUDIT scores and EtG concentration in hair had a moderate but significant Spearman correlation (r=0.331, p<0.05). The combination of psychological tests and hair analysis seems to be a promising tool to identify individuals with chronic and problematic consumption of alcohol and drugs of abuse. Moreover, their application during driving license regranting procedures could increase the effectiveness of DARE courses, reduce recidivism and improve road safety. Copyright © 2018 Elsevier B.V. All rights reserved.

New psychoactive substances in oral fluid of French and Belgian drivers in 2016.

PubMed

Richeval, Camille; Wille, Sarah Maria Richarda; Nachon-Phanithavong, Mélodie; Samyn, Nele; Allorge, Delphine; Gaulier, Jean-Michel

2018-04-06

Driving under the influence of drugs (DUID) is a worldwide problem with potentially major judiciary and life-threatening consequences. Up to now, only classical drugs of abuse (DOA) are tested for DUID detection. A challenging issue for drafting up-dated international drug policies is to take into account the recent and expanding new psychoactive substances (NPS) market. NPS consist in various narcotic or psychotropic drugs, most of them having a "legal" status, that replicate chemical structures and/or pharmacological effects of classical DOA. Although it is obvious that NPS can lead to impaired driving, the prevalence of NPS use in a DUID context is unknown since the applied roadside screening tests are not yet adapted for these compounds. Between January and December 2016, a total of 391 oral fluid specimens were obtained from used roadside immunochemical test devices for DOA (Drugwipe-5S ® device). These specimens were analyzed using liquid chromatography coupled with tandem mass spectrometry and high resolution mass spectrometry. NPS (mainly cathinone derivatives) were detected in 33 out of the 391 oral fluid samples. This NPS positivity rate of 8.4% in oral fluid of drivers who were submitted to a roadside drug testing in 2016 in France and in Belgium is comparable to the available blood data (NPS positivity rate of 7%) observed in 2015 in similar populations. Our results demonstrate the reality of driving after NPS use in French and Belgian drivers who were submitted to a roadside DOA test. As there is a lack of on-site detection methods to screen for NPS, the detection of NPS in a rapid and cost-effective DUID detection strategy is currently impossible. The expanding use of NPS, notably by drivers as reported here, and the inability of currently used drug detection tests, should be urgently addressed by road safety and law enforcement authorities. Copyright © 2018 Elsevier B.V. All rights reserved.

49 CFR Appendix A to Part 355 - Guidelines for the Regulatory Review

Code of Federal Regulations, 2012 CFR

2012-10-01

... COMPATIBILITY OF STATE LAWS AND REGULATIONS AFFECTING INTERSTATE MOTOR CARRIER OPERATIONS Pt. 355, App. A... drug and alcohol abuse; require a motor carrier to maintain a driver qualification file for each driver... Vehicles Prohibit possession, use, or driving under the influence of alcohol or other controlled substances...

49 CFR Appendix A to Part 355 - Guidelines for the Regulatory Review

Code of Federal Regulations, 2014 CFR

2014-10-01

... COMPATIBILITY OF STATE LAWS AND REGULATIONS AFFECTING INTERSTATE MOTOR CARRIER OPERATIONS Pt. 355, App. A... drug and alcohol abuse; require a motor carrier to maintain a driver qualification file for each driver... Vehicles Prohibit possession, use, or driving under the influence of alcohol or other controlled substances...

49 CFR Appendix A to Part 355 - Guidelines for the Regulatory Review

Code of Federal Regulations, 2013 CFR

2013-10-01

... COMPATIBILITY OF STATE LAWS AND REGULATIONS AFFECTING INTERSTATE MOTOR CARRIER OPERATIONS Pt. 355, App. A... drug and alcohol abuse; require a motor carrier to maintain a driver qualification file for each driver... Vehicles Prohibit possession, use, or driving under the influence of alcohol or other controlled substances...

49 CFR Appendix A to Part 355 - Guidelines for the Regulatory Review

Code of Federal Regulations, 2011 CFR

2011-10-01

... COMPATIBILITY OF STATE LAWS AND REGULATIONS AFFECTING INTERSTATE MOTOR CARRIER OPERATIONS Pt. 355, App. A... drug and alcohol abuse; require a motor carrier to maintain a driver qualification file for each driver... Vehicles Prohibit possession, use, or driving under the influence of alcohol or other controlled substances...

Choking Prevention and Rescue Tips

MedlinePlus

... Workplace Training Driver Training First Aid Training Consulting Surveys Research Safety Topics Fatigue Drugs at Work Driving Workplace ... of an Effective Safety Management System Employee Perception Surveys Research Safety Topics Fatigue Drugs at Work Driving Workplace ...

[Persistent amphetamine consumption by truck drivers in São Paulo State, Brazil, despite the ban on production, prescription, and use].

PubMed

Oliveira, Lúcio Garcia de; Endo, Ligia Goes; Sinagawa, Daniele Mayumi; Yonamine, Maurício; Munoz, Daniel Romero; Leyton, Vilma

2013-09-01

Amphetamine use by truck drivers for occupational purposes is widely known. The production and consumption of amphetamines was banned by the Brazilian National Health Surveillance Agency (ANVISA) in October 2011. This study analyzes persistent amphetamine use by truck drivers since the ban was implemented. A convenience sample of 427 truck drivers was taken along highways in São Paulo State in 2012. Participants were asked to answer a structured questionnaire and provide a urine sample to screen for recent amphetamine consumption through toxicological analysis. Among the interviewed drivers, 7% had used some illicit drug recently and 2.7% had used amphetamines. Amphetamines are still consumed by truck drivers despite the risks and the recent ban. The authorities should thus monitor the possession and use of amphetamines by drivers in order to effectively enforce the ban.

Combinatorial drug screening and molecular profiling reveal diverse mechanisms of intrinsic and adaptive resistance to BRAF inhibition in V600E BRAF mutant melanomas.

PubMed

Roller, Devin G; Capaldo, Brian; Bekiranov, Stefan; Mackey, Aaron J; Conaway, Mark R; Petricoin, Emanuel F; Gioeli, Daniel; Weber, Michael J

2016-01-19

Over half of BRAFV600E melanomas display intrinsic resistance to BRAF inhibitors, in part due to adaptive signaling responses. In this communication we ask whether BRAFV600E melanomas share common adaptive responses to BRAF inhibition that can provide clinically relevant targets for drug combinations. We screened a panel of 12 treatment-naïve BRAFV600E melanoma cell lines with MAP Kinase pathway inhibitors in pairwise combination with 58 signaling inhibitors, assaying for synergistic cytotoxicity. We found enormous diversity in the drug combinations that showed synergy, with no two cell lines having an identical profile. Although the 6 lines most resistant to BRAF inhibition showed synergistic benefit from combination with lapatinib, the signaling mechanisms by which this combination generated synergistic cytotoxicity differed between the cell lines. We conclude that adaptive responses to inhibition of the primary oncogenic driver (BRAFV600E) are determined not only by the primary oncogenic driver but also by diverse secondary genetic and epigenetic changes ("back-seat drivers") and hence optimal drug combinations will be variable. Because upregulation of receptor tyrosine kinases is a major source of drug resistance arising from diverse adaptive responses, we propose that inhibitors of these receptors may have substantial clinical utility in combination with inhibitors of the MAP Kinase pathway.

Is law enforcement of drug-impaired driving cost-efficient? An explorative study of a methodology for cost-benefit analysis.

PubMed

Veisten, Knut; Houwing, Sjoerd; Mathijssen, M P M René; Akhtar, Juned

2013-03-01

Road users driving under the influence of psychoactive substances may be at much higher relative risk (RR) in road traffic than the average driver. Legislation banning blood alcohol concentrations above certain threshold levels combined with roadside breath-testing of alcohol have been in lieu for decades in many countries, but new legislation and testing of drivers for drug use have recently been implemented in some countries. In this article we present a methodology for cost-benefit analysis (CBA) of increased law enforcement of roadside drug screening. This is an analysis of the profitability for society, where costs of control are weighed against the reduction in injuries expected from fewer drugged drivers on the roads. We specify assumptions regarding costs and the effect of the specificity of the drug screening device, and quantify a deterrence effect related to sensitivity of the device yielding the benefit estimates. Three European countries with different current enforcement levels were studied, yielding benefit-cost ratios in the approximate range of 0.5-5 for a tripling of current levels of enforcement, with costs of about 4000 EUR per convicted and in the range of 1.5 and 13 million EUR per prevented fatality. The applied methodology for CBA has involved a simplistic behavioural response to enforcement increase and control efficiency. Although this methodology should be developed further, it is clearly indicated that the cost-efficiency of increased law enforcement of drug driving offences is dependent on the baseline situation of drug-use in traffic and on the current level of enforcement, as well as the RR and prevalence of drugs in road traffic. Copyright © 2012 Elsevier B.V. All rights reserved.

49 CFR 392.4 - Drugs and other substances.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Drugs and other substances. 392.4 Section 392.4... VEHICLES General § 392.4 Drugs and other substances. (a) No driver shall be on duty and possess, be under the influence of, or use, any of the following drugs or other substances: (1) Any 21 CFR 1308.11...

49 CFR 392.4 - Drugs and other substances.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 5 2012-10-01 2012-10-01 false Drugs and other substances. 392.4 Section 392.4... VEHICLES General § 392.4 Drugs and other substances. (a) No driver shall be on duty and possess, be under the influence of, or use, any of the following drugs or other substances: (1) Any 21 CFR 1308.11...

49 CFR 392.4 - Drugs and other substances.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 5 2013-10-01 2013-10-01 false Drugs and other substances. 392.4 Section 392.4... VEHICLES General § 392.4 Drugs and other substances. (a) No driver shall be on duty and possess, be under the influence of, or use, any of the following drugs or other substances: (1) Any 21 CFR 1308.11...

49 CFR 392.4 - Drugs and other substances.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 5 2011-10-01 2011-10-01 false Drugs and other substances. 392.4 Section 392.4... VEHICLES General § 392.4 Drugs and other substances. (a) No driver shall be on duty and possess, be under the influence of, or use, any of the following drugs or other substances: (1) Any 21 CFR 1308.11...

49 CFR 392.4 - Drugs and other substances.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 5 2014-10-01 2014-10-01 false Drugs and other substances. 392.4 Section 392.4... VEHICLES General § 392.4 Drugs and other substances. (a) No driver shall be on duty and possess, be under the influence of, or use, any of the following drugs or other substances: (1) Any 21 CFR 1308.11...

Drinking, cannabis use and driving among Ontario students.

PubMed

Adlaf, Edward M; Mann, Robert E; Paglia, Angela

2003-03-04

Little is known about the risk of injury among adolescents who drive after the use of alcohol or cannabis or ride in cars driven by drunk drivers. We examined data from self-administered interviews with 1846 students in grades 7 to 13 who participated in the 2001 Ontario Student Drug Use Survey about their experiences related to alcohol, cannabis and driving during the 12 months preceding the survey. In all, 31.9% of the students reported being a passenger in a car driven by a drunk driver; of the students in grades 10 to 13 who had a driver's licence, 15.1% reported driving within an hour after consuming 2 or more drinks, and 19.7% reported driving within an hour after using cannabis. Our study shows that a sizeable proportion of adolescents are exposed to alcohol- and drug-related driving risks.

The incidence of driving under the influence of drugs 1985 : an update of the state of knowledge

DOT National Transportation Integrated Search

1985-12-01

This report reviews recent studies of the incidence of drug use by drivers. Only reports published since a 1980 state of knowledge report were included. The report is divided into three sections covering the incidence of drug use by: (1) fatally inju...

Precision medicine driven by cancer systems biology.

PubMed

Filipp, Fabian V

2017-03-01

Molecular insights from genome and systems biology are influencing how cancer is diagnosed and treated. We critically evaluate big data challenges in precision medicine. The melanoma research community has identified distinct subtypes involving chronic sun-induced damage and the mitogen-activated protein kinase driver pathway. In addition, despite low mutation burden, non-genomic mitogen-activated protein kinase melanoma drivers are found in membrane receptors, metabolism, or epigenetic signaling with the ability to bypass central mitogen-activated protein kinase molecules and activating a similar program of mitogenic effectors. Mutation hotspots, structural modeling, UV signature, and genomic as well as non-genomic mechanisms of disease initiation and progression are taken into consideration to identify resistance mutations and novel drug targets. A comprehensive precision medicine profile of a malignant melanoma patient illustrates future rational drug targeting strategies. Network analysis emphasizes an important role of epigenetic and metabolic master regulators in oncogenesis. Co-occurrence of driver mutations in signaling, metabolic, and epigenetic factors highlights how cumulative alterations of our genomes and epigenomes progressively lead to uncontrolled cell proliferation. Precision insights have the ability to identify independent molecular pathways suitable for drug targeting. Synergistic treatment combinations of orthogonal modalities including immunotherapy, mitogen-activated protein kinase inhibitors, epigenetic inhibitors, and metabolic inhibitors have the potential to overcome immune evasion, side effects, and drug resistance.

"I drove after drinking alcohol" and other risky driving behaviours reported by young novice drivers.

PubMed

Scott-Parker, Bridie; Watson, Barry; King, Mark J; Hyde, Melissa K

2014-09-01

Volitional risky driving behaviours such as drink- and drug-driving (i.e. substance-impaired driving) and speeding contribute to the overrepresentation of young novice drivers in road crash fatalities, and crash risk is greatest during the first year of independent driving in particular. To explore the: (1) self-reported compliance of drivers with road rules regarding substance-impaired driving and other risky driving behaviours (e.g., speeding, driving while tired), one year after progression from a Learner to a Provisional (intermediate) licence; and (2) interrelationships between substance-impaired driving and other risky driving behaviours (e.g., crashes, offences, and Police avoidance). Drivers (n=1076; 319 males) aged 18-20 years were surveyed regarding their sociodemographics (age, gender) and self-reported driving behaviours including crashes, offences, Police avoidance, and driving intentions. A relatively small proportion of participants reported driving after taking drugs (6.3% of males, 1.3% of females) and drinking alcohol (18.5% of males, 11.8% of females). In comparison, a considerable proportion of participants reported at least occasionally exceeding speed limits (86.7% of novices), and risky behaviours like driving when tired (83.6% of novices). Substance-impaired driving was associated with avoiding Police, speeding, risky driving intentions, and self-reported crashes and offences. Forty-three percent of respondents who drove after taking drugs also reported alcohol-impaired driving. Behaviours of concern include drink driving, speeding, novice driving errors such as misjudging the speed of oncoming vehicles, violations of graduated driver licensing passenger restrictions, driving tired, driving faster if in a bad mood, and active punishment avoidance. Given the interrelationships between the risky driving behaviours, a deeper understanding of influential factors is required to inform targeted and general countermeasure implementation and evaluation during this critical driving period. Notwithstanding this, a combination of enforcement, education, and engineering efforts appear necessary to improve the road safety of the young novice driver, and for the drink-driving young novice driver in particular. Copyright © 2014 Elsevier Ltd. All rights reserved.

Association between travel length and drug use among Brazilian truck drivers.

PubMed

Sinagawa, Daniele Mayumi; De Carvalho, Heráclito Barbosa; Andreuccetti, Gabriel; Do Prado, Natanael Vitoriano; De Oliveira, Keziah Cristina Barbosa Gruber; Yonamine, Mauricio; Muñoz, Daniel Romero; Gjerde, Hallvard; Leyton, Vilma

2015-01-01

To investigate whether the use of the stimulants amphetamines and cocaine by truck drivers in Brazil was related to travel length. Truck drivers were randomly stopped by the Federal Highway Police on interstate roads in Sao Paulo State during morning hours from 2008 to 2011 and invited to participate in the project "Comandos de Saúde nas Rodovias" (Health Commands on the Roads). Participants were asked about the use of drugs, travel distance, and age, and gender was recorded. Samples of urine were collected and analyzed for amphetamine, benzoylecgonine (a metabolite of cocaine), and carboxytetrahydrocannabinol (THC-COOH; a metabolite of cannabis) by immunological screening and quantification by gas chromatography-mass spectroscopy. Current use of amphetamine, cocaine, and cannabis was reported by 5.7%, 0.7%, and 0.3% of the truck drivers, respectively. Amphetamine, benzoylecgonine, and THC-COOH were found in urine samples from 5.4%, 2.6,% and in 1.0% of the drivers, respectively. There was a significant association between the positive cases for amphetamine and reported travel length; 9.9% of urine samples from drivers who reported travel length of more than 270 km were positive for amphetamine, and 10.9% of those drivers reported current use of amphetamines. In most cases, appetite suppressants containing amphetamines had been used, but the purpose was most often to stay awake and alert while driving. Truck drivers with travel length of more than 270 km had significantly higher odds ratio (OR) for having a urine sample that was positive for amphetamine when adjusted for age as confounding factor (OR = 9.41, 95% confidence interval [CI], 3.97-22.26). No significant association was found between the use of cocaine or cannabis and travel length. Truck drivers who reported driving more than 270 km had significantly higher frequencies of urine samples positive for amphetamine and reported significantly more frequent current use of amphetamines than those who reported shorter driving distances.

Analyses of factors of crash avoidance maneuvers using the general estimates system.

PubMed

Yan, Xuedong; Harb, Rami; Radwan, Essam

2008-06-01

Taking an effective corrective action to a critical traffic situation provides drivers an opportunity to avoid crash occurrence and minimize crash severity. The objective of this study is to investigate the relationship between the probability of taking corrective actions and the characteristics of drivers, vehicles, and driving environments. Using the 2004 GES crash database, this study classified drivers who encountered critical traffic events (identified as P_CRASH3 in the GES database) into two pre-crash groups: corrective avoidance actions group and no corrective avoidance actions group. Single and multiple logistic regression analyses were performed to identify potential traffic factors associated with the probability of drivers taking corrective actions. The regression results showed that the driver/vehicle factors associated with the probability of taking corrective actions include: driver age, gender, alcohol use, drug use, physical impairments, distraction, sight obstruction, and vehicle type. In particular, older drivers, female drivers, drug/alcohol use, physical impairment, distraction, or poor visibility may increase the probability of failing to attempt to avoid crashes. Moreover, drivers of larger size vehicles are 42.5% more likely to take corrective avoidance actions than passenger car drivers. On the other hand, the significant environmental factors correlated with the drivers' crash avoidance maneuver include: highway type, number of lanes, divided/undivided highway, speed limit, highway alignment, highway profile, weather condition, and surface condition. Some adverse highway environmental factors, such as horizontal curves, vertical curves, worse weather conditions, and slippery road surface conditions are correlated with a higher probability of crash avoidance maneuvers. These results may seem counterintuitive but they can be explained by the fact that motorists may be more likely to drive cautiously in those adverse driving environments. The analyses revealed that drivers' distraction could be the highest risk factor leading to the failure of attempting to avoid crashes. Further analyses entailing distraction causes (e.g., cellular phone use) and their possible countermeasures need to be conducted. The age and gender factors are overrepresented in the "no avoidance maneuver." A possible solution could involve the integration of a new function in the current ITS technologies. A personalized system, which could be related to the expected type of maneuver for a driver with certain characteristics, would assist different drivers with different characteristics to avoid crashes. Further crash database studies are recommended to investigate the association of drivers' emergency maneuvers such as braking, steering, or their combination with crash severity.

What to Do When Winter Has You in its Icy Grip

MedlinePlus

... Workplace Training Driver Training First Aid Training Consulting Surveys Research Safety Topics Fatigue Drugs at Work Driving Workplace ... of an Effective Safety Management System Employee Perception Surveys Research Safety Topics Fatigue Drugs at Work Driving Workplace ...

Driver gene classification reveals a substantial overrepresentation of tumor suppressors among very large chromatin-regulating proteins.

PubMed

Waks, Zeev; Weissbrod, Omer; Carmeli, Boaz; Norel, Raquel; Utro, Filippo; Goldschmidt, Yaara

2016-12-23

Compiling a comprehensive list of cancer driver genes is imperative for oncology diagnostics and drug development. While driver genes are typically discovered by analysis of tumor genomes, infrequently mutated driver genes often evade detection due to limited sample sizes. Here, we address sample size limitations by integrating tumor genomics data with a wide spectrum of gene-specific properties to search for rare drivers, functionally classify them, and detect features characteristic of driver genes. We show that our approach, CAnceR geNe similarity-based Annotator and Finder (CARNAF), enables detection of potentially novel drivers that eluded over a dozen pan-cancer/multi-tumor type studies. In particular, feature analysis reveals a highly concentrated pool of known and putative tumor suppressors among the <1% of genes that encode very large, chromatin-regulating proteins. Thus, our study highlights the need for deeper characterization of very large, epigenetic regulators in the context of cancer causality.

International trends in alcohol and drug use among vehicle drivers.

PubMed

Christophersen, A S; Mørland, J; Stewart, K; Gjerde, H

2016-01-01

Trends in the use of alcohol and drugs among motor vehicle drivers in Australia, Brazil, Norway, Spain, and the United States have been reviewed. Laws, regulations, enforcement, and studies on alcohol and drugs in biological samples from motor vehicle drivers in general road traffic and fatal road traffic crashes (RTCs) are discussed. Roadside surveys showed a reduction of drunk driving over time in the studied countries; however, the pattern varied within and between different countries. The reduction of alcohol use may be related to changes in road traffic laws, public information campaigns, and enforcement, including implementation of random breath testing or sobriety checkpoints. For non-alcohol drugs, the trend in general road traffic is an increase in use. However, drugs were not included in older studies; it is therefore impossible to assess the trends over longer time periods. Data from the studied countries, except Brazil, have shown a significant decrease in fatal RTCs per 100,000 inhabitants over the last decades; from 18.6 to 4.9 in Australia, 14.5 to 2.9 in Norway, 11.1 to 3.6 in Spain, and 19.3 to 10.3 in the United States. The number of alcohol-related fatal RTCs also decreased during the same time period. The proportion of fatal RTCs related to non-alcohol drugs increased, particularly for cannabis and stimulants. A general challenge when comparing alcohol and drug findings in biological samples from several countries is connected to differences in study design, particularly the time period for performing roadside surveys, biological matrix types, drugs included in the analytical program, and the cutoff limits used for evaluation of results. For RTC fatalities, the cases included are based on the police requests for legal autopsy or drug testing, which may introduce a significant selection bias. General comparisons between high-income countries and low- and middle-income countries as well as a discussion of possible future trends are included. Copyright © 2016 Central Police University.

Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

PubMed Central

2014-01-01

Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

Continuous subcutaneous infusion in palliative care: a review of current practice.

PubMed

Thomas, Tabitha; Barclay, Stephen

2015-02-01

Syringe drivers are widely used in palliative care, and this article reviews the challenges and outstanding questions associated with their use. Misperceptions among the lay public and some health professionals can be addressed by sensitive communication with patients and families and clear thinking in clinical teams concerning the drugs and doses used, particularly in non-malignant disease. Good levels of knowledge concerning syringe driver use has been found among GPs and community nurses, although this is not the case in some nursing home teams. The advantages of newer devices, safety and efficacy of drug combinations, selection of diluent, and management of site reactions are discussed.

3 CFR 8461 - Proclamation 8461 of December 2, 2009. National Impaired Driving Prevention Month, 2009

Code of Federal Regulations, 2010 CFR

2010-01-01

... and illegal drugs. During this holiday season, we must all be especially vigilant in protecting our families, friends, and neighbors from drivers who are under the influence of drugs or alcohol. Although we... increase in Americans driving under the influence of drugs. Operating a vehicle under the influence of...

Kin-Driver: a database of driver mutations in protein kinases.

PubMed

Simonetti, Franco L; Tornador, Cristian; Nabau-Moretó, Nuria; Molina-Vila, Miguel A; Marino-Buslje, Cristina

2014-01-01

Somatic mutations in protein kinases (PKs) are frequent driver events in many human tumors, while germ-line mutations are associated with hereditary diseases. Here we present Kin-driver, the first database that compiles driver mutations in PKs with experimental evidence demonstrating their functional role. Kin-driver is a manual expert-curated database that pays special attention to activating mutations (AMs) and can serve as a validation set to develop new generation tools focused on the prediction of gain-of-function driver mutations. It also offers an easy and intuitive environment to facilitate the visualization and analysis of mutations in PKs. Because all mutations are mapped onto a multiple sequence alignment, analogue positions between kinases can be identified and tentative new mutations can be proposed for studying by transferring annotation. Finally, our database can also be of use to clinical and translational laboratories, helping them to identify uncommon AMs that can correlate with response to new antitumor drugs. The website was developed using PHP and JavaScript, which are supported by all major browsers; the database was built using MySQL server. Kin-driver is available at: http://kin-driver.leloir.org.ar/ © The Author(s) 2014. Published by Oxford University Press.

A mechanistic pan-cancer pathway model informed by multi-omics data interprets stochastic cell fate responses to drugs and mitogens

PubMed Central

Bouhaddou, Mehdi; Koch, Rick J.; DiStefano, Matthew S.; Tan, Annie L.; Mertz, Alex E.

2018-01-01

Most cancer cells harbor multiple drivers whose epistasis and interactions with expression context clouds drug and drug combination sensitivity prediction. We constructed a mechanistic computational model that is context-tailored by omics data to capture regulation of stochastic proliferation and death by pan-cancer driver pathways. Simulations and experiments explore how the coordinated dynamics of RAF/MEK/ERK and PI-3K/AKT kinase activities in response to synergistic mitogen or drug combinations control cell fate in a specific cellular context. In this MCF10A cell context, simulations suggest that synergistic ERK and AKT inhibitor-induced death is likely mediated by BIM rather than BAD, which is supported by prior experimental studies. AKT dynamics explain S-phase entry synergy between EGF and insulin, but simulations suggest that stochastic ERK, and not AKT, dynamics seem to drive cell-to-cell proliferation variability, which in simulations is predictable from pre-stimulus fluctuations in C-Raf/B-Raf levels. Simulations suggest MEK alteration negligibly influences transformation, consistent with clinical data. Tailoring the model to an alternate cell expression and mutation context, a glioma cell line, allows prediction of increased sensitivity of cell death to AKT inhibition. Our model mechanistically interprets context-specific landscapes between driver pathways and cell fates, providing a framework for designing more rational cancer combination therapy. PMID:29579036

Drug and alcohol crash risk : a case-control study.

DOT National Transportation Integrated Search

2016-12-01

This study used a case-control design to estimate the risk of crashes involving drivers using drugs, alcohol or both. Data was collected in Virginia Beach, Virginia, for 20 months. The study obtained biological measures on more than 3,000 crash...

Identification of druggable cancer driver genes amplified across TCGA datasets.

PubMed

Chen, Ying; McGee, Jeremy; Chen, Xianming; Doman, Thompson N; Gong, Xueqian; Zhang, Youyan; Hamm, Nicole; Ma, Xiwen; Higgs, Richard E; Bhagwat, Shripad V; Buchanan, Sean; Peng, Sheng-Bin; Staschke, Kirk A; Yadav, Vipin; Yue, Yong; Kouros-Mehr, Hosein

2014-01-01

The Cancer Genome Atlas (TCGA) projects have advanced our understanding of the driver mutations, genetic backgrounds, and key pathways activated across cancer types. Analysis of TCGA datasets have mostly focused on somatic mutations and translocations, with less emphasis placed on gene amplifications. Here we describe a bioinformatics screening strategy to identify putative cancer driver genes amplified across TCGA datasets. We carried out GISTIC2 analysis of TCGA datasets spanning 16 cancer subtypes and identified 486 genes that were amplified in two or more datasets. The list was narrowed to 75 cancer-associated genes with potential "druggable" properties. The majority of the genes were localized to 14 amplicons spread across the genome. To identify potential cancer driver genes, we analyzed gene copy number and mRNA expression data from individual patient samples and identified 42 putative cancer driver genes linked to diverse oncogenic processes. Oncogenic activity was further validated by siRNA/shRNA knockdown and by referencing the Project Achilles datasets. The amplified genes represented a number of gene families, including epigenetic regulators, cell cycle-associated genes, DNA damage response/repair genes, metabolic regulators, and genes linked to the Wnt, Notch, Hedgehog, JAK/STAT, NF-KB and MAPK signaling pathways. Among the 42 putative driver genes were known driver genes, such as EGFR, ERBB2 and PIK3CA. Wild-type KRAS was amplified in several cancer types, and KRAS-amplified cancer cell lines were most sensitive to KRAS shRNA, suggesting that KRAS amplification was an independent oncogenic event. A number of MAP kinase adapters were co-amplified with their receptor tyrosine kinases, such as the FGFR adapter FRS2 and the EGFR family adapters GRB2 and GRB7. The ubiquitin-like ligase DCUN1D1 and the histone methyltransferase NSD3 were also identified as novel putative cancer driver genes. We discuss the patient tailoring implications for existing cancer drug targets and we further discuss potential novel opportunities for drug discovery efforts.

Identification of Druggable Cancer Driver Genes Amplified across TCGA Datasets

PubMed Central

Chen, Ying; McGee, Jeremy; Chen, Xianming; Doman, Thompson N.; Gong, Xueqian; Zhang, Youyan; Hamm, Nicole; Ma, Xiwen; Higgs, Richard E.; Bhagwat, Shripad V.; Buchanan, Sean; Peng, Sheng-Bin; Staschke, Kirk A.; Yadav, Vipin; Yue, Yong; Kouros-Mehr, Hosein

2014-01-01

The Cancer Genome Atlas (TCGA) projects have advanced our understanding of the driver mutations, genetic backgrounds, and key pathways activated across cancer types. Analysis of TCGA datasets have mostly focused on somatic mutations and translocations, with less emphasis placed on gene amplifications. Here we describe a bioinformatics screening strategy to identify putative cancer driver genes amplified across TCGA datasets. We carried out GISTIC2 analysis of TCGA datasets spanning 14 cancer subtypes and identified 461 genes that were amplified in two or more datasets. The list was narrowed to 73 cancer-associated genes with potential “druggable” properties. The majority of the genes were localized to 14 amplicons spread across the genome. To identify potential cancer driver genes, we analyzed gene copy number and mRNA expression data from individual patient samples and identified 40 putative cancer driver genes linked to diverse oncogenic processes. Oncogenic activity was further validated by siRNA/shRNA knockdown and by referencing the Project Achilles datasets. The amplified genes represented a number of gene families, including epigenetic regulators, cell cycle-associated genes, DNA damage response/repair genes, metabolic regulators, and genes linked to the Wnt, Notch, Hedgehog, JAK/STAT, NF-KB and MAPK signaling pathways. Among the 40 putative driver genes were known driver genes, such as EGFR, ERBB2 and PIK3CA. Wild-type KRAS was amplified in several cancer types, and KRAS-amplified cancer cell lines were most sensitive to KRAS shRNA, suggesting that KRAS amplification was an independent oncogenic event. A number of MAP kinase adapters were co-amplified with their receptor tyrosine kinases, such as the FGFR adapter FRS2 and the EGFR family adapter GRB7. The ubiquitin-like ligase DCUN1D1 and the histone methyltransferase NSD3 were also identified as novel putative cancer driver genes. We discuss the patient tailoring implications for existing cancer drug targets and we further discuss potential novel opportunities for drug discovery efforts. PMID:24874471

Drug per se laws: a review of their use in the states : traffic tech.

DOT National Transportation Integrated Search

2010-09-01

Research has indicated that per se laws for alcohol have been : effective in reducing alcohol-related fatalities. A difficulty : in prosecuting drivers for driving impaired by drugs other : than alcohol is that there is no scientific basis for specif...

Use of controlled substances and highway safety : a report to Congress

DOT National Transportation Integrated Search

1988-03-01

This report reviews what is currently known about the relationship of drug use to highway safety. While much remains to be learned, we have made considerable progress in the last several decades in understanding the effects of drugs on driver behavio...

Concentrations of alprazolam in blood from impaired drivers and forensic autopsies were not much different but showed a high prevalence of co-ingested illicit drugs.

PubMed

Jones, Alan Wayne; Holmgren, Anita

2013-03-01

Alprazolam is a benzodiazepine anxiolytic widely prescribed for treatment of panic-disorder and social phobias, although this medication is also subject to abuse. In this paper, the concentrations of alprazolam in venous blood samples from impaired drivers were compared with femoral blood samples from forensic autopsies classified as intoxication or other causes of death (e.g. natural, trauma). After liquid-liquid extraction (n-butyl acetate) alprazolam was determined in blood by capillary gas chromatography with a nitrogen-phosphorous detector. The mean (median) and range of alprazolam concentrations in blood from impaired drivers (n = 773) were 0.08 mg/L (0.05 mg/L) and 0.02-3.9 mg/L, respectively. Many traffic offenders had co-ingested ethanol (13%), amphetamine (46%), cannabis (32%), or heroin (14%), as well as other drugs. In deaths attributed to drug intoxication, the mean (median) and range of alprazolam concentrations in blood (n = 438) were 0.10 mg/L (0.06 mg/L) and 0.02-1.6 mg/L, respectively, which were not much different from other causes of death (n = 278); 0.08 mg/L (0.05 mg/L) and 0.02-0.9 mg/L. Median concentrations of alprazolam in blood from living and deceased persons did not seem to depend on the number of co-ingested substances. The result of this pharmacoepidemiological study suggests that alprazolam is a fairly innocent drug when used as monotherapy, but toxicity problems arise when co-ingested with illicit drugs and/or psychoactive medication.

Alcohol- and Drug-Involved Driving in the United States: Methodology for the 2007 National Roadside Survey

ERIC Educational Resources Information Center

Lacey, John H.; Kelley-Baker, Tara; Voas, Robert B.; Romano, Eduardo; Furr-Holden, C. Debra; Torres, Pedro; Berning, Amy

2011-01-01

This article describes the methodology used in the 2007 U.S. National Roadside Survey to estimate the prevalence of alcohol- and drug-impaired driving and alcohol- and drug-involved driving. This study involved randomly stopping drivers at 300 locations across the 48 continental U.S. states at sites selected through a stratified random sampling…

46 CFR 10.213 - National Driver Register.

Code of Federal Regulations, 2011 CFR

2011-10-01

... of, or impaired by, alcohol or a controlled substance; and any traffic violations arising in connection with a fatal traffic accident, reckless driving, or racing on the highways). (b) The Coast Guard... Guard in evaluating applicants who have drug or alcohol related NDR-listed convictions. Non-drug or...

46 CFR 10.213 - National Driver Register.

Code of Federal Regulations, 2010 CFR

2010-10-01

... of, or impaired by, alcohol or a controlled substance; and any traffic violations arising in connection with a fatal traffic accident, reckless driving, or racing on the highways). (b) The Coast Guard... Guard in evaluating applicants who have drug or alcohol related NDR-listed convictions. Non-drug or...

Adult correlates of early behavioral maladjustment: a study of injured drivers.

PubMed

Ryb, Gabriel; Dischinger, Patricia; Smith, Gordon; Soderstrom, Carl

2008-10-01

To establish whether a history of school suspension (HSS) predicts adult driver behavior. 323 injured drivers were interviewed as part of a study of psychoactive substance use disorders (PSUD) and injury. Drivers with a HSS were compared to those without HSS in relation to demographics, SES, PSUD, risky behaviors, trauma history and driving history using student's t test and chi-square. Multiple logistic regression models were constructed to adjust for demographics, SES and PSUD. HSS drivers represented 31% of the population and were younger, more likely to be male and had higher rates of alcohol and drug dependence than drivers without HSS. Educational achievement was worse for drivers with HSS. Drivers with HSS were more likely to have a history of prior vehicular trauma and assault. Seat-belt non-use, drinking and driving, riding with drunk driver, binge drinking, driving fast for the thrill, license suspension and drinking and driving convictions were more common among drivers with HSS. In multiple logistic regression models adjusting for demographics and SES, HSS revealed higher odds ratios for the same outcomes. After adding PSUD to the models HSS remained significant only for seat belt non use, binge drinking and previous assault history. HSS is associated with risky behaviors, repeated vehicular injury, and poor driver history. The association with driver history, however, disappears when PSUD are included in the models. The association of HSS (a marker of early behavioral maladjustment) with behavioral risks suggests that undiagnosed psychopathology may be linked to injury recidivism.

Illicit drugs in Emergency Department patients injured in road traffic accidents.

PubMed

Papa, Pietro; Rocchi, Loretta; Rolandi, Laura Maria; Di Tuccio, Marcello; Biffi, Marco; Valli, Antonella

2017-01-01

Urine and blood samples from 1730 drivers involved in road accidents (July 2012 - December 2015) were analyzed for the evaluation of driving under influence of drug of abuse according to the Lombardia Region guideline. The 22.5% (95% CI 20.5 to 24.5) of urine screenings tested positive for at least one class of drugs. 10.6% (95% CI 9.2 to 12.1) of the 1730 drivers were under the influence of drug, being blood concentration above the cut-off limit for at least one active substance; the proportion of illicit drugs in blood was cocaine 5.7 % (95% CI 4.7 to 6.9), cannabinoids 3.7 % (95% CI 2.9 to 4.7), opiates 1.4% (95% CI 0.9 to 2.1), methadone 1.4% (95% CI 0.9 to 2.1), amphetamines 0.2% (95% CI 0.04 to 0.5). Trend in proportion showed similar percentage (about 5%) of cocaine and cannabinoids consumption in the last two years. Poly-drug of abuse consumption emerged in the 10.4% (95% CI 6.4 to 15.7) of the positive blood and alcohol was above the legal limit in 47% (95% CI 39.6 to 54.5) of the subjects driving under the influence of drugs.

Has the intake of THC by cannabis users changed over the last decade? Evidence of increased exposure by analysis of blood THC concentrations in impaired drivers.

PubMed

Vindenes, Vigdis; Strand, Dag Helge; Kristoffersen, Lena; Boix, Fernando; Mørland, Jørg

2013-03-10

The main psychoactive substance, Δ9-tetrahydrocannabinol (THC) can be present in highly variable amounts in different cannabis preparations. An increase in THC content in cannabis products has been suggested, and reported from several countries. However, it has not yet been investigated if products with high potency lead to increased human exposure, and thus to higher risk of adverse effects. In this study, we examined the mean concentrations of THC in whole blood samples from drivers apprehended in Norway in the period between 2000 and 2010 suspected of driving under the influence of drugs. Cases with only THC (n=1747) have been compared to cases with only ethanol (n=38796) or amphetamines (n=2493). The increase in mean THC concentration measured from 2000 to 2010 was from 4.0 ± 0.3 to 6.6 ± 0.4 ng/ml (58%), compared to 3% for ethanol and 16% for the amphetamines. This increase in THC concentrations was to some extent paralleled by an increase in the percentage of drivers which were judged as lightly impaired by a physician. Monitoring concentrations of drugs of abuse in blood from apprehended drivers indicated an increasing exposure to THC in Norway. If similar trends are observed globally, it should be further explored if this type of information could be used to elucidate the drug consumption patterns in a population and accordingly the consequences with regard to adverse effects of cannabis from a public health perspective. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

32 CFR 634.12 - Army administrative actions against intoxicated drivers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MOTOR VEHICLE TRAFFIC SUPERVISION Driving Privileges... requested test to measure alcohol or drug content of the blood, breath, or urine, either on or off the installation, when there is reasonable belief of driving under the influence of alcohol or drugs. (3) Driving...

23 CFR 1313.6 - Requirements for a programmatic state.

Code of Federal Regulations, 2010 CFR

2010-04-01

... alcohol and/or other drugs. (ii) Saturation patrol means a law enforcement activity during which enhanced... detecting drivers operating motor vehicles while impaired by alcohol and/or other drugs. (iii) Law... activities; (C) A list of law enforcement agencies expected to participate; and (D) A paid media buy plan, if...

Driver seat belt use indicates decreased risk for child passengers in a motor vehicle crash.

PubMed

Olsen, Cody S; Cook, Lawrence J; Keenan, Heather T; Olson, Lenora M

2010-03-01

We examined the association between driver restraint use and child emergency department (ED) evaluation following a motor vehicle crash (MVC). This cohort study included child passengers aged 0-12 years riding with an adult driver aged 21 years or older involved in a MVC in Utah from 1999 to 2004. The 6 years of Utah MVC records were probabilistically linked to statewide Utah ED records. We estimated the relative risk of ED evaluation following a MVC for children riding with restrained versus unrestrained drivers. Generalized estimating equations were used to calculate relative risks adjusted for child, driver, and crash characteristics. Six percent (6%) of children riding with restrained adult drivers were evaluated in the ED compared to twenty-two percent (22%) of children riding with unrestrained adult drivers following a MVC (relative risk 0.29, 95% confidence interval 0.26-0.32). After adjusting for child, vehicle, and crash characteristics, the relative risk of child ED evaluation associated with driver restraint remained significant (relative risk 0.82, 95% confidence interval 0.72-0.94). Driver restraint use was associated with child restraint use, less alcohol/drug involvement, and lower relative risk of severe collision types (head-on, rollover). Driver seat belt use is associated with decreased risk of ED evaluation for child passengers in the event of a MVC. Copyright 2009 Elsevier Ltd. All rights reserved.

Characteristics of fatal road crashes involving unlicensed drivers or riders: Implications for countermeasures.

PubMed

Sagberg, Fridulv

2018-08-01

Drivers or riders without a valid license are involved in 10% of fatal road crashes in Norway. This was shown by an analysis of data from all fatal crashes in the period 2005-2014. A literature review shows that unlicensed drivers have a considerably increased crash risk. Such crashes could be prevented by electronic driver authentication, i.e., a technical system for checking that a driver or rider has legal access to a vehicle before driving is permitted. This can be done by requiring the driver/rider to identify themselves with a national identity number and a unique code or biometric information before driving may commence. The vehicle thereafter verifies license availability and vehicle access by communication with a central register. In more than 80% of fatal crashes with unlicensed drivers/riders, speeding and/or drug influence contributed to the crash. This means that a majority of crashes with unlicensed drivers alternatively could be prevented by already available systems, such as alcolock and speed limit dependent speed adapters. These systems will have a wider influence, by preventing crashes also among licensed drivers. Mandatory implementation of alcolock, speed limiter, and electronic driver authentication in all motorized vehicles is estimated to prevent up to 28% of fatal road crashes, depending on effectiveness of the systems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Occupational conditions and the risk of the use of amphetamines by truck drivers.

PubMed

de Oliveira, Lúcio Garcia; de Souza, Letícia Maria de Araújo; Barroso, Lúcia Pereira; Gouvêa, Marcela Júlio César; de Almeida, Carlos Vinícius Dias; Muñoz, Daniel Romero; Leyton, Vilma

2015-01-01

OBJECTIVE To test whether the occupational conditions of professional truck drivers are associated with amphetamine use after demographic characteristics and ones regarding mental health and drug use are controlled for.METHODS Cross-sectional study, with a non-probabilistic sample of 684 male truck drivers, which was collected in three highways in Sao Paulo between years 2012 and 2013. Demographic and occupational information was collected, as well as data on drug use and mental health (sleep quality, emotional stress, and psychiatric disorders). A logistic regression model was developed to identify factors associated with amphetamine use. Odds ratio (OR; 95%CI) was defined as the measure for association. The significance level was established as p < 0.05.RESULTS The studied sample was found to have an average age of 36.7 (SD = 7.8) years, as well as low education (8.6 [SD = 2.3] years); 29.0% of drivers reported having used amphetamines within the twelve months prior to their interviews. After demographic and occupational variables had been controlled for, the factors which indicated amphetamine use among truck drivers were the following: being younger than 38 years (OR = 3.69), having spent less than nine years at school (OR = 1.76), being autonomous (OR = 1.65), working night shifts or irregular schedules (OR = 2.05), working over 12 hours daily (OR = 2.14), and drinking alcohol (OR = 1.74).CONCLUSIONS Occupational aspects are closely related to amphetamine use among truck drivers, which reinforces the importance of closely following the application of law (Resting Act ("Lei do Descanso"); Law 12,619/2012) which regulates the workload and hours of those professionals. Our results show the need for increased strictness on the trade and prescription of amphetamines in Brazil.

Occupational conditions and the risk of the use of amphetamines by truck drivers

PubMed Central

de Oliveira, Lúcio Garcia; de Souza, Letícia Maria de Araújo; Barroso, Lúcia Pereira; Gouvêa, Marcela Júlio César; de Almeida, Carlos Vinícius Dias; Muñoz, Daniel Romero; Leyton, Vilma

2015-01-01

OBJECTIVE To test whether the occupational conditions of professional truck drivers are associated with amphetamine use after demographic characteristics and ones regarding mental health and drug use are controlled for. METHODS Cross-sectional study, with a non-probabilistic sample of 684 male truck drivers, which was collected in three highways in Sao Paulo between years 2012 and 2013. Demographic and occupational information was collected, as well as data on drug use and mental health (sleep quality, emotional stress, and psychiatric disorders). A logistic regression model was developed to identify factors associated with amphetamine use. Odds ratio (OR; 95%CI) was defined as the measure for association. The significance level was established as p < 0.05. RESULTS The studied sample was found to have an average age of 36.7 (SD = 7.8) years, as well as low education (8.6 [SD = 2.3] years); 29.0% of drivers reported having used amphetamines within the twelve months prior to their interviews. After demographic and occupational variables had been controlled for, the factors which indicated amphetamine use among truck drivers were the following: being younger than 38 years (OR = 3.69), having spent less than nine years at school (OR = 1.76), being autonomous (OR = 1.65), working night shifts or irregular schedules (OR = 2.05), working over 12 hours daily (OR = 2.14), and drinking alcohol (OR = 1.74). CONCLUSIONS Occupational aspects are closely related to amphetamine use among truck drivers, which reinforces the importance of closely following the application of law (Resting Act (“Lei do Descanso”); Law 12,619/2012) which regulates the workload and hours of those professionals. Our results show the need for increased strictness on the trade and prescription of amphetamines in Brazil. PMID:26398875

Cell phone use and traffic crash risk: a culpability analysis.

PubMed

Asbridge, Mark; Brubacher, Jeff R; Chan, Herbert

2013-02-01

The use of a cell phone or communication device while driving is illegal in many jurisdictions, yet evidence evaluating the crash risk associated with cell phone use in naturalistic settings is limited. This article aims to determine whether cell phone use while driving increases motor vehicle crash culpability. Method Drivers involved in crashes where police reported cell phone use (n = 312) and propensity matched drivers (age, sex, suspect alcohol/drug impairment, crash type, date, time of day, geographical location) without cell phone use (n = 936) were drawn from Insurance Corporation of British Columbia Traffic Accident System data. A standardized scoring tool, modified to account for Canadian driving conditions, was used to determine crash culpability from police reports on all drivers from the crashes. The association between crash culpability and cell phone use was determined, with additional subgroup analyses based on crash severity, driver characteristics and type of licence. A comparison of crashes with vs without cell phones revealed an odds ratio of 1.70 (95% confidence interval 1.22-2.36; P = 0.002). This association was consistent after adjustment for matching variables and other covariates. Subgroup analyses demonstrated an association for male drivers, unimpaired drivers, injured and non-injured drivers, and for drivers aged between 26 and 65 years. Crash culpability was found to be significantly associated with cell phone use by drivers, increasing the odds of a culpable crash by 70% compared with drivers who did not use a cell phone. This increased risk was particularly high for middle-aged drivers.

Associating crash avoidance maneuvers with driver attributes and accident characteristics: a mixed logit model approach.

PubMed

Kaplan, Sigal; Prato, Carlo Giacomo

2012-01-01

The current study focuses on the propensity of drivers to engage in crash avoidance maneuvers in relation to driver attributes, critical events, crash characteristics, vehicles involved, road characteristics, and environmental conditions. The importance of avoidance maneuvers derives from the key role of proactive and state-aware road users within the concept of sustainable safety systems, as well as from the key role of effective corrective maneuvers in the success of automated in-vehicle warning and driver assistance systems. The analysis is conducted by means of a mixed logit model that represents the selection among 5 emergency lateral and speed control maneuvers (i.e., "no avoidance maneuvers," "braking," "steering," "braking and steering," and "other maneuvers) while accommodating correlations across maneuvers and heteroscedasticity. Data for the analysis were retrieved from the General Estimates System (GES) crash database for the year 2009 by considering drivers for which crash avoidance maneuvers are known. The results show that (1) the nature of the critical event that made the crash imminent greatly influences the choice of crash avoidance maneuvers, (2) women and elderly have a relatively lower propensity to conduct crash avoidance maneuvers, (3) drowsiness and fatigue have a greater negative marginal effect on the tendency to engage in crash avoidance maneuvers than alcohol and drug consumption, (4) difficult road conditions increase the propensity to perform crash avoidance maneuvers, and (5) visual obstruction and artificial illumination decrease the probability to carry out crash avoidance maneuvers. The results emphasize the need for public awareness campaigns to promote safe driving style for senior drivers and warning about the risks of driving under fatigue and distraction being comparable to the risks of driving under the influence of alcohol and drugs. Moreover, the results suggest the need to educate drivers about hazard perception, designing a forgiving infrastructure within a sustainable safety systems, and rethinking in-vehicle collision warning systems. Future research should address the effectiveness of crash avoidance maneuvers and joint modeling of maneuver selection and crash severity.

Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics.

PubMed

Sattler, Sebastian; Mehlkop, Guido; Graeff, Peter; Sauer, Carsten

2014-02-01

The use of cognitive enhancement (CE) by means of pharmaceutical agents has been the subject of intense debate both among scientists and in the media. This study investigates several drivers of and obstacles to the willingness to use prescription drugs non-medically for augmenting brain capacity. We conducted a web-based study among 2,877 students from randomly selected disciplines at German universities. Using a factorial survey, respondents expressed their willingness to take various hypothetical CE-drugs; the drugs were described by five experimentally varied characteristics and the social environment by three varied characteristics. Personal characteristics and demographic controls were also measured. We found that 65.3% of the respondents staunchly refused to use CE-drugs. The results of a multivariate negative binomial regression indicated that respondents' willingness to use CE-drugs increased if the potential drugs promised a significant augmentation of mental capacity and a high probability of achieving this augmentation. Willingness decreased when there was a high probability of side effects and a high price. Prevalent CE-drug use among peers increased willingness, whereas a social environment that strongly disapproved of these drugs decreased it. Regarding the respondents' characteristics, pronounced academic procrastination, high cognitive test anxiety, low intrinsic motivation, low internalization of social norms against CE-drug use, and past experiences with CE-drugs increased willingness. The potential severity of side effects, social recommendations about using CE-drugs, risk preferences, and competencies had no measured effects upon willingness. These findings contribute to understanding factors that influence the willingness to use CE-drugs. They support the assumption of instrumental drug use and may contribute to the development of prevention, policy, and educational strategies.

Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics

PubMed Central

2014-01-01

Background The use of cognitive enhancement (CE) by means of pharmaceutical agents has been the subject of intense debate both among scientists and in the media. This study investigates several drivers of and obstacles to the willingness to use prescription drugs non-medically for augmenting brain capacity. Methods We conducted a web-based study among 2,877 students from randomly selected disciplines at German universities. Using a factorial survey, respondents expressed their willingness to take various hypothetical CE-drugs; the drugs were described by five experimentally varied characteristics and the social environment by three varied characteristics. Personal characteristics and demographic controls were also measured. Results We found that 65.3% of the respondents staunchly refused to use CE-drugs. The results of a multivariate negative binomial regression indicated that respondents’ willingness to use CE-drugs increased if the potential drugs promised a significant augmentation of mental capacity and a high probability of achieving this augmentation. Willingness decreased when there was a high probability of side effects and a high price. Prevalent CE-drug use among peers increased willingness, whereas a social environment that strongly disapproved of these drugs decreased it. Regarding the respondents’ characteristics, pronounced academic procrastination, high cognitive test anxiety, low intrinsic motivation, low internalization of social norms against CE-drug use, and past experiences with CE-drugs increased willingness. The potential severity of side effects, social recommendations about using CE-drugs, risk preferences, and competencies had no measured effects upon willingness. Conclusions These findings contribute to understanding factors that influence the willingness to use CE-drugs. They support the assumption of instrumental drug use and may contribute to the development of prevention, policy, and educational strategies. PMID:24484640

Taxi 'sugar daddies' and taxi queens: male taxi driver attitudes regarding transactional relationships in the Western Cape, South Africa.

PubMed

Potgieter, Cheryl; Strebel, Anna; Shefer, Tamara; Wagner, Claire

2012-11-01

Media reports are emerging on the phenomenon of young girls who travel with older mini-bus taxi drivers, and who are thought to have sex with the drivers in exchange for gifts and money. The extent to which such relationships might facilitate unsafe sexual practices and increased risks for both the men and the young women, often referred to as taxi queens, remains an important question in the light of the current challenges of HIV/AIDS in sub-Saharan Africa. However, very little research has been undertaken on this issue, especially regarding the perceptions and experiences of taxi drivers. Thus this paper aims to provide some preliminary findings on taxi drivers' attitudes and beliefs about taxi queens and their relationships with taxi drivers. A 22-item questionnaire was administered to 223 male taxi drivers in two regions in the Western Cape Province, South Africa. Taxi drivers in this study largely saw the relationship between taxi drivers and the young girls who ride with them as providing status for both the girls and drivers, and there seemed to be recognition of the transactional nature of the relationship between taxi drivers and taxi queens. The stigmatisation of young girls who ride with taxi drivers was evident. Drivers had knowledge and awareness of the risks of unsafe sex and supported condom use, although there appeared to be some uncertainty and confusion about the likelihood of HIV infection between drivers and girls. While taxi drivers recognised the role of alcohol in relationships with young girls, they seemed to deny that the abuse of drugs was common. The study highlights a number of key areas that need to be explored with men in the taxi industry, in order to address risk behaviours for both taxi drivers and the girls who ride with them.

Prevalence of driving with blood drug concentrations above proposed new legal limits in Norway: estimations based on drug concentrations in oral fluid.

PubMed

Gjerde, Hallvard; Normann, Per T; Christophersen, Asbjørg S; Mørland, Jørg

2011-07-15

To estimate the prevalence of driving with blood drug concentrations above the recently proposed Norwegian legal limits for drugged driving in random traffic. The results from a roadside survey of 10,816 drivers was used as basis for the estimation, and the most prevalent drugs were included. Three approaches were used to estimate the prevalence of drug concentrations above the proposed legal limits in blood based on drug concentrations in oral fluid: comparison with drug concentrations observed in oral fluid and blood in pharmacokinetic studies, estimating the prevalence of drug concentrations in blood by calculating the prevalence of drug concentrations in oral fluid that were larger than the limit in blood multiplied with mean oral fluid/blood ratios, and a mathematical simulation mimicking the relationship between drug concentration distributions in blood and oral fluid for populations of drug users. In total, alcohol or drugs were detected in 5.7% of the samples of oral fluid from drivers in normal traffic; 3.8% (n=410) were positive for the drugs that we included in the assessment. The estimation of drug concentrations in blood suggested that about 1.5% had concentrations above the proposed legal limits in blood for the studied drugs, which is about 40% of those who were positive for the drugs in oral fluid. The estimated prevalence of driving with concentrations of psychoactive drugs in blood above the proposed legal limits was for illegal drugs 0.4% and for medicinal drugs 1.1%. These may be regarded as minimum estimates as some drugs were not included in the assessment. These prevalences are higher than the prevalence of driving with blood alcohol concentrations above the legal limit of 0.2g/kg in Norway. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Examination of the role of the combination of alcohol and cannabis in South Australian road crashes.

PubMed

Baldock, M R J; Lindsay, V L

2015-01-01

The aim of the present study was to examine the role of cannabis in road crashes in South Australia, with a particular focus on the extent to which crashes involving cannabis also involve alcohol. Hospital data, police-reported crash data, and the results of forensic tests of blood samples for drugs and alcohol were collected for 1,074 crash participants (drivers or motorcyclists) admitted to hospital. A sample of 135 coroners' reports was also examined to determine the role of alcohol and cannabis in fatal crashes. The 3 years of linked data for hospital admission cases revealed that alcohol played a greater role in road crashes than other drugs. Approximately 1 in 5 drivers or motorcyclists had a blood alcohol concentration (BAC) above the legal limit of 0.05. Routine testing for cannabis, methamphetamine, and MDMA revealed a drug-positive rate of approximately 1 in 10 of those tested, with over half of these positive to cannabis. More than a third of cannabis cases also involved alcohol. The majority of those who were positive for alcohol had a BAC above 0.15 g/100 mL. BACs were similarly high among drivers positive for both alcohol and cannabis. The findings of the hospital data and the coroners' reports were consistent with each other in terms of providing confirmation that alcohol is still the drug associated with the greatest level of road trauma on South Australian roads. Furthermore, alcohol was also present in around half of the cannabis cases and, when present, tended to be present at very high levels. The results of this study emphasize that, although drug driving is clearly a problem, the most important form of impaired driving that needs to be the target of enforcement is drink driving. Roadside drug testing is important but should not be conducted in such a way that reduces the deterrent value of random breath testing.

Drugs of abuse detection in saliva based on actuated optical method

NASA Astrophysics Data System (ADS)

Shao, Jie; Li, Zhenyu; Jiang, Hong; Wang, Wenlong; Wu, Yixuan

2014-12-01

There has been a considerable increase in the abuse of drugs during the past decade. Combing drug use with driving is very dangerous. More than 11% of drivers in a roadside survey tested positive for drugs, while 18% of drivers killed in accidents tested positive for drugs as reported in USA, 2007. Toward developing a rapid drug screening device, we use saliva as the sample, and combining the traditional immunoassays method with optical magnetic technology. There were several methods for magnetic nanoparticles detection, such as magnetic coils, SQUID, microscopic imaging, and Hall sensors. All of these methods were not suitable for our demands. By developing a novel optical scheme, we demonstrate high-sensitivity detection in saliva. Drugs of abuse are detected at sub-nano gram per milliliter levels in less than 120 seconds. Evanescent wave principle has been applied to sensitively monitor the presence of magnetic nanoparticles on the binding surface. Like the total internal reflection fluorescence microscope (TIRFM), evanescent optical field is generated at the plastic/fluid interface, which decays exponentially and penetrates into the fluid by only a sub-wavelength distance. By disturbance total internal reflection with magnetic nanoparticles, the optical intensity would be influenced. We then detected optical output by imaging the sensor surface onto a CCD camera. We tested four drugs tetrahydrocannabinol (THC), methamphetamine (MAMP), ketamine (KET), morphine (OPI), using this technology. 100 ng mL-1 sensitivity was achieved, and obvious evidence showed that this results could be improved in further researches.

Blood alcohol analysis alone versus comprehensive toxicological analysis - Systematic investigation of missed co-ingested other drugs in suspected alcohol-impaired drivers.

PubMed

Steuer, Andrea E; Eisenbeiss, Lisa; Kraemer, Thomas

2016-10-01

Driving under the influence of alcohol and/or drugs (DUID) is a safety issue of increasing public concern. When a police officer has reasonable grounds to classify a driver as impaired, he may arrange for a blood sample to be taken. In many countries, alcohol analysis only is ordered if impairment is suspected to be exclusively due to alcohol while comprehensive toxicological screening will be performed if additional suspicion for other illegal drugs of abuse (DoA) or medicinal drugs is on hand. The aim of the present study was firstly to evaluate whether signs of impairment can be differentiated to be caused by alcohol alone or a combination of alcohol and other driving-impairing drugs and secondly to which extent additional drugs are missed in suspected alcohol-impaired drivers. A total of 293 DUID cases (negative n=41; alcohol positive only, n=131; alcohol+active drug positive, n=121) analyzed in 2015 in the Canton of Zurich were evaluated for their documented impairment symptoms by translating these into a severity score and comparing them applying principle component analysis (PCA). Additional 500 cases suspected for alcohol-impaired driving only were reanalyzed using comprehensive LC-MS/MS screening methods covering about 1500 compounds. Drugs detected were classified for severity of driving impairment using the classification system established in the DRUID study of the European Commission. As partly expected from the pharmacological and toxicological point of view, PCA analysis revealed no differences between signs of impairment caused by alcohol alone and those caused by alcohol plus at least one active drug. Breaking it down to different blood alcohol concentration ranges, only between 0.3 and 0.5g/kg trends could be observed in terms of more severe impairment for combined alcohol and drug intake. In the 500 blood samples retrospectively analyzed in this study, a total of 330 additional drugs could be detected; in some cases up to 9 co-ingested ones. In total, 37% of all cases were positive for additional drugs, thereby 15% of classic DoAs and further 9% of prescription drugs with a severe risk to cause driving impairment based on the DRUID classification system. A decision whether signs of impairment are related to alcohol alone or to the combination of alcohol and other drugs is impossible. Taking into consideration the high rate of missed drugs in DUI cases, police should think about increasing the number of DUID cases in countries were sanctioning differs between alcohol and alcohol plus drug impaired driving. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

North-South Corridor Demonstration Project: Ethical and Logistical Challenges in the Design of a Demonstration Study of Early Antiretroviral Treatment for Long Distance Truck Drivers along a Transport Corridor through South Africa, Zimbabwe, and Zambia

PubMed Central

Gomez, G. B.; Venter, W. D. F.; Lange, J. M. A.; Rees, H.; Hankins, C.

2013-01-01

Background. Long-distance truck drivers are at risk of acquiring and transmitting HIV and have suboptimal access to care. New HIV prevention strategies using antiretroviral drugs to reduce transmission risk (early antiretroviral therapy (ART) at CD4 count >350 cells/μL) have shown efficacy in clinical trials. Demonstration projects are needed to evaluate “real world” programme effectiveness. We present the protocol for a demonstration study to evaluate the feasibility, acceptability, and cost of an early ART intervention for HIV-positive truck drivers along a transport corridor across South Africa, Zimbabwe, and Zambia, as part of an enhanced strategy to improve treatment adherence and retention in care. Methods and Analysis. This demonstration study would follow an observational cohort of truck drivers receiving early treatment. Our mixed methods approach includes quantitative, qualitative, and economic analyses. Key ethical and logistical issues are discussed (i.e., choice of drug regimen, recruitment of participants, and monitoring of adherence, behavioural changes, and adverse events). Conclusion. Questions specific to the design of tailored early ART programmes are amenable to operational research approaches but present substantial ethical and logistical challenges. Addressing these in demonstration projects can inform policy decisions regarding strategies to reduce health inequalities in access to HIV prevention and treatment programmes. PMID:23606977

Administration of drugs by infusion pumps in palliative medicine.

PubMed

Thorsen, A B; Yung, N S; Leung, A C

1994-03-01

A retrospective study was carried out in 100 adult patients with advanced malignant disease. They were given subcutaneous continuous infusions of medication for symptom relief. The drugs were administered through a butterfly needle inserted subcutaneously in the anterior chest wall using a battery-operated infusion pump. The indications for using this technique were inability to swallow due to deteriorating general condition, oesophageal obstruction, intestinal obstruction, severe nausea and vomiting, terminal dyspnoea and poor pain control with oral opiates. All patients received morphine; other drugs administered through the syringe driver included hyoscine, metoclopramide, cyclizine, dexamethasone and midazolam. Ninety-four patients continued subcutaneous infusion until death. The mean duration of treatment was 9.1 days. The treatment was well tolerated by the patients and controlled their symptoms satisfactorily in the great majority. The use of continuous subcutaneous infusion via a syringe driver gives good symptom control. In the last days of life when the patients have difficulty tolerating oral medication, continuous subcutaneous infusion is a superior alternative to frequent intermittent parenteral injections.

Which young people accept a lift from a drunk or drugged driver?

PubMed

Calafat, A; Adrover-Roig, D; Blay, N; Juan, M; Bellis, M; Hughes, K; Mendes, F; Kokkevi, A

2009-07-01

Riding with a drunk and/or a drugged driver (RDD) is a risk behaviour that has received very little attention in spite of its potential dangers. Young people involved in the recreational nightlife context are especially at risk. 1363 regular users of recreational nightlife from nine European countries (mean age: 21.75; 51.5% women) filled out a self-administered and anonymous questionnaire (in 2006). 37.2% had practised RDD during the previous month. RDD is related to drunkenness and use of drugs, personality factors such as impulsivity, preferring to use a private car to get to nightlife venues, living in a southern European country and being unemployed. No significant influence was found for age, gender, educational level or socioeconomic status. It is important to raise awareness about the high prevalence of RDD. This lack of awareness can be related to its social acceptance among young people. The use of private cars for going to nightlife venues should be discouraged.

Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors

PubMed Central

Bii, Victor M.; Trobridge, Grant D.

2016-01-01

Identifying novel genes that drive tumor metastasis and drug resistance has significant potential to improve patient outcomes. High-throughput sequencing approaches have identified cancer genes, but distinguishing driver genes from passengers remains challenging. Insertional mutagenesis screens using replication-incompetent retroviral vectors have emerged as a powerful tool to identify cancer genes. Unlike replicating retroviruses and transposons, replication-incompetent retroviral vectors lack additional mutagenesis events that can complicate the identification of driver mutations from passenger mutations. They can also be used for almost any human cancer due to the broad tropism of the vectors. Replication-incompetent retroviral vectors have the ability to dysregulate nearby cancer genes via several mechanisms including enhancer-mediated activation of gene promoters. The integrated provirus acts as a unique molecular tag for nearby candidate driver genes which can be rapidly identified using well established methods that utilize next generation sequencing and bioinformatics programs. Recently, retroviral vector screens have been used to efficiently identify candidate driver genes in prostate, breast, liver and pancreatic cancers. Validated driver genes can be potential therapeutic targets and biomarkers. In this review, we describe the emergence of retroviral insertional mutagenesis screens using replication-incompetent retroviral vectors as a novel tool to identify cancer driver genes in different cancer types. PMID:27792127

Alcohol, Drugs and Driving: Implications for Evaluating Driver Impairment

PubMed Central

Brown, Timothy; Milavetz, Gary; Murry, Daryl J.

2013-01-01

Impaired driving is a significant traffic safety problem, and alcohol and drugs taken before driving contribute substantially to this problem. With the increase in use of prescription medication and the decriminalization of some drugs, it has become increasingly important to understand the manifestation of driver impairment. Building upon previous alcohol research conducted at the National Advanced Driving Simulator (NADS), this study enrolled commercial bus drivers to evaluate the effect of triazolam on driving performance to assess difference between placebo, 0.125, and 0.25 mg doses in a randomized and double-blind design. On each of three randomized visits, subjects drove a simulator scenario that had previously been used to demonstrate effects of alcohol on driving performance. Plasma triazolam levels were obtained before the simulator drive. The protocol included participants receiving study medication and placebo over a 3-week period of time one to two weeks apart. The simulator drives used for this analysis occurred approximately 140 minutes after dosing—after the subjects had completed four bus simulator drives and neuropsychological tests over a 2-hour period of time surrounding dosing. The driving scenario contained representative situations on three types of roadways (urban, freeway, and rural) under nighttime driving conditions. Lane keeping performance (ability to drive straight in the lane) under the three doses of triazolam demonstrates that at the 0.25 mg dose, statistically significant effects on performance are observed, but no effects are found at the 0.125 mg level when testing at this time period after dosing. This differs from the effects of alcohol, which shows impairing effects at a 0.05% blood alcohol concentration (BAC) and a greater effect at 0.10% BAC. These results demonstrate the importance of understanding how different types of drugs affect driving performance in realistic driving environments. Although some compounds may have an effect that correlates linearly to dosage, that is not always the case. An understanding of these differences and how they vary across driving tasks is essential to developing a robust evaluation protocol that can accurately describe the effects of a wide variety of drugs on driver impairment. This information can be used to reduce the risk of deleterious effects of therapeutic medications while ensuring their safe and beneficial use. PMID:24406943

Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development.

PubMed

Burt, T; Yoshida, K; Lappin, G; Vuong, L; John, C; de Wildt, S N; Sugiyama, Y; Rowland, M

2016-04-01

A number of drivers and developments suggest that microdosing and other phase 0 applications will experience increased utilization in the near-to-medium future. Increasing costs of drug development and ethical concerns about the risks of exposing humans and animals to novel chemical entities are important drivers in favor of these approaches, and can be expected only to increase in their relevance. An increasing body of research supports the validity of extrapolation from the limited drug exposure of phase 0 approaches to the full, therapeutic exposure, with modeling and simulations capable of extrapolating even non-linear scenarios. An increasing number of applications and design options demonstrate the versatility and flexibility these approaches offer to drug developers including the study of PK, bioavailability, DDI, and mechanistic PD effects. PET microdosing allows study of target localization, PK and receptor binding and occupancy, while Intra-Target Microdosing (ITM) allows study of local therapeutic-level acute PD coupled with systemic microdose-level exposure. Applications in vulnerable populations and extreme environments are attractive due to the unique risks of pharmacotherapy and increasing unmet healthcare needs. All phase 0 approaches depend on the validity of extrapolation from the limited-exposure scenario to the full exposure of therapeutic intent, but in the final analysis the potential for controlled human data to reduce uncertainty about drug properties is bound to be a valuable addition to the drug development process.

Long-term effects of lowering the alcohol minimum purchasing age on traffic crash injury rates in New Zealand.

PubMed

Kypri, Kypros; Davie, Gabrielle; McElduff, Patrick; Langley, John; Connor, Jennie

2017-03-01

In December 1999, New Zealand lowered the alcohol minimum purchasing age from 20 to 18 years. We tested hypotheses that this change was associated with long-term increases in traffic injury attributable to alcohol-impaired driving among 18- to 19-year-olds (target age group) and 15- to 17-year-olds (affected by 'trickle-down'). We undertook a controlled before-and-after comparison of rates of fatal and non-fatal traffic injury to persons of any age attributable to impaired drivers aged 18-19 years and 15-17 years, versus 20- to 21-year-olds. Crash data including assessment of driver alcohol impairment were recorded by New Zealand Police. The pre-change period was 1996-1999. Post-change periods were 2000-2003, 2004-2007 and 2008-2010. Outcomes were population-based and vehicle travel-based rates. Compared with the change in injury rates attributable to alcohol-impaired 20- to 21-year-old male drivers, injuries attributable to 18- to 19-year-old male drivers increased in all post-change periods and significantly so in the second post-change period (incidence rate ratio [IRR] 1.3, 95% confidence interval [CI] 1.1 to 1.5). For 15- to 17-year-old male drivers, rates increased in all post-change periods compared with 20- to 21-year-olds, and more so in the second (IRR 1.2, 95% CI 1.1 to 1.4) and third (IRR 1.2, 95% CI 1.1 to 1.4) periods. There was a short-term relative increase in harm attributable to 18- to 19-year-old female drivers (IRR 1.5; 1.1 to 2.0). Results were similar for vehicle travel-based rates. Reducing the alcohol minimum purchasing age was followed by long-term increases in the incidence of traffic injury attributable to male 15- to 19-year-old alcohol-impaired drivers. [Kypri K, Davie G, McElduff P, Langley J, Connor J. Long-term effects of lowering the alcohol minimum purchasing age on traffic crash injury rates in New Zealand. Drug Alcohol Rev 2017;36:178-185]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

Evaluation of the elderly driver with arthritis.

PubMed

Roberts, W N; Roberts, P C

1993-05-01

Examination focusing upon the two clusters of function necessary for turning and braking is important as is nonthreatening questioning about driving. The effects of drugs used for arthritis on the CNS and a heightened emphasis upon the psychosocial implications of immobility complicate the management of older drivers with arthritis. Assuming optimal treatment of the arthritis, the two most important management tools are actually power-steering and automatic transmission. Less expensive adaptive available thorough rehabilitation services (e.g., auxiliary mirrors) are also of value.

El Salvador: Background and U.S. Relations

DTIC Science & Technology

2017-03-08

money laundering ; and drug, auto, and weapons smuggling. Gangs earn millions of dollars by extorting residents, bus drivers, and business owners...allegedly laundered the gang’s money through motels, brothels, and other businesses.20 Drug-trafficking organizations, including Mexican groups such as...the Sinaloa criminal organization, have increased their illicit activities in El Salvador, including money laundering , albeit to a lesser extent than

Risk for DWI: A New Look at Gender Differences in Drinking and Driving Influences, Experiences, and Attitudes among New Adolescent Drivers.

ERIC Educational Resources Information Center

Farrow, James A.; Brissing, Peter

1990-01-01

A group of 343 tenth-graders was studied measuring demographics, family characteristics and influences, drug and alcohol use, perception of driving skill, and personality factors. Females used drugs/alcohol more often. Males used the automobile more to enhance self-efficacy. Few significant gender differences appeared in analysis of risky driving…

Friends Don't Let Friends Drive Drunk, But Do They Let Friends Drive High?

ERIC Educational Resources Information Center

Glascoff, Mary A.; Shrader, Joe S.; Haddock, Rose K.

2013-01-01

This study reports on a study of college students at a state supported university regarding the use of designated drivers associated with illicit drug use, especially marijuana use. The purpose of the study was to examine whether college students report that they drive under the influence of illicit drugs, if they use the strategy of designating a…

Differential physiological and behavioral cues observed in individuals smoking botanical marijuana versus synthetic cannabinoid drugs.

PubMed

Chase, Peter B; Hawkins, Jeff; Mosier, Jarrod; Jimenez, Ernest; Boesen, Keith; Logan, Barry K; Walter, Frank G

2016-01-01

Synthetic cannabinoid use has increased in many states, and medicinal and/or recreational marijuana use has been legalized in some states. These changes present challenges to law enforcement drug recognition experts (DREs) who determine whether drivers are impaired by synthetic cannabinoids or marijuana, as well as to clinical toxicologists who care for patients with complications from synthetic cannabinoids and marijuana. Our goal was to compare what effects synthetic cannabinoids and marijuana had on performance and behavior, including driving impairment, by reviewing records generated by law enforcement DREs who evaluated motorists arrested for impaired driving. Data were from a retrospective, convenience sample of de-identified arrest reports from impaired drivers suspected of using synthetic cannabinoids (n = 100) or marijuana (n = 33). Inclusion criteria were arrested drivers who admitted to using either synthetic cannabinoids or marijuana, or who possessed either synthetic cannabinoids or marijuana; who also had a DRE evaluation at the scene; and whose blood screens were negative for alcohol and other drugs. Exclusion criteria were impaired drivers arrested with other intoxicants found in their drug or alcohol blood screens. Blood samples were analyzed for 20 popular synthetic cannabinoids by using liquid chromatography-tandem mass spectrometry. Delta-9-tetrahydrocannabinol (THC) and THC-COOH were quantified by gas chromatography-mass spectrometry. Statistical significance was determined by using Fisher's exact test or Student's t-test, where appropriate, to compare the frequency of characteristics of those in the synthetic cannabinoid group versus those in the marijuana group. 16 synthetic cannabinoid and 25 marijuana records met selection criteria; the drivers of these records were arrested for moving violations. Median age for the synthetic cannabinoid group (n = 16, 15 males) was 20 years (IQR 19-23 years). Median age for the marijuana group (n = 25, 21 males) was 20 years (IQR 19-24 years) (p = 0.46). In the synthetic cannabinoid group, 94% (15/16) admitted to using synthetic cannabinoids. In the marijuana group, 96% (24/25) admitted to using marijuana. Blood was available for testing in 96% (24/25) of the marijuana group; 21 of these 24 had quantitative levels of THC (mean + SD = 10.7 + 5 ng/mL) and THC-COOH (mean + SD = 57.8 + 3 ng/mL). Blood was available for testing in 63% (10/16) of the synthetic cannabinoid group, with 80% (8/10) of these positive for synthetic cannabinoids. Those in the synthetic cannabinoid group were more frequently confused (7/16 [44%] vs. 0/25 [0%], p ≤ 0.003) and disoriented (5/16 [31%] vs. 0/25 [0%], p ≤ 0.003), and more frequently had incoherent, slurred speech (10/16 [63%] vs. 3/25 [12%], p = 0.0014) and horizontal gaze nystagmus (8/16 [50%] vs. 3/25 [12%], p = 0.01) than those in the marijuana group. Drivers under the influence of synthetic cannabinoids were more frequently impaired with confusion, disorientation, and incoherent, slurred speech than drivers under the influence of marijuana in this population evaluated by DREs.

Cannabis, alcohol and fatal road accidents

PubMed Central

Martin, Jean-Louis; Gadegbeku, Blandine; Wu, Dan; Viallon, Vivian; Laumon, Bernard

2017-01-01

Introduction This research aims to estimate the relative risks of responsibility for a fatal accident linked to driving under the influence of cannabis or alcohol, the prevalence of these influences among drivers and the corresponding attributable risk ratios. A secondary goal is to estimate the same items for three other groups of illicit drugs (amphetamines, cocaine and opiates), and to compare the results to a similar study carried out in France between 2001 and 2003. Methodology Police procedures for fatal accidents in Metropolitan France during 2011 were analyzed and 300 characteristics encoded to provide a database of 4,059 drivers. Information on alcohol and four groups of illicit drugs derived from tests for positivity and potential confirmation through blood analysis. The study compares drivers responsible for causing the accident, that is to say having directly contributed to its occurrence, to drivers involved in an accident for which they were not responsible, and who can be assimilated to drivers in general. Results The proportion of persons driving under the influence of alcohol is estimated at 2.1% (95% CI: 1.4–2.8) and under the influence of cannabis at 3.4% (2.9%-3.9%). Drivers under the influence of alcohol are 17.8 times (12.1–26.1) more likely to be responsible for a fatal accident, and the proportion of fatal accidents which would be prevented if no drivers ever exceeded the legal limit for alcohol is estimated at 27.7% (26.0%-29.4%). Drivers under the influence of cannabis multiply their risk of being responsible for causing a fatal accident by 1.65 (1.16–2.34), and the proportion of fatal accidents which would be prevented if no drivers ever drove under the influence of cannabis is estimated at 4.2% (3.7%-4.8%). An increased risk linked to opiate use has also been found to be significant, but with low prevalence, requiring caution in interpreting this finding. Other groups of narcotics have even lower prevalence, and the associated extra risks cannot be assessed. Conclusion Almost a decade separates the present study from a similar one previously conducted in France, and there have been numerous developments in the intervening years. Even so, the prevalence of drivers responsible for causing fatal accidents under the influence of alcohol or narcotics has stayed remarkably stable, as have the proportion of fatal accidents which could in theory be prevented if no drivers ever exceeded the legal limits. The overall number of deaths from traffic accidents has dropped sharply during this period, and the number of victims attributable to alcohol and/or cannabis declined proportionally. Alcohol remains the main problem in France. It is just as important to note that one in two drivers considered to be under the influence of cannabis was also under the influence of alcohol. With risks cumulating between the two, it is particularly important to point out the danger of consuming them together. PMID:29117206

Cannabis, alcohol and fatal road accidents.

PubMed

Martin, Jean-Louis; Gadegbeku, Blandine; Wu, Dan; Viallon, Vivian; Laumon, Bernard

2017-01-01

This research aims to estimate the relative risks of responsibility for a fatal accident linked to driving under the influence of cannabis or alcohol, the prevalence of these influences among drivers and the corresponding attributable risk ratios. A secondary goal is to estimate the same items for three other groups of illicit drugs (amphetamines, cocaine and opiates), and to compare the results to a similar study carried out in France between 2001 and 2003. Police procedures for fatal accidents in Metropolitan France during 2011 were analyzed and 300 characteristics encoded to provide a database of 4,059 drivers. Information on alcohol and four groups of illicit drugs derived from tests for positivity and potential confirmation through blood analysis. The study compares drivers responsible for causing the accident, that is to say having directly contributed to its occurrence, to drivers involved in an accident for which they were not responsible, and who can be assimilated to drivers in general. The proportion of persons driving under the influence of alcohol is estimated at 2.1% (95% CI: 1.4-2.8) and under the influence of cannabis at 3.4% (2.9%-3.9%). Drivers under the influence of alcohol are 17.8 times (12.1-26.1) more likely to be responsible for a fatal accident, and the proportion of fatal accidents which would be prevented if no drivers ever exceeded the legal limit for alcohol is estimated at 27.7% (26.0%-29.4%). Drivers under the influence of cannabis multiply their risk of being responsible for causing a fatal accident by 1.65 (1.16-2.34), and the proportion of fatal accidents which would be prevented if no drivers ever drove under the influence of cannabis is estimated at 4.2% (3.7%-4.8%). An increased risk linked to opiate use has also been found to be significant, but with low prevalence, requiring caution in interpreting this finding. Other groups of narcotics have even lower prevalence, and the associated extra risks cannot be assessed. Almost a decade separates the present study from a similar one previously conducted in France, and there have been numerous developments in the intervening years. Even so, the prevalence of drivers responsible for causing fatal accidents under the influence of alcohol or narcotics has stayed remarkably stable, as have the proportion of fatal accidents which could in theory be prevented if no drivers ever exceeded the legal limits. The overall number of deaths from traffic accidents has dropped sharply during this period, and the number of victims attributable to alcohol and/or cannabis declined proportionally. Alcohol remains the main problem in France. It is just as important to note that one in two drivers considered to be under the influence of cannabis was also under the influence of alcohol. With risks cumulating between the two, it is particularly important to point out the danger of consuming them together.

Drug Free Commercial Driver Act of 2013

THOMAS, 113th Congress

Sen. Pryor, Mark L. [D-AR

2013-10-30

Senate - 10/30/2013 Read twice and referred to the Committee on Commerce, Science, and Transportation. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

32 CFR 636.6 - Remedial driver training program.

Code of Federal Regulations, 2011 CFR

2011-07-01

... ENFORCEMENT AND CRIMINAL INVESTIGATIONS MOTOR VEHICLE TRAFFIC SUPERVISION (SPECIFIC INSTALLATIONS) Fort... alcohol and drug rehabilitation programs in accordance with AR 190-5, paragraphs 2-12c and d, and 5-4f (32...

32 CFR 636.6 - Remedial driver training program.

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENFORCEMENT AND CRIMINAL INVESTIGATIONS MOTOR VEHICLE TRAFFIC SUPERVISION (SPECIFIC INSTALLATIONS) Fort... alcohol and drug rehabilitation programs in accordance with AR 190-5, paragraphs 2-12c and d, and 5-4f (32...

The Integrity bare-metal stent made by continuous sinusoid technology.

PubMed

Turco, Mark A

2011-05-01

The Integrity Coronary Stent System (Medtronic Vascular, CA, USA) is a low-profile, open-cell, cobalt-chromium-alloy advanced bare-metal iteration of the well-known Driver/Micro-Driver Coronary Stent System (Medtronic Vascular). The Integrity stent is made with a process called continuous sinusoid technology. This process allows stent construction via wrapping a single thin strand of wire around a mandrel in a sinusoid configuration, with laser fusion of adjacent crowns. The wire-forming process and fusion pattern provide the stent with a continuous preferential bending plane, intended to allow easier access to, and smoother tracking within, distal and tortuous vessels while radial strength is maintained. Continuous sinusoid technology represents innovation in the design of stent platforms and will provide a future stent platform for newer technology, including drug-eluting stent platforms, drug-filled stents and core wire stents.

Clonal status of actionable driver events and the timing of mutational processes in cancer evolution

PubMed Central

McGranahan, Nicholas; Favero, Francesco; de Bruin, Elza C.; Birkbak, Nicolai Juul; Szallasi, Zoltan; Swanton, Charles

2015-01-01

Deciphering whether actionable driver mutations are found in all or a subset of tumor cells will likely be required to improve drug development and precision medicine strategies. We analyzed nine cancer types to determine the subclonal frequencies of driver events, to time mutational processes during cancer evolution, and to identify drivers of subclonal expansions. Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal “actionable” mutations, including BRAF(V600E), IDH1(R132H), PIK3CA(E545K), EGFR(L858R), and KRAS(G12D), which may compromise the efficacy of targeted therapy approaches. More than 20% of IDH1 mutations in glioblastomas, and 15% of mutations in genes in the PI3K(phosphatidylinositol 3-kinase)–AKT–mTOR (mammalian target of rapamycin) signaling axis across all tumor types were subclonal. Mutations in the RAS–MEK (mitogen-activated protein kinase kinase) signaling axis were less likely to be subclonal than mutations in genes associated with PI3K-AKT-mTORsignaling. Analysis of late mutations revealed a link between APOBEC-mediated mutagenesis and the acquisition of subclonal driver mutations and uncovered putative cancer genes involved in subclonal expansions, including CTNNA2 and ATXN1. Our results provide a pan-cancer census of driver events within the context of intratumor heterogeneity and reveal patterns of tumor evolution across cancers. The frequent presence of subclonal driver mutations suggests the need to stratify targeted therapy response according to the proportion of tumor cells in which the driver is identified. PMID:25877892

Tolerability of continuous subcutaneous octreotide used in combination with other drugs.

PubMed

Mercadante, S

1995-01-01

Continuous subcutaneous infusion of octreotide combined with other drugs has proved to be useful in some circumstances in palliative care setting when theoral route is no longer available. Forty-four patients were administered octreotide alone or in combination with other drugs in the same syringe driver for symptom control in advanced cancer patients. Good tolerability and compatibility were observed without visual drug precipitation for a period of 48 hours at room temperature, the standard clinical situation in patients' homes. Such a combination of drugs administered by the subcutaneous route makes possible the adequate control of symptoms in the final days of life.

Examining driver injury severity outcomes in rural non-interstate roadway crashes using a hierarchical ordered logit model.

PubMed

Chen, Cong; Zhang, Guohui; Huang, Helai; Wang, Jiangfeng; Tarefder, Rafiqul A

2016-11-01

Rural non-interstate crashes induce a significant amount of severe injuries and fatalities. Examination of such injury patterns and the associated contributing factors is of practical importance. Taking into account the ordinal nature of injury severity levels and the hierarchical feature of crash data, this study employs a hierarchical ordered logit model to examine the significant factors in predicting driver injury severities in rural non-interstate crashes based on two-year New Mexico crash records. Bayesian inference is utilized in model estimation procedure and 95% Bayesian Credible Interval (BCI) is applied to testing variable significance. An ordinary ordered logit model omitting the between-crash variance effect is evaluated as well for model performance comparison. Results indicate that the model employed in this study outperforms ordinary ordered logit model in model fit and parameter estimation. Variables regarding crash features, environment conditions, and driver and vehicle characteristics are found to have significant influence on the predictions of driver injury severities in rural non-interstate crashes. Factors such as road segments far from intersection, wet road surface condition, collision with animals, heavy vehicle drivers, male drivers and driver seatbelt used tend to induce less severe driver injury outcomes than the factors such as multiple-vehicle crashes, severe vehicle damage in a crash, motorcyclists, females, senior drivers, driver with alcohol or drug impairment, and other major collision types. Research limitations regarding crash data and model assumptions are also discussed. Overall, this research provides reasonable results and insight in developing effective road safety measures for crash injury severity reduction and prevention. Copyright © 2016 Elsevier Ltd. All rights reserved.

[A KABP (knowledge, attitude, belief and behavior) study about AIDS among taxi drivers and hotel attendants in Beijing].

PubMed

Zhang, X; Luo, B; Zhang, K

1994-12-01

This article reports the KABP study on 448 taxi drivers and 556 hotel attendants in Beijing for the first time in China. A self-administered questionnaire was used to investigate knowledge, attitude, belief and practice (KABP) about AIDS. In terms of knowledge, 23.8% of hotel attendants and 36.8% of taxi drivers did not know that contact with blood could transmit HIV. Thirtyfive percent of hotel attendants and 42.2% of taxi drivers did not believe that intravenous drug users were at high risk. Some drivers (13.6%) and hotel attendants (3.4%) reported having multiple sexual partners. Forty-one point nine percent of taxi drivers and 16.6% of hotel attendants preferred the idea of multiple sexual partners. Among hotel attendants, a negative association was found between knowledge about AIDS and multiple sexual behavior (P < 0.01). Regarding attitude toward condom use, 56.2% of taxi drivers and 47.8% of hotel attendants who have had a sexual experience thought that condom use interfered with sexual pleasure. Seventy-six point eight percent of taxi drivers and 79.8% of hotel attendants believed that they could change their behaviors in order to minimize the chances of getting HIV. This study indicates that HIV education is important in reducing the number of sexual partners and promoting the use of safe sex practices like condom use. Furthermore, as reported by the study population, education can change behavior.

Industry Perspectives on Market Access of Innovative Drugs: The Relevance for Oncology Drugs.

PubMed

Pauwels, Kim; Huys, Isabelle; Casteels, Minne; Simoens, Steven

2016-01-01

Key Points - Representatives of the pharmaceutical industry call for a broader recognition of value within the assessment and appraisal of innovative drugs- Focus on value within the assessment and appraisal of drugs is jeopardized by financial drives as the side of industry and at the side of the payers- A well-considered value-framework, with attention for patient reported outcomes, societal preferences and dynamic approach on the drug life cycle, needs to be incorporated in assessment and appraisal at national and European level in order to coordinate the views of different stakeholders and allow efficient resource allocation This study presents industry perspectives on the challenges related to market access of innovative drugs in general and oncology drugs in specific. Fifteen interviews were conducted with representatives of pharmaceutical companies and industry associations. Interviewees call for a broader recognition of value within the assessment and appraisal of drugs. According to interviewees, focus on value is jeopardized by the lack of a common value definition across Europe, poor availability and validity of value measures and cost-saving measures such as external reference price setting and cost-effectiveness analysis at the side of the payers. Centralized assessment of relative-effectiveness at European level would provide a common value estimate across member states, independent of financial drivers. Empirical evidence on PRO and societal preferences is however essential in the development of a value definition. Furthermore, value-based pricing would imply a dynamic approach where the price is differentiated across indications and across the lifecycle of the drug, especially in fields such as oncology. Financial drivers however also threat the application of value-based pricing at the side of the industry, making value-based profitability a more appropriate term.

Prescription and illicit psychoactive drugs in oral fluid--LC-MS/MS method development and analysis of samples from Brazilian drivers.

PubMed

Zancanaro, Ivomar; Limberger, Renata Pereira; Bohel, Paula O; dos Santos, Maíra Kerpel; De Boni, Raquel B; Pechansky, Flavio; Caldas, Eloisa Dutra

2012-11-30

This study is part of a larger project designed to investigate the prevalence of psychoactive drug (PAD) use among Brazilian drivers. In this paper we describe the development and validation of an analytical method to analyze 32 prescription and illicit PADs (amphetamines, benzodiazepines, cocaine, cannabis, opioids, ketamine and m-CPP) and metabolites in oral fluid samples collected with a Quantisal™ device. Samples were extracted with ethyl acetate:hexane and analyzed by LC-MS/MS. Instrumental LOD ranged from 0.26 to 0.65 ng/mL. Mean procedural recoveries at 1.3 ng/mL (LLOQ) ranged from 50% to 120% for 24 compounds. Recoveries were concentration independent, with the exception of femproporex, heroin and ecgonine methyl-ester (EME) for which the recovery decreased significantly at higher levels (13 and 52 ng/mL). RSD was <20% for all compounds at all spiking levels. Ion suppression due to the matrix was <20% for most compounds, and higher than 60% for EME and diethylpropion. Analysis was performed against a in-matrix standard curve. About 10% of the 2235 oral fluid samples collected from drivers on Brazilian Federal highways were positive (≥LOD) for at least one analyte investigated. Alone or in combination with other drugs, cocaine/metabolites were the analytes most detected in the samples (129; 5.8%), followed by amphetamines/metabolite (69; 3.1%), benzodiazepines (28; 1.2%), cannabinoids (23; 1.1%) and opioids (8; 0.4%). Detection of at least two PADs from different classes accounted for 9.3% of the 236 positive samples. Cocaine was found at higher levels in the samples (up to 1165 ng/mL). Preventive measures aimed at reducing the use of PADs by drivers in Brazil will certainly contribute to decrease the country's highway death rates. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Estimation of cocaine consumption in the community: a critical comparison of the results from three complimentary techniques

PubMed Central

Reid, Malcolm J; Langford, Katherine H; Grung, Merete; Gjerde, Hallvard; Amundsen, Ellen J; Morland, Jorg; Thomas, Kevin V

2012-01-01

Objectives A range of approaches are now available to estimate the level of drug use in the community so it is desirable to critically compare results from the differing techniques. This paper presents a comparison of the results from three methods for estimating the level of cocaine use in the general population. Design The comparison applies to; a set of regional-scale sample survey questionnaires, a representative sample survey on drug use among drivers and an analysis of the quantity of cocaine-related metabolites in sewage. Setting 14 438 participants provided data for the set of regional-scale sample survey questionnaires; 2341 drivers provided oral-fluid samples and untreated sewage from 570 000 people was analysed for biomarkers of cocaine use. All data were collected in Oslo, Norway. Results 0.70 (0.36–1.03) % of drivers tested positive for cocaine use which suggest a prevalence that is higher than the 0.22 (0.13–0.30) % (per day) figure derived from regional-scale survey questionnaires, but the degree to which cocaine consumption in the driver population follows the general population is an unanswered question. Despite the comparatively low-prevalence figure the survey questionnaires did provide estimates of the volume of consumption that are comparable with the amount of cocaine-related metabolites in sewage. Per-user consumption estimates are however highlighted as a significant source of uncertainty as little or no data on the quantities consumed by individuals are available, and much of the existing data are contradictory. Conclusions The comparison carried out in the present study can provide an excellent means of checking the quality and accuracy of the three measurement techniques because they each approach the problem from a different viewpoint. Together the three complimentary techniques provide a well-balanced assessment of the drug-use situation in a given community and identify areas where more research is needed. PMID:23144259

77 FR 12360 - Qualification of Drivers; Exemption Applications; Epilepsy and Seizure Disorders

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-29

... known medical condition (e.g., drug reaction, high temperature, acute infectious disease, dehydration... exemption, he would return to driving a school bus. His physician has released him to return to driving...

Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development

DOE PAGES

Burt, T.; Yoshida, K.; Lappin, G.; ...

2016-02-26

A number of drivers and developments suggest that microdosing and other phase 0 applications will experience increased utilization in the near-to-medium future. Increasing costs of drug development and ethical concerns about the risks of exposing humans and animals to novel chemical entities are important drivers in favor of these approaches, and can be expected only to increase in their relevance. An increasing body of research supports the validity of extrapolation from the limited drug exposure of phase 0 approaches to the full, therapeutic exposure, with modeling and simulations capable of extrapolating even non-linear scenarios. An increasing number of applications andmore » design options demonstrate the versatility and flexibility these approaches offer to drug developers including the study of PK, bioavailability, DDI, and mechanistic PD effects. PET microdosing allows study of target localization, PK and receptor binding and occupancy, while Intra-Target Microdosing (ITM) allows study of local therapeutic-level acute PD coupled with systemic microdose-level exposure. Applications in vulnerable populations and extreme environments are attractive due to the unique risks of pharmacotherapy and increasing unmet healthcare needs. Lastly, all phase 0 approaches depend on the validity of extrapolation from the limited-exposure scenario to the full exposure of therapeutic intent, but in the final analysis the potential for controlled human data to reduce uncertainty about drug properties is bound to be a valuable addition to the drug development process.« less

Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burt, T.; Yoshida, K.; Lappin, G.

A number of drivers and developments suggest that microdosing and other phase 0 applications will experience increased utilization in the near-to-medium future. Increasing costs of drug development and ethical concerns about the risks of exposing humans and animals to novel chemical entities are important drivers in favor of these approaches, and can be expected only to increase in their relevance. An increasing body of research supports the validity of extrapolation from the limited drug exposure of phase 0 approaches to the full, therapeutic exposure, with modeling and simulations capable of extrapolating even non-linear scenarios. An increasing number of applications andmore » design options demonstrate the versatility and flexibility these approaches offer to drug developers including the study of PK, bioavailability, DDI, and mechanistic PD effects. PET microdosing allows study of target localization, PK and receptor binding and occupancy, while Intra-Target Microdosing (ITM) allows study of local therapeutic-level acute PD coupled with systemic microdose-level exposure. Applications in vulnerable populations and extreme environments are attractive due to the unique risks of pharmacotherapy and increasing unmet healthcare needs. Lastly, all phase 0 approaches depend on the validity of extrapolation from the limited-exposure scenario to the full exposure of therapeutic intent, but in the final analysis the potential for controlled human data to reduce uncertainty about drug properties is bound to be a valuable addition to the drug development process.« less

Traces of illegal drugs on body surfaces: indicator for consumption or dealing?

NASA Astrophysics Data System (ADS)

Aberl, Franz; Bonenberger, Johannes; Berg, Ralf-Peter; Zimmermann, Rudolph; Sachs, Hans W.

1997-01-01

Customs investigation and drug enforcement services are interest in a rapid and reliable identification of smugglers and dealers. In contrast workplace testing and traffic controls are aiming at the detection of intoxicated persons via the determination of illegal narcotics in body fluids like urine or blood. DRUGWIPE is a pen size, test strip based immunochemical detector for narcotic contaminations on surfaces. It is extremely simple to apply and takes about two minutes to read test results without depending upon any further technical means. This paper describes the applicability of DRUGWIPE to identify drug smugglers or dealers as well as consumers. With respect to the situation and the initial suspicion the test indicates handling as well as consumption. In cooperation with the Institute for Legal Medicine in Munich suspicious drivers were examined with DRUGWIPE for the abuse of illegal narcotics. Test results from this test series are presented and compared with the results from the blood or urine analysis. The question whether the detected traces of illegal narcotics on the body surface of suspicious drivers are combing transpiration or external contamination are discussed.

Advances towards the design and development of personalized non-small-cell lung cancer drug therapy.

PubMed

Vari, Sabrina; Pilotto, Sara; Maugeri-Saccà, Marcello; Ciuffreda, Ludovica; Cesta Incani, Ursula; Falcone, Italia; Del Curatolo, Anais; Ceribelli, Anna; Gelibter, Alain; De Maria, Ruggero; Tortora, Giampaolo; Cognetti, Francesco; Bria, Emilio; Milella, Michele

2013-11-01

Non-small-cell lung cancer (NSCLC) subtypes are driven by specific genetic aberrations. For reasons such as this, there is a call for treatment personalization. The ability to instigate NSCLC fragmentation poses new methodological problems, and new 'driver' molecular aberrations are being discovered at an unprecedented pace. This article describes the clinical development of epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib for EGFR-mutant and anaplastic lymphoma kinase (ALK)-rearranged NSCLC. Further, the authors briefly describe the emerging molecular targets in NSCLC, in terms of both rationale for therapeutic targeting and strategies, for clinical development. Target identification and validation in NSCLC still requires considerable effort, as not all of the molecular alterations are clear 'drivers' nor can they be efficiently targeted with available drugs. However, 50% of the NSCLC cases are without clear-defined molecular aberrations. Clinical trial methodology will need to develop novel paradigms for targeted drug development, aiming at the validation of an ideal 'biology-to-trial' approach. Despite significant challenges, a truly 'personalized' approach to NSCLC therapy appears to be within our reach.

Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma.

PubMed

Head, R J; Fay, M F; Cosgrove, L; Y C Fung, K; Rundle-Thiele, D; Martin, J H

2017-12-02

Glioblastoma is a lethal form of brain tumour usually treated by surgical resection followed by radiotherapy and an alkylating chemotherapeutic agent. Key to the success of this multimodal approach is maintaining apoptotic sensitivity of tumour cells to the alkylating agent. This initial treatment likely establishes conditions contributing to development of drug resistance as alkylating agents form the O 6 -methylguanine adduct. This activates the mismatch repair (MMR) process inducing apoptosis and mutagenesis. This review describes key juxtaposed drivers in the balance between alkylation induced mutagenesis and apoptosis. Mutations in MMR genes are the probable drivers for alkylation based drug resistance. Critical to this interaction are the dose-response and temporal interactions between adduct formation and MMR mutations. The precision in dose interval, dose-responses and temporal relationships dictate a role for alkylating agents in either promoting experimental tumour formation or inducing tumour cell death with chemotherapy. Importantly, this resultant loss of chemotherapeutic selective pressure provides opportunity to explore novel therapeutics and appropriate combinations to minimise alkylation based drug resistance and tumour relapse.

The problem of suspended and revoked drivers who avoid detection at checkpoints.

PubMed

Parrish, Kelly E; Masten, Scott V

2015-01-01

Although driver license suspension and revocation have been shown to improve traffic safety, suspended or revoked (SR) drivers who continue to drive-which appears to be the majority-are about 3 times more likely to be involved in crashes and to cause a fatal crash. In California and many other U.S. states, drivers are typically mailed notices requesting that they surrender their licenses when they are SR for reasons other than driving under the influence of alcohol or drugs (DUI), yet they frequently do not comply. Typical procedures at DUI checkpoints in California and other U.S. states include inspecting driver licenses and checking for signs of intoxication during brief contacts with law enforcement officers. Hence, these checkpoints are in fact DUI/license checkpoints in California and many other states. The purpose of this study was to estimate the extent to which SR drivers avoid being detected at DUI/license checkpoints for SR driving, because they illegally retained possession of their license cards. Law enforcement officers used electronic license card readers at DUI/license checkpoints in Sacramento, California, to record data for 13,705 drivers. The SR status of all contacted drivers was determined after the checkpoints and compared to law enforcement citation records from the checkpoints. Although only 3% of the drivers contacted at the checkpoints were SR, about 41% of SR drivers were able to pass through undetected because they presented license cards that they illegally retained. Drivers SR for DUI-related reasons were more likely to be detected, whereas those SR for failure to provide proof of financial responsibility (insurance) were less likely to be detected. The fact that many SR drivers are able to pass through DUI/license checkpoints undetected weakens both the specific and general impacts of checkpoints for deterring SR driving and may diminish the effectiveness of suspension and revocation actions for reducing the crash risk posed by problem drivers. Using license card readers that can quickly identify SR drivers in real time during routine traffic stops and at DUI/license checkpoints warrants further consideration.

Combinatorial drug screening and molecular profiling reveal diverse mechanisms of intrinsic and adaptive resistance to BRAF inhibition in V600E BRAF mutant melanomas

PubMed Central

Roller, Devin G.; Capaldo, Brian; Bekiranov, Stefan; Mackey, Aaron J.; Conaway, Mark R.; Petricoin, Emanuel F.; Gioeli, Daniel; Weber, Michael J.

2016-01-01

Over half of BRAFV600E melanomas display intrinsic resistance to BRAF inhibitors, in part due to adaptive signaling responses. In this communication we ask whether BRAFV600E melanomas share common adaptive responses to BRAF inhibition that can provide clinically relevant targets for drug combinations. We screened a panel of 12 treatment-naïve BRAFV600E melanoma cell lines with MAP Kinase pathway inhibitors in pairwise combination with 58 signaling inhibitors, assaying for synergistic cytotoxicity. We found enormous diversity in the drug combinations that showed synergy, with no two cell lines having an identical profile. Although the 6 lines most resistant to BRAF inhibition showed synergistic benefit from combination with lapatinib, the signaling mechanisms by which this combination generated synergistic cytotoxicity differed between the cell lines. We conclude that adaptive responses to inhibition of the primary oncogenic driver (BRAFV600E) are determined not only by the primary oncogenic driver but also by diverse secondary genetic and epigenetic changes (“back-seat drivers”) and hence optimal drug combinations will be variable. Because upregulation of receptor tyrosine kinases is a major source of drug resistance arising from diverse adaptive responses, we propose that inhibitors of these receptors may have substantial clinical utility in combination with inhibitors of the MAP Kinase pathway. PMID:26673621

A case-control study estimating accident risk for alcohol, medicines and illegal drugs.

PubMed

Kuypers, Kim Paula Colette; Legrand, Sara-Ann; Ramaekers, Johannes Gerardus; Verstraete, Alain Gaston

2012-01-01

The aim of the present study was to assess the risk of having a traffic accident after using alcohol, single drugs, or a combination, and to determine the concentrations at which this risk is significantly increased. A population-based case-control study was carried out, collecting whole blood samples of both cases and controls, in which a number of drugs were detected. The risk of having an accident when under the influence of drugs was estimated using logistic regression adjusting for gender, age and time period of accident (cases)/sampling (controls). The main outcome measures were odds ratio (OR) for accident risk associated with single and multiple drug use. In total, 337 cases (negative: 176; positive: 161) and 2726 controls (negative: 2425; positive: 301) were included in the study. Main findings were that 1) alcohol in general (all the concentrations together) caused an elevated crash risk; 2) cannabis in general also caused an increase in accident risk; at a cut-off of 2 ng/mL THC the risk of having an accident was four times the risk associated with the lowest THC concentrations; 3) when ranking the adjusted OR from lowest to highest risk, alcohol alone or in combination with other drugs was related to a very elevated crash risk, with the highest risk for stimulants combined with sedatives. The study demonstrated a concentration-dependent crash risk for THC positive drivers. Alcohol and alcohol-drug combinations are by far the most prevalent substances in drivers and subsequently pose the largest risk in traffic, both in terms of risk and scope.

State Medical Marijuana Laws and the Prevalence of Opioids Detected Among Fatally Injured Drivers

PubMed Central

Santaella-Tenorio, Julian; Mauro, Christine; Wrobel, Julia; Cerdà, Magdalena; Keyes, Katherine M.; Hasin, Deborah; Martins, Silvia S.; Li, Guohua

2016-01-01

Objectives. To assess the association between medical marijuana laws (MMLs) and the odds of a positive opioid test, an indicator for prior use. Methods. We analyzed 1999–2013 Fatality Analysis Reporting System (FARS) data from 18 states that tested for alcohol and other drugs in at least 80% of drivers who died within 1 hour of crashing (n = 68 394). Within-state and between-state comparisons assessed opioid positivity among drivers crashing in states with an operational MML (i.e., allowances for home cultivation or active dispensaries) versus drivers crashing in states before a future MML was operational. Results. State-specific estimates indicated a reduction in opioid positivity for most states after implementation of an operational MML, although none of these estimates were significant. When we combined states, we observed no significant overall association (odds ratio [OR] = 0.79; 95% confidence interval [CI] = 0.61, 1.03). However, age-stratified analyses indicated a significant reduction in opioid positivity for drivers aged 21 to 40 years (OR = 0.50; 95% CI = 0.37, 0.67; interaction P < .001). Conclusions. Operational MMLs are associated with reductions in opioid positivity among 21- to 40-year-old fatally injured drivers and may reduce opioid use and overdose. PMID:27631755

[Reaction time of drivers who caused road traffic accidents].

PubMed

Durić, Predrag; Filipović, Danka

2009-01-01

Human factor is the single cause of road traffic injuries in 57%, and together with other factors in more than 90% of all road traffic accidents. Human factor includes many aspects, where reaction time is very important. Thirty healthy drivers 28-40 y.o. with 50-500 km passed per week, having caused at least one road traffic accident in the last ten years were selected, provided they were not under the influence of alcohol and drugs during traffic accident. The same number of control were selected. Both cases and controls were tested to reaction time. We found statistically significant difference between car drivers who caused car accidents and those who did not in both simple and choice reaction times. Car drivers who caused road traffic accidents have longer reaction time (both simple and choice reaction time), but as the tasks were more complex, that difference was less visible. Since drivers involved in this study had introductory phase before measuring their reaction times, they faced with unpleasant sound when they made mistake, which forced them to be aware not to make a mistake in further tasks, so they showed longer reaction times. Measuring of reaction time seems to be important, and as we have showed they are different in drivers who have caused road traffic accidents and those who have do not.

Evaluation of use and lose laws.

DOT National Transportation Integrated Search

2001-06-01

The term 'Use and Lose' describes laws that authorize driver licensing actions against persons found to be using or in possession of illicit drugs, and against young persons found to be drinking, purchasing or in possession of alcoholic beverages.

Drug abuse and driving performance

DOT National Transportation Integrated Search

1972-10-01

Data on 1562 methadone maintenance patients in New York State were gathered through face-to-face interviews. A control group of 1059 people was constructed by asking the experimentals to volunteer names of non-addicted friends. State driver records f...

75 FR 8524 - Procedures for Transportation Workplace Drug and Alcohol Testing Programs

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-25

... drivers are kept from behind the wheel of a large truck until they are successfully rehabilitated.'' Other... with State laws without running afoul of Part 40. We have not created compliance responsibilities under...

Functional genomic Landscape of Human Breast Cancer drivers, vulnerabilities, and resistance

PubMed Central

Marcotte, Richard; Sayad, Azin; Brown, Kevin R.; Sanchez-Garcia, Felix; Reimand, Jüri; Haider, Maliha; Virtanen, Carl; Bradner, James E.; Bader, Gary D.; Mills, Gordon B.; Pe’er, Dana; Moffat, Jason; Neel, Benjamin G.

2016-01-01

Summary Large-scale genomic studies have identified multiple somatic aberrations in breast cancer, including copy number alterations, and point mutations. Still, identifying causal variants and emergent vulnerabilities that arise as a consequence of genetic alterations remain major challenges. We performed whole genome shRNA “dropout screens” on 77 breast cancer cell lines. Using a hierarchical linear regression algorithm to score our screen results and integrate them with accompanying detailed genetic and proteomic information, we identify vulnerabilities in breast cancer, including candidate “drivers,” and reveal general functional genomic properties of cancer cells. Comparisons of gene essentiality with drug sensitivity data suggest potential resistance mechanisms, effects of existing anti-cancer drugs, and opportunities for combination therapy. Finally, we demonstrate the utility of this large dataset by identifying BRD4 as a potential target in luminal breast cancer, and PIK3CA mutations as a resistance determinant for BET-inhibitors. PMID:26771497

Dose Schedule Optimization and the Pharmacokinetic Driver of Neutropenia

PubMed Central

Patel, Mayankbhai; Palani, Santhosh; Chakravarty, Arijit; Yang, Johnny; Shyu, Wen Chyi; Mettetal, Jerome T.

2014-01-01

Toxicity often limits the utility of oncology drugs, and optimization of dose schedule represents one option for mitigation of this toxicity. Here we explore the schedule-dependency of neutropenia, a common dose-limiting toxicity. To this end, we analyze previously published mathematical models of neutropenia to identify a pharmacokinetic (PK) predictor of the neutrophil nadir, and confirm this PK predictor in an in vivo experimental system. Specifically, we find total AUC and Cmax are poor predictors of the neutrophil nadir, while a PK measure based on the moving average of the drug concentration correlates highly with neutropenia. Further, we confirm this PK parameter for its ability to predict neutropenia in vivo following treatment with different doses and schedules. This work represents an attempt at mechanistically deriving a fundamental understanding of the underlying pharmacokinetic drivers of neutropenia, and provides insights that can be leveraged in a translational setting during schedule selection. PMID:25360756

Clonal status of actionable driver events and the timing of mutational processes in cancer evolution.

PubMed

McGranahan, Nicholas; Favero, Francesco; de Bruin, Elza C; Birkbak, Nicolai Juul; Szallasi, Zoltan; Swanton, Charles

2015-04-15

Deciphering whether actionable driver mutations are found in all or a subset of tumor cells will likely be required to improve drug development and precision medicine strategies. We analyzed nine cancer types to determine the subclonal frequencies of driver events, to time mutational processes during cancer evolution, and to identify drivers of subclonal expansions. Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal "actionable" mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), and KRAS (G12D), which may compromise the efficacy of targeted therapy approaches. More than 20% of IDH1 mutations in glioblastomas, and 15% of mutations in genes in the PI3K (phosphatidylinositol 3-kinase)-AKT-mTOR (mammalian target of rapamycin) signaling axis across all tumor types were subclonal. Mutations in the RAS-MEK (mitogen-activated protein kinase kinase) signaling axis were less likely to be subclonal than mutations in genes associated with PI3K-AKT-mTOR signaling. Analysis of late mutations revealed a link between APOBEC-mediated mutagenesis and the acquisition of subclonal driver mutations and uncovered putative cancer genes involved in subclonal expansions, including CTNNA2 and ATXN1. Our results provide a pan-cancer census of driver events within the context of intratumor heterogeneity and reveal patterns of tumor evolution across cancers. The frequent presence of subclonal driver mutations suggests the need to stratify targeted therapy response according to the proportion of tumor cells in which the driver is identified. Copyright © 2015, American Association for the Advancement of Science.

Canada's new drug-impaired driving law: the need to consider other approaches.

PubMed

Solomon, Robert; Chamberlain, Erika

2014-01-01

The objects of this study were: To review the state of drug-impaired driving in Canada, particularly in light of the 2008 amendments to the Criminal Code, which authorized police to demand standardized field sobriety testing and drug recognition evaluations, and to consider whether alternative enforcement models would be more effective in terms of detecting and prosecuting drug-impaired drivers and thereby achieve greater deterrence. This article provides a review of survey data, roadside screening studies, and postmortem reports that indicate the prevalence of driving after drug use in Canada. It evaluates the Criminal Code's 2008 amendments and their impact on charges and convictions for drug-impaired driving. It then reviews some alternative enforcement models for drug-impaired driving that have been adopted in other jurisdictions, particularly toxicological testing, and evaluates them against Canada's social, political, and constitutional framework. Survey data, roadside screening studies, and postmortem reports indicate that driving after drug use is commonplace and is now more prevalent among young people than driving after drinking. Unfortunately, the 2008 Criminal Code amendments have not had their desired effects. The measures have proven to be costly, time-consuming, and cumbersome, and are readily susceptible to challenge in the courts. Accordingly, the charge rates for drug-impaired driving remain extremely low, and the law has had minimal deterrent effects. The review of alternative enforcement models suggests that a system of random roadside saliva screening, somewhat similar to the model used in Victoria, Australia, will be the most effective in terms of detecting and prosecuting drug-impaired drivers and most consistent with Canada's legal and constitutional system. Canada should establish per se limits for the most commonly used drugs, enforceable through a system of screening and evidentiary tests. This will be more efficient and cost-effective and will result in more reliable evidence for criminal trials. Although this system will inevitably be subject to constitutional challenge, existing case law suggests that it should be upheld as a reasonable limit on constitutional rights.

The incidence of drugs in fatally injured drivers

DOT National Transportation Integrated Search

1972-09-01

Method for the collection of blood, urine, bile and alcohol washes of face and fingers from fatally injured drivershave been developed. Specimens have been collected ffom Alcohol Safety ALtion Project areas and other cooperating areas. The samples we...

Evaluation of use and lose laws

DOT National Transportation Integrated Search

2001-06-01

The term "Use and Lose" describes laws that authorize driver licensing actions against persons found to be using or in possession of illicit drugs, and against young persons found to be drinking, purchasing or in possession of alcoholic beverages. Th...

An assessment of behavioral tests to detect impaired drivers

DOT National Transportation Integrated Search

1981-12-01

This study was conducted to assess the feasibility and practicality of roadside behavioral tests for driving impairment. Such tests are seen as complementary to chemical tests of blood drug concentration. Methodological issues in the use of behaviora...

The pharmacogenomics of drug resistance to protein kinase inhibitors

PubMed Central

Gillis, Nancy K.; McLeod, Howard L.

2016-01-01

Dysregulation of growth factor cell signaling is a major driver of most human cancers. This has led to development of numerous drugs targeting protein kinases, with demonstrated efficacy in the treatment of a wide spectrum of cancers. Despite their high initial response rates and survival benefits, the majority of patients eventually develop resistance to these targeted therapies. This review article discusses examples of established mechanisms of drug resistance to anticancer therapies, including drug target mutations or gene amplifications, emergence of alternate signaling pathways, and pharmacokinetic variation. This reveals a role for pharmacogenomic analysis to identify and monitor for resistance, with possible therapeutic strategies to combat chemoresistance. PMID:27620953

A practical guide for nurses in diluent selection for subcutaneous infusion using a syringe driver.

PubMed

McLeod, Fiona; Flowers, Charne

2006-12-01

Appropriate diluent selection in continuous subcutaneous infusion optimises symptom management and client well-being. The responsibility of diluent selection is commonly one of the attending nurse. This paper was developed with the intention of providing nurses with practical instruction for diluent selection when preparing medications for administration subcutaneously using a syringe driver. A literature review was undertaken of published journal databases and published guidelines sites. Recommendations regarding diluent choice were reviewed in two iterations by an expert panel of palliative care nurse clinicians. The principles for diluent selection are presented. They are based primarily on expert opinion level of evidence given a lack of primary research evidence in the area of diluent selection. There is a pressing need for manufacturers' guidance on diluent selection and independent research to establish the impact of diluents on drug and drug combinations when using syringe drivers. Until such time that this evidence is available to guide practice, clinicians need to be trained to inspect solutions and assess the effectiveness of the medication in controlling symptoms. The capacity of this paper to provide practical instruction has been limited by the lack of rigorous evidence available, and indeed, the process of developing this guide identified perhaps more questions than answers available at the present time.

A centralized storage system for the delivery of subcutaneous infusions.

PubMed

Stuart, Peter; Lee, Jane; Arnold, Gill; Davis, Melanie

Symptom control is an important part of maintaining a palliative patient's comfort and dignity, particularly in the end stages of their illness. Within the discipline of palliative care, the use of continuous subcutaneous syringe drivers is an important way of administering drugs at the end stages of a patient's illness to maintain symptom control. This study identified that ward staff had difficulty in obtaining the correct equipment, such as administration sets and Luer-lock syringes, leading to significant delays in patients being given drugs, affecting patient care and, when unable to obtain the correct equipment, the incorrect equipment was used. It was also identified that there was no consistent approach to the use or maintenance of syringe drivers, with a clear risk to patient safety. The study aim was to identify whether the introduction of a centralized storage system of set boxes containing all the relevant equipment would resolve these issues and improve patient care and safety. The audit showed that a centralized storage system enhanced practice by ensuring that there was a standardized approach to the initiation and care of syringe drivers, including equipment when used in the palliative care setting. The system also provided easy access to the correct equipment, reducing in the delay of commencing treatment, as well as the risk of any adverse events.

Risk factors for roadway single- and multi-vehicle all-terrain vehicle crashes in Pennsylvania: 2010-2013.

PubMed

Gorucu, Serap; Murphy, Dennis; Kassab, Cathy

2017-01-01

All Terrain Vehicles on public roadways become major risk factors for the motorists. To compare characteristics of crashes and injury severity related to single vehicle (SV) and multi-vehicle (MV) All-Terrain Vehicle (ATV) roadway crashes in Pennsylvania, USA. Data on ATV crashes occurring on public roads during the years 2010-2013 was obtained from the Pennsylvania Department of Transportation (PennDOT) and analyzed. Almost two-thirds of the incidents were single-vehicle incidents. Single-ATV incidents have a greater risk for incapacitating injury to drivers than do multi-vehicle ATV incidents. Other factors that increase risk for incapacitating injury in SV crashes include being male, being a driver, alcohol/drug involvement, hitting a fixed object, and the incidents in non-daylight hours. For MV ATV incidents, head on and rear-end crashes and drivers who had alcohol/drug involvement were the two major incapacitating injury risk factors. This study has enabled us to better understand roadway ATV incidents, characteristics of SV and MV ATV crashes, and the incapacitating injury risks in both SV and MV crash incidents. Our study suggests that road safety and public health programs should focus on the users' knowledge on laws regarding ATV usage on public roadways.

Ethical Challenges in Biomarker-Driven Drug Development.

PubMed

Hey, Spencer Phillips

2018-01-01

The increasing importance of biomarkers-as drivers of research and drug development activity, surrogate outcomes in clinical trials, and the centerpiece of precision medicine-raises many new ethical challenges. In what follows, I briefly review some of the major ethical challenges and debates already identified in the literature, and then describe a new ethical challenge that arises from the abstract nature of biomarker hypotheses. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Motor-park people shift gear.

PubMed

Nnoli, C

1992-01-01

White, U.S. homosexual males were primarily affected in the early stages of the AIDS pandemic. Some Western researchers argued, however, that the syndrome originated in Africa. Strong political and social response to this notion resulted in only an anemic response to the growing AIDS epidemic in Nigeria. Nonetheless, the Stop AIDS Organization finally launched the Motor Park AIDS Education Program (MPAEP) in 1988, for health and education outreach to populations at risk of STDs and HIV infection. Specifically targeted are long-distance truck drivers, their young male assistants known as motor boys, and the barmaids, prostitutes, and homeless juveniles who frequent motor parks where these drivers rest while on the road. Many of these long-haul drivers have unprotected casual and commercial sex, both homosexual and heterosexual, take drugs, and suffer high rates of STDs. Marginalized, 75% illiterate, and speaking a variety of languages, these populations tend to be largely ignorant of the incurable nature of AIDS. Over 45% of motor park populations are estimated to be infected with an STD, or to have a future re-infection. These drivers are optimal vectors for the spread of HIV both internationally and within Nigeria. MPAEP workers work 6 days/week in the larger interstate motor parks to reach out to their predominantly male customers. They meet a host of primary health needs, and refer STD clients for testing and treatment. Drug use and homosexuality are 2 topics of discussion especially taboo in African society which have nonetheless been vigorously researched by MPAEP. Many drivers are unacknowledged bisexuals who have sex with their motor boys. Workers therefore explain the need to use condoms in same-sex activity without specifically mentioning homosexuality. Many Nigerians deny the existence of HIV and AIDS, are reluctant to speak about sex, and consider MPAEP workers to be intruders. Despite opposition in Muslim- dominated Northern Nigeria, however, program efforts continue.

A Case-Control Study Estimating Accident Risk for Alcohol, Medicines and Illegal Drugs

PubMed Central

Kuypers, Kim Paula Colette; Legrand, Sara-Ann; Ramaekers, Johannes Gerardus; Verstraete, Alain Gaston

2012-01-01

Background The aim of the present study was to assess the risk of having a traffic accident after using alcohol, single drugs, or a combination, and to determine the concentrations at which this risk is significantly increased. Methods A population-based case-control study was carried out, collecting whole blood samples of both cases and controls, in which a number of drugs were detected. The risk of having an accident when under the influence of drugs was estimated using logistic regression adjusting for gender, age and time period of accident (cases)/sampling (controls). The main outcome measures were odds ratio (OR) for accident risk associated with single and multiple drug use. In total, 337 cases (negative: 176; positive: 161) and 2726 controls (negative: 2425; positive: 301) were included in the study. Results Main findings were that 1) alcohol in general (all the concentrations together) caused an elevated crash risk; 2) cannabis in general also caused an increase in accident risk; at a cut-off of 2 ng/mL THC the risk of having an accident was four times the risk associated with the lowest THC concentrations; 3) when ranking the adjusted OR from lowest to highest risk, alcohol alone or in combination with other drugs was related to a very elevated crash risk, with the highest risk for stimulants combined with sedatives. Conclusion The study demonstrated a concentration-dependent crash risk for THC positive drivers. Alcohol and alcohol-drug combinations are by far the most prevalent substances in drivers and subsequently pose the largest risk in traffic, both in terms of risk and scope. PMID:22952694

Evolving trends in mAb production processes

PubMed Central

Wolfe, Leslie S.; Mostafa, Sigma S.; Norman, Carnley

2017-01-01

Abstract Monoclonal antibodies (mAbs) have established themselves as the leading biopharmaceutical therapeutic modality. The establishment of robust manufacturing platforms are key for antibody drug discovery efforts to seamlessly translate into clinical and commercial successes. Several drivers are influencing the design of mAb manufacturing processes. The advent of biosimilars is driving a desire to achieve lower cost of goods and globalize biologics manufacturing. High titers are now routinely achieved for mAbs in mammalian cell culture. These drivers have resulted in significant evolution in process platform approaches. Additionally, several new trends in bioprocessing have arisen in keeping with these needs. These include the consideration of alternative expression systems, continuous biomanufacturing and non‐chromatographic separation formats. This paper discusses these drivers in the context of the kinds of changes they are driving in mAb production processes. PMID:29313024

Health survey of U.S. long-haul truck drivers: work environment, physical health, and healthcare access.

PubMed

Apostolopoulos, Yorghos; Sönmez, Sevil; Shattell, Mona M; Gonzales, Clifford; Fehrenbacher, Caitlin

2013-01-01

While trucking in industrialized nations is linked with driver health afflictions, the role of trucking in U.S. truckers' health remains largely unknown. This paper sheds light on links between the trucking work environment and drivers' physical health. Using a cross-sectional design, 316 truckers were enrolled in the Healthy Trucker Survey. Questions included work history, physical and mental health, and healthcare access. PASW 18 was used to examine patterns among factors. 316 truckers participated. Respondents were mainly full-time, long-haul drivers with over 5 years of experience, and who spent over 17 days on the road per month. While almost 75% described their health as good, 83.4% were overweight/obese, 57.9% had sleeping disturbances, 56.3% fatigue, 42.3% musculoskeletal disorders, and about 40% cardiovascular disease concerns. About 33% had no health insurance, 70% had no regular healthcare visits, 24.4% could not afford insurance, and 42.1% took over-the-counter drugs when sick, while 20.1% waited to reach home for medical care. Exercise facilities were unavailable in over 70% of trucking worksites and 70% of drivers did not exercise regularly. The trucking occupation places drivers at high risk for poor health outcomes. Prospective studies are needed to delve into how continued exposure to trucking influences the progression of disease burden.

Patient, physician, and consumer drivers: referrals for short stature and access to specialty drugs.

PubMed

Cuttler, Leona; Marinova, Detelina; Mercer, Mary Beth; Connors, Alfred; Meehan, Rebecca; Silvers, J B

2009-08-01

Candidates for specialty drugs, the fastest growing and costliest pharmaceuticals, typically originate with primary care referrals. However, little is known about what drives such referrals-especially for large populations such as short, otherwise normal children (idiopathic short stature). Recent expanded approval of growth hormone (GH) makes more than 585,000 US children eligible for such treatment, potentially costing over $11 billion/y. To quantify the relative impact of patient physiological indicators, physician characteristics, and consumer preferences on referrals to endocrinologists (and potential access to GH) for short children, a national study of 1268 randomly selected US pediatricians was conducted, based on a full factorial experimental design in a structured survey. While patient indicators (height, growth pattern) influenced referrals (P < 0.001), consumer drivers (family concern) and physician attitudes had almost as great an impact-especially for children with less severe growth impairment (P < 0.001). Physician belief that short stature impairs emotional well-being and physician characteristics (female, older, shorter, beliefs about drug company information) increased referrals (P < 0.03-0.001)-independent of growth parameters. Referral recommendations that create the pool of candidates for the specialty drug GH are heavily swayed by physician characteristics and consumer preferences, particularly in the absence of compelling physiological evidence. This makes most of children with short stature strikingly susceptible to nonphysiological influences on referrals that render them candidates for this specialty drug. Only 1 additional referral per US pediatrician would likely increase GH costs by over $100 million/y.

Seniors' prescription drug cost inflation and cost containment: evidence from British Columbia.

PubMed

Morgan, Steven G; Agnew, Jonathan D; Barer, Morris L

2004-06-01

We develop an analytic framework to map out the nature and relative importance of different cost-driving trends in the prescription drug market. This is used to measure prescription drug cost-drivers for the population of seniors in British Columbia during a period when they received comprehensive public drug coverage. Between 1991 and 2001, expenditures on prescription drugs for BC seniors increased from dollar 149 to 320 million. Increases in the population of seniors, and the rate at which they utilized therapies contributed under half of the total cost increase over the period. Changes in the mix of therapies and the type of product selected explained over half of the observed drug expenditure inflation. Increased generic substitution significantly reduced the price of products selected over the period.

Evolution and intelligent design in drug development.

PubMed

Agafonov, Roman V; Wilson, Christopher; Kern, Dorothee

2015-01-01

Sophisticated protein kinase networks, empowering complexity in higher organisms, are also drivers of devastating diseases such as cancer. Accordingly, these enzymes have become major drug targets of the twenty-first century. However, the holy grail of designing specific kinase inhibitors aimed at specific cancers has not been found. Can new approaches in cancer drug design help win the battle with this multi-faced and quickly evolving enemy? In this perspective we discuss new strategies and ideas that were born out of a recent breakthrough in understanding the molecular basis underlying the clinical success of the cancer drug Gleevec. An "old" method, stopped-flow kinetics, combined with old enzymes, the ancestors dating back up to about billion years, provides an unexpected outlook for future intelligent design of drugs.

The impact of childhood symptoms of conduct disorder on driver aggression in adulthood.

PubMed

Wickens, Christine M; Vingilis, Evelyn; Mann, Robert E; Erickson, Patricia; Toplak, Maggie E; Kolla, Nathan J; Seeley, Jane; Ialomiteanu, Anca R; Stoduto, Gina; Ilie, Gabriela

2015-05-01

Despite limited empirical investigation, existing scientific literature suggests that individuals with a history or current diagnosis of conduct disorder (CD) may be more likely to demonstrate reckless and aggressive driving. Much of the limited research in this field examines the impact of childhood CD on driver behaviour and collision risk in young adults. Few if any, studies assess the impact of this disorder on driver behaviour beyond age 21 years. The current research is a population-based study of the impact of CD symptoms during childhood on the risk of engaging in driver aggression during adulthood. Data are based on telephone interviews with 5230 respondents who reported having driven in the past year. Data are derived from the 2011-2013 cycles of the CAMH Monitor, an ongoing cross-sectional survey of adults in Ontario, Canada aged 18 years and older. A binary logistic regression analysis of self-reported driver aggression in the previous 12 months was conducted, consisting of measures of demographic characteristics, driving exposure, problem substance use, alcohol- and drug-impaired driving, symptoms of attention deficit hyperactivity disorder, and childhood (before age 15) symptoms of CD. When entered with demographic characteristics, driving exposure, and other potential confounders, childhood symptoms of CD increased the odds of reporting driver aggression more than two-fold (adjusted OR=2.12). Exploratory analyses of the interaction between childhood symptoms of CD and age was not a significant predictor of driver aggression. Results suggest that symptoms of CD during childhood are associated with significantly increased odds of self-reported driver aggression during adulthood. Limitations and future directions of the research are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Resistance to MEK inhibitors: should we co-target upstream?

PubMed

Poulikakos, Poulikos I; Solit, David B

2011-03-29

Aberrant activation of the ERK pathway is common in human tumors. This pathway consists of a three-tiered kinase module [comprising the kinases RAF, mitogen-activated protein kinase (MAPK) kinase (MEK), and extracellular signal-regulated kinase (ERK)] that functions as a negative feedback amplifier to confer robustness and stabilization of pathway output. Because this pathway is frequently dysregulated in human cancers, intense efforts are under way to develop selective inhibitors of the ERK pathway as anticancer drugs. Although promising results have been reported in early trials for inhibitors of RAF or MEK, resistance invariably occurs. Amplification of the upstream oncogenic driver of ERK signaling has been identified as a mechanism for MEK inhibitor resistance in cells with mutant BRAF or KRAS. Increased abundance of the oncogenic driver (either KRAS or BRAF in the appropriate cellular context) in response to prolonged drug treatment results in increased flux through the ERK pathway and restoration of ERK activity above the threshold required for cell growth. For patients with BRAF mutant tumors, the results suggest that the addition of a RAF inhibitor to a MEK inhibitor may delay or overcome drug resistance. The data thus provide a mechanistic basis for ongoing trials testing concurrent treatment with RAF and MEK inhibitors.

23 CFR 192.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Definitions. 192.3 Section 192.3 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192.3 Definitions. As used in this part: (a) Convicted includes adjudicated under juvenile...

23 CFR 192.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Definitions. 192.3 Section 192.3 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192.3 Definitions. As used in this part: (a) Convicted includes adjudicated under juvenile...

23 CFR 192.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Definitions. 192.3 Section 192.3 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192.3 Definitions. As used in this part: (a) Convicted includes adjudicated under juvenile...

U.S. Compounding Pharmacy-related Outbreaks, 2001–2013—Public Health and Patient Safety Lessons Learned

PubMed Central

Shehab, Nadine; Brown, Megan N.; Kallen, Alexander J.; Perz, Joseph F.

2015-01-01

Objectives Pharmacy-compounded sterile preparations (P-CSPs) are frequently relied upon in U.S. healthcare, but are increasingly being linked to outbreaks of infections. We provide an updated overview of outbreak burden and characteristics, identify drivers of P-CSP demand, and discuss public health and patient safety lessons learned to help inform prevention. Methods Outbreaks of infections linked to contaminated P-CSPs that occurred between January 1, 2001 and December 31, 2013 were identified from internal Centers for Disease Control and Prevention reports, Food and Drug Administration drug safety communications, and published literature. Results We identified 19 outbreaks linked to P-CSPs, resulting in at least 1000 cases, including deaths. Outbreaks were reported across two-thirds of states, with almost one-half (8/19) involving cases in more than one state. Almost one-half of outbreaks were linked to injectable steroids (5/19) and intraocular bevacizumab (3/19). Non-patient-specific compounding originating from non-sterile ingredients and re-packaging of already sterile products were the most common practices associated with P-CSP contamination. Breaches in aseptic processing and deficiencies in sterilization procedures or in sterility/endotoxin testing were consistent findings. Hospital outsourcing, preference for variations of commercially available products, commercial drug shortages, and lower prices were drivers of P-CSP demand. Conclusions Recognized outbreaks linked to P-CSPs have been most commonly associated with non-patient-specific re-packaging and non-sterile to sterile compounding, and linked to lack of adherence to sterile compounding standards. Recently-enhanced regulatory oversight of compounding may improve adherence to such standards. Additional measures to limit and control these outbreaks include vigilance when outsourcing P-CSPs, scrutiny of drivers for P-CSP demand, and early recognition and notification of possible outbreaks. PMID:26001553

Risky car following in abstinent users of MDMA.

PubMed

Dastrup, Elizabeth; Lees, Monica N; Bechara, Antoine; Dawson, Jeffrey D; Rizzo, Matthew

2010-05-01

Ecstasy (MDMA) use raises concerns because of its association with risky driving. We evaluated driving performance and risk taking in abstinent recreational MDMA users in a simulated car following task that required continuous attention and vigilance. Drivers were asked to follow two car lengths behind a lead vehicle (LV). Three sinusoids generated unpredictable LV velocity changes. Drivers could mitigate risk by following further behind the erratic LV. From vehicle trajectory data we performed a Fourier analysis to derive measures of coherence, gain, and delay. These measures and headway distance were compared between the different groups. All MDMA drivers met coherence criteria indicating cooperation in the car following task. They matched periodic changes in LV velocity similar to controls (abstinent THC users, abstinent alcohol users, and non-drug users), militating against worse vigilance. While all participants traveled approximately 55 mph (89 kph), the MDMA drivers followed 64 m closer to the LV and demonstrated 1.04 s shorter delays to LV velocity changes than other driver groups. The simulated car following task safely discriminated between driving behavior in abstinent MDMA users and controls. Abstinent MDMA users do not perform worse than controls, but may assume extra risk. The control theory framework used in this study revealed behaviors that might not otherwise be evident. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Risky Car Following in Abstinent Users of MDMA

PubMed Central

Dastrup, Elizabeth; Lees, Monica; Bechara, Antoine; Dawson, Jeffrey D.; Rizzo, Matthew

2011-01-01

Ecstasy (MDMA) use raises concerns because of its association with risky driving. We evaluated driving performance and risk taking in abstinent recreational MDMA users in a simulated car following task that required continuous attention and vigilance. Drivers were asked to follow two car lengths behind a lead vehicle (LV). Three sinusoids generated unpredictable LV velocity changes. Drivers could mitigate risk by following further behind the erratic LV. From vehicle trajectory data we performed a Fourier analysis to derive measures of coherence, gain, and delay. These measures and headway distance were compared between the different groups. All MDMA drivers met coherence criteria indicating cooperation in the car following task. They matched periodic changes in LV velocity similar to controls (abstinent THC users, abstinent alcohol users, and non-drug users), militating against worse vigilance. While all participants traveled approximately 55mph (89kph), the MDMA drivers followed 64m closer to the LV and demonstrated 1.04s shorter delays to LV velocity changes than other driver groups. The simulated car following task safely discriminated between driving behavior in abstinent MDMA users and controls. Abstinent MDMA users do not perform worse than controls, but may assume extra risk. The control theory framework used in this study revealed behaviors that might not otherwise be evident. PMID:20380914

Have drivers at alcohol outlets changed their behavior after the new traffic law?

PubMed

De Boni, Raquel B; Pechansky, Flavio; Vasconcellos, Mauricio T de; Bastos, Francisco I

2014-01-01

In an attempt to reduce high levels of traffic crashes, a new legislation was approved in Brazil in 2008. This study aimed to assess behavioral change among drivers who had drunk at alcohol outlets (AO) after implementation of the law. A three-stage probability sampling survey was conducted in Porto Alegre, state of Rio Grande do Sul, Brazil. Individuals seen leaving AOs after drinking were approached (n=3,018). Selected drivers (n=683) answered a structured interview, were breathalyzed, and had saliva specimens collected for drug screening. Overall, 60.3% (SE 4.5) of drivers reported they did not change their behavior. Among those who reported behavioral changes, most reported drinking less as their main strategy toward safer driving behavior. Variables independently associated with behavior change included having drunk at a high outlet density area (odds ratio [OR] 1.7 [1.1-2.8]) and having a favorable opinion about the law (OR 4.3 [2.1-8.9]). Our findings suggest that awareness of the law has not been enough to promote behavioral change. As most drivers had a favorable opinion of the law and this variable was found to be the strongest predictor of behavior change, efforts to better integrate education and enforcement seem to be pivotal and might be well received by the population.

Two traffic fatalities related to the use of difluoroethane.

PubMed

Broussard, L A; Brustowicz, T; Pittman, T; Atkins, K D; Presley, L

1997-11-01

The 18-year-old white male driver and 17-year-old white male passenger of an automobile were killed when their vehicle crossed the median of a 4-lane highway and collided with a minivan. A can of airbrush propellant was found in the automobile of the deceased. The only drug detected during initial toxicological analyses was 130 mg/L ethanol in the blood of the driver. When performing ethanol analysis by headspace gas chromatography, an unidentified peak was observed in the blood of both deceased. This peak was identified as difuoroethane (Freon 152), the propellant in the aerosol can found in the automobile. The concentrations of difluoroethane in the blood of the driver and passenger were 78 mg/L and 35 mg/L, respectively. Based on a literature search we believe that this is the first report of the quantitation of difluoroethane in biological samples.

23 CFR 192.2 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Purpose. 192.2 Section 192.2 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192... the withholding of Federal-aid highway funds for noncompliance with 23 U.S.C. 159. ...

23 CFR 192.2 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Purpose. 192.2 Section 192.2 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192... the withholding of Federal-aid highway funds for noncompliance with 23 U.S.C. 159. ...

23 CFR 192.2 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Purpose. 192.2 Section 192.2 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192... the withholding of Federal-aid highway funds for noncompliance with 23 U.S.C. 159. ...

23 CFR 192.2 - Purpose.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Purpose. 192.2 Section 192.2 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192... the withholding of Federal-aid highway funds for noncompliance with 23 U.S.C. 159. ...

Functional Genomic Landscape of Human Breast Cancer Drivers, Vulnerabilities, and Resistance.

PubMed

Marcotte, Richard; Sayad, Azin; Brown, Kevin R; Sanchez-Garcia, Felix; Reimand, Jüri; Haider, Maliha; Virtanen, Carl; Bradner, James E; Bader, Gary D; Mills, Gordon B; Pe'er, Dana; Moffat, Jason; Neel, Benjamin G

2016-01-14

Large-scale genomic studies have identified multiple somatic aberrations in breast cancer, including copy number alterations and point mutations. Still, identifying causal variants and emergent vulnerabilities that arise as a consequence of genetic alterations remain major challenges. We performed whole-genome small hairpin RNA (shRNA) "dropout screens" on 77 breast cancer cell lines. Using a hierarchical linear regression algorithm to score our screen results and integrate them with accompanying detailed genetic and proteomic information, we identify vulnerabilities in breast cancer, including candidate "drivers," and reveal general functional genomic properties of cancer cells. Comparisons of gene essentiality with drug sensitivity data suggest potential resistance mechanisms, effects of existing anti-cancer drugs, and opportunities for combination therapy. Finally, we demonstrate the utility of this large dataset by identifying BRD4 as a potential target in luminal breast cancer and PIK3CA mutations as a resistance determinant for BET-inhibitors. Copyright © 2016 Elsevier Inc. All rights reserved.

Driving personalized medicine: capturing maximum net present value and optimal return on investment.

PubMed

Roth, Mollie; Keeling, Peter; Smart, Dave

2010-01-01

In order for personalized medicine to meet its potential future promise, a closer focus on the work being carried out today and the foundation it will provide for that future is imperative. While big picture perspectives of this still nascent shift in the drug-development process are important, it is more important that today's work on the first wave of targeted therapies is used to build specific benchmarking and financial models against which further such therapies may be more effectively developed. Today's drug-development teams need a robust tool to identify the exact drivers that will ensure the successful launch and rapid adoption of targeted therapies, and financial metrics to determine the appropriate resource levels to power those drivers. This special report will describe one such benchmarking and financial model that is specifically designed for the personalized medicine field and will explain how the use of this or similar models can help to capture the maximum net present value of targeted therapies and help to realize optimal return on investment.

The effects of medical marijuana laws on cannabis-involved driving.

PubMed

Sevigny, Eric L

2018-06-06

This study uses data from the Fatality Analysis Reporting System and a differences-in-differences model to examine the effect of state medical marijuana laws (MMLs) on cannabis-involved driving among U.S. drivers involved in a fatal crash between 1993-2014. Findings indicate that MMLs in general have a null effect on cannabis-positive driving, as do state laws with specific supply provisions including home cultivation and unlicensed or quasi-legal dispensaries. Only in jurisdictions with state-licensed medical marijuana dispensaries did the odds of marijuana-involved driving increase significantly by 14 percent, translating into an additional 87 to 113 drivers testing positive for marijuana per year. Sensitivity analyses reveal these findings to be generally robust to alternate specifications, although an observed spillover effect consistent with elevated drugged driving enforcement in bordering states weakens a causal interpretation. Still, reasonable policy implications are drawn regarding drugged driving prevention/enforcement and regulations governing dispensary delivery services and business siting decisions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Correlation between driving-related skill and alcohol use in young-adults from six European countries: the TEN-D by Night Project

PubMed Central

2011-01-01

Background Only few studies with small experimental samples investigated the impact of psychoactive substances on driving performance. We conducted a multicenter international cross-sectional study to evaluate the correlation between alcohol use and driving-related skill as measured by brake reaction time (RT). Methods Before and after the entrance into randomly selected recreational sites from six European countries, all subjects aged 16-35 years, owning a driver license, were asked to compile a structured socio-demographic questionnaire and measure RT (SimuNomad3 driving simulator), breath alcohol concentration (BAC; Drager Alcoltest), and drug use (Oratect III saliva test, only at the exit). Mixed regression modeling was used to evaluate the independent association between RT and alcohol concentration or drug use. Results Before the entrance into the recreational site, 4534 subjects completed all assessments and composed the final sample. Their mean age was 23.1 ± 4.2y; 68.3% were males; 54.7% had BAC > 0 g/L (assumed alcoholics); 7.5% declared illegal drug assumption (mostly cannabis). After the exit, 3019 also completed the second assessment: 71.7% showed BAC > 0 g/L. Controlling for age, gender, educational level, occupation, driver license years, and drug use, BAC was positively associated with RT, achieving significance, however, only when BAC was higher than 0.49 g/L. Significant interaction terms were found between BAC and female gender or drug use, with highest RTs (> 1 sec.) recorded among drug users with BAC > = 1 g/L. Conclusions This field study confirms previous experimental data on the negative impact of alcohol use on driving-related skill, supporting regulations and educational campaigns aimed at discouraging driving after consumption of psychoactive substances. PMID:21722358

Toxicological investigation in blood samples from suspected impaired driving cases in the Milan area: Possible loss of evidence due to late blood sampling.

PubMed

Ferrari, Davide; Manca, Monica; Premaschi, Simone; Banfi, Giuseppe; Locatelli, Massimo

2018-05-01

Driving under the influence of illicit drugs (DUID) represents a significant menace to public safety and is therefore sanctioned with severe fines and penalties such as driving disqualification or even arrest in case the accident has caused serious injury or death. In Italy, DUID is regulated by the article 187 of the National Street Code, however, the list of the substances to be searched and their threshold concentrations are left to the 20 Italian regional authorities. A further lack of legislative standardization concerns the type of detection methods and moreover the time gap between the car accident and blood sampling. This interval can be as high as 5h, enough to significantly reduce the concentration of drugs with fast pharmacokinetic. By analyzing 1258 blood tests performed on drivers involved in road traffic crashes in the Milan area between 2012 and 2016 we show that approximately 75% of such drivers who tested positive for THC and 15% of the drivers who tested positive for cocaine are at risk of misjudgment. Considering the severe sanctions associated with DUID, we emphasize the urgency of introducing a corrective factor that takes into account the time elapsed between the accident and blood sampling in order to avoid unfair treatment, including the unjust application of sanctions. Copyright © 2018 Elsevier B.V. All rights reserved.

Prevalence of drug abuse among workers: strengths and pitfalls of the recent Italian Workplace Drug Testing (WDT) legislation.

PubMed

Kazanga, Isabel; Tameni, Silvia; Piccinotti, Alberto; Floris, Ivan; Zanchetti, Gabriele; Polettini, Aldo

2012-02-10

In 2008 a Workplace Drug Testing (WDT) law became effective in Italy for workers involved in public/private transportation, oil/gas companies, and explosives/fireworks industry with the aim to ensure public safety for the community. To examine and elaborate WDT data collected on a large group of workers (over 43,500) during March 2009-February 2010 in order to highlight pros and cons and to draw suggestions for policies in the field. Northern Italy. After ≤ 24 h notification, workers provided a urine sample screened for opiates, methadone, buprenorphine, cocaine, amphetamines, ecstasy, and cannabinoids (THC) by immunoassay. Positives were confirmed by GC-MS. The positive rate was 2.0%, THC being most frequent drug (1.3%; cocaine, 0.4%; opioids, 0.3%). 6.9% of the positive workers tested positive for ≥ 2 classes (most often THC+cocaine). Gender ratio and mean age were significantly lower in positives (F/M=0.007; 35.5 ± 8.3 years) than negatives (0.016 and 40.7 ± 9.5, respectively). No decline in rates of positives and an increase of diluted samples over time were observed. The highest rates of positives were detected when sampling was performed just before/after week-end and during morning hours. Possible correlation between job type and drugs used were observed (e.g. more cocaine positives among road vehicle-drivers than among lift truck-drivers). Declared use of medicine/illicit drugs during the preceding week showed that illicit drug use was likely not always detected in urine and that almost 4% workers declared use of medicine drugs possibly affecting performance. This survey enabled to evidence relevant pitfalls of the law and to define strategies to improve the outcomes of WDT policies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Orphan drug development: an economically viable strategy for biopharma R&D.

PubMed

Meekings, Kiran N; Williams, Cory S M; Arrowsmith, John E

2012-07-01

Orphan drug incentives have stimulated research into diseases with significant unmet medical need. Although the targeting of orphan diseases is seen by industry as an attractive strategy, there are limited economic data available to support its use. In this paper we show that the revenue-generating potential of orphan drugs is as great as for non-orphan drugs, even though patient populations for rare diseases are significantly smaller. Moreover, we suggest that orphan drugs have greater profitability when considered in the full context of developmental drivers including government financial incentives, smaller clinical trial sizes, shorter clinical trial times and higher rates of regulatory success. The data support the targeting of rare diseases as an important component of a successful biopharma R&D strategy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Silicon to syringe: Cryptomarkets and disruptive innovation in opioid supply chains.

PubMed

Gilbert, Michael; Dasgupta, Nabarun

2017-08-01

Cryptomarkets offer insight into the evolving interplay between online black markets and cartel-based distribution. The types and forms of heroin, fentanyl, and prescription drugs show wide diversification. In this commentary we describe changes in the conceptualizations, technologies and structures of drug supply chains in the 21st Century, with special attention to the role of cryptomarkets as tools, contexts, and drivers of innovation in public health research. Copyright © 2017 Elsevier B.V. All rights reserved.

Future Infectious Disease Threats to Europe

PubMed Central

Suk, Jonathan E.

2011-01-01

We examined how different drivers of infectious disease could interact to threaten control efforts in Europe. We considered projected trends through 2020 for 3 broad groups of drivers: globalization and environmental change, social and demographic change, and health system capacity. Eight plausible infectious disease threats with the potential to be significantly more problematic than they are today were identified through an expert consultation: extensively drug-resistant bacteria, vector-borne diseases, sexually transmitted infections, food-borne infections, a resurgence of vaccine-preventable diseases, health care–associated infections, multidrug-resistant tuberculosis, and pandemic influenza. Preemptive measures to be taken by the public health community to counteract these threats were identified. PMID:21940915

Evidence report : licit schedule II drug use and commercial motor vehicle driver safety (comprehensive review)

DOT National Transportation Integrated Search

2006-10-21

Of all occupations in the United States, workers in the trucking industry experience the third-highest fatality rate, accounting for 12 percent of all worker deaths. About two-thirds of fatally injured truck workers were involved in highway crashes. ...

23 CFR 192.7 - Apportionment of withheld funds after compliance.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Apportionment of withheld funds after compliance. 192.7 Section 192.7 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192.7 Apportionment of withheld funds after compliance...

23 CFR 192.1 - Scope.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Scope. 192.1 Section 192.1 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192.1 Scope. This part prescribes the requirements necessary to implement 23 U.S.C. § 159, which...

23 CFR 192.1 - Scope.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Scope. 192.1 Section 192.1 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192.1 Scope. This part prescribes the requirements necessary to implement 23 U.S.C. § 159, which...

23 CFR 192.1 - Scope.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Scope. 192.1 Section 192.1 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192.1 Scope. This part prescribes the requirements necessary to implement 23 U.S.C. § 159, which...

23 CFR 192.7 - Apportionment of withheld funds after compliance.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Apportionment of withheld funds after compliance. 192.7 Section 192.7 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192.7 Apportionment of withheld funds after compliance...

23 CFR 192.1 - Scope.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Scope. 192.1 Section 192.1 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192.1 Scope. This part prescribes the requirements necessary to implement 23 U.S.C. § 159, which...

23 CFR 192.7 - Apportionment of withheld funds after compliance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Apportionment of withheld funds after compliance. 192.7 Section 192.7 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192.7 Apportionment of withheld funds after compliance...

23 CFR 192.7 - Apportionment of withheld funds after compliance.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Apportionment of withheld funds after compliance. 192.7 Section 192.7 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES DRUG OFFENDER'S DRIVER'S LICENSE SUSPENSION § 192.7 Apportionment of withheld funds after compliance...

Urgency and austerity as drivers of success.

PubMed

Stouch, Terry R

2017-03-01

This piece describes the approach by which even a small CADD (Computer-Aided Drug Design) group with limited resources and limited time can achieve substantial success given short budgets and the compressed, urgent environment of a biotech. Some comparisons are made with CADD operations in big pharma.

Urgency and austerity as drivers of success

NASA Astrophysics Data System (ADS)

Stouch, Terry R.

2017-03-01

This piece describes the approach by which even a small CADD (Computer-Aided Drug Design) group with limited resources and limited time can achieve substantial success given short budgets and the compressed, urgent environment of a biotech. Some comparisons are made with CADD operations in big pharma.

Working conditions and illicit psychoactive substance use among truck drivers in Brazil.

PubMed

Girotto, Edmarlon; de Andrade, Selma Maffei; Mesas, Arthur Eumann; González, Alberto Durán; Guidoni, Camilo Molino

2015-11-01

The aim of this study was to identify the role that working conditions play in predicting the consumption of illicit psychoactive substances (IPS) among truck drivers. This cross-sectional study was conducted with truck drivers who transport grains to Paranaguá Port, PR, Brazil. The truck drivers were interviewed, and they completed a self-administered questionnaire regarding their sociodemographics, lifestyles, working conditions, and consumption of IPS over the past 30 days. The statistical analysis included logistic regression models progressively adjusted for sociodemographic and lifestyle variables. A total of 670 male drivers with a mean age of 41.9 (±11.1) years were assessed. The prevalence of IPS consumption over the past 30 days was 10.9% (n=73). The drugs used primarily consisted of amphetamines (n=61). After adjusting for working characteristics, sociodemographic and lifestyle variables, the following working conditions were associated with the consumption of IPS: driving mostly at night (OR=3.91; 95% CI 1.75 to 8.74), driving while tired (OR=2.26; 95% CI 1.31 to 3.89), and earning a higher monthly income (OR=2.08; 95% CI 1.16 to 3.72). Drivers who were 39 years old or younger (OR=2.11; 95% CI 1.05 to 4.25) and not living with a partner (OR=2.22; 95% CI 1.17 to 4.22) were also more likely to consume IPS. Driving mostly at night, being tired, and earning more increase the use of IPS among truck drivers, regardless of other working characteristics, sociodemographic, and lifestyle variables. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cannabis and crash responsibility while driving below the alcohol per se legal limit.

PubMed

Romano, Eduardo; Voas, Robert B; Camp, Bayliss

2017-11-01

There is a growing interest in how extensively the use of marijuana by drivers relates to crash involvement. While cognitive, lab-based studies are consistent in showing that the use of cannabis impairs driving tasks, epidemiological, field-based studies have been inconclusive regarding whether cannabis use causes an increased risk of accidents. There is ample evidence that the presence of cannabis among drivers with a BAC≥0.08g/dL highly increases the likelihood of a motor vehicle crash. Less clear, however, is the contribution of cannabis to crash risk when drivers have consumed very little or no alcohol. This effort addresses this gap in knowledge. We took advantage of a unique database that merged fatal crashes in the California Statewide Integrated Traffic Records System (SWITRS) and the Fatality Analysis Reporting System (FARS), which allows for a precise identification of crash responsibility. To account for recent increase in lab testing, we restricted our sample to cover only the years 1993-2009. A total of 4294 drivers were included in the analyses. Descriptive analyses and logistic regressions were run to model the contribution of alcohol and drugs to the likelihood of being responsible in a fatal crash. We found evidence that compared with drivers negative for alcohol and cannabis, the presence of cannabis elevates crash responsibility in fatal crashes among drivers at zero BACs (OR=1.89) and with 0

Standard dose valproic acid does not cause additional cognitive impact in a rodent model of intractable epilepsy.

PubMed

Jellett, Adam P; Jenks, Kyle; Lucas, Marcella; Scott, Rod C

2015-02-01

Children with epilepsy face significant cognitive and behavioral impairments. These impairments are due to a poorly characterized interaction between the underlying etiology, the effect of seizures and the effect of medication. The large variation in these factors make understanding the main drivers of cognitive impairment in humans extremely difficult. Therefore, we investigated the cognitive effect of seizures and the antiepileptic drug valproic acid in a rodent model of cortical dysplasia. Rats were divided into seizure-receiving and non-receiving groups. Rats experienced frequent early life seizures using the flurothyl inhalation method: 50 seizures between postnatal day 5 and 15 and then one seizure a day following that. Rats were further divided into drug-treated and vehicle treated groups. Valproic acid treated animals were treated from 5 days preceding behavioral testing in the Morris water maze at a clinically relevant concentration. We show here that the main driver of cognitive impairments are the brain malformations, and that persistent seizures in animals with brain malformations and valproic acid caused no additional impact. These findings suggest that neither an appropriate dose of a standard antiepileptic drug or intractable seizures worsen cognition associated with a malformation of cortical development and that alternative treatment strategies to improve cognition are required. Copyright © 2014 Elsevier B.V. All rights reserved.

TEFL/TESL Newsletter, Volume 4, Number 4.

ERIC Educational Resources Information Center

Australian Dept. of Education, Canberra. Language Teaching Branch.

This issue is devoted to driving and traffic safety. Based on information found in drivers' manuals from the various Australian states, instructions are given vis-a-vis pedestrians, cyclists and motorcyclists, driving regulations, seat belts, alcohol and drugs, lines and signs, and registration and licensing. Sample questions and suggested…

The role of interleukin-18 in glioblastoma pathology implies therapeutic potential of two old drugs-disulfiram and ritonavir.

PubMed

Kast, Richard E

2015-04-09

Based on reporting in the last several years, an impressive but dismal list of cytotoxic chemotherapies that fail to prolong the median overall survival of patients with glioblastoma has prompted the development of treatment protocols designed to interfere with growth-facilitating signaling systems by using non-cytotoxic, non-oncology drugs. Recent recognition of the pro-mobility stimulus, interleukin-18, as a driver of centrifugal glioblastoma cell migration allows potential treatment adjuncts with disulfiram and ritonavir. Disulfiram and ritonavir are well-tolerated, non-cytotoxic, non-oncology chemotherapeutic drugs that are marketed for the treatment of alcoholism and human immunodeficiency virus (HIV) infection, respectively. Both drugs exhibit an interleukin-18-inhibiting function. Given the favorable tolerability profile of disulfiram and ritonavir, the unlikely drug-drug interaction with temozolomide, and the poor prognosis of glioblastoma, trials of addition of disulfiram and ritonavir to current standard initial treatment of glioblastoma would be warranted.

ActiveDriverDB: human disease mutations and genome variation in post-translational modification sites of proteins

PubMed Central

Krassowski, Michal; Paczkowska, Marta; Cullion, Kim; Huang, Tina; Dzneladze, Irakli; Ouellette, B F Francis; Yamada, Joseph T; Fradet-Turcotte, Amelie

2018-01-01

Abstract Interpretation of genetic variation is needed for deciphering genotype-phenotype associations, mechanisms of inherited disease, and cancer driver mutations. Millions of single nucleotide variants (SNVs) in human genomes are known and thousands are associated with disease. An estimated 21% of disease-associated amino acid substitutions corresponding to missense SNVs are located in protein sites of post-translational modifications (PTMs), chemical modifications of amino acids that extend protein function. ActiveDriverDB is a comprehensive human proteo-genomics database that annotates disease mutations and population variants through the lens of PTMs. We integrated >385,000 published PTM sites with ∼3.6 million substitutions from The Cancer Genome Atlas (TCGA), the ClinVar database of disease genes, and human genome sequencing projects. The database includes site-specific interaction networks of proteins, upstream enzymes such as kinases, and drugs targeting these enzymes. We also predicted network-rewiring impact of mutations by analyzing gains and losses of kinase-bound sequence motifs. ActiveDriverDB provides detailed visualization, filtering, browsing and searching options for studying PTM-associated mutations. Users can upload mutation datasets interactively and use our application programming interface in pipelines. Integrative analysis of mutations and PTMs may help decipher molecular mechanisms of phenotypes and disease, as exemplified by case studies of TP53, BRCA2 and VHL. The open-source database is available at https://www.ActiveDriverDB.org. PMID:29126202

HIT'nDRIVE: patient-specific multidriver gene prioritization for precision oncology

PubMed Central

Hodzic, Ermin; Sauerwald, Thomas; Dao, Phuong; Wang, Kendric; Yeung, Jake; Anderson, Shawn; Vandin, Fabio; Haffari, Gholamreza; Collins, Colin C.; Sahinalp, S. Cenk

2017-01-01

Prioritizing molecular alterations that act as drivers of cancer remains a crucial bottleneck in therapeutic development. Here we introduce HIT'nDRIVE, a computational method that integrates genomic and transcriptomic data to identify a set of patient-specific, sequence-altered genes, with sufficient collective influence over dysregulated transcripts. HIT'nDRIVE aims to solve the “random walk facility location” (RWFL) problem in a gene (or protein) interaction network, which differs from the standard facility location problem by its use of an alternative distance measure: “multihitting time,” the expected length of the shortest random walk from any one of the set of sequence-altered genes to an expression-altered target gene. When applied to 2200 tumors from four major cancer types, HIT'nDRIVE revealed many potentially clinically actionable driver genes. We also demonstrated that it is possible to perform accurate phenotype prediction for tumor samples by only using HIT'nDRIVE-seeded driver gene modules from gene interaction networks. In addition, we identified a number of breast cancer subtype-specific driver modules that are associated with patients’ survival outcome. Furthermore, HIT'nDRIVE, when applied to a large panel of pan-cancer cell lines, accurately predicted drug efficacy using the driver genes and their seeded gene modules. Overall, HIT'nDRIVE may help clinicians contextualize massive multiomics data in therapeutic decision making, enabling widespread implementation of precision oncology. PMID:28768687

Investigating the correlation between wastewater analysis and roadside drug testing in South Australia.

PubMed

Bade, Richard; Tscharke, Benjamin J; Longo, Marie; Cooke, Richard; White, Jason M; Gerber, Cobus

2018-06-01

The societal impact of drug use is well known. An example is when drug-intoxicated drivers increase the burden on policing and healthcare services. This work presents the correlation of wastewater analysis (using UHPLC-MS/MS) and positive roadside drug testing results for methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and cannabis from December 2011-December 2016 in South Australia. Methamphetamine and MDMA showed similar trends between the data sources with matching increases and decreases, respectively. Cannabis was relatively steady based on wastewater analysis, but the roadside drug testing data started to diverge in the final part of the measurement period. The ability to triangulate data as shown here validates both wastewater analysis and roadside drug testing. This suggests that changes in overall population drug use revealed by WWA is consistent and proportional with changes in drug-driving behaviours. The results show that, at higher levels of drug use as measured by wastewater analysis, there is an increase in drug driving in the community and therefore more strain on health services and police. Copyright © 2018 Elsevier B.V. All rights reserved.

Drug spend and acquisitive offending by substance misusers.

PubMed

Hayhurst, Karen P; Jones, Andrew; Millar, Tim; Pierce, Matthias; Davies, Linda; Weston, Samantha; Donmall, Michael

2013-06-01

The need to generate income to fund drug misuse is assumed to be a driver of involvement in acquisitive crime. We examined the influence of drug misuse expenditure, and other factors, on acquisitive offending. Clients (N=1380) seeking drug treatment within 94 of 149 Drug Action Teams (DATs) across England completed a comprehensive survey, incorporating validated scales and self-report measures, such as levels of drug and alcohol use and offending. Forty per cent (N=554) had committed acquisitive crime in the previous month. Regression analysis showed that acquisitive offending was associated with the presence of problematic use of crack cocaine, poly-drug use, sharing injecting equipment, unsafe sex, overdose risk, higher drug spend, unemployment, reduced mental wellbeing, and younger age. Rates of acquisitive crime among drug users are high. Drug using offenders can be distinguished from drug using non-offenders by problematic crack cocaine use, younger age, income-related factors, and indicators of a chaotic life style and complex needs. Behavioural and demographic factors were associated more strongly with acquisitive crime than drug use expenditure, suggesting that the need to finance drug use is not necessarily the main factor driving acquisitive offending by drug users. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Blood concentrations of new designer benzodiazepines in forensic cases.

PubMed

Høiseth, Gudrun; Tuv, Silja Skogstad; Karinen, Ritva

2016-11-01

A number of new designer benzodiazepines have reached the illegal drug market over the past years. Toxicological interpretation of concentrations of these drugs in blood is quite challenging as very limited human data have previously been published. The aim of this study was to report blood concentrations of new designer benzodiazepines in a population of drugged drivers as well as some other criminal offenders, and to relate this to clinical impairment. The present material represents cases involving new designer benzodiazepines (clonazolam, diclazepam, flubromazepam, flubromazolam and pyrazolam) and etizolam, submitted for analyses during the period July 1, 2013-May 31, 2016. Analyses were performed using an ultra-performance liquid chromatography-tandem mass spectrometry method. Blood concentrations and results from the clinical test of impairment are reported. New designer benzodiazepines were detected in 77 cases during the study period. The median (range) concentrations were 0.012mg/L (0.00048-0.10) for flubromazolam (n=25), 0.055mg/L (0.0047-1.2) for flubromazepam (n=24), 0.013mg/L (0.0021-0.057) for diclazepam (n=15), 0.050mg/L (0.019-0.17) for etizolam (n=14), 0.0053mg/L (0.0019-0.011) for clonazolam (n=7) and 0.074mg/L for pyrazolam (n=1). In six cases, designer benzodiazepines were the only drugs detected in blood, and in two of those cases, the physician had given the conclusion of "considerably impaired" upon performing the clinical test for impairment. Given the lack of previously published data on human concentrations, results presented in this study could be helpful in interpretation of blood concentrations of new designer benzodiazepines. This is crucial for the assessment of the importance of toxicological results in suspected drugged drivers, rape victims, etc. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Alcohol use, illicit drug use, and road rage.

PubMed

Fierro, Inmaculada; Morales, Claudia; Alvarez, F Javier

2011-03-01

This article examines the relationship between the consumption of alcohol and illicit drugs and the experience of road-rage victimization and perpetration among drivers and nondrivers in the general population. A cross-sectional survey was designed with 2,500 subjects, ages 14-70 years, living in Castile and León, Spain, of which 1,276 (51 %) were males and 1,224 (49%) females. The Alcohol-Use And Drug-Use Survey of Castile and León, Spain 2008 focused on patterns of alcohol, tobacco, and illicit drug consumption. Potential risk factors for road-rage experience for the previous 12 months was assessed, including sociodemographics (7 variables), patterns of alcohol consumption (7 variables), and patterns of drug consumption (10 variables). Among drivers, driving under the influence of alcohol and/or cannabis during the previous year was associated with being a perpetrator of road rage (odds ratio [OR] = 3.72, 95% CI [1.71, 8.10] and 6.77 [1.55, 29.48], respectively), being both a victim and perpetrator of road rage (OR = 1.80 [1.05, 3.07] for alcohol, 5.34 [1.64, 17.41] for cannabis, and 4.81 [1.09, 21.16] for alcohol and cannabis), and with serious road-rage perpetration (OR = 4.97 [2.40, 10.30] for alcohol and 17.75 [5.88, 53.56] for cannabis). Problem drinking (CAGE scores ≥ 2) was associated with being both a victim and perpetrator of road rage (OR = 2.74 [1.67, 4.50]) and with low (OR = 1.77 [1.09, 2.85]) and serious (OR = 3.47 [1.65, 7.30]) road-rage perpetration. Driving under the influence of alcohol or cannabis and being a problem drinker are associated with the perpetration of serious road-rage behavior, as well as experiencing road-rage victimization and perpetration.

Ventilation and Heart Rate Monitoring in Drivers using a Contactless Electrical Bioimpedance System

NASA Astrophysics Data System (ADS)

Macías, R.; García, M. A.; Ramos, J.; Bragós, R.; Fernández, M.

2013-04-01

Nowadays, the road safety is one of the most important priorities in the automotive industry. Many times, this safety is jeopardized because of driving under inappropriate states, e.g. drowsiness, drugs and/or alcohol. Therefore several systems for monitoring the behavior of subjects during driving are researched. In this paper, a device based on a contactless electrical bioimpedance system is shown. Using the four-wire technique, this system is capable of obtaining the heart rate and the ventilation of the driver through multiple textile electrodes. These textile electrodes are placed on the car seat and the steering wheel. Moreover, it is also reported several measurements done in a controlled environment, i.e. a test room where there are no artifacts due to the car vibrations or the road state. In the mentioned measurements, the system response can be observed depending on several parameters such as the placement of the electrodes or the number of clothing layers worn by the driver.

The study of possible influences of licit and illicit drugs on driver behavior

DOT National Transportation Integrated Search

1971-12-01

Study authors were S. William Berg, M.D., John T. Fryback, A.B.; Donald M. Goldenbaum, Ph.D.; Ralph K. Jones, B.S.; Kent B. Joscelyn, J.D.; Roger P. Maickel, Ph.D.; William Z. Potter, M.D.; and Joseph Zabik, M.S. The study investigated the relationsh...

78 FR 68074 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-13

...). Background and Brief Description In 2009, drug overdose deaths became the leading cause of injury death in the United States (U.S.), exceeding motor vehicle traffic crash deaths for the first time, a trend... the main driver of this increase. The number of overdose deaths per year involving opioid pain...

Analysis of MDPV in blood--determination and interpretation.

PubMed

Adamowicz, Piotr; Gil, Dominika; Skulska, Agnieszka; Tokarczyk, Bogdan

2013-06-01

3,4-Methylenedioxypyrovalerone (MDPV) is a cathinone derivative. It has recently been classified as a controlled substance in many countries. This substance is a stimulant that can be snorted, smoked or taken orally. MDPV has been determined in biological material from four cases sent to the Institute of Forensic Research in 2011. In the first case, a passenger car crashed into a truck; the driver of the vehicle suffered severe injuries, resulting in his death. In the second case, biological material was obtained from the decedent male individual, who did not wake up after a party. In the two cases, the material was secured on suspicion of the possession of narcotic drugs or psychotropic substances, in which the suspects admitted to using "legal highs." The MDPV blood concentrations of the deceased driver and deceased man were 38 and 17 ng/mL, respectively. In the two other cases, the determined concentrations were 306 and 124 ng/mL. However, MDPV was not the sole substance detected in these cases: in each, other drugs were also determined. Analyses of blood were conducted using liquid chromatography-tandem mass spectrometry.

Systematic review on the evaluation criteria of orphan medicines in Central and Eastern European countries.

PubMed

Zelei, Tamás; Molnár, Mária J; Szegedi, Márta; Kaló, Zoltán

2016-06-04

In case of orphan drugs applicability of the standard health technology assessment (HTA) process is limited due to scarcity of good clinical and health economic evidence. Financing these premium priced drugs is more controversial in the Central and Eastern European (CEE) region where the public funding resources are more restricted, and health economic justification should be an even more important aspect of policy decisions than in higher income European countries. To explore and summarize the recent scientific evidence on value drivers related to the health technology assessment of ODs with a special focus on the perspective of third party payers in CEE countries. The review aims to list all potentially relevant value drivers in the reimbursement process of orphan drugs. A systematic literature review was performed; PubMed and Scopus databases were systematically searched for relevant publications until April 2015. Extracted data were summarized along key HTA elements. From the 2664 identified publications, 87 contained relevant information on the evaluation criteria of orphan drugs, but only 5 had direct information from the CEE region. The presentation of good clinical evidence seems to play a key role especially since this should be the basis of cost-effectiveness analyses, which have more importance in resource-constrained economies. Due to external price referencing of pharmaceuticals, the relative budget impact of orphan drugs is expected to be higher in CEE than in Western European (WE) countries unless accessibility of patients remains more limited in poorer European regions. Equity principles based on disease prevalence and non-availability of alternative treatment options may increase the price premium, however, societies must have some control on prices and a rationale based on multiple criteria in reimbursement decisions. The evaluation of orphan medicines should include multiple criteria to appropriately measure the clinical added value of orphan drugs. The search found only a small number of studies coming from CEE, therefore European policies on orphan drugs may be based largely on experiences in WE countries. More research should be done in the future in CEE because financing high-priced orphan drugs involves a greater burden for these countries.

Identification of critical regulatory genes in cancer signaling network using controllability analysis

NASA Astrophysics Data System (ADS)

Ravindran, Vandana; Sunitha, V.; Bagler, Ganesh

2017-05-01

Cancer is characterized by a complex web of regulatory mechanisms which makes it difficult to identify features that are central to its control. Molecular integrative models of cancer, generated with the help of data from experimental assays, facilitate use of control theory to probe for ways of controlling the state of such a complex dynamic network. We modeled the human cancer signaling network as a directed graph and analyzed it for its controllability, identification of driver nodes and their characterization. We identified the driver nodes using the maximum matching algorithm and classified them as backbone, peripheral and ordinary based on their role in regulatory interactions and control of the network. We found that the backbone driver nodes were key to driving the regulatory network into cancer phenotype (via mutations) as well as for steering into healthy phenotype (as drug targets). This implies that while backbone genes could lead to cancer by virtue of mutations, they are also therapeutic targets of cancer. Further, based on their impact on the size of the set of driver nodes, genes were characterized as indispensable, dispensable and neutral. Indispensable nodes within backbone of the network emerged as central to regulatory mechanisms of control of cancer. In addition to probing the cancer signaling network from the perspective of control, our findings suggest that indispensable backbone driver nodes could be potentially leveraged as therapeutic targets. This study also illustrates the application of structural controllability for studying the mechanisms underlying the regulation of complex diseases.

Relationship of aggression, negative affect, substance use problems, and childhood delinquency to DWI recidivism.

PubMed

Linn, Braden K; Nochajski, Thomas; Wieczorek, William

2016-01-01

Driving under the influence remains a pervasive problem. Approximately 30% of those arrested for impaired driving offenses each year are repeat offenders, suggesting that current rehabilitative efforts are not sufficiently effective for reducing driving while intoxicated (DWI) recidivism. Aggression, negative affect, substance use problems, and childhood delinquency have been noted in the population of impaired drivers, but study of these variables on recidivism has been limited. The aim of the current study was to examine the effects of aggression, negative affect, substance use problems, and childhood delinquency on DWI recidivism among first time offenders. In 1992, 6436 individuals in impaired driver programs in New York State were surveyed. A total of 3511 individuals provided names so that state driver abstracts could be reviewed in the future. A total of 2043 matches were found and 1770 remained after excluding those with previous DWI convictions. Driver records were reviewed in 2010 and 2012, providing between 18 and 20 years of follow-up. During the follow-up period, 16.5% of individuals were arrested for an impaired driving offense. Multivariate analysis suggested that recidivism was a function of several problems, including: alcohol problem severity, aggression, negative affect, drug problem severity, criminal history, and childhood delinquency. Impaired driving programs should assess for childhood delinquency, aggressive tendencies, and negative affect as these constructs, along with substance use, are evident among impaired drivers who recidivate. Interventions addressing aggression and negative affect may ultimately prove useful in reducing recidivism.

Cell Death Pathways in Mutant Rhodopsin Rat Models Identifies Genotype-Specific Targets Controlling Retinal Degeneration.

PubMed

Viringipurampeer, Ishaq A; Gregory-Evans, Cheryl Y; Metcalfe, Andrew L; Bashar, Emran; Moritz, Orson L; Gregory-Evans, Kevin

2018-06-18

Retinitis pigmentosa (RP) is a group of inherited neurological disorders characterized by rod photoreceptor cell death, followed by secondary cone cell death leading to progressive blindness. Currently, there are no viable treatment options for RP. Due to incomplete knowledge of the molecular signaling pathways associated with RP pathogenesis, designing therapeutic strategies remains a challenge. In particular, preventing secondary cone photoreceptor cell loss is a key goal in designing potential therapies. In this study, we identified the main drivers of rod cell death and secondary cone loss in the transgenic S334ter rhodopsin rat model, tested the efficacy of specific cell death inhibitors on retinal function, and compared the effect of combining drugs to target multiple pathways in the S334ter and P23H rhodopsin rat models. The primary driver of early rod cell death in the S334ter model was a caspase-dependent process, whereas cone cell death occurred though RIP3-dependent necroptosis. In comparison, rod cell death in the P23H model was via necroptotic signaling, whereas cone cell loss occurred through inflammasome activation. Combination therapy of four drugs worked better than the individual drugs in the P23H model but not in the S334ter model. These differences imply that treatment modalities need to be tailored for each genotype. Taken together, our data demonstrate that rationally designed genotype-specific drug combinations will be an important requisite to effectively target primary rod cell loss and more importantly secondary cone survival.

Common mental disorders in public transportation drivers in Lima, Peru.

PubMed

Ruiz-Grosso, Paulo; Ramos, Mariana; Samalvides, Frine; Vega-Dienstmaier, Johann; Kruger, Hever

2014-01-01

Traffic related injuries are leading contributors to burden of disease worldwide. In developing countries a high proportion of them can be attributed to public transportation vehicles. Several mental disorders including alcohol and drug abuse, psychotic disorders, mental stress, productivity pressure, and low monetary income were found predictors of high rates of traffic related injuries in public transportation drivers. The goal of this study was to estimate the prevalence of common mental disorders in the population of public transportation drivers of buses and rickshaws in Lima, Peru. Cross sectional study. A sample of bus and rickshaw drivers was systematically selected from formal public transportation companies using a snowball approach. Participants completed self-administered questionnaires for assessing major depressive episode, anxiety symptoms, alcohol abuse, and burnout syndrome. Socio demographic information was also collected. The analyses consisted of descriptive measurement of outcomes taking into account both between and within cluster standard deviation (BCSD and WCSD). A total of 278 bus and 227 rickshaw drivers out of 25 companies agreed to participate in the study. BCSD for major depressive episode, anxiety symptoms and burnout syndrome was not found significant (p>0.05). The estimated prevalence of each variable was 13.7% (IC95%: 10.7-16.6%), 24.1% (IC95%: 19.4-28.8%) and 14.1% (IC95%: 10.8-17.4%) respectively. The estimated prevalence of alcohol abuse was 75.4% (IC95%: 69-81.7%, BCSD = 12.2%, WCSD = 41.9%, intra class correlation (ICC): 7.8%). Common mental disorders such as alcohol abuse, major depressive episode, anxiety symptoms and burnout syndrome presented higher rates in public transportation drivers than general population.

Roadside opioid testing of drivers using oral fluid: the case of a country with a zero tolerance law, Spain.

PubMed

Fierro, Inmaculada; Colás, Mónica; González-Luque, Juan Carlos; Álvarez, F Javier

2017-05-10

Opioids can impair psychomotor performance, and driving under the influence of opioids is associated with an increased risk of accidents. The goals of this study were i) to determine the prevalence of opioids (heroin, morphine, codeine, methadone and tramadol) in Spanish drivers and ii) to explore the presence of opioids, more specifically whether they are used alone or in combination with other drugs. The 2008/9 DRUID database regarding Spain was used, which provided information on 3302 drivers. All drivers included in the study provided a saliva sample and mass-chromatographic analyses were carried out in all cases. To determine the prevalence, the sample was weighted according to traffic intensity. In the case of opioid use combinations, the sample was not weighted. The detection limit for each substance was considered a positive result. The prevalence of opioids in Spanish drivers was 1.8% (95% CI, 1.4-2.3). Polydrug detection was common (56.2%): of these, in two out of three cases, two opioids were detected and cocaine was also detected in 86% of the cases. The concentration (median [Q1-Q3] ng/ml) of the substances was low: methadone 1.71 [0.10-15.30], codeine 40.55 [2.10-120.77], 6-acetylmorphine 5.71 [1.53-84.05], and morphine 37.40 [2.84-200.00]. Morphine was always detected with 6-acetylmorphine (heroin use). Driving under the influence of opioids is relatively infrequent, but polydrug use is common. Our study shows that 6 out of 10 drivers with methadone in their OF (likely in methadone maintenance programs) are using other substances. This should be taken into account by health professionals in order to properly inform patients about the added risks of mixing substances when driving.

Clinical and health care aspects of respiratory tract disorders in Poland.

PubMed

Kanecki, Krzysztof; Zycinska, Katarzyna; Tyszko, Piotr

2016-01-01

Respiratory diseases constitute a public health priority worldwide. This is related to the increasing exposure to microorganisms, toxic factors, allergens, drugs and smoking, as the most important factors. Increasing costs of health promotion, prevention, diagnosis and treatment of respiratory tract diseases forces the search for effective strategies in the reduction of costs without making a significant impact of these activities on health results. Chronic obstructive pulmonary disease (COPD) is an example of these diseases with increasing incidence, which has few known modifiable factors and absorbs large medical and social costs. The aim of this study is to present the conception of cost driver analysis that could be useful in constructing a good combination of the EBM-based treatment with cost reduction decisions. Analysis of cost drivers was based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and Polish recommendations of COPD diagnosis and treatment. The proposition of cost reduction strategy in COPD treatment was based on identification of cost drivers in value chain conception. An increasing incidence and treatment costs of COPD force the search for methods of costs reduction in health care. Identifying, evaluating and modifying the cost drivers with use of the value chain conception could be an effective method in achieving these objectives.

Drug use as a driver of HIV Risks: Re-emerging and emerging issues

PubMed Central

El-Bassel, Nabila; Shaw, Stacey A.; Dasgupta, Anindita; Strathdee, Steffanie A.

2014-01-01

Purpose of Review We reviewed papers published in 2012–2013 that focused on re-emerging and emerging injection and non-injection drug use trends driving HIV risk behaviors and transmission in some parts of the world. Recent Findings While HIV incidence has declined in many countries, HIV epidemics remain at troubling levels among key drug using populations including females who inject drugs (FWID), FWID who trade sex, sex partners of people who inject drugs (SP-PWID), young PWID, and people who use non-injection drugs in a number of low- and middle- income countries such as in Central Asia, Eastern Europe, Southeast Asia, and parts of Africa. Summary HIV epidemics occur within contexts of global economic and political forces, including poverty, human rights violations, discrimination, drug policies, trafficking, and other multi-level risk environments. Trends of injection and non-injection drug use and risk environments driving HIV epidemics in Central Asia, Eastern Europe, Southeast Asia, and parts of Africa call for political will to improve HIV and substance use service delivery, access to combination HIV prevention, and harm reduction programs. PMID:24406532

The evolving drug development landscape: from blockbusters to niche busters in the orphan drug space.

PubMed

Kumar Kakkar, Ashish; Dahiya, Neha

2014-06-01

Strategy, Management and Health Policy Large pharmaceutical companies have traditionally focused on the development of blockbuster drugs that target disease states with large patient populations. However, with large-scale patent expirations and competition from generics and biosimilars, anemic pipelines, escalating clinical trial costs, and global health-care reform, the blockbuster model has become less viable. Orphan drug initiatives and the incentives accompanied by these have fostered renewed research efforts in the area of rare diseases and have led to the approval of more than 400 orphan products. Despite targeting much smaller patient populations, the revenue-generating potential of orphan drugs has been shown to be huge, with a greater return on investment than non-orphan drugs. The success of these "niche buster" therapeutics has led to a renewed interest from "Big Pharma" in the rare disease landscape. This article reviews the key drivers for orphan drug research and development, their profitability, and issues surrounding the emergence of large pharmaceutical firms into the orphan drug space. © 2014 Wiley Periodicals, Inc.

The combined effects of alcohol and cannabis on driving: Impact on crash risk.

PubMed

Dubois, Sacha; Mullen, Nadia; Weaver, Bruce; Bédard, Michel

2015-03-01

Driving under the influence of alcohol or cannabis alone is associated with increased crash risk. This study explores the combined influence of low levels of alcohol (BAC≤0.08) and cannabis on crash risk. Drivers aged 20 years or older who had been tested for both drugs and alcohol after involvement in a fatal crash in the United States (1991-2008) were examined using a case-control design. Cases were drivers with at least one potentially unsafe driving action (UDA) recorded in relation to the crash (e.g., weaving); controls had none recorded. We examined the prevalence of driving under the influence of alcohol, cannabis, and both agents, for drivers involved in a fatal crash. Adjusted odds ratios of committing an UDA for alcohol alone, THC alone, and their combined effect were computed via logistic regression and adjusted for a number of potential confounders. Over the past two decades, the prevalence of THC and alcohol in car drivers involved in a fatal crash has increased approximately five-fold from below 2% in 1991 to above 10% in 2008. Each 0.01 BAC unit increased the odds of an UDA by approximately 9-11%. Drivers who were positive for THC alone had 16% increased odds of an UDA. When alcohol and THC were combined the odds of an UDA increased by approximately 8-10% for each 0.01 BAC unit increase over alcohol or THC alone. Drivers positive for both agents had greater odds of making an error than drivers positive for either alcohol or cannabis only. Further research is needed to better examine the interaction between cannabis concentration levels, alcohol, and driving. This research would support enforcement agencies and public health educators by highlighting the combined effect of cannabis at low BAC levels. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Manual control analysis of drug effects on driving performance

NASA Technical Reports Server (NTRS)

Smiley, A.; Ziedman, K.; Moskowitz, H.

1981-01-01

The effects of secobarbital, diazepam, alcohol, and marihuana on car-driver transfer functions obtained using a driving simulator were studied. The first three substances, all CNS depressants, reduced gain, crossover frequency, and coherence which resulted in poorer tracking performance. Marihuana also impaired tracking performance but the only effect on the transfer function parameters was to reduce coherence.

32 CFR 634.12 - Army administrative actions against intoxicated drivers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... or being in physical control of a motor vehicle on post when the blood alcohol content is 0.08... violation of the law of the State involved. (4) Driving, or being in physical control of a motor vehicle... drugs. (b) Review by the commander of the service records of active duty soldiers apprehended for...

Safe Rides: A Controlled Investigation in Two Major California Cities.

ERIC Educational Resources Information Center

Caudill, Barry D.; And Others

This study was designed to examine the community impact from introducing free alternative transportation for the drunk/drugged driver in two California cities. Baseline data were obtained in February of 1988 from 1,522 bar and nightclub patrons in Sacramento and San Jose, California. Over one-half of the respondents had consumed alcohol before…

Alcohol- and Drug-Involved Driving in the United States: Methodology for the 2007 National Roadside Survey

PubMed Central

Lacey, John H.; Kelley-Baker, Tara; Voas, Robert B.; Romano, Eduardo; Furr-Holden, C. Debra; Torres, Pedro; Berning, Amy

2013-01-01

This article describes the methodology used in the 2007 U.S. National Roadside Survey to estimate the prevalence of alcohol- and drug-impaired driving and alcohol- and drug-involved driving. This study involved randomly stopping drivers at 300 locations across the 48 continental U.S. states at sites selected through a stratified random sampling procedure. Data were collected during a 2-hour Friday daytime session at 60 locations and during 2-hour nighttime weekend periods at 240 locations. Both self-report and biological measures were taken. Biological measures included breath alcohol measurements from 9,413 respondents, oral fluid samples from 7,719 respondents, and blood samples from 3,276 respondents. PMID:21997324

LABONFOIL: investigations regarding microfluidic skin patches for drug detection using flexible OLEDs

NASA Astrophysics Data System (ADS)

Scholles, M.; Kroker, L.; Vogel, U.; Krüger, J.; Walczak, R.; Ruano-Lopez, J.

2010-02-01

This contribution describes first results concerning the overall and especially optical system design of microfluidic skin patches for drug detection based on fluorescence analysis of sweat samples. This work has been carried out within the European project LABONFOIL which aims to develop low-cost lab-on-chip systems for four different applications, one of them for the detection of cocaine abuse by professional drivers. To date work has focused on the integrated design of the skin patch itself including methods for sweat collection as well as studies concerning the feasibility of OLEDs for optical excitation of the fluorescence signal.

Precision medicine in the age of big data: The present and future role of large-scale unbiased sequencing in drug discovery and development.

PubMed

Vicini, P; Fields, O; Lai, E; Litwack, E D; Martin, A-M; Morgan, T M; Pacanowski, M A; Papaluca, M; Perez, O D; Ringel, M S; Robson, M; Sakul, H; Vockley, J; Zaks, T; Dolsten, M; Søgaard, M

2016-02-01

High throughput molecular and functional profiling of patients is a key driver of precision medicine. DNA and RNA characterization has been enabled at unprecedented cost and scale through rapid, disruptive progress in sequencing technology, but challenges persist in data management and interpretation. We analyze the state-of-the-art of large-scale unbiased sequencing in drug discovery and development, including technology, application, ethical, regulatory, policy and commercial considerations, and discuss issues of LUS implementation in clinical and regulatory practice. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Drug and alcohol-impaired driving among electronic music dance event attendees

PubMed Central

Furr-Holden, Debra; Voas, Robert B.; Kelley-Baker, Tara; Miller, Brenda

2011-01-01

Background Drug-impaired driving has received increased attention resulting from development of rapid drug-screening procedures used by police and state laws establishing per se limits for drug levels in drivers. Venues that host electronic music dance events (EMDEs) provide a unique opportunity to assess drug-impaired driving among a high proportion of young adult drug users. EMDEs are late-night dance parties marked by a substantial number of young adult attendees and elevated drug involvement. No studies to date have examined drug-impaired driving in a natural environment with active drug and alcohol users. Methods Six EMDEs were sampled in San Diego, California, and Baltimore, Maryland. A random sample of approximately 40 attendees per event were administered surveys about alcohol and other drug (AOD) use and driving status, given breath tests for alcohol, and asked to provide oral fluid samples to test for illicit drug use upon entering and exiting the events. Results Driving status reduced the level of alcohol use (including abstaining) but the impact on drug-taking was not significant. However, 62% of individuals who reported their intention to drive away from the events were positive for drugs or alcohol upon leaving. This suggests that these events and settings are appropriate ones for developing interventions for reducing risks for young adults. PMID:16675160

Drug and alcohol-impaired driving among electronic music dance event attendees.

PubMed

Furr-Holden, Debra; Voas, Robert B; Kelley-Baker, Tara; Miller, Brenda

2006-10-15

Drug-impaired driving has received increased attention resulting from development of rapid drug-screening procedures used by police and state laws establishing per se limits for drug levels in drivers. Venues that host electronic music dance events (EMDEs) provide a unique opportunity to assess drug-impaired driving among a high proportion of young adult drug users. EMDEs are late-night dance parties marked by a substantial number of young adult attendees and elevated drug involvement. No studies to date have examined drug-impaired driving in a natural environment with active drug and alcohol users. Six EMDEs were sampled in San Diego, California, and Baltimore, Maryland. A random sample of approximately 40 attendees per event were administered surveys about alcohol and other drug (AOD) use and driving status, given breath tests for alcohol, and asked to provide oral fluid samples to test for illicit drug use upon entering and exiting the events. Driving status reduced the level of alcohol use (including abstaining) but the impact on drug-taking was not significant. However, 62% of individuals who reported their intention to drive away from the events were positive for drugs or alcohol upon leaving. This suggests that these events and settings are appropriate ones for developing interventions for reducing risks for young adults.

Intensive care unit drug costs in the context of total hospital drug expenditures with suggestions for targeted cost containment efforts.

PubMed

Altawalbeh, Shoroq M; Saul, Melissa I; Seybert, Amy L; Thorpe, Joshua M; Kane-Gill, Sandra L

2018-04-01

To assess costs of intensive care unit (ICU) related pharmacotherapy relative to hospital drug expenditures, and to identify potential targets for cost-effectiveness investigations. We offer the unique advantage of comparing ICU drug costs with previously published data a decade earlier to describe changes over time. Financial transactions for all ICU patients during fiscal years (FY) 2009-2012 were retrieved from the hospital's data repository. ICU drug costs were evaluated for each FY. ICU departments' charges were also retrieved and calculated as percentages of total ICU charges. Albumin, prismasate (dialysate), voriconazole, factor VII and alteplase denoted the highest percentages of ICU drug costs. ICU drug costs contributed to an average of 31% (SD 1.0%) of the hospital's total drug costs. ICU drug costs per patient day increased by 5.8% yearly versus 7.8% yearly for non-ICU drugs. This rate was higher for ICU drugs costs at 12% a decade previous. Pharmacy charges contributed to 17.7% of the total ICU charges. Growth rates of costs per year have declined but still drug expenditures in the ICU are consistently a significant driver in this resource intensive environment with a high impact on hospital drug expenditures. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacokinetic drivers of toxicity for basic molecules: Strategy to lower pKa results in decreased tissue exposure and toxicity for a small molecule Met inhibitor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diaz, Dolores, E-mail: diaz.dolores@gene.com; Ford, Kevin A.; Hartley, Dylan P.

Several toxicities are clearly driven by free drug concentrations in plasma, such as toxicities related to on-target exaggerated pharmacology or off-target pharmacological activity associated with receptors, enzymes or ion channels. However, there are examples in which organ toxicities appear to correlate better with total drug concentrations in the target tissues, rather than with free drug concentrations in plasma. Here we present a case study in which a small molecule Met inhibitor, GEN-203, with significant liver and bone marrow toxicity in preclinical species was modified with the intention of increasing the safety margin. GEN-203 is a lipophilic weak base as demonstratedmore » by its physicochemical and structural properties: high LogD (distribution coefficient) (4.3) and high measured pKa (7.45) due to the basic amine (N-ethyl-3-fluoro-4-aminopiperidine). The physicochemical properties of GEN-203 were hypothesized to drive the high distribution of this compound to tissues as evidenced by a moderately-high volume of distribution (Vd > 3 l/kg) in mouse and subsequent toxicities of the compound. Specifically, the basicity of GEN-203 was decreased through addition of a second fluorine in the 3-position of the aminopiperidine to yield GEN-890 (N-ethyl-3,3-difluoro-4-aminopiperidine), which decreased the volume of distribution of the compound in mouse (Vd = 1.0 l/kg), decreased its tissue drug concentrations and led to decreased toxicity in mice. This strategy suggests that when toxicity is driven by tissue drug concentrations, optimization of the physicochemical parameters that drive tissue distribution can result in decreased drug concentrations in tissues, resulting in lower toxicity and improved safety margins. -- Highlights: ► Lower pKa for a small molecule: reduced tissue drug levels and toxicity. ► New analysis tools to assess electrostatic effects and ionization are presented. ► Chemical and PK drivers of toxicity can be leveraged to improve safety.« less

[Analysis of tools, methods and results of toxicological screening for detection of drug abuse in Italian professional drivers].

PubMed

Rosso, G L

2013-01-01

Three years after a protocol agreement between the State and the Regions came into force in 2008 (drug testing at the workplace Law) a large number of studies have been conducted to analyse and test the efficacy of on-site screening tests for detection of drug consumption (opiates, cocaine, cannabinoids, amphetamine and methamphetamine, MDMA and methadone), which are frequently used by the occupational health physician, and also to present data resulting from workplace drug testing obtained during health surveillance programmes. The aim of the present study was to verify whether the features of sensitivity and specificity of the most common on-site testing ensure correct application of the provisions of current Italian legislation and also to analyse published studies showing the frequency of positive drug testing. A review of Italian and international literature was carried out aimed at identifying studies relating to: (1) performance of on-site screening tests frequently used by the occupational health physician, (2) prevalence of drug use/abuse among Italian public and commercial transport drivers. A comparison between the studies was then carried out. Several rapid on-site screening tests are commercially available (Italian law does not provide standards for the technical specifications of the tests), the sensitivity and specificity of which varies depending on the model and the substance tested. The sensitivity of these tools is poor when used for the detection of low concentrations of drugs and/or their metabolites in urine (close to the cut-off). Studies are lacking that compare on-site tests performed by the occupational health physician and confirmative tests in specialized laboratories (with particular regard to false positives found by the occupational health physician). The major studies in terms of methods and/or size reported a positive rate (confirmed at the first level) between 1.6% and 1.9%. The drugs most frequently used/abused were cannabis and cocaine. The performance of on-site screening tests (to detect psychotropic substances on urine matrix) and the methodology required by Italian law show that the aims of Italian workplace drug testing legislation have not been achieved The low positive rate observed in Italian studies could be due to an error in the first phase of screening performed by the occupational health physician.

Identification of a Non-Gatekeeper Hot Spot for Drug-Resistant Mutations in mTOR Kinase.

PubMed

Wu, Tzung-Ju; Wang, Xiaowen; Zhang, Yanjie; Meng, Linghua; Kerrigan, John E; Burley, Stephen K; Zheng, X F Steven

2015-04-21

Protein kinases are therapeutic targets for human cancer. However, "gatekeeper" mutations in tyrosine kinases cause acquired clinical resistance, limiting long-term treatment benefits. mTOR is a key cancer driver and drug target. Numerous small-molecule mTOR kinase inhibitors have been developed, with some already in human clinical trials. Given our clinical experience with targeted therapeutics, acquired drug resistance in mTOR is thought likely, but not yet documented. Herein, we describe identification of a hot spot (L2185) for drug-resistant mutations, which is distinct from the gatekeeper site, and a chemical scaffold refractory to drug-resistant mutations. We also provide new insights into mTOR kinase structure and function. The hot spot mutations are potentially useful as surrogate biomarkers for acquired drug resistance in ongoing clinical trials and future treatments and for the design of the next generation of mTOR-targeted drugs. Our study provides a foundation for further research into mTOR kinase function and targeting. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The EML4-ALK oncogene: targeting an essential growth driver in human cancer.

PubMed

Mano, Hiroyuki

2015-01-01

Targeting of essential growth drivers represents an ideal approach to cancer treatment. To identify such molecules in clinical specimens, we developed a highly sensitive functional screening system based on the preparation of retroviral cDNA expression libraries. By screening such a library of lung adenocarcinoma with a focus formation assay, we discovered the EML4-ALK fusion-type oncogene. A small chromosomal inversion thus leads to fusion of the amino-terminal portion of the microtubule-associated protein EML4 to the intracellular kinase domain of ALK, a receptor-type protein tyrosine kinase. Constitutive dimerization of EML4-ALK mediated by a dimerization motif of EML4 results in kinase activation. Specific inhibitors of the kinase activity of ALK have been developed as therapeutic drugs for EML4-ALK-positive lung cancer, three of which (crizotinib, ceritinib, and alectinib) have already been approved for clinical use. An overall clinical response rate of 93.5% for alectinib has shown that agents that target essential growth drivers can become magic bullets for cancer treatment.

The EML4-ALK oncogene: targeting an essential growth driver in human cancer

PubMed Central

MANO, Hiroyuki

2015-01-01

Targeting of essential growth drivers represents an ideal approach to cancer treatment. To identify such molecules in clinical specimens, we developed a highly sensitive functional screening system based on the preparation of retroviral cDNA expression libraries. By screening such a library of lung adenocarcinoma with a focus formation assay, we discovered the EML4-ALK fusion-type oncogene. A small chromosomal inversion thus leads to fusion of the amino-terminal portion of the microtubule-associated protein EML4 to the intracellular kinase domain of ALK, a receptor-type protein tyrosine kinase. Constitutive dimerization of EML4-ALK mediated by a dimerization motif of EML4 results in kinase activation. Specific inhibitors of the kinase activity of ALK have been developed as therapeutic drugs for EML4-ALK–positive lung cancer, three of which (crizotinib, ceritinib, and alectinib) have already been approved for clinical use. An overall clinical response rate of 93.5% for alectinib has shown that agents that target essential growth drivers can become magic bullets for cancer treatment. PMID:25971657

Did Ontario's Zero Tolerance & Graduated Licensing Law Reduce Youth Drunk Driving?

ERIC Educational Resources Information Center

Carpenter, Christopher

2006-01-01

On April 1, 1994, Ontario, Canada, instituted a new graduated driver license (GDL) system that effectively set the legal blood alcohol content (BAC) threshold at zero for the first few years of a youth's driving eligibility. I use data from the 1983-2001 Ontario Student Drug Use Surveys (OSDUS) to examine whether the Zero Tolerance (ZT) policy…

Peculiarities of US Border Guard Officers' Training at the Federal Law Enforcement Training Center Using Online Campus

ERIC Educational Resources Information Center

Bloshchynskyi, Ihor

2015-01-01

Professional training of future US border guard officers at the Federal Law Enforcement Training Center using e-FLETC Online Campus has been substantiated in the article. Special attention has been paid to revealing such topical areas of Online Campus computer-based training modules (crime scene, driver training, drugs, firearms, health,…

[Influencing factors for job satisfaction in train drivers in a railway bureau: an analysis of 1413 cases].

PubMed

Gu, G Z; Yu, S F; Zhou, W H; Wu, H; Kang, L; Chen, R

2017-01-20

Objective: To investigate the influencing factors for job satisfaction in train drivers. Methods: In March 2012, cluster sampling was used to conduct a cross-sectional survey in 1413 male train drivers (including 301 passenger train drivers, 683 freight train drivers, 350 passenger shunting train drivers, and 79 high-speed train drivers) from a locomotive depot of a railway bureau. The occupational stress instruments, job content questionnaire, and effort-reward imbalance questionnaire were used to analyze job satisfaction, occupational stress factors, stress reaction, individual characteristics, coping strategies, and social support. Results: There were significant differences in job satisfaction score between the drivers with different posts, working years, ages, smoking status, and drinking status ( P <0.01). The correlation analysis revealed that job satisfaction score was positively correlated with reward, working stability, promotion opportunity, positive emotion, social support, self-esteem, and coping strategy scores ( P <0.01) and negatively correlated with sleep disorders, effort, role conflict, intergroup conflict, responsibility for persons, responsibility for things, psychological needs, physiological needs, daily stress, negative emotion, and depressive symptom scores ( P < 0.01). The analysis of variance showed that compared with the moderate and low job satisfaction groups, the high job satisfaction group had significantly higher reward, positive emotion, promotion opportunity, and role ambiguity scores ( P <0.01) , as well as significantly lower scores of responsibility for persons and responsibility for things ( P <0.01). Compared with the moderate and high job satisfaction groups the low job satisfaction group had significantly higher scores of psychological needs, effort, role conflict, sleep disorders, daily stress, depressive symptom, negative emotion, drug use, intragroup conflict, and social support ( P <0.01) , and the moderate job satisfaction group had a significantly higher score of self-esteem than the other two groups ( P <0.05). The logistic regression analysis showed that the risk of job dissatisfaction in the drivers with low so-cial support and high daily stress was more than 2 times that in those with high social support and low daily stress ( OR =2.176 and 2.171) , and sleep disorders, effort, depressive symptom, low self-esteem, and role conflict were risk factors for job dissatisfaction ( OR =1.48-1.625). Conclusion: Occupational stress, stress re-sponse, emotion, individual characteristics, and social support have great influence on job satisfaction. Im-proving social support, increasing positive emotion, and reducing occupational stress are main measures for increasing job satisfaction in train drivers.

From lead optimization to NDA approval for a new antimicrobial: Use of pre-clinical effect models and pharmacokinetic/pharmacodynamic mathematical modeling.

PubMed

Drusano, G L

2016-12-15

Because of our current crisis of resistance, particularly in nosocomial pathogens, the discovery and development of new antimicrobial agents has become a societal imperative. Changes in regulatory pathways by the Food and Drug Administration and the European Medicines Agency place great emphasis on the use of preclinical models coupled with pharmacokinetic/pharmacodynamic analysis to rapidly and safely move new molecular entities with activity against multi-resistant pathogens through the approval process and into the treatment of patients. In this manuscript, the use of the murine pneumonia system and the Hollow Fiber Infection Model is displayed and the way in which the mathematical analysis of the data arising from these models contributes to the robust choice of dose and schedule for Phase 3 clinical trials is shown. These data and their proper analysis act to de-risk the conduct of Phase 3 trials for anti-infective agents. These trials are the most expensive part of drug development. Further, given the seriousness of the infections treated, they represent the riskiest element for patients. Consequently, these preclinical model systems and their proper analysis have become a central part of accelerated anti-infective development. A final contention of this manuscript is that it is possible to embed these models and in particular, the Hollow Fiber Infection Model earlier in the drug discovery/development process. Examples of 'dynamic driver switching' and the impact of this phenomenon on clinical trial outcome are provided. Identifying dynamic drivers early in drug discovery may lead to improved decision making in the lead optimization process, resulting in the best molecules transitioning to clinical development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biomarkers that currently affect clinical practice: EGFR, ALK, MET, KRAS

PubMed Central

Vincent, M.D.; Kuruvilla, M.S.; Leighl, N.B.; Kamel–Reid, S.

2012-01-01

New drugs such as pemetrexed, the epidermal growth factor receptor (egfr) tyrosine kinase inhibitors, and the Alk inhibitor crizotinib have recently enabled progress in the management of advanced non-small-cell lung cancer (nsclc). More drugs, especially Met inhibitors, will follow. However, the benefits of these agents are not uniform across the spectrum of nsclc, and optimizing their utility requires some degree of subgrouping of nsclc by the presence or absence of certain biomarkers. The biomarkers of current or imminent value are EGFR and KRAS mutational status, ALK rearrangements, and MET immunohistochemistry. As a predictor of benefit for anti-egfr monoclonal antibodies, EGFR immunohistochemistry is also of potential interest. Some of the foregoing biomarkers (EGFR, ALK, MET) are direct drivers of the malignant phenotype. As such, they are, quite rationally, the direct targets of inhibitory drugs. However, KRAS, while definitely a driver, has resisted attempts at direct pharmacologic manipulation, and its main value might lie in its role as part of an efficient testing algorithm, because KRAS mutations appear to exclude EGFR and ALK mutations. The indirect value of KRAS in determining sensitivity to other targeted agents or to pemetrexed remains controversial. The other biomarkers (EGFR, ALK, MET) may also have indirect value as predictors of sensitivity to chemotherapy in general, to pemetrexed specifically, and to radiotherapy and molecularly targeted agents. These biomarkers have all enabled the co-development of new drugs with companion diagnostics, and they illustrate the paradigm that will govern progress in oncology in the immediate future. However, in nsclc, the acquisition of sufficient biopsy material remains a stubborn obstacle to the evolution of novel targeted therapies. PMID:22787409

The compatibility and stability of midazolam and dexamethasone in infusion solutions.

PubMed

Good, Phillip D; Schneider, Jennifer J; Ravenscroft, Peter J

2004-05-01

The delivery of subcutaneous medication by continuous infusion is common in palliative medicine. Many centers combine multiple medications, but the analytical confirmation of the compatibility and stability of these combinations has rarely been performed. This study examined the compatibility and stability of midazolam and dexamethasone using high performance liquid chromatography. Nine different solutions were prepared in polypropylene syringes by combining these two drugs with 0.9% sodium chloride. When these two drugs were combined in a syringe, there was significant loss of midazolam over 48 hours, with only 60-80% of the initial concentration remaining in syringes stored at 35-39 degrees C. This study demonstrates that cloudiness of a solution is not the only predictor of drug loss and that drug loss may occur even in solutions that remain clear at time of preparation. The clinical implications of these results are that dexamethasone and midazolam should not be combined in syringe driver solutions.

The impact of transcription on metabolism in prostate and breast cancers.

PubMed

Poulose, Ninu; Mills, Ian G; Steele, Rebecca E

2018-05-14

Metabolic dysregulation is regarded as an important driver in cancer development and progression. The impact of transcriptional changes on metabolism have been intensively studied in hormone-dependent cancers, and in particular in prostate and breast cancer. These cancers have strong similarities in the function of important transcriptional drivers, such as the estrogen and androgen receptor, at the level of dietary risk and epidemiology, genetics and therapeutically. In this review we will focus on the function of these nuclear hormone receptors and their downstream impact on metabolism, with a particular focus on lipid metabolism. We go on to discuss how lipid metabolism remains dysregulated as the cancers progress. We conclude by discussing the opportunities that this presents for drug repurposing, imaging and the development and testing of new therapeutics and treatment combinations.

Changing costs of metastatic non small cell lung cancer in the Netherlands.

PubMed

Keusters, W R; de Weger, V A; Hövels, A; Schellens, J H M; Frederix, G W J

2017-12-01

The primary objective of this study was to identify the total intramural cost of illness of metastatic non-small cell lung cancer (NSCLC) in the Netherlands between 2006-2012. Secondary objective was to identify whether changes in cost patterns of metastatic NSCLC have occurred over the last years. Patients diagnosed with metastatic NSCLC between 1-1-2006 and 31-12-2012, who had follow-up to death or the date of data cut-off and no trial participation were included. A structured chart review was performed using a case report form. Data collection started after diagnosis of metastatic NSCLC and ended at death or April first, 2015. Data regarding outpatient visits, clinical attendance, oncolytic drug use, imaging, lab tests, radiotherapy and surgery were collected. Sixty-seven patients were included with a median age of 67 years. The median follow-up was 234days. On average patients had 28 outpatient visits and 11 inpatient days. Oncolytic drugs were administered to 76% of the patients. Mean per patient expenditures amounted up to €17,463, with oncolytic drugs (€6,390) as the main cost driver. In comparison with the time-period of 2003-2005 total per patient per year expenses decreased by 44%. The contribution to total yearly costs of oncolytic drugs increased from 18% to 35%, while costs for inpatient stay decreased from 52% to 28% of total expenditures. Outcomes in this study demonstrate that average treatment costs for metastatic NSCLC in the Netherlands Cancer Institute amount to €17,463. Compared to a prior study the average cost for metastatic NSCLC over time in the Netherlands has decreased. A shift of main cost drivers seems to have occurred from inpatient stay, to oncolytic drugs as main contributor. The shift towards treatment cost might become more visible with the introduction of immunotherapy. These results mark the importance of up-to-date cost of illness studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Sensing cocaine in saliva with infrared laser spectroscopy

NASA Astrophysics Data System (ADS)

Hans, Kerstin M.-C.; Müller, Matthias; Gianella, Michele; Wägli, Ph.; Sigrist, Markus W.

2013-02-01

Increasing numbers of accidents caused by drivers under the influence of drugs, raise drug tests to worldwide interest. We developed a one-step extraction technique for cocaine in saliva and analyzed reference samples with laser spectroscopy employing two different schemes. The first is based on attenuated total reflection (ATR), which is applied to dried samples. The second scheme uses transmission measurements for the analysis of liquid samples. ATR spectroscopy achieved a limit of detection (LOD) of 3μg/ml. The LOD for the transmission approach in liquid samples is < 10 μg/ml. These LODs are realistic as such concentration ranges are encountered in the saliva of drug users after the administration of a single dose of cocaine. An improved stabilization of the set-up should lower the limit of detection significantly.

Challenges in Drug Discovery for Neurofibromatosis Type 1-Associated Low-Grade Glioma

PubMed Central

Ricker, Cora A.; Pan, Yuan; Gutmann, David H.; Keller, Charles

2016-01-01

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that results from germline mutations of the NF1 gene, creating a predisposition to low-grade gliomas (LGGs; pilocytic astrocytoma) in young children. Insufficient data and resources represent major challenges to identifying the best possible drug therapies for children with this tumor. Herein, we summarize the currently available cell lines, genetically engineered mouse models, and therapeutic targets for these LGGs. Conspicuously absent are human tumor-derived cell lines or patient-derived xenograft models for NF1-LGG. New collaborative initiatives between patients and their families, research groups, and pharmaceutical companies are needed to create transformative resources and broaden the knowledge base relevant to identifying cooperating genetic drivers and possible drug therapeutics for this common pediatric brain tumor. PMID:28066715

Identifying candidate drivers of drug response in heterogeneous cancer by mining high throughput genomics data.

PubMed

Nabavi, Sheida

2016-08-15

With advances in technologies, huge amounts of multiple types of high-throughput genomics data are available. These data have tremendous potential to identify new and clinically valuable biomarkers to guide the diagnosis, assessment of prognosis, and treatment of complex diseases, such as cancer. Integrating, analyzing, and interpreting big and noisy genomics data to obtain biologically meaningful results, however, remains highly challenging. Mining genomics datasets by utilizing advanced computational methods can help to address these issues. To facilitate the identification of a short list of biologically meaningful genes as candidate drivers of anti-cancer drug resistance from an enormous amount of heterogeneous data, we employed statistical machine-learning techniques and integrated genomics datasets. We developed a computational method that integrates gene expression, somatic mutation, and copy number aberration data of sensitive and resistant tumors. In this method, an integrative method based on module network analysis is applied to identify potential driver genes. This is followed by cross-validation and a comparison of the results of sensitive and resistance groups to obtain the final list of candidate biomarkers. We applied this method to the ovarian cancer data from the cancer genome atlas. The final result contains biologically relevant genes, such as COL11A1, which has been reported as a cis-platinum resistant biomarker for epithelial ovarian carcinoma in several recent studies. The described method yields a short list of aberrant genes that also control the expression of their co-regulated genes. The results suggest that the unbiased data driven computational method can identify biologically relevant candidate biomarkers. It can be utilized in a wide range of applications that compare two conditions with highly heterogeneous datasets.

Research Costs Investigated: A Study Into the Budgets of Dutch Publicly Funded Drug-Related Research.

PubMed

van Asselt, Thea; Ramaekers, Bram; Corro Ramos, Isaac; Joore, Manuela; Al, Maiwenn; Lesman-Leegte, Ivonne; Postma, Maarten; Vemer, Pepijn; Feenstra, Talitha

2018-01-01

The costs of performing research are an important input in value of information (VOI) analyses but are difficult to assess. The aim of this study was to investigate the costs of research, serving two purposes: (1) estimating research costs for use in VOI analyses; and (2) developing a costing tool to support reviewers of grant proposals in assessing whether the proposed budget is realistic. For granted study proposals from the Netherlands Organization for Health Research and Development (ZonMw), type of study, potential cost drivers, proposed budget, and general characteristics were extracted. Regression analysis was conducted in an attempt to generate a 'predicted budget' for certain combinations of cost drivers, for implementation in the costing tool. Of 133 drug-related research grant proposals, 74 were included for complete data extraction. Because an association between cost drivers and budgets was not confirmed, we could not generate a predicted budget based on regression analysis, but only historic reference budgets given certain study characteristics. The costing tool was designed accordingly, i.e. with given selection criteria the tool returns the range of budgets in comparable studies. This range can be used in VOI analysis to estimate whether the expected net benefit of sampling will be positive to decide upon the net value of future research. The absence of association between study characteristics and budgets may indicate inconsistencies in the budgeting or granting process. Nonetheless, the tool generates useful information on historical budgets, and the option to formally relate VOI to budgets. To our knowledge, this is the first attempt at creating such a tool, which can be complemented with new studies being granted, enlarging the underlying database and keeping estimates up to date.

Overweight and obesity on the island of Ireland: an estimation of costs

PubMed Central

Dee, Anne; Callinan, Aoife; Doherty, Edel; O'Neill, Ciaran; McVeigh, Treasa; Sweeney, Mary Rose; Staines, Anthony; Kearns, Karen; Fitzgerald, Sarah; Sharp, Linda; Kee, Frank; Hughes, John; Balanda, Kevin; Perry, Ivan J

2015-01-01

Objectives The increasing prevalence of overweight and obesity worldwide continues to compromise population health and creates a wider societal cost in terms of productivity loss and premature mortality. Despite extensive international literature on the cost of overweight and obesity, findings are inconsistent between Europe and the USA, and particularly within Europe. Studies vary on issues of focus, specific costs and methods. This study aims to estimate the healthcare and productivity costs of overweight and obesity for the island of Ireland in 2009, using both top-down and bottom-up approaches. Methods Costs were estimated across four categories: healthcare utilisation, drug costs, work absenteeism and premature mortality. Healthcare costs were estimated using Population Attributable Fractions (PAFs). PAFs were applied to national cost data for hospital care and drug prescribing. PAFs were also applied to social welfare and national mortality data to estimate productivity costs due to absenteeism and premature mortality. Results The healthcare costs of overweight and obesity in 2009 were estimated at €437 million for the Republic of Ireland (ROI) and €127.41 million for NI. Productivity loss due to overweight and obesity was up to €865 million for ROI and €362 million for NI. The main drivers of healthcare costs are cardiovascular disease, type II diabetes, colon cancer, stroke and gallbladder disease. In terms of absenteeism, low back pain is the main driver in both jurisdictions, and for productivity loss due to premature mortality the primary driver of cost is coronary heart disease. Conclusions The costs are substantial, and urgent public health action is required in Ireland to address the problem of increasing prevalence of overweight and obesity, which if left unchecked will lead to unsustainable cost escalation within the health service and unacceptable societal costs. PMID:25776042

Driving under the influence behaviours among high school students who mix alcohol with energy drinks.

PubMed

Wilson, Maria N; Cumming, Tammy; Burkhalter, Robin; Langille, Donald B; Ogilvie, Rachel; Asbridge, Mark

2018-06-01

Alcohol and energy drinks are commonly used substances by youth in Canada, and are often mixed (AmED). While several studies have shown that AmED can have dangerous effects, less well understood is how AmED is associated with driving under the influence of either alcohol or drugs. This study sought to determine whether youth who use AmED were more likely to engage in driving, or being a passenger of a driver, under the influence of alcohol or cannabis compared to youth who use either alcohol or energy drinks alone. This study used data from grade 10-12 students who took part in the 2014/2015 Canadian Student Tobacco, Alcohol and Drugs Survey (N=17,450). The association of past-year AmED use with past-30day: driving under the influence of alcohol or cannabis, and riding with an alcohol- or cannabis-influenced driver, was assessed using logistic regression. One in four youth had consumed AmED in the previous 12months. AmED users were more likely to engage in all risk behaviours except riding with a drinking driver, relative to youth who only consumed alcohol. No association was observed for youth who consumed alcohol and energy drinks on separate occasions. Youth who use AmED demonstrate a higher risk profile for driving under the influence of alcohol or cannabis, than youth who use alcohol alone. Future research should explore the biopsychosocial pathways that may explain why using energy drinks enhances the already heightened risk posed by alcohol on other health-related behaviours such as driving under the influence. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A comparison of generic drug prices in seven European countries: a methodological analysis.

PubMed

Wouters, Olivier J; Kanavos, Panos G

2017-03-31

Policymakers and researchers frequently compare the prices of medicines between countries. Such comparisons often serve as barometers of how pricing and reimbursement policies are performing. The aim of this study was to examine methodological challenges to comparing generic drug prices. We calculated all commonly used price indices based on 2013 IMS Health data on sales of 3156 generic drugs in seven European countries. There were large differences in generic drug prices between countries. However, the results varied depending on the choice of index, base country, unit of volume, method of currency conversion, and therapeutic category. The results also differed depending on whether one looked at the prices charged by manufacturers or those charged by pharmacists. Price indices are a useful statistical approach for comparing drug prices across countries, but researchers and policymakers should interpret price indices with caution given their limitations. Price-index results are highly sensitive to the choice of method and sample. More research is needed to determine the drivers of price differences between countries. The data suggest that some governments should aim to reduce distribution costs for generic drugs.

Safety of Cancer Therapies: At What Cost?

PubMed

Fitzner, Karen; Oteng-Mensah, Frederick; Donley, Patrick; Heckinger, Elizabeth A F

2017-08-01

The cost of cancer drugs has increased concurrently with drug safety resulting in both increased survivorship and increased out-of-pocket costs and co-payments for patients. This article evaluates the interplay between patient safety and cancer drug costs to determine how cancer drug costs affect patient safety and well-being. A literature review was performed that identified the main drivers of drug safety costs: drug-drug interactions, adverse drug events, medication errors, and nonadherence. Three main types of costs were identified: out-of-pocket spending, drug cost growth, and safety-related costs. Insured patients receiving chemotherapy pay an average of $10,000/month on out-of-pocket expenses. Annual drug cost growth has been as much as 21% in recent years. Over a span of 13 years, 1999-2013, insurance premiums and out-of-pocket payments have increased by 182% and 200%, respectively. Safety-related concerns include the high cost of developing a new drug, estimated at $5 billion. The cost of development is reflected in the cost of the 12 new cancer drugs that received Food and Drug Administration approval in 2012; 11 were priced at 6 figures. Although advances in pharmaceutical technology and research have yielded effective cancer therapies that reduce physical or treatment-related toxicity, patients have had to face worsening financial uncertainty both during and after treatment. Actions are needed to achieve financial safety, as well as therapeutic and clinical safety, for cancer patients.

What are the factors that contribute to road accidents? An assessment of law enforcement views, ordinary drivers' opinions, and road accident records.

PubMed

Rolison, Jonathan J; Regev, Shirley; Moutari, Salissou; Feeney, Aidan

2018-06-01

What are the main contributing factors to road accidents? Factors such as inexperience, lack of skill, and risk-taking behaviors have been associated with the collisions of young drivers. In contrast, visual, cognitive, and mobility impairment have been associated with the collisions of older drivers. We investigated the main causes of road accidents by drawing on multiple sources: expert views of police officers, lay views of the driving public, and official road accident records. In Studies 1 and 2, police officers and the public were asked about the typical causes of road traffic collisions using hypothetical accident scenarios. In Study 3, we investigated whether the views of police officers and the public about accident causation influence their recall accuracy for factors reported to contribute to hypothetical road accidents. The results show that both expert views of police officers and lay views of the driving public closely approximated the typical factors associated with the collisions of young and older drivers, as determined from official accident records. The results also reveal potential underreporting of factors in existing accident records, identifying possible inadequacies in law enforcement practices for investigating driver distraction, drug and alcohol impairment, and uncorrected or defective eyesight. Our investigation also highlights a need for accident report forms to be continuously reviewed and updated to ensure that contributing factor lists reflect the full range of factors that contribute to road accidents. Finally, the views held by police officers and the public on accident causation influenced their memory recall of factors involved in hypothetical scenarios. These findings indicate that delay in completing accident report forms should be minimised, possibly by use of mobile reporting devices at the accident scene. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cost drivers for breast, lung, and colorectal cancer care in a commercially insured population over a 6-month episode: an economic analysis from a health plan perspective.

PubMed

Sagar, Bhuvana; Lin, Yu Shen; Castel, Liana D

2017-10-01

In the absence of clinical data, accurate identification of cost drivers is needed for economic comparison in an alternate payment model. From a health plan perspective using claims data in a commercial population, the objective was to identify and quantify the effects of cost drivers in economic models of breast, lung, and colorectal cancer costs over a 6-month episode following initial chemotherapy. This study analyzed claims data from 9,748 Cigna beneficiaries with diagnosis of breast, lung, and colorectal cancer following initial chemotherapy from January 1, 2014 to December 31, 2015. We used multivariable regression models to quantify the impact of key factors on cost during the initial 6-month cancer care episode. Metastasis, facility provider affiliation, episode risk group (ERG) risk score, and radiation were cost drivers for all three types of cancer (breast, lung, and colorectal). In addition, younger age (p < .0001) and human epidermal growth factor receptor-2 oncogene overexpression (HER2+)-directed therapy (p < .0001) were associated with higher costs in breast cancer. Younger age (p < .0001) and female gender (p < .0001) were also associated with higher costs in colorectal cancer. Metastasis was also associated with 50% more hospital admissions and increased hospital length of stay (p < .001) in all three cancers over the 6-month episode duration. Chemotherapy and supportive drug therapies accounted for the highest proportion (48%) of total medical costs among beneficiaries observed. Value-based reimbursement models in oncology should appropriately account for key cost drivers. Although claims-based methodologies may be further augmented with clinical data, this study recommends adjusting for the factors identified in these models to predict costs in breast, lung, and colorectal cancers.

Risk Factors for Cardiovascular Disease, Metabolic Syndrome and Sleepiness in Truck Drivers.

PubMed

Mansur, Antonio de Padua; Rocha, Marcos Abs; Leyton, Vilma; Takada, Julio Yashio; Avakian, Solange Desirée; Santos, Alexandre J; Novo, Gisele C; Nascimento, Arledson Lima; Muñoz, Daniel Romero; Rohlfs, Waldo J C

2015-12-01

Truck driver sleepiness is a primary cause of vehicle accidents. Several causes are associated with sleepiness in truck drivers. Obesity and metabolic syndrome (MetS) are associated with sleep disorders and with primary risk factors for cardiovascular diseases (CVD). We analyzed the relationship between these conditions and prevalence of sleepiness in truck drivers. We analyzed the major risk factors for CVD, anthropometric data and sleep disorders in 2228 male truck drivers from 148 road stops made by the Federal Highway Police from 2006 to 2011. Alcohol consumption, illicit drugs and overtime working hours were also analyzed. Sleepiness was assessed using the Epworth Sleepiness Scale. Mean age was 43.1 ± 10.8 years. From 2006 to 2011, an increase in neck (p = 0.011) and abdominal circumference (p < 0.001), total cholesterol (p < 0.001), triglyceride plasma levels (p = 0.014), and sleepiness was observed (p < 0.001). In addition, a reduction in hypertension (39.6% to 25.9%, p < 0.001), alcohol consumption (32% to 23%, p = 0.033) and overtime hours (52.2% to 42.8%, p < 0.001) was found. Linear regression analysis showed that sleepiness correlated closely with body mass index (β = 0.19, Raj2 = 0.659, p = 0.031), abdominal circumference (β = 0.24, Raj2 = 0.826, p = 0.021), hypertension (β = -0.62, Raj2 = 0.901, p = 0.002), and triglycerides (β = 0.34, Raj2 = 0.936, p = 0.022). Linear multiple regression indicated that hypertension (p = 0.008) and abdominal circumference (p = 0.025) are independent variables for sleepiness. Increased prevalence of sleepiness was associated with major components of the MetS.

Urban bus drivers' sleep problems and crash accidents.

PubMed

Razmpa, Ebrahim; Sadegh Niat, Khosro; Saedi, Babak

2011-07-01

Sleep problems and their direct consequence, sleepiness, results in critical effects on psychomotor skills, memory, decision making, concentration and learning; all of which may play roles in accidents and errors. Despite the importance of quality of sleep among drivers there are only few researches that deal with them. Therefore, we designed this research to better understand possible relationships. This cross-sectional study was performed between 2006 and 2007 among 175 bus drivers of a transportation company in Tehran, the capital of Iran. Participants filled out a questionnaire concerning their demographic and personal history, associated disease, the insomnia index, the Epworth sleepiness scale (ESS), and the apnea index. Then they elaborated their history of crashes. Data was analyzed with the SPSS software through χ(2), Oneway ANOVAs, and Pearson correlation tests. The mean age, and body mass index (BMI) were 43.47 ± 6.85 years and 26.35 ± 3.87 kg/m(2). The mean duration of sleep among these drivers was 6.37 ± 1.62 h per day. The mean accident rate was 2.31 ± 1.83 per year. There was a significant correlation between the insomnia index and BMI (P = 0.014), age (0.00), marital status (0.00), associated disease (0.005), and drug history (0.028). There was a significant relationship between marital status and the ESS, and also between age and accident rate in the past years. Sleep problems were a frequent finding among the studied group and had a significant relationship with their crash history. These results can be an alarming sign to choose bus drivers more carefully and pay more attention to treating their sleep disorders.

Identifying candidate driver genes by integrative ovarian cancer genomics data

NASA Astrophysics Data System (ADS)

Lu, Xinguo; Lu, Jibo

2017-08-01

Integrative analysis of molecular mechanics underlying cancer can distinguish interactions that cannot be revealed based on one kind of data for the appropriate diagnosis and treatment of cancer patients. Tumor samples exhibit heterogeneity in omics data, such as somatic mutations, Copy Number Variations CNVs), gene expression profiles and so on. In this paper we combined gene co-expression modules and mutation modulators separately in tumor patients to obtain the candidate driver genes for resistant and sensitive tumor from the heterogeneous data. The final list of modulators identified are well known in biological processes associated with ovarian cancer, such as CCL17, CACTIN, CCL16, CCL22, APOB, KDF1, CCL11, HNF1B, LRG1, MED1 and so on, which can help to facilitate the discovery of biomarkers, molecular diagnostics, and drug discovery.

Complement, a target for therapy in inflammatory and degenerative diseases.

PubMed

Morgan, B Paul; Harris, Claire L

2015-12-01

The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies.

The cost of molecular-guided therapy in oncology: a prospective cost study alongside the MOSCATO trial.

PubMed

Pagès, Arnaud; Foulon, Stéphanie; Zou, Zhaomin; Lacroix, Ludovic; Lemare, François; de Baère, Thierry; Massard, Christophe; Soria, Jean-Charles; Bonastre, Julia

2017-06-01

There is increasing use of molecular technologies to guide cancer treatments, but few cost data are available. Our objective was to assess the costs of molecular-guided therapy for patients with advanced solid tumors alongside the Molecular Screening for Cancer Treatment and Optimization (MOSCATO) trial. The study population consisted of 529 patients. The molecular diagnosis included seven steps from tumor biopsy to the multidisciplinary molecular tumor board. The cost of a complete molecular diagnosis was assessed by micro-costing. Direct costs incurred from enrollment until progression were assessed from the French National Health Insurance perspective. The patients' mean age was 54 years (range: 3-82) and the mean follow-up period was 145 days (range: 1-707 days). A complete molecular diagnosis cost [euro ]2,396. There were 220 patients with an actionable target (42%), among whom 105 (20%) actually received a targeted therapy. The cost of molecular-guided therapy per patient was [euro ]31,269. The main cost drivers were anticancer drugs (54%) and hospitalizations (35%). This prospective cost analysis showed that molecular diagnosis accounts for only 6% of the cost of molecular-guided therapy per patient. The costs of drugs and hospitalizations are the main cost drivers.Genet Med advance online publication 01 December 2016.

Disease ecology, health and the environment: a framework to account for ecological and socio-economic drivers in the control of neglected tropical diseases

PubMed Central

Sokolow, S. H.; Ngonghala, C. N.; Jocque, M.; Lund, A.; Barry, M.; Mordecai, E. A.; Daily, G. C.; Andrews, J. R.; Bendavid, E.; Luby, S. P.; LaBeaud, A. D.; Seetah, K.; Guégan, J. F.; De Leo, G. A.

2017-01-01

Reducing the burden of neglected tropical diseases (NTDs) is one of the key strategic targets advanced by the Sustainable Development Goals. Despite the unprecedented effort deployed for NTD elimination in the past decade, their control, mainly through drug administration, remains particularly challenging: persistent poverty and repeated exposure to pathogens embedded in the environment limit the efficacy of strategies focused exclusively on human treatment or medical care. Here, we present a simple modelling framework to illustrate the relative role of ecological and socio-economic drivers of environmentally transmitted parasites and pathogens. Through the analysis of system dynamics, we show that periodic drug treatments that lead to the elimination of directly transmitted diseases may fail to do so in the case of human pathogens with an environmental reservoir. Control of environmentally transmitted diseases can be more effective when human treatment is complemented with interventions targeting the environmental reservoir of the pathogen. We present mechanisms through which the environment can influence the dynamics of poverty via disease feedbacks. For illustration, we present the case studies of Buruli ulcer and schistosomiasis, two devastating waterborne NTDs for which control is particularly challenging. This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications’. PMID:28438917

Bilastine: a new antihistamine with an optimal benefit-to-risk ratio for safety during driving.

PubMed

Jáuregui, Ignacio; Ramaekers, Johannes G; Yanai, Kazuhiko; Farré, Magí; Redondo, Esther; Valiente, Román; Labeaga, Luis

2016-01-01

Rational selection of a second-generation H1-antihistamine requires efficacy and safety considerations, particularly regarding central nervous system (CNS) effects (cognitive and psychomotor function), potential for driving impairment, minimal sedative effects and a lack of interactions. This review evaluates the key safety features of the non-sedating antihistamine, bilastine, during driving and in preventing road traffic accidents. Among the second-generation H1-antihistamines, sedative effects which can affect cognitive and psychomotor performance, and possibly driving ability, may not be similar. Bilastine is absorbed rapidly, undergoes no hepatic metabolism or cytochrome P450 interaction (minimal drug-drug interaction potential), and is a substrate for P-glycoprotein (limiting CNS entry). Positron emission tomography showed that, compared with other second-generation H1-antihistamines, bilastine has the lowest cerebral histamine H1-receptor occupancy. Bilastine 20 mg once daily (therapeutic dose) is non-sedating, does not enhance the effects of alcohol or CNS sedatives, does not impair driving performance and has at least similar efficacy as other second-generation H1-antihistamines in the treatment of allergic rhinoconjunctivitis and urticaria. Current evidence shows that bilastine has an optimal benefit-to-risk ratio, meeting all conditions for contributing to safety in drivers who need antihistamines, and hence for being considered as an antihistamine of choice for drivers.

Levels and Types of Alcohol Biomarkers in DUI and Clinic Samples for Estimating Workplace Alcohol Problemsa

PubMed Central

Marques, Paul R

2013-01-01

Widespread concern about illicit drugs as an aspect of workplace performance potentially diminishes attention on employee alcohol use. Alcohol is the dominant drug contributing to poor job performance; it also accounts for a third of the worldwide public health burden. Evidence from public roadways – a workplace for many – provides an example for work-related risk exposure and performance lapses. In most developed countries, alcohol is involved in 20-35% of fatal crashes; drugs other than alcohol are less prominently involved in fatalities. Alcohol biomarkers can improve detection by extending the timeframe for estimating problematic exposure levels and thereby provide better information for managers. But what levels and which markers are right for the workplace? In this report, an established high-sensitivity proxy for alcohol-driving risk proclivity is used: an average 8 months of failed blood alcohol concentration (BAC) breath tests from alcohol ignition interlock devices. Higher BAC test fail rates are known to presage higher rates of future impaired-driving convictions (DUI). Drivers in alcohol interlock programs log 5-7 daily BAC tests; in 12 months, this yields thousands of samples. Also, higher program entry levels of alcohol biomarkers predict a higher likelihood of failed interlock BAC tests during subsequent months. This report summarizes selected biomarkers’ potential for workplace screening. Markers include phosphatidylethanol (PEth), percent carbohydrate deficient transferrin (%CDT), gammaglutamyltransferase (GGT), gamma %CDT (γ%CDT), and ethylglucuronide (EtG) in hair. Clinical cutoff levels and median/mean levels of these markers in abstinent people, the general population, DUI drivers, and rehabilitation clinics are summarized for context. PMID:22311827

VarWalker: Personalized Mutation Network Analysis of Putative Cancer Genes from Next-Generation Sequencing Data

PubMed Central

Jia, Peilin; Zhao, Zhongming

2014-01-01

A major challenge in interpreting the large volume of mutation data identified by next-generation sequencing (NGS) is to distinguish driver mutations from neutral passenger mutations to facilitate the identification of targetable genes and new drugs. Current approaches are primarily based on mutation frequencies of single-genes, which lack the power to detect infrequently mutated driver genes and ignore functional interconnection and regulation among cancer genes. We propose a novel mutation network method, VarWalker, to prioritize driver genes in large scale cancer mutation data. VarWalker fits generalized additive models for each sample based on sample-specific mutation profiles and builds on the joint frequency of both mutation genes and their close interactors. These interactors are selected and optimized using the Random Walk with Restart algorithm in a protein-protein interaction network. We applied the method in >300 tumor genomes in two large-scale NGS benchmark datasets: 183 lung adenocarcinoma samples and 121 melanoma samples. In each cancer, we derived a consensus mutation subnetwork containing significantly enriched consensus cancer genes and cancer-related functional pathways. These cancer-specific mutation networks were then validated using independent datasets for each cancer. Importantly, VarWalker prioritizes well-known, infrequently mutated genes, which are shown to interact with highly recurrently mutated genes yet have been ignored by conventional single-gene-based approaches. Utilizing VarWalker, we demonstrated that network-assisted approaches can be effectively adapted to facilitate the detection of cancer driver genes in NGS data. PMID:24516372

VarWalker: personalized mutation network analysis of putative cancer genes from next-generation sequencing data.

PubMed

Jia, Peilin; Zhao, Zhongming

2014-02-01

A major challenge in interpreting the large volume of mutation data identified by next-generation sequencing (NGS) is to distinguish driver mutations from neutral passenger mutations to facilitate the identification of targetable genes and new drugs. Current approaches are primarily based on mutation frequencies of single-genes, which lack the power to detect infrequently mutated driver genes and ignore functional interconnection and regulation among cancer genes. We propose a novel mutation network method, VarWalker, to prioritize driver genes in large scale cancer mutation data. VarWalker fits generalized additive models for each sample based on sample-specific mutation profiles and builds on the joint frequency of both mutation genes and their close interactors. These interactors are selected and optimized using the Random Walk with Restart algorithm in a protein-protein interaction network. We applied the method in >300 tumor genomes in two large-scale NGS benchmark datasets: 183 lung adenocarcinoma samples and 121 melanoma samples. In each cancer, we derived a consensus mutation subnetwork containing significantly enriched consensus cancer genes and cancer-related functional pathways. These cancer-specific mutation networks were then validated using independent datasets for each cancer. Importantly, VarWalker prioritizes well-known, infrequently mutated genes, which are shown to interact with highly recurrently mutated genes yet have been ignored by conventional single-gene-based approaches. Utilizing VarWalker, we demonstrated that network-assisted approaches can be effectively adapted to facilitate the detection of cancer driver genes in NGS data.

Combined image and genomic analysis of high-grade serous ovarian cancer reveals PTEN loss as a common driver event and prognostic classifier.

PubMed

Martins, Filipe C; Santiago, Ines de; Trinh, Anne; Xian, Jian; Guo, Anne; Sayal, Karen; Jimenez-Linan, Mercedes; Deen, Suha; Driver, Kristy; Mack, Marie; Aslop, Jennifer; Pharoah, Paul D; Markowetz, Florian; Brenton, James D

2014-12-17

TP53 and BRCA1/2 mutations are the main drivers in high-grade serous ovarian carcinoma (HGSOC). We hypothesise that combining tissue phenotypes from image analysis of tumour sections with genomic profiles could reveal other significant driver events. Automatic estimates of stromal content combined with genomic analysis of TCGA HGSOC tumours show that stroma strongly biases estimates of PTEN expression. Tumour-specific PTEN expression was tested in two independent cohorts using tissue microarrays containing 521 cases of HGSOC. PTEN loss or downregulation occurred in 77% of the first cohort by immunofluorescence and 52% of the validation group by immunohistochemistry, and is associated with worse survival in a multivariate Cox-regression model adjusted for study site, age, stage and grade. Reanalysis of TCGA data shows that hemizygous loss of PTEN is common (36%) and expression of PTEN and expression of androgen receptor are positively associated. Low androgen receptor expression was associated with reduced survival in data from TCGA and immunohistochemical analysis of the first cohort. PTEN loss is a common event in HGSOC and defines a subgroup with significantly worse prognosis, suggesting the rational use of drugs to target PI3K and androgen receptor pathways for HGSOC. This work shows that integrative approaches combining tissue phenotypes from images with genomic analysis can resolve confounding effects of tissue heterogeneity and should be used to identify new drivers in other cancers.

[Drug use and involvement in risky driving styles in a sample of university students. The uniHcos project].

PubMed

Jiménez-Mejías, Eladio; Medina-García, Miguel Ángel; Martínez-Ruiz, Virginia; Pulido-Manzanero, José; Fernández-Villa, Tania

2015-09-01

Drug and alcohol use are known to increase the risk of traffic accidents, especially among youth. However, the association between habitual drug use and the adoption of risky driving behavior is not well known. The aim of this study was to identify and quantify the association between habitual drug use and involvement in risky driving practices overall and by gender among university students. A cross sectional study was conducted. The study population was composed of 559 car drivers younger than 31 years who completed an online questionnaire during the 2011-2012 academic year. Among other factors, the questionnaire assessed the following items: habitual drug consumption (20 or more days) during the last year and involvement in other risky driving practices during the last month. A total of 27.7% of students reported they had used drugs regularly during the last year. Drug use was associated with a higher frequency of involvement in risky driving practices. In men, the factors most strongly associated with drug consumption were speeding, driving under influence of alcohol, and feeling drowsy while driving. In women, drug consumption was mainly associated with smoking while driving, drunk driving, and driving without rest. The results of our study support the hypothesis that habitual drug use is associated with an increased frequency of risky driving behavior. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

Targeting EGFR in lung cancer: Lessons learned and future perspectives

PubMed Central

Steuer, Conor E.; Ramalingam, Suresh S.

2016-01-01

The development of individualized therapies has become the focus of current oncology research. Precision medicine has demonstrated great potential for bringing safe and effective drugs to those patients stricken with cancer, and is becoming a reality as more oncogenic drivers of malignancy are discovered. The discovery of Epidermal Growth Factor Receptor (EGFR) mutations as a driving mutation in non-small cell lung cancer (NSCLC) and the subsequent success of the tyrosine kinase inhibitors (TKI) have led the way for NSCLC to be at the forefront of biomarker-based drug development. However, this direction was not always so clear, and this article describes the lessons learned in targeted therapy development from EGFR in NSCLC. PMID:26022942

Antibacterial Drug Discovery: Some Assembly Required.

PubMed

Tommasi, Rubén; Iyer, Ramkumar; Miller, Alita A

2018-05-11

Our limited understanding of the molecular basis for compound entry into and efflux out of Gram-negative bacteria is now recognized as a key bottleneck for the rational discovery of novel antibacterial compounds. Traditional, large-scale biochemical or target-agnostic phenotypic antibacterial screening efforts have, as a result, not been very fruitful. A main driver of this knowledge gap has been the historical lack of predictive cellular assays, tools, and models that provide structure-activity relationships to inform optimization of compound accumulation. A variety of recent approaches has recently been described to address this conundrum. This Perspective explores these approaches and considers ways in which their integration could successfully redirect antibacterial drug discovery efforts.

Community health workers' experiences and perspectives on mass drug administration for schistosomiasis control in western Kenya: the SCORE Project.

PubMed

Omedo, Martin O; Matey, Elizabeth J; Awiti, Alphonce; Ogutu, Michael; Alaii, Jane; Karanja, Diana M S; Montgomery, Susan P; Secor, W Evan; Mwinzi, Pauline N M

2012-12-01

Abstract. The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) includes communitywide treatment in areas with ≥ 25% prevalence of schistosomiasis along the shores of Lake Victoria using community health workers (CHWs). The CHWs are key drivers in community-owned mass drug administration (MDA) intervention programs. We explored their experiences and perceptions after initial MDA participation. Unstructured open-ended group discussions were conducted after completion of MDA activities. Narratives were obtained from CHWs using a digital audio recorder during the group discussion, transcribed verbatim and translated into English where applicable. Thematic decomposition of data was done using ATLAS.t.i. software. From the perspective of the CHWs, factors influencing MDA compliance included drug side effects, food supply stability, and conspiracy theories about the "real" purpose of treatment. The interest of CHWs to serve as community drug distributors stemmed from both intrinsic and extrinsic factors. Feedback from CHWs can promote more effective MDA in rural Kenyan communities.

The Growing Problem of New Psychoactive Substances (NPS).

PubMed

Madras, Bertha K

The term "new psychoactive substances" (NPS) can be defined as individual drugs in pure form or in complex preparations that are not scheduled under the Single Convention on Narcotic Drugs (1961) or the Convention on Psychotropic Substances (1971). NPS may be categorized by chemical structure, by psychoactive properties, by biological targets, or by source (plant, synthetic, or combined). The emergence of hundreds of NPS in the past decade is challenging for public health and drug policies globally. The novelty of NPS, their ambiguous legal status, ability to evade toxicological tests, swift adaptation to legal restrictions, global Internet marketing, and scant public knowledge of their adverse effects are among the key drivers of this twenty-first century phenomenon. Multi-disciplinary research in areas of biology, epidemiology, prevention, and web analytics are needed to develop effective responses in a domain capable of overwhelming current international conventions and national drug control policies. Ultimately, research-guided prevention education will fortify societies against this tidal wave.

A spatio-temporal analysis of forest loss related to cocaine trafficking in Central America

NASA Astrophysics Data System (ADS)

Sesnie, Steven E.; Tellman, Beth; Wrathall, David; McSweeney, Kendra; Nielsen, Erik; Benessaiah, Karina; Wang, Ophelia; Rey, Luis

2017-05-01

A growing body of evidence suggests that criminal activities associated with drug trafficking networks are a progressively important driver of forest loss in Central America. However, the scale at which drug trafficking represents a driver of forest loss is not presently known. We estimated the degree to which narcotics trafficking may contribute to forest loss using an unsupervised spatial clustering of 15 spatial and temporal forest loss patch metrics developed from global forest change data. We distinguished anomalous forest loss from background loss patches for each country exhibiting potential ‘narco-capitalized’ signatures which showed a statistically significant dissimilarity from other patches in terms of size, timing, and rate of forest loss. We also compared annual anomalous forest loss with the number of cocaine shipments and volume of cocaine seized, lost, or delivered at country- and department-level. For Honduras, results from linear mixed effects models showed a highly significant relationship between anomalous forest loss and the timing of increased drug trafficking (F = 9.90, p = 0.009) that also differed significantly from temporal patterns of background forest loss (t-ratio = 2.98, p = 0.004). Other locations of high forest loss in Central America showed mixed results. The timing of increased trafficking was not significantly related to anomalous forest loss in Guatemala and Nicaragua, but significantly differed in patch size compared to background losses. We estimated that cocaine trafficking could account for between 15% and 30% of annual national forest loss in these three countries over the past decade, and 30% to 60% of loss occurred within nationally and internationally designated protected areas. Cocaine trafficking is likely to have severe and lasting consequences in terms of maintaining moist tropical forest cover in Central America. Addressing forest loss in these and other tropical locations will require a stronger linkage between national and international drug interdiction and conservation policies.

Characterizing the interaction between physicians, pharmacists and pharmaceutical representatives in a middle-income country: A qualitative study

PubMed Central

Naser El Dine, Rabie; Traboulsy, Sarah; Haddadin, Fadi; Honein-AbouHaidar, Gladys

2017-01-01

Background Studies around the world have shown that interactions between pharmaceutical companies, pharmacists and physicians have a great influence on prescribing and drug dispensing practices. In middle-income countries, the nature and extent of these interactions have not been well researched. Our objectives were to qualitatively explore the nature of the interactions between pharmaceutical companies, physicians and pharmacists, their impact on drug prescription and dispensing practices in Lebanon. Methods and findings We used grounded theory approach as well as the known sponsor, purposive, and snowballing sampling strategies to identify interviewees from the three respective groups: physicians, pharmacists, and pharmaceutical representatives. We conducted semi-structured and analyzed transcripts thematically. This study encompassed 6 pharmaceutical representatives, 13 physicians and 13 pharmacists. The following themes emerged: purpose and driver for the interactions, nature of the interactions, incentives, impact on prescription practices, ethical considerations, and suggestions for managing the interactions. The main purposes for the interaction were educational, promotional, and monitoring prescription practices and dispensing, while the main drivers for these interactions were market potential and neighborhood socio-economic status. Physicians, pharmacists and pharmaceutical representatives who engage in these interactions benefit from a variety of incentives, some of which were characterized as unethical. It appears that pharmaceutical companies give prominence to selected physicians within their communities. Although members of the three interviewed groups refer to some of the interactions as being problematic, they described a culture of acceptance of gift giving. We developed a framework that depicts the prevailing politico-cultural environment, the interactions between the three professional groups, and their impact on drug prescription. Underreporting is the main limitation of this study. Conclusion Interactions between physicians, pharmacists and pharmaceutical representatives are frequent. Although these interactions can be beneficial, they still have a substantial effect on drug prescription and dispensing practices. Hence, the need for new policies that regulate these interactions and penalize any misconduct. PMID:28898296

Characterizing the interaction between physicians, pharmacists and pharmaceutical representatives in a middle-income country: A qualitative study.

PubMed

Hajjar, Rima; Bassatne, Aya; Cheaito, Mohamad Ali; Naser El Dine, Rabie; Traboulsy, Sarah; Haddadin, Fadi; Honein-AbouHaidar, Gladys; Akl, Elie A

2017-01-01

Studies around the world have shown that interactions between pharmaceutical companies, pharmacists and physicians have a great influence on prescribing and drug dispensing practices. In middle-income countries, the nature and extent of these interactions have not been well researched. Our objectives were to qualitatively explore the nature of the interactions between pharmaceutical companies, physicians and pharmacists, their impact on drug prescription and dispensing practices in Lebanon. We used grounded theory approach as well as the known sponsor, purposive, and snowballing sampling strategies to identify interviewees from the three respective groups: physicians, pharmacists, and pharmaceutical representatives. We conducted semi-structured and analyzed transcripts thematically. This study encompassed 6 pharmaceutical representatives, 13 physicians and 13 pharmacists. The following themes emerged: purpose and driver for the interactions, nature of the interactions, incentives, impact on prescription practices, ethical considerations, and suggestions for managing the interactions. The main purposes for the interaction were educational, promotional, and monitoring prescription practices and dispensing, while the main drivers for these interactions were market potential and neighborhood socio-economic status. Physicians, pharmacists and pharmaceutical representatives who engage in these interactions benefit from a variety of incentives, some of which were characterized as unethical. It appears that pharmaceutical companies give prominence to selected physicians within their communities. Although members of the three interviewed groups refer to some of the interactions as being problematic, they described a culture of acceptance of gift giving. We developed a framework that depicts the prevailing politico-cultural environment, the interactions between the three professional groups, and their impact on drug prescription. Underreporting is the main limitation of this study. Interactions between physicians, pharmacists and pharmaceutical representatives are frequent. Although these interactions can be beneficial, they still have a substantial effect on drug prescription and dispensing practices. Hence, the need for new policies that regulate these interactions and penalize any misconduct.

Sexual behaviour and substance use patterns amongst adolescent truck cleaners and risk of HIV / AIDS.

PubMed

Bansal, R K

1992-01-01

This study was conducted at transport nagar in Indore, a major industrial and commercial center of Madhya Pradesh. Usually each truck has a staff of 3, comprising 1 senior driver, 1 junior driver, and a cleaner, usually a child or an adolescent. 210 such adolescent truck cleaners were surveyed by random sampling of the parked trucks present in the transport nagar. A semi-structured questionnaire was administered to these adolescents using the oral interview technique. The age distribution of the adolescents indicated that 17 were 15-16 years old, 63 were 16-17, 61 were 17-18, and 69 were 18-19. When the income was low, the owners or the senior drivers provided the meals and minor expenses. 80% of the adolescents were illiterate, 10.5% were literate, 6.2% had primary education, and 3.3% had middle school education. 88.1% of the cleaners were away from home for 24-28 days a month, 7.1% for less than 24 days, and 4.8% for over 28 days. 25.2% of the cleaners had a history of sexual activity, commonly with prostitutes. 88.6% of the senior drivers regularly visited prostitutes, and in many cases the adolescents' payment to the prostitute was financed by the senior driver. 94.3% of these adolescents had engaged in unprotected sexual intercourse, and the remaining 5.7% had used condoms infrequently. 98.5% of them had not heard of HIV and AIDS. 4.3% had a history of sexually transmitted diseases and had been treated by general practitioners. Substance abuse was fairly common among these young people (140 smoked, 9 chewed tobacco, 2 used opium, and 2 used alcohol more than twice per week), and the cost for those substances was primarily met by the senior truck driver or the owner. The trend was similar for sexual activity, as 25.2% had engaged in sex (12.9% once, 7.1% twice, and 5.2% several times). Special programs are required for these adolescents to educate them about the risks of unprotected sex and drugs in order to prevent them from contracting HIV/AIDS.

Clinical predictors of older driver performance on a standardized road test.

PubMed

Classen, Sherrilene; Horgas, Ann; Awadzi, Kezia; Messinger-Rapport, Barbara; Shechtman, Orit; Joo, Yongsung

2008-10-01

To determine the relationship between clinical variables (demographics, cognitive testing, comorbidities, and medications) and failing a standardized road test in older adults. Analysis of on-the road studies performed in optimal weather conditions, between January 1, 2005, and May 1, 2007. The standardized testing was held at the National Older Driver Research and Training Center (NODRTC), Florida, and included 127 adults aged 65 and older with current driver licenses, recruited by advertisement from the Gainesville, Florida, community. Measurements consist of demographics, self-reported medications and medical conditions, cognitive testing including Trail Making Part B, global rating score (pass/fail), and driver maneuver score (0-273, with 273 indicating perfect driving or zero errors). A total of 127 older adults completed the protocol. Mean age was 74.8 years (SD = 6.3); 46.5% females. Mean time for Trail Making Part B was 114.3 seconds (SD of 83). Among the 127 drivers, the mean Sum of Maneuvers Score was 238.9 (SD of 25.0) and 24 (19%) failed the driver test. Odds ratio estimates for failing the test included advanced age (6.7, 95% CI 2.2 to 19.8), presence of a neurological disease (2.8, 95% CI 1.2 to 6.5), and prolonged time to complete the Trail Making Part B cognitive test (2.5, 95% CI 1.0 to 5.9). Conversely, odds ratio estimates lowering the risk of failure included taking a non-diabetic hormonal medications (e.g., thyroid and estrogen drugs; 0.3, 95% CI .09 to 0.7) and having a musculoskeletal diagnosis (0.3, 95% CI .1 to 0.7). To our knowledge, this is the first study to examine the medical predictors of failing a standardized road test. Advanced age and prolonged time on Trail Making Part B were the two major predictors of test failure and a lower Sum of Maneuvers Score. Our study also found that having a neurological diagnosis (primarily cerebrovascular and Parkinson's disease) predicted test failure. Medications from neurological class also predicted a lower Sum of Maneuvers Score. Further study needs to be done to explain the apparent protective effect of musculoskeletal conditions and hormonal medications.

[Assessment of the pharmaceutical expenditure in Hungary].

PubMed

Inotai, András; Merész, Gergo; Kaló, Zoltán

2010-01-01

Scarcity of health care resources draws attention to the expenditure on pharmaceuticals, as drugs are considered to be one of the major growth drivers of health care spending. This article assesses the Hungarian expenditure on pharmaceuticals by taking into account the economic status of the country and benchmarks from other OECD countries with special focus on indicators of Visegrad V4 countries (Czech Republic, Slovakia, Poland and Hungary). Our results highlight the heterogeneity of pharmaceutical expenditure data derived from different indicators among observed countries. Pharmaceutical spending is relatively higher in middle-income countries, mainly due the price convergence of innovative drug's, on contrary manpower cost of health care services are adjusted to local price levels, therefore the price differential of health care services between middle income and developed countries is greater. International trends of the global pharmaceutical market are also valid in Hungary. Increased private funding, mainly out of pocket payments above the average of V4 countries, has been the major growth driver of pharmaceutical expenditure recently in Hungary. Increased private pharmaceutical expenditure was mainly derived from the severe cost-containment measures in 2006. The annual growth rate of the National Health Insurance Fund's pharmaceutical budget for drug reimbursement was 1.37% in real terms between 1994 and 2009. This is much beneath the expansion of global pharmaceutical market. Consequently, cost-containment of public pharmaceutical spending was very successful in the last fifteen years, and the burden of market growth has been shifted to households. Public health programmes, investment into preventive care, with consideration on unfavourable Hungarian morbidity and mortality indicators, however, necessitate the increase of public pharmaceutical budget. In order to improve the allocative efficiency of health care spending, available resources should be spent only on effective, cost-effective, economically affordable medicines.

Cannabis effects on driving skills.

PubMed

Hartman, Rebecca L; Huestis, Marilyn A

2013-03-01

Cannabis is the most prevalent illicit drug identified in impaired drivers. The effects of cannabis on driving continue to be debated, making prosecution and legislation difficult. Historically, delays in sample collection, evaluating the inactive Δ(9)-tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-THC, and polydrug use have complicated epidemiologic evaluations of driver impairment after cannabis use. We review and evaluate the current literature on cannabis' effects on driving, highlighting the epidemiologic and experimental data. Epidemiologic data show that the risk of involvement in a motor vehicle accident (MVA) increases approximately 2-fold after cannabis smoking. The adjusted risk of driver culpability also increases substantially, particularly with increased blood THC concentrations. Studies that have used urine as the biological matrix have not shown an association between cannabis and crash risk. Experimental data show that drivers attempt to compensate by driving more slowly after smoking cannabis, but control deteriorates with increasing task complexity. Cannabis smoking increases lane weaving and impaired cognitive function. Critical-tracking tests, reaction times, divided-attention tasks, and lane-position variability all show cannabis-induced impairment. Despite purported tolerance in frequent smokers, complex tasks still show impairment. Combining cannabis with alcohol enhances impairment, especially lane weaving. Differences in study designs frequently account for inconsistencies in results between studies. Participant-selection bias and confounding factors attenuate ostensible cannabis effects, but the association with MVA often retains significance. Evidence suggests recent smoking and/or blood THC concentrations 2-5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Future cannabis-and-driving research should emphasize challenging tasks, such as divided attention, and include occasional and chronic daily cannabis smokers.

Comprehensive Characterization of Oncogenic Drivers in Asian Lung Adenocarcinoma.

PubMed

Li, Shiyong; Choi, Yoon-La; Gong, Zhuolin; Liu, Xiao; Lira, Maruja; Kan, Zhengyan; Oh, Ensel; Wang, Jian; Ting, Jason C; Ye, Xiangsheng; Reinhart, Christoph; Liu, Xiaoqiao; Pei, Yunfei; Zhou, Wei; Chen, Ronghua; Fu, Shijun; Jin, Gang; Jiang, Awei; Fernandez, Julio; Hardwick, James; Kang, Min Woong; I, Hoseok; Zheng, Hancheng; Kim, Jhingook; Mao, Mao

2016-12-01

The incidence rate of lung adenocarcinoma (LUAD), the predominant histological subtype of lung cancer, is elevated in Asians, particularly in female nonsmokers. The mutation patterns in LUAD in Asians might be distinct from those in LUAD in whites. We profiled 271 resected LUAD tumors (mainly stage I) to characterize the genomic landscape of LUAD in Asians with a focus on female nonsmokers. Mutations in EGFR, KRAS, erb-b2 receptor tyrosine kinase 2 gene (ERBB2), and BRAF; gene fusions involving anaplastic lymphoma receptor tyrosine kinase gene (ALK), ROS1, and ret proto-oncogene (RET); and Met Proto-Oncogene Tyrosine Kinase (MET) exon 14 skipping were the major drivers in LUAD in Asians, exhibiting mutually exclusive and differing prevalence from those reported in studies of LUAD in non-Asians. In addition, we identified a novel mutational signature of XNX (the mutated base N in the middle flanked by two identical bases at the 5' and 3' positions) that was overrepresented in LUAD tumors in nonsmokers and negatively correlated with the overall mutational frequency. In this cohort, approximately 85% of individuals have known driver mutations (EGFR 59.4%, KRAS 7.4%, ALK 7.4%, ERBB2 2.6%, ROS1 2.2%, RET 2.2%, MET 1.8%, BRAF 1.1%, and NRAS 0.4%). Seventy percent of smokers and 90% of nonsmokers had defined oncogenic drivers matching the U.S. Food and Drug Administration-approved targeted therapies. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Sleep Disorders as a Cause of Motor Vehicle Collisions

PubMed Central

de Mello, Marco Túlio; Narciso, Fernanda Veruska; Tufik, Sergio; Paiva, Teresa; Spence, David Warren; BaHammam, Ahmed S.; Verster, Joris C.; Pandi-Perumal, Seithikurippu R.

2013-01-01

Studies have shown that a large proportion of traffic accidents around the world are related to inadequate or disordered sleep. Recent surveys have linked driver fatigue to 16% to 20% of serious highway accidents in the UK, Australia, and Brazil. Fatigue as a result of sleep disorders (especially obstructive sleep apnea), excessive workload and lack of physical and mental rest, have been shown to be major contributing factors in motor vehicle accidents. A number of behavioral, physiological, and psychometric tests are being used increasingly to evaluate the impact of fatigue on driver performance. These include the oculography, polysomnography, actigraphy, the maintenance of wakefulness test, and others. Various strategies have been proposed for preventing or reducing the impact of fatigue on motor vehicle accidents. These have included: Educational programs emphasizing the importance of restorative sleep and the need for drivers to recognize the presence of fatigue symptoms, and to determine when to stop to sleep; The use of exercise to increase alertness and to promote restorative sleep; The use of substances or drugs to promote sleep or alertness (i.e. caffeine, modafinil, melatonin and others), as well as specific sleep disorders treatment; The use of CPAP therapy for reducing excessive sleepiness among drivers who have been diagnosed with obstructive sleep apnea. The evidence cited in this review justifies the call for all efforts to be undertaken that may increase awareness of inadequate sleep as a cause of traffic accidents. It is strongly recommended that, for the purpose of promoting highway safety and saving lives, all disorders that cause excessive sleepiness should be investigated and monitored. PMID:23626880

Predictors of micro-costing components in liver transplantation

PubMed Central

de Paiva Haddad, Luciana Bertocco; Ducatti, Liliana; Mendes, Luana Regina Baratelli Carelli; Andraus, Wellington; D’Albuquerque, Luiz Augusto Carneiro

2017-01-01

OBJECTIVES: Although liver transplantation procedures are common and highly expensive, their cost structure is still poorly understood. This study aimed to develop models of micro-costs among patients undergoing liver transplantation procedures while comparing the role of individual clinical predictors using tree regression models. METHODS: We prospectively collected micro-cost data from patients undergoing liver transplantation in a tertiary academic center. Data collection was conducted using an Intranet registry integrated into the institution’s database for the storing of financial and clinical data for transplantation cases. RESULTS: A total of 278 patients were included and accounted for 300 procedures. When evaluating specific costs for the operating room, intensive care unit and ward, we found that in all of the sectors but the ward, human resources were responsible for the highest costs. High cost supplies were important drivers for the operating room, whereas drugs were among the top four drivers for all sectors. When evaluating the predictors of total cost, a MELD score greater than 30 was the most important predictor of high cost, followed by a Donor Risk Index greater than 1.8. CONCLUSION: By focusing on the highest cost drivers and predictors, hospitals can initiate programs to reduce cost while maintaining high quality care standards. PMID:28658432

Prescription of antiepileptics and the risk of road traffic crash.

PubMed

Orriols, Ludivine; Foubert-Samier, Alexandra; Gadegbeku, Blandine; Delorme, Bernard; Tricotel, Aurore; Philip, Pierre; Moore, Nicholas; Lagarde, Emmanuel

2013-03-01

Studies assessing the impact of epilepsy and its medication on the risk of road traffic crashes have shown inconsistent results. The aim in this study was to assess this risk using French databases. Data from three French national databases were extracted and matched: the national health care insurance database, police reports, and the national police database of injurious crashes. Only antiepileptics prescribed predominantly in epilepsy were studied (phenobarbital, phenytoin, ethosuximide, valproic acid, vigabatrin, tiagabin, levitiracetam, zonisamide, and lacosamide). A case-control analysis comparing responsible and non-responsible drivers and a case-crossover analysis were performed. Drivers (72 685) involved in an injurious crash in France between July 2005 and May 2008, were included. Drivers exposed to prescribed antiepileptic medicines (n = 251) had an increased risk of being responsible for a crash (OR 1.74 [1.29-2.34]). The association was also significant for the most severe epileptic patients (n = 99; OR = 2.20 [1.31-3.69]). Case-crossover analysis found no association between crash risk and treatment prescription. Patients with prescription of antiepileptic drugs should be cautioned about their potential risk of road traffic crash. This risk is however more likely to be related to seizures than to the effect of antiepileptic medicines. © The Author(s) 2013.

Cost of Illness of Multiple Sclerosis - A Systematic Review

PubMed Central

Ernstsson, Olivia; Gyllensten, Hanna; Alexanderson, Kristina; Tinghög, Petter; Friberg, Emilie; Norlund, Anders

2016-01-01

Background Cost-of-illness (COI) studies of Multiple Sclerosis (MS) are vital components for describing the economic burden of MS, and are frequently used in model studies of interventions of MS. We conducted a systematic review of studies estimating the COI of MS, to compare costs between studies and examine cost drivers, emphasizing generalizability and methodological choices. Material and method A literature search on studies published in English on COI of MS was performed in PubMed for the period January 1969 to January 2014, resulting in 1,326 publications. A mapping of studies using a bottom-up approach or top-down approach, respectively, was conducted for the 48 studies assessed as relevant. In a second analysis, the cost estimates were compared between the 29 studies that used a societal perspective on costs, human capital approach for indirect costs, presenting number of patients included, time-period studied, and year of price level used. Results The mapping showed that bottom-up studies and prevalence approaches were most common. The cost ratios between different severity levels within studies were relatively stable, to the ratio of 1 to 2 to 3 for disability level categories. Drugs were the main cost drivers for MS-patients with low disease severity, representing 29% to 82% of all costs in this patient group, while the main cost components for groups with more advanced MS symptoms were production losses due to MS and informal care, together representing 17% to 67% of costs in those groups. Conclusion The bottom-up method and prevalence approach dominated in studies of COI of MS. Our findings show that there are difficulties in comparing absolute costs across studies, nevertheless, the relative costs expressed as cost ratios, comparing different severity levels, showed higher resemblance. Costs of drugs were main cost drivers for less severe MS and informal care and production losses for the most severe MS. PMID:27411042

Overweight and obesity on the island of Ireland: an estimation of costs.

PubMed

Dee, Anne; Callinan, Aoife; Doherty, Edel; O'Neill, Ciaran; McVeigh, Treasa; Sweeney, Mary Rose; Staines, Anthony; Kearns, Karen; Fitzgerald, Sarah; Sharp, Linda; Kee, Frank; Hughes, John; Balanda, Kevin; Perry, Ivan J

2015-03-16

The increasing prevalence of overweight and obesity worldwide continues to compromise population health and creates a wider societal cost in terms of productivity loss and premature mortality. Despite extensive international literature on the cost of overweight and obesity, findings are inconsistent between Europe and the USA, and particularly within Europe. Studies vary on issues of focus, specific costs and methods. This study aims to estimate the healthcare and productivity costs of overweight and obesity for the island of Ireland in 2009, using both top-down and bottom-up approaches. Costs were estimated across four categories: healthcare utilisation, drug costs, work absenteeism and premature mortality. Healthcare costs were estimated using Population Attributable Fractions (PAFs). PAFs were applied to national cost data for hospital care and drug prescribing. PAFs were also applied to social welfare and national mortality data to estimate productivity costs due to absenteeism and premature mortality. The healthcare costs of overweight and obesity in 2009 were estimated at €437 million for the Republic of Ireland (ROI) and €127.41 million for NI. Productivity loss due to overweight and obesity was up to €865 million for ROI and €362 million for NI. The main drivers of healthcare costs are cardiovascular disease, type II diabetes, colon cancer, stroke and gallbladder disease. In terms of absenteeism, low back pain is the main driver in both jurisdictions, and for productivity loss due to premature mortality the primary driver of cost is coronary heart disease. The costs are substantial, and urgent public health action is required in Ireland to address the problem of increasing prevalence of overweight and obesity, which if left unchecked will lead to unsustainable cost escalation within the health service and unacceptable societal costs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Disease ecology, health and the environment: a framework to account for ecological and socio-economic drivers in the control of neglected tropical diseases.

PubMed

Garchitorena, A; Sokolow, S H; Roche, B; Ngonghala, C N; Jocque, M; Lund, A; Barry, M; Mordecai, E A; Daily, G C; Jones, J H; Andrews, J R; Bendavid, E; Luby, S P; LaBeaud, A D; Seetah, K; Guégan, J F; Bonds, M H; De Leo, G A

2017-06-05

Reducing the burden of neglected tropical diseases (NTDs) is one of the key strategic targets advanced by the Sustainable Development Goals. Despite the unprecedented effort deployed for NTD elimination in the past decade, their control, mainly through drug administration, remains particularly challenging: persistent poverty and repeated exposure to pathogens embedded in the environment limit the efficacy of strategies focused exclusively on human treatment or medical care. Here, we present a simple modelling framework to illustrate the relative role of ecological and socio-economic drivers of environmentally transmitted parasites and pathogens. Through the analysis of system dynamics, we show that periodic drug treatments that lead to the elimination of directly transmitted diseases may fail to do so in the case of human pathogens with an environmental reservoir. Control of environmentally transmitted diseases can be more effective when human treatment is complemented with interventions targeting the environmental reservoir of the pathogen. We present mechanisms through which the environment can influence the dynamics of poverty via disease feedbacks. For illustration, we present the case studies of Buruli ulcer and schistosomiasis, two devastating waterborne NTDs for which control is particularly challenging.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'. © 2017 The Author(s).

Statistical Characteristics of Wrong-Way Driving Crashes on Illinois Freeways.

PubMed

Zhou, Huaguo; Zhao, Jiguang; Pour-Rouholamin, Mahdi; Tobias, Priscilla A

2015-01-01

Driving the wrong way on freeways, namely wrong-way driving (WWD), has been found to be a major concern for more than 6 decades. The purpose of this study was to identify characteristics of this type of crash as well as to rank the locations/interchanges according to their vulnerability to WWD entries. The WWD crash data on Illinois freeways were statistically analyzed for a 6-year time period (2004 to 2009) from 3 aspects: crash, vehicle, and person. The temporal distributions, geographical distributions, roadway characteristics, and crash locations were analyzed for WWD crashes. The driver demographic information, physical condition, and injury severity were analyzed for wrong-way drivers. The vehicle characteristics, vehicle operation, and collision results were analyzed for WWD vehicles. A method was brought about to identify wrong-way entry points that was then used to develop a relative-importance technique and rank different interchange types in terms of potential WWD incidents. The findings revealed that a large proportion of WWD crashes occurred during the weekend from midnight to 5 a.m. Approximately 80% of WWD crashes were located in urban areas and nearly 70% of wrong-way vehicles were passenger cars. Approximately 58% of wrong-way drivers were driving under the influence (DUI). Of those, nearly 50% were confirmed to be impaired by alcohol, about 4% were impaired by drugs, and more than 3% had been drinking. The analysis of interchange ranking found that compressed diamond interchanges, single point diamond interchanges (SPDIs), partial cloverleaf interchanges, and freeway feeders had the highest wrong-way crash rates (wrong-way crashes per 100 interchanges per year). The findings of this study call for more attention to WWD crashes from different aspects such as driver age group, time of day, day of week, and DUI drivers. Based on the analysis results of WWD distance, the study explained why a 5-mile radius of WWD crash location should be studied for WWD fatal crashes with unknown entry points.

Constrained target controllability of complex networks

NASA Astrophysics Data System (ADS)

Guo, Wei-Feng; Zhang, Shao-Wu; Wei, Ze-Gang; Zeng, Tao; Liu, Fei; Zhang, Jingsong; Wu, Fang-Xiang; Chen, Luonan

2017-06-01

It is of great theoretical interest and practical significance to study how to control a system by applying perturbations to only a few driver nodes. Recently, a hot topic of modern network researches is how to determine driver nodes that allow the control of an entire network. However, in practice, to control a complex network, especially a biological network, one may know not only the set of nodes which need to be controlled (i.e. target nodes), but also the set of nodes to which only control signals can be applied (i.e. constrained control nodes). Compared to the general concept of controllability, we introduce the concept of constrained target controllability (CTC) of complex networks, which concerns the ability to drive any state of target nodes to their desirable state by applying control signals to the driver nodes from the set of constrained control nodes. To efficiently investigate the CTC of complex networks, we further design a novel graph-theoretic algorithm called CTCA to estimate the ability of a given network to control targets by choosing driver nodes from the set of constrained control nodes. We extensively evaluate the CTC of numerous real complex networks. The results indicate that biological networks with a higher average degree are easier to control than biological networks with a lower average degree, while electronic networks with a lower average degree are easier to control than web networks with a higher average degree. We also show that our CTCA can more efficiently produce driver nodes for target-controlling the networks than existing state-of-the-art methods. Moreover, we use our CTCA to analyze two expert-curated bio-molecular networks and compare to other state-of-the-art methods. The results illustrate that our CTCA can efficiently identify proven drug targets and new potentials, according to the constrained controllability of those biological networks.

The social biography of antibiotic use in smallholder dairy farms in India.

PubMed

Chauhan, Abhimanyu Singh; George, Mathew Sunil; Chatterjee, Pranab; Lindahl, Johanna; Grace, Delia; Kakkar, Manish

2018-01-01

Antimicrobial resistance (AMR) has been identified as one of the major threats to global health, food security and development today. While there has been considerable attention about the use and misuse of antibiotics amongst human populations in both research and policy environments, there is no definitive estimate of the extent of misuse of antibiotics in the veterinary sector and its contribution to AMR in humans. In this study, we explored the drivers ofirrational usage of verterinary antibiotics in the dairy farming sector in peri-urban India. The study was conducted in the peri-urban belts of Ludhiana, Guwahati and Bangalore. A total of 54 interviews (formal and non-formal) were carried out across these three sites. Theme guides were developed to explore different drivers of veterinary antimicrobial use. Data was audio recorded and transcribed. Analysis of the coded data set was carried out using AtlasTi. Version 7. Themes emerged inductively from the set of codes. Findings were presented based on concept of 'levels of analyses'. Emergent themes were categorised as individual, health systems, and policy level drivers. Low level of knowledge related to antibiotics among farmers, active informal service providers, direct marketing of drugs to the farmers and easily available antibiotics, dispensed without appropriate prescriptions contributed to easy access to antibiotics, and were identified to be the possible drivers contributing to the non-prescribed and self-administered use of antibiotics in the dairy farms. Smallholding dairy farmers operated within very small margins of profits. The paucity of formal veterinary services at the community level, coupled with easy availability of antibiotics and the need to ensure profits and minimise losses, promoted non-prescribed antibiotic consumption. It is essential that these local drivers of irrational antibiotic use are understood in order to develop interventions and policies that seek to reduce antibiotic misuse.

Improving pharmaceutical innovation by building a more comprehensive database on drug development and use.

PubMed

Daniel, Gregory W; Cazé, Alexis; Romine, Morgan H; Audibert, Céline; Leff, Jonathan S; McClellan, Mark B

2015-02-01

New drugs and biologics have had a tremendous impact on the treatment of many diseases. However, available measures suggest that pharmaceutical innovation has remained relatively flat, despite substantial growth in research and development spending. We review recent literature on pharmaceutical innovation to identify limitations in measuring and assessing innovation, and we describe the framework and collaborative approach we are using to develop more comprehensive, publicly available metrics for innovation. Our research teams at the Brookings Institution and Deerfield Institute are collaborating with experts from multiple areas of drug development and regulatory review to identify and collect comprehensive data elements related to key development and regulatory characteristics for each new molecular entity approved over the past several decades in the United States and the European Union. Subsequent phases of our effort will add data on downstream product use and patient outcomes and will also include drugs that have failed or been abandoned in development. Such a database will enable researchers to better analyze the drivers of drug innovation, trends in the output of new medicines, and the effect of policy efforts designed to improve innovation. Project HOPE—The People-to-People Health Foundation, Inc.

Detection of phenazepam in impaired driving.

PubMed

Kerrigan, Sarah; Mellon, Monica Brady; Hinners, Paige

2013-10-01

Phenazepam is a potent 1,4-benzodiazepine that has gained notoriety among recreational drug users. First synthesized in Ukraine in the 1970s, it is one of the most commonly prescribed benzodiazepines in Russia and other commonwealth of independent state nations, where it is used therapeutically as a prescription drug. Reports of abuse are widespread and several European countries have taken steps to control its use. However, in the USA, phenazepam is not approved for use by the Food and Drug Administration, nor scheduled under the Federal Controlled Substances Act. Phenazepam is widely available on the Internet, and recreational drug users report a potency 10-fold greater than that of nordiazepam. We report a case of a 24-year-old male driver who was apprehended for impaired driving following a two-vehicle crash. The subject exhibited slurred speech and profound psychomotor impairment. Toxicology testing revealed phenazepam at a concentration of 76 ng/mL in blood, with no other drugs detected. This case report not only demonstrates the potential for adverse traffic safety consequences following the misuse of phenazepam, but also highlights the importance of analytical factors such as immunoassay cutoff concentration, cross-reactivity and comprehensive screening using chromatographic-based techniques for impaired driving investigations.

[Time profile of serum THC levels in occasional and chronic marihuana smokers after acute drog use - implication for drivind motor vehicles].

PubMed

Balíková, Marie; Hložek, Tomáš; Páleníček, Tomáš; Tylš, Filip; Viktorinová, Michaela; Melicher, Tomáš; Androvičová, Renáta; Tomíček, Pavel; Roman, Michal; Horáček, Jiří

2014-01-01

Cannabis consumption has individual influence to cognitive and psychomotor functions of drivers and it has been generally accepted that driving under influence is risky in the perspective of traffic safety. However, rules how to assess fitness to drive are not quite clear. The psychoactive compound delta-9-tetrahydrocannabinol (THC) impairs cognition, psychomotor behaviour and driving performance in a dose-related manner approximately. After a single drug dose, THC blood concentration peaks within minutes, before the end of smoking, with a subsequent rapid decrease to the analytical limit of detection. Peak euphoria is delayed compared to THC peak blood concentration and physiological and behavioural effects return to baseline within 3-5 hours. In chronic users, the lipophilic THC accumulates in fat tissues, where its slow redistribution into blood is the rate limiting process in its terminal elimination. In our experimental study we have attempted to contribute to this discussion with results obtained from human volunteers - cannabis consumers in Czech Republic. Aim of our study was to document the time profile of serum THC level in occasional and chronic cannabis users. The observational interval covered the time immediately after the drug consumption (an own cigarette/joint) till 24 hours after. Our preliminary results have shown that in occasional users, THC serum levels cannot be detected already 4 hours after usual cannabis dose, whereas in chronic users measurable THC concentrations in serum persist longer. Moreover, some chronic consumers were practically with permanent THC detection during our observation period and also the chronic users consumed higher THC doses significantly related to doses in occasional ones. Presented results of the experimental study with human volunteers confirm a great individual variability of the kinetic profile of THC in blood due to complicated redistribution. The practical forensic question is how long the psychotropic effects of THC can persist after the last drug dose. In chronic users there are well documented indications of long term adverse effects to neurocognitive functions. THC blood level itself can not directly document the intensity of impairment of a driver. Moreover, the concentration of THC in blood at the time of driving is probably substantially higher than at the time of blood sampling. Therefore due to the prevention of traffic risk, some countries adopted per se traffic legislation based on analytical principle with minimum tolerance to illegal drugs in blood of drivers at driving. Low blood concentrations of THC close to the limit of detection of a specific toxicological method (GC-MS or LC-MS) are justified in an effective traffic legislation.

Hedonic Homeostatic Dysregulation as a Driver of Drug-Seeking Behavior

PubMed Central

Koob, George F.

2009-01-01

Drug addiction can be defined by a compulsion to seek and take drug and loss of control in limiting intake, and the excessive drug taking derives from multiple motivational mechanisms. One such mechanism is the emergence of a negative emotional state when access to the drug is prevented, reflecting hedonic homeostatic dysregulation. Excessive drug taking then results in part via the construct of negative reinforcement. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in reward and stress within basal forebrain structures, including the ventral striatum and extended amygdala. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreases in dopamine and opioid peptide function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Chronic exposure or extended access to self-administration of all major drugs of abuse produces during abstinence increases in reward thresholds, increases in aversive anxiety-like responses, increases in extracellular levels of CRF in the central nucleus of the amygdala, and increases in drug self-administration. CRF receptor antagonists block excessive drug intake produced by dependence. A combination of decreased reward system function and increased brain stress response system function is hypothesized to be responsible for hedonic homeostatic dysregulation that drives drug seeking behavior in dependence. Such hedonic dysregulation is hypothesized to extend into protracted abstinence to provide a residual negative emotional state that enhances the salience of cues eliciting drug seeking and relapse. PMID:20054425

Importance of Urinary Drug Screening in the Multiple Sleep Latency Test and Maintenance of Wakefulness Test.

PubMed

Anniss, Angela M; Young, Alan; O'Driscoll, Denise M

2016-12-15

Multiple sleep latency testing (MSLT) and the maintenance of wakefulness test (MWT) are gold-standard objective tests of daytime sleepiness and alertness; however, there is marked variability in their interpretation and practice. This study aimed to determine the incidence of positive drug screens and their influence on MSLT, MWT, and polysomnographic variables. All patients attending Eastern Health Sleep Laboratory for MSLT or MWT over a 21-mo period were included in the study. Urinary drug screening for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates was performed following overnight polysomnography (PSG). Demographics and PSG variables were compared. Of 69 studies, MSLT (43) and MWT (26), 16% of patients had positive urinary drug screening (7 MSLT; 4 MWT). Drugs detected included amphetamines, cannabinoids, opiates, and benzodiazepines. No patient self-reported use of these medications prior to testing. No demographic, MSLT or MWT PSG data or overnight PSG data showed any statistical differences between positive and negative drug screen groups. Of seven MSLT patients testing positive for drug use, one met criteria for the diagnosis of narcolepsy and five for idiopathic hypersomnia. On MWT, three of the four drug-positive patients had a history of a motor vehicle accident and two patients were occupational drivers. These findings indicate drug use is present in patients attending for daytime testing of objective sleepiness and wakefulness. These data support routine urinary drug screening in all patients undergoing MSLT or MWT studies to ensure accurate interpretation in the context of illicit and prescription drug use. © 2016 American Academy of Sleep Medicine

Trends in reports of driving following illicit drug consumption among regular drug users in Australia, 2007-2013: Has random roadside drug testing had a deterrent effect?

PubMed

Horyniak, Danielle; Dietze, Paul; Lenton, Simon; Alati, Rosa; Bruno, Raimondo; Matthews, Allison; Breen, Courtney; Burns, Lucy

2017-07-01

Driving following illicit drug consumption ('drug-driving') is a potential road safety risk. Roadside drug testing (RDT) is conducted across Australia with the dual aims of prosecuting drivers with drugs in their system and deterring drug-driving. We examined trends over time in self-reported past six-month drug-driving among sentinel samples of regular drug users and assessed the impact of experiences of RDT on drug-driving among these participants. Data from 1913 people who inject drugs (PWID) and 3140 regular psychostimulant users (RPU) who were first-time participants in a series of repeat cross-sectional sentinel studies conducted in Australian capital cities from 2007 to 2013 and reported driving in the past six months were analysed. Trends over time were assessed using the χ 2 test for trend. Multivariable logistic regressions assessed the relationship between experiences of RDT and recent drug-driving, adjusting for survey year, jurisdiction of residence and socio-demographic and drug use characteristics. The percentage of participants reporting recent (past six months) drug-driving decreased significantly over time among both samples (PWID: 83% [2007] vs. 74% [2013], p<0.001; RPU: 72% vs. 56%, p<0.001), but drug-driving remained prevalent. Lifetime experience of RDT increased significantly over time (PWID: 6% [2007] vs. 32% [2013], p<0.001; RPU: 2% vs. 11%, p<0.001). There were no significant associations between experiencing RDT and drug-driving among either PWID or RPU. Although there is some evidence that drug-driving among key risk groups of regular drug users is declining in Australia, possibly reflecting a general deterrent effect of RDT, experiencing RDT appears to have no specific deterrent effect on drug-driving. Further intervention, with a particular focus on changing attitudes towards drug-driving, may be needed to further reduce this practice among these groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

Capitalising upon political opportunities to reform drug policy: a case study into the development of the Australian "Tough on Drugs-Illicit Drug Diversion Initiative".

PubMed

Hughes, Caitlin Elizabeth

2009-09-01

The introduction of political "war on drug" strategies and Prime Ministerial advisory groups increase opportunities for drug policy reform. Yet the strengths and limitations of capitalising upon political opportunities remain unclear. This paper provides a unique insight into the development of an Australian reform, the "Tough on Drugs-Illicit Drug Diversion Initiative." This reform was one of the major policies to emerge out of the Federal Coalition "Tough on Drugs" strategy. In spite of the rhetoric the Illicit Drug Diversion Initiative (IDDI) has diverted minor drug users away from the traditional criminal justice system. This paper draws upon interviews with 16 expert policy makers involved in the advocacy and negotiations leading up to the adoption of the IDDI to examine what drove the reform and how and why a pragmatic reform emerged. The IDDI culminated from the presence of five main drivers: a crisis in relation to heroin and crime, antagonism towards the government, a weak but growing evidence-base on the merits of drug diversion, a shift in law enforcement attitudes and persuasive advocacy by a group of non-government experts. This paper contends that the Prime Minister's new "Tough on Drugs" strategy and expanded governance arrangements created new space for policy actors to intervene in the policy formulation process and to convert the governments proposed "zero tolerance" response into a more humane and potentially effective response. This paper concludes that contrary to popular opinion political venues and politicisation may offer valuable opportunities for drug policy reform. The challenge for researchers and policy advocates is to see how they can best utilise political venues to obtain pragmatic reform.

[Driving and the elderly: aspects of aging and handicap].

PubMed

Clément, R; Ferreol, S; Ould-Aoudia, V; Berger, M; Rodat, O

2005-10-08

Impairment of cognitive performance is associated with an excess risk of accidents. Adaptation of driving behavior in subjects with benign cognitive disorders reduces risk of automobile accidents. Cessation of driving or at least not driving alone limits the excess accident risk for drivers with dementia. Alterations in visual field and acuity increase risk of traffic accidents. Drugs affecting vigilance and neurological, cardiovascular and osteoarticular disorders increase accident risk. Screening for these disorders in the elderly is a necessary public safety measure.

Increased thalamic resting-state connectivity as a core driver of LSD-induced hallucinations.

PubMed

Müller, F; Lenz, C; Dolder, P; Lang, U; Schmidt, A; Liechti, M; Borgwardt, S

2017-12-01

It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system. 100 μg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI-to-ROI and ROI-to-voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects. LSD caused significant alterations in all dimensions of the 5D-ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD-induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects. Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5-HT 2A -receptor in altered states of consciousness. © 2017 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.

Patient-derived tumour xenografts for breast cancer drug discovery.

PubMed

Cassidy, John W; Batra, Ankita S; Greenwood, Wendy; Bruna, Alejandra

2016-12-01

Despite remarkable advances in our understanding of the drivers of human malignancies, new targeted therapies often fail to show sufficient efficacy in clinical trials. Indeed, the cost of bringing a new agent to market has risen substantially in the last several decades, in part fuelled by extensive reliance on preclinical models that fail to accurately reflect tumour heterogeneity. To halt unsustainable rates of attrition in the drug discovery process, we must develop a new generation of preclinical models capable of reflecting the heterogeneity of varying degrees of complexity found in human cancers. Patient-derived tumour xenograft (PDTX) models prevail as arguably the most powerful in this regard because they capture cancer's heterogeneous nature. Herein, we review current breast cancer models and their use in the drug discovery process, before discussing best practices for developing a highly annotated cohort of PDTX models. We describe the importance of extensive multidimensional molecular and functional characterisation of models and combination drug-drug screens to identify complex biomarkers of drug resistance and response. We reflect on our own experiences and propose the use of a cost-effective intermediate pharmacogenomic platform (the PDTX-PDTC platform) for breast cancer drug and biomarker discovery. We discuss the limitations and unanswered questions of PDTX models; yet, still strongly envision that their use in basic and translational research will dramatically change our understanding of breast cancer biology and how to more effectively treat it. © 2016 The authors.

Impact of Expanding ELISA Screening in DUID Investigations to Include Carisoprodol/Meprobamate and Zolpidem.

PubMed

Lu, Aileen; Scott, Karen S; Chan-Hosokawa, Aya; Logan, Barry K

2017-03-01

In 2013, the National Safety Council's Alcohol Drugs and Impairment Division added zolpidem and carisoprodol and its metabolite meprobamate to the list of Tier 1 drugs that should be tested for in all suspected drug impaired driving and motor vehicle fatality investigations. We describe the validation of an enzyme linked immunosorbent assays (ELISA) for both drugs in whole blood, and the utilization of the ELISA to assess their positivity in a sample of 322 suspected impaired driving cases that was retrospectively screened using the validated assays. The occurrence of carisoprodol/meprobamate was found to be 1.2%, and for zolpidem, 1.6%. In addition, we analyzed a large dataset (n = 1,672) of Driving Under the Influence of Drugs (DUID) test results from a laboratory performing high volume DUID testing to assess the frequency of detection of both drugs after implementing the expanded NSC scope. Carisoprodol or meprobamate were found positive in 5.9% (n = 99) of these samples, while zolpidem was found positive in 5.3% (n = 89) in drivers who in many cases had been found to be negative for other drugs. Carisoprodol and zolpidem are both potent CNS depressants and are appropriate additions to the recommended NSC scope of testing. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evolution of antiretroviral drug costs in Brazil in the context of free and universal access to AIDS treatment.

PubMed

Nunn, Amy S; Fonseca, Elize M; Bastos, Francisco I; Gruskin, Sofia; Salomon, Joshua A

2007-11-13

Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil's AIDS treatment program has been cited widely as the developing world's largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART) for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs), procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005. We compared Brazil's ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil's reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir-ritonavir (lopinavir/r) have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six specific drugs: patented lopinavir/r, efavirenz, tenofovir, atazanavir, enfuvirtide, and a locally produced generic, fixed-dose combination of zidovudine and lamivudine (AZT/3TC). Because prices declined for many of the patented drugs that constitute the largest share of drug costs, nearly the entire increase in overall drug expenditures between 2001 and 2005 is attributable to increases in drug quantities. Had all drug quantities been held constant from 2001 until 2005 (or for those drugs entering treatment guidelines after 2001, held constant between the year of introduction and 2005), total costs would have increased by only an estimated US$7 million. We estimate that in the absence of price declines for patented drugs, Brazil would have spent a cumulative total of US$2 billion on drugs for HAART between 2001 and 2005, implying a savings of US$1.2 billion from price declines. Finally, in comparing Brazilian prices for locally produced generic ARVs to the lowest international prices meeting global pharmaceutical quality standards, we find that current prices for Brazil's locally produced generics are generally much higher than corresponding global prices, and note that these prices have risen in Brazil while declining globally. We estimate the excess costs of Brazil's locally produced generics totaled US$110 million from 2001 to 2005. Despite Brazil's more costly generic ARVs, the net result of ARV price changes has been a cost savings of approximately US$1 billion since 2001. HAART costs have nevertheless risen steeply as Brazil has scaled up treatment. These trends may foreshadow future AIDS treatment cost trends in other developing countries as more people start treatment, AIDS patients live longer and move from first-line to second and third-line treatment, AIDS treatment becomes more complex, generic competition emerges, and newer patented drugs become available. The specific application of the Brazilian model to other countries will depend, however, on the strength of their health systems, intellectual property regulations, epidemiological profiles, AIDS treatment guidelines, and differing capacities to produce drugs locally.

Drug Solubility in Fatty Acids as a Formulation Design Approach for Lipid-Based Formulations: A Technical Note.

PubMed

Lee, Yung-Chi; Dalton, Chad; Regler, Brian; Harris, David

2018-06-06

Lipid-based drug delivery systems have been intensively investigated as a means of delivering poorly water-soluble drugs. Upon ingestion, the lipases in the gastrointestinal tract digest lipid ingredients, mainly triglycerides, within the formulation into monoglycerides and fatty acids. While numerous studies have addressed the solubility of drugs in triglycerides, comparatively few publications have addressed the solubility of drugs in fatty acids, which are the end product of digestion and responsible for the solubility of drug within mixed micelles. The objective of this investigation was to explore the solubility of a poorly water-soluble drug in fatty acids and raise the awareness of the importance of drug solubility in fatty acids. The model API (active pharmaceutical ingredient), a weak acid, is considered a BCS II compound with an aqueous solubility of 0.02 μg/mL and predicted partition coefficient >7. The solubility of API ranged from 120 mg/mL to over 1 g/mL in fatty acids with chain lengths across the range C18 to C6. Hydrogen bonding was found to be the main driver of the solubilization of API in fatty acids. The solubility of API was significantly reduced by water uptake in caprylic acid but not in oleic acid. This report demonstrates that solubility data generated in fatty acids can provide an indication of the solubility of the drug after lipid digestion. This report also highlights the importance of measuring the solubility of drugs in fatty acids in the course of lipid formulation development.

Drug Penetration Gradients Associated with Acquired Drug Resistance in Tuberculosis Patients.

PubMed

Dheda, Keertan; Lenders, Laura; Magombedze, Gesham; Srivastava, Shashikant; Raj, Prithvi; Arning, Erland; Ashcraft, Paula; Bottiglieri, Teodoro; Wainwright, Helen; Pennel, Timothy; Linegar, Anthony; Moodley, Loven; Pooran, Anil; Pasipanodya, Jotam G; Sirgel, Frederick A; van Helden, Paul D; Wakeland, Edward; Warren, Robin M; Gumbo, Tawanda

2018-06-07

Acquired resistance is an important driver of multidrug-resistant tuberculosis, even with good treatment adherence. However, exactly what initiates the resistance, and how it arises remains poorly understood. To identify the relationship between drug concentrations and drug susceptibility readouts (MICs) in the tuberculosis cavity. We recruited patients with medically incurable tuberculosis who were undergoing therapeutic lung resection whilst on treatment with the cocktail of second line anti-tuberculosis drugs. On the day of surgery antibiotic concentrations were measured in the blood and at seven pre-specified biopsy sites within each cavity. Mycobacterium tuberculosis was grown from each biopsy site, MICs of each drug identified, and whole genome sequencing performed. Spearman correlation coefficients between drug concentration and MIC were calculated. Fourteen patients treated for a median of 13 (range: 5-31) months were recruited. MICs and drug resistance-associated single nucleotide variants differed between the different geospatial locations within each cavity, and with pretreatment and serial sputum isolates, consistent with ongoing acquisition of resistance. However, pre-treatment sputum MIC had an accuracy of only 49.48% in predicting cavitary MICs. There were large concentration-distance gradients for each antibiotic. The location-specific concentrations inversely correlated with MICs (p<0.05), and therefore acquired resistance. Moreover, pharmacokinetic/pharmacodynamic exposures known to amplify drug-resistant subpopulations were encountered in all positions. These data inform interventional strategies relevant to drug delivery, dosing, and diagnostics to prevent the development of acquired resistance. The role of high intracavitary penetration as a biomarker of antibiotic efficacy, when assessing new regimens, requires clarification.

Cannabis Effects on Driving Skills

PubMed Central

Hartman, Rebecca L.; Huestis, Marilyn A.

2013-01-01

BACKGROUND Cannabis is the most prevalent illicit drug identified in impaired drivers. The effects of cannabis on driving continue to be debated, making prosecution and legislation difficult. Historically, delays in sample collection, evaluating the inactive Δ9-tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-THC, and polydrug use have complicated epidemiologic evaluations of driver impairment after cannabis use. CONTENT We review and evaluate the current literature on cannabis’ effects on driving, highlighting the epidemiologic and experimental data. Epidemiologic data show that the risk of involvement in a motor vehicle accident (MVA) increases approximately 2-fold after cannabis smoking. The adjusted risk of driver culpability also increases substantially, particularly with increased blood THC concentrations. Studies that have used urine as the biological matrix have not shown an association between cannabis and crash risk. Experimental data show that drivers attempt to compensate by driving more slowly after smoking cannabis, but control deteriorates with increasing task complexity. Cannabis smoking increases lane weaving and impaired cognitive function. Critical-tracking tests, reaction times, divided-attention tasks, and lane-position variability all show cannabis-induced impairment. Despite purported tolerance in frequent smokers, complex tasks still show impairment. Combining cannabis with alcohol enhances impairment, especially lane weaving. SUMMARY Differences in study designs frequently account for inconsistencies in results between studies. Participant-selection bias and confounding factors attenuate ostensible cannabis effects, but the association with MVA often retains significance. Evidence suggests recent smoking and/or blood THC concentrations 2–5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Future cannabis-and-driving research should emphasize challenging tasks, such as divided attention, and include occasional and chronic daily cannabis smokers. PMID:23220273

Analysis of EGFR, EML4-ALK, KRAS, and c-MET mutations in Chinese lung adenocarcinoma patients.

PubMed

Xia, Ning; An, Jian; Jiang, Qing-qing; Li, Min; Tan, Jun; Hu, Cheng-ping

2013-10-01

Mutation analysis of cancer driver genes is helpful for determining an optimal treatment strategy. We evaluated mutations in four driver genes, namely epidermal growth factor receptor (EGFR), Kirsten ras oncogene (KRAS), c-MET, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), in Chinese lung adenocarcinoma patients from Hunan Province. We enrolled 110 lung adenocarcinoma patients in a single institution. EGFR and KRAS mutations were examined by direct sequencing, the EML4-ALK fusion gene was analyzed by fluorescence in situ hybridization, and c-MET amplification and c-Met protein expression were detected by quantitative PCR and immunohistochemistry, respectively. EGFR and KRAS mutations were observed in 52.7% (58/110) and 3.6% (4/106) of patients, respectively. c-MET amplification was detected in 5.5% (6/110) of patients. In addition, 30% (33/110) of the cases expressed c-Met protein, including all of the patients harboring c-MET amplification. Ten percent (11/110) of patients harbored the EML4-ALK fusion gene, and the frequency of ALK rearrangement was higher than that of other cohort analyses involving patients from other regions in China. Almost all of these gene mutations were exclusive except that in two female non-smoking patients, who harbored an EGFR mutation and EML4-ALK rearrangement simultaneously. In total, 70% of patients in the study harbored one of the four gene mutations. Most Chinese lung adenocarcinoma patients harbor driver gene mutations, among which ALK rearrangements were more common in Hunan patients than in previously reported populations. Future clinical trials should be conducted to determine the safety and efficacy of drug combination targeting different driver mutations.

Effects of alcohol (BAC 0.5‰) and ecstasy (MDMA 100 mg) on simulated driving performance and traffic safety.

PubMed

Veldstra, Janet L; Brookhuis, Karel A; de Waard, Dick; Molmans, Barbara H W; Verstraete, Alain G; Skopp, Gisela; Jantos, Ricarda

2012-08-01

An increasing number of fatal road-accidents have been reported in which ecstasy was found in the blood of drivers. Although, ecstasy is frequently found to have been used in combination with alcohol, studies on the acute effects of ecstasy co-administered with alcohol on driving performance are relatively rare. The present study was designed to establish the extent of driver impairment as a consequence of ecstasy or combined ecstasy and alcohol use as compared to driving under the influence of 0.3‰, 0.5‰ and 0.8‰ alcohol. Furthermore, subjective performance was also assessed. Alcohol and ecstasy mainly influenced automated driving performance such as lateral and speed control. However, small to no effects of the substances were found on more complex driving behaviour. Overall, variance within the different driving measures was high especially when participants were treated with 3.4-methylenedioxy-methamphetamine (MDMA) and alcohol. Furthermore, equivalence testing showed that combined use may lead to impaired driving for some, but not all, drivers. Participants rated their own performance to be slightly worse than normal in both studies. Since driving was actually seriously deteriorated, this was a falsely positive assessment of their condition. The dissociation between subjective perceptions and objective performance decrements are important notions for traffic safety since this may affect a driver's judgement of whether or not it is safe to drive. For example, an intoxicated individual might decide to drive because the feelings of alertness caused by MDMA cloud the impairing effects of other drugs such as alcohol, thereby creating a potentially serious risk for traffic safety.

Teen driving behaviors in a rural southern state.

PubMed

Irons, Elizabeth; Nichols, Michele; King, William D; Crew, Marie; Monroe, Kathy

2014-12-01

Motor vehicle crashes are the leading cause of death for teenagers. Alabama ranks fourth in the United States for teen crash fatalities. We sought to describe risky driving behaviors among teens in the rural areas of the state's most populous county. A questionnaire was adapted from the Youth Risk Behavior Surveillance System. Each of the schools in Jefferson County, Alabama, participated in 2009 and 2010. Surveys were anonymous and data were entered into an Excel spreadsheet. Inclusion criteria were age 15 years and older. A total of 1399 surveys met inclusion criteria. A total of 52% of respondents were boys; 64% were white, 29% were African American, and 3% were Hispanic. Respondents were 15 (38%), 16 (36%), 17 (21%), and 18 (5%) years old. When asked about behaviors during driving in the last 30 days, 41% reported texting and 11% reported driving after drinking. Teens reported being a passenger in a car with the driver texting (67%) or after the driver had been drinking (27%) in the last 30 days. Overall, 58% reported not wearing a seatbelt; 13% reported driving after using drugs; 60% reported routinely exceeding the speed limit; 80% reported having discussed safe driving with a parent, but only 16% with their doctor; 25% had signed a safe driving contract; and 63% had taken a driving class. Many risky behaviors were identified for both teen drivers and passengers. A concerning number of teens are not receiving safe driving educational messages from parents, doctors, or driver's education classes. Some interventions have been instituted; however, more outreach efforts should be made to focus on strengthening driving laws and educating parents and teens.

Systematic Identification of Combinatorial Drivers and Targets in Cancer Cell Lines

PubMed Central

Tabchy, Adel; Eltonsy, Nevine; Housman, David E.; Mills, Gordon B.

2013-01-01

There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance. PMID:23577104

Systematic identification of combinatorial drivers and targets in cancer cell lines.

PubMed

Tabchy, Adel; Eltonsy, Nevine; Housman, David E; Mills, Gordon B

2013-01-01

There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance.

The power of r - pharmaceutical sales decomposition in Cyprus public healthcare sector and determinants of drug expenditure evolution: any lessons learned?

PubMed

Petrou, Panagiotis

2014-04-01

The pharmaceutical sector has been established as the primary cost driver in health. The scope of this paper is to explore the drivers of pharmaceutical expenditure in Cyprus by decomposing sales and assessing impact of prices, volumes and substitution effect. We used a statistical approach to decompose the growth of public pharmaceutical expenditure during 2005-2011 into three elements: 1) substitution effect; 2) price effect; and 3) increase of consumption. We further decomposed consumption into: 1) prescription/visits; 2) visits/beneficiaries; and 3) beneficiaries. Pharmaceutical expenditure grew by 31.4 % and volume of medicines dispensed increased by 55%. Prices declined by 11% and product-mix residual was -5.5%, indicating that Cyprus experienced a switch to cheaper medicines (generics) without compromising access of patients to innovative medicines. This was enhanced by guidelines, monitoring of prescribing behavior, generic substitution and efficient tendering. The increasing number of products per prescriptions should be monitored with caution.

A Manual Control Test for the Detection and Deterrence of Impaired Drivers

NASA Technical Reports Server (NTRS)

Stein, A. C.; Allen, R. W.; Jex, H. R.

1984-01-01

A brief manual control test and a decision strategy were developed, laboratory tested, and field validated which provide a means for detecting human operator impairment from alcohol or other drugs. The test requires the operator to stabilize progressively unstable controlled element dynamics. Control theory and experimental data verify that the human operator's control ability on this task is constrained by basic cybernetic characteristics, and that task performance is reliably affected by impairment effects on these characteristics. Assessment of human operator control ability is determined by a statistically based decision strategy. The operator is allowed several chances to exceed a preset pass criterion. Procedures are described for setting the pass criterion based on individual ability and a desired unimpaired failure rate. These procedures were field tested with apparatus installed in automobiles that were designed to discourage drunk drivers from operating their vehicles. This test program demonstrated that the control task and detection strategy could be applied in a practical setting to screen human operators for impairment in their basic cybernetic skills.

Emotional abilities as predictors of risky driving behavior among a cohort of middle aged drivers.

PubMed

Arnau-Sabatés, Laura; Sala-Roca, Josefina; Jariot-Garcia, Mercè

2012-03-01

The aim of this study is to analyze the relationship between emotional abilities and the influence of this relationship on self reported drivers' risky attitudes. The risky driving attitudes and emotional abilities of 177 future driving instructors were measured. The results demonstrate that risky attitudes correlate negatively with emotional abilities. Regression analysis showed that adaptability and interpersonal abilities explained the differences observed in the global risk attitude index. There were some differences in the specific risk factors. The variability observed in the speed and distraction and fatigue factors could also be explained by interpersonal and adaptability abilities. Nevertheless the tendency to take risks was explained by stress management and also interpersonal components. Emotional abilities have the weakest relation with alcohol and drugs factor, and in this case the variability observed was explained by the adaptability component. The results obtained highlight the importance take off including emotional abilities in prevention programs to reduce risky driving behaviors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics.

PubMed

Ding, Li; Bailey, Matthew H; Porta-Pardo, Eduard; Thorsson, Vesteinn; Colaprico, Antonio; Bertrand, Denis; Gibbs, David L; Weerasinghe, Amila; Huang, Kuan-Lin; Tokheim, Collin; Cortés-Ciriano, Isidro; Jayasinghe, Reyka; Chen, Feng; Yu, Lihua; Sun, Sam; Olsen, Catharina; Kim, Jaegil; Taylor, Alison M; Cherniack, Andrew D; Akbani, Rehan; Suphavilai, Chayaporn; Nagarajan, Niranjan; Stuart, Joshua M; Mills, Gordon B; Wyczalkowski, Matthew A; Vincent, Benjamin G; Hutter, Carolyn M; Zenklusen, Jean Claude; Hoadley, Katherine A; Wendl, Michael C; Shmulevich, Llya; Lazar, Alexander J; Wheeler, David A; Getz, Gad

2018-04-05

The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Elucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma through multi-region exome sequencing.

PubMed

Nahar, Rahul; Zhai, Weiwei; Zhang, Tong; Takano, Angela; Khng, Alexis J; Lee, Yin Yeng; Liu, Xingliang; Lim, Chong Hee; Koh, Tina P T; Aung, Zaw Win; Lim, Tony Kiat Hon; Veeravalli, Lavanya; Yuan, Ju; Teo, Audrey S M; Chan, Cheryl X; Poh, Huay Mei; Chua, Ivan M L; Liew, Audrey Ann; Lau, Dawn Ping Xi; Kwang, Xue Lin; Toh, Chee Keong; Lim, Wan-Teck; Lim, Bing; Tam, Wai Leong; Tan, Eng-Huat; Hillmer, Axel M; Tan, Daniel S W

2018-01-15

EGFR-mutant lung adenocarcinomas (LUAD) display diverse clinical trajectories and are characterized by rapid but short-lived responses to EGFR tyrosine kinase inhibitors (TKIs). Through sequencing of 79 spatially distinct regions from 16 early stage tumors, we show that despite low mutation burdens, EGFR-mutant Asian LUADs unexpectedly exhibit a complex genomic landscape with frequent and early whole-genome doubling, aneuploidy, and high clonal diversity. Multiple truncal alterations, including TP53 mutations and loss of CDKN2A and RB1, converge on cell cycle dysregulation, with late sector-specific high-amplitude amplifications and deletions that potentially beget drug resistant clones. We highlight the association between genomic architecture and clinical phenotypes, such as co-occurring truncal drivers and primary TKI resistance. Through comparative analysis with published smoking-related LUAD, we postulate that the high intra-tumor heterogeneity observed in Asian EGFR-mutant LUAD may be contributed by an early dominant driver, genomic instability, and low background mutation rates.

Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.

PubMed

Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Lorsch, Zachary S; Walker, Deena M; Wang, Junshi; Huang, Xiaojie; Schlüter, Oliver M; Maze, Ian; Peña, Catherine J; Heller, Elizabeth A; Issler, Orna; Wang, Minghui; Song, Won-Min; Stein, Jason L; Liu, Xiaochuan; Doyle, Marie A; Scobie, Kimberly N; Sun, Hao Sheng; Neve, Rachael L; Geschwind, Daniel; Dong, Yan; Shen, Li; Zhang, Bin; Nestler, Eric J

2016-06-01

Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

PubMed

Gao, Qingsong; Liang, Wen-Wei; Foltz, Steven M; Mutharasu, Gnanavel; Jayasinghe, Reyka G; Cao, Song; Liao, Wen-Wei; Reynolds, Sheila M; Wyczalkowski, Matthew A; Yao, Lijun; Yu, Lihua; Sun, Sam Q; Chen, Ken; Lazar, Alexander J; Fields, Ryan C; Wendl, Michael C; Van Tine, Brian A; Vij, Ravi; Chen, Feng; Nykter, Matti; Shmulevich, Ilya; Ding, Li

2018-04-03

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

CRISPR-Barcoding for Intratumor Genetic Heterogeneity Modeling and Functional Analysis of Oncogenic Driver Mutations.

PubMed

Guernet, Alexis; Mungamuri, Sathish Kumar; Cartier, Dorthe; Sachidanandam, Ravi; Jayaprakash, Anitha; Adriouch, Sahil; Vezain, Myriam; Charbonnier, Françoise; Rohkin, Guy; Coutant, Sophie; Yao, Shen; Ainani, Hassan; Alexandre, David; Tournier, Isabelle; Boyer, Olivier; Aaronson, Stuart A; Anouar, Youssef; Grumolato, Luca

2016-08-04

Intratumor genetic heterogeneity underlies the ability of tumors to evolve and adapt to different environmental conditions. Using CRISPR/Cas9 technology and specific DNA barcodes, we devised a strategy to recapitulate and trace the emergence of subpopulations of cancer cells containing a mutation of interest. We used this approach to model different mechanisms of lung cancer cell resistance to EGFR inhibitors and to assess effects of combined drug therapies. By overcoming intrinsic limitations of current approaches, CRISPR-barcoding also enables investigation of most types of genetic modifications, including repair of oncogenic driver mutations. Finally, we used highly complex barcodes inserted at a specific genome location as a means of simultaneously tracing the fates of many thousands of genetically labeled cancer cells. CRISPR-barcoding is a straightforward and highly flexible method that should greatly facilitate the functional investigation of specific mutations, in a context that closely mimics the complexity of cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Convection shapes the trade-off between antibiotic efficacy and the selection for resistance in spatial gradients.

PubMed

Gralka, Matti; Fusco, Diana; Martis, Stephen; Hallatschek, Oskar

2017-07-19

Since penicillin was discovered about 90 years ago, we have become used to using drugs to eradicate unwanted pathogenic cells. However, using drugs to kill bacteria, viruses or cancer cells has the serious side effect of selecting for mutant types that survive the drug attack. A crucial question therefore is how one could eradicate as many cells as possible for a given acceptable risk of drug resistance evolution. We address this general question in a model of drug resistance evolution in spatial drug gradients, which recent experiments and theories have suggested as key drivers of drug resistance. Importantly, our model takes into account the influence of convection, resulting for instance from blood flow. Using stochastic simulations, we study the fates of individual resistance mutations and quantify the trade-off between the killing of wild-type cells and the rise of resistance mutations: shallow gradients and convection into the antibiotic region promote wild-type death, at the cost of increasing the establishment probability of resistance mutations. We can explain these observed trends by modeling the adaptation process as a branching random walk. Our analysis reveals that the trade-off between death and adaptation depends on the relative length scales of the spatial drug gradient and random dispersal, and the strength of convection. Our results show that convection can have a momentous effect on the rate of establishment of new mutations, and may heavily impact the efficiency of antibiotic treatment.

Convection shapes the trade-off between antibiotic efficacy and the selection for resistance in spatial gradients

NASA Astrophysics Data System (ADS)

Gralka, Matti; Fusco, Diana; Martis, Stephen; Hallatschek, Oskar

2017-08-01

Since penicillin was discovered about 90 years ago, we have become used to using drugs to eradicate unwanted pathogenic cells. However, using drugs to kill bacteria, viruses or cancer cells has the serious side effect of selecting for mutant types that survive the drug attack. A crucial question therefore is how one could eradicate as many cells as possible for a given acceptable risk of drug resistance evolution. We address this general question in a model of drug resistance evolution in spatial drug gradients, which recent experiments and theories have suggested as key drivers of drug resistance. Importantly, our model takes into account the influence of convection, resulting for instance from blood flow. Using stochastic simulations, we study the fates of individual resistance mutations and quantify the trade-off between the killing of wild-type cells and the rise of resistance mutations: shallow gradients and convection into the antibiotic region promote wild-type death, at the cost of increasing the establishment probability of resistance mutations. We can explain these observed trends by modeling the adaptation process as a branching random walk. Our analysis reveals that the trade-off between death and adaptation depends on the relative length scales of the spatial drug gradient and random dispersal, and the strength of convection. Our results show that convection can have a momentous effect on the rate of establishment of new mutations, and may heavily impact the efficiency of antibiotic treatment.

Underage female DUI offenders: personality characteristics, psychosocial stressors, alcohol and other drug use, and driving-risk.

PubMed

Moore, R H

1994-04-01

164 underage female DUI offenders were evaluated on measures of personality, driving-risk, psychosocial stressors, alcohol and other drug use, alcohol abuse, and symptoms of depression. Empirical classification of 10 groups represented five distinct types. 31 youth who were classified as Antisocial exhibited highest rates of alcohol misuse, other drug use, deviant driving behavior, traffic offenses and accidents, and psychosocial stressors. About 56% or 92 appeared to experience impaired functioning serious enough to warrant interventions more intense than educational classes. A measure of driving-risk developed and used in studies of male adults, the Donovan Research Questionnaire, did not appear to differentiate driving-risk among the young women. In contrast to male drivers, who often expressed anger or aggression through driving, most subjects appeared to react to emotion-eliciting stimuli with feelings of low self-worth or dysphoric affect rather than anger. Specialized screening suitable for young female DUI offenders should be considered.

Pharmacological cognitive enhancement: treatment of neuropsychiatric disorders and lifestyle use by healthy people.

PubMed

Sahakian, Barbara J; Morein-Zamir, Sharon

2015-04-01

Neuropsychiatric disorders typically manifest as problems with attentional biases, aberrant learning, dysfunctional reward systems, and an absence of top-down cognitive control by the prefrontal cortex. In view of the cost of common mental health disorders, in terms of distress to the individual and family in addition to the financial cost to society and governments, new developments for treatments that address cognitive dysfunction should be a priority so that all members of society can flourish. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used as treatments for the cognitive symptoms of Alzheimer's disease and attention deficit hyperactivity disorder. However, these drugs and others, including modafinil, are being increasingly used by healthy people for enhancement purposes. Importantly for ethical and safety reasons, the drivers for this increasing lifestyle use of so-called smart drugs by healthy people should be considered and discussions must occur about how to ensure present and future pharmacological cognitive enhancers are used for the benefit of society. Copyright © 2015 Elsevier Ltd. All rights reserved.

Treatment of acute myeloid leukemia in the next decade - Towards real-time functional testing and personalized medicine.

PubMed

Lam, Stephen Sze-Yuen; He, Alex Bai-Liang; Leung, Anskar Yu-Hung

2017-11-01

Information arising from next generation sequencing of leukemia genome has shed important light on the heterogeneous and combinatorial driver events in acute myeloid leukemia (AML). It has also provided insight into its intricate signaling pathways operative in the disease pathogenesis. These have also become biomarkers and targets for therapeutic intervention. Emerging evidence from in vitro drug screening has demonstrated its potential value in predicting clinical drug responses in specific AML subtypes. However, the best culture conditions and readouts have yet to be standardized and the drugs included in these screening exercises frequently revised in view of the rapid emergence of new therapeutic agents in the oncology field. Testing of leukemia cell functions, including BCL2 profiling, has also been used to predict treatment response to conventional chemotherapy and hypomethylating agents as well as BCL2 antagonist in small patient cohorts. These platforms should be integrated into future clinical trials to develop personalized treatment of AML. Copyright © 2017 Elsevier Ltd. All rights reserved.

Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

PubMed

Pool, Martin; de Boer, H Rudolf; Hooge, Marjolijn N Lub-de; van Vugt, Marcel A T M; de Vries, Elisabeth G E

2017-01-01

Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.

Cost Drivers of a Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Phase 3 Clinical Trial

PubMed Central

Stergiopoulos, Stella; Calvert, Sara B; Brown, Carrie A; Awatin, Josephine; Tenaerts, Pamela; Holland, Thomas L; DiMasi, Joseph A; Getz, Kenneth A

2018-01-01

Abstract Background Studies indicate that the prevalence of multidrug-resistant infections, including hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), has been rising. There are many challenges associated with these disease conditions and the ability to develop new treatments. Additionally, HABP/VABP clinical trials are very costly to conduct given their complex protocol designs and the difficulty in recruiting and retaining patients. Methods With input from clinicians, representatives from industry, and the US Food and Drug Administration, we conducted a study to (1) evaluate the drivers of HABP/VABP phase 3 direct and indirect clinical trial costs; (2) to identify opportunities to lower these costs; and (3) to compare (1) and (2) to endocrine and oncology clinical trials. Benchmark data were gathered from proprietary and commercial databases and used to create a model that calculates the fully loaded (direct and indirect) cost of typical phase 3 HABP/VABP endocrine and oncology clinical trials. Results Results indicate that the cost per patient for a 200-site, 1000-patient phase 3 HABP/VABP study is $89600 per patient. The cost of screen failures and screen failure rates are the main cost drivers. Conclusions Results indicate that biopharmaceutical companies and regulatory agencies should consider strategies to improve screening and recruitment to decrease HABP/VABP clinical trial costs. PMID:29020279

Pricing and reimbursement of orphan drugs: the need for more transparency

PubMed Central

2011-01-01

Pricing and reimbursement of orphan drugs are an issue of high priority for policy makers, legislators, health care professionals, industry leaders, academics and patients. This study aims to conduct a literature review to provide insight into the drivers of orphan drug pricing and reimbursement. Although orphan drug pricing follows the same economic logic as drug pricing in general, the monopolistic power of orphan drugs results in high prices: a) orphan drugs benefit from a period of marketing exclusivity; b) few alternative health technologies are available; c) third-party payers and patients have limited negotiating power; d) manufacturers attempt to maximise orphan drug prices within the constraints of domestic pricing and reimbursement policies; and e) substantial R&D costs need to be recouped from a small number of patients. Although these conditions apply to some orphan drugs, they do not apply to all orphan drugs. Indeed, the small number of patients treated with an orphan drug and the limited economic viability of orphan drugs can be questioned in a number of cases. Additionally, manufacturers have an incentive to game the system by artificially creating monopolistic market conditions. Given their high price for an often modest effectiveness, orphan drugs are unlikely to provide value for money. However, additional criteria are used to inform reimbursement decisions in some countries. These criteria may include: the seriousness of the disease; the availability of other therapies to treat the disease; and the cost to the patient if the medicine is not reimbursed. Therefore, the maximum cost per unit of outcome that a health care payer is willing to pay for a drug could be set higher for orphan drugs to which society attaches a high social value. There is a need for a transparent and evidence-based approach towards orphan drug pricing and reimbursement. Such an approach should be targeted at demonstrating the relative effectiveness, cost-effectiveness and economic viability of orphan drugs with a view to informing pricing and reimbursement decisions. PMID:21682893

Pricing and reimbursement of orphan drugs: the need for more transparency.

PubMed

Simoens, Steven

2011-06-17

Pricing and reimbursement of orphan drugs are an issue of high priority for policy makers, legislators, health care professionals, industry leaders, academics and patients. This study aims to conduct a literature review to provide insight into the drivers of orphan drug pricing and reimbursement. Although orphan drug pricing follows the same economic logic as drug pricing in general, the monopolistic power of orphan drugs results in high prices: a) orphan drugs benefit from a period of marketing exclusivity; b) few alternative health technologies are available; c) third-party payers and patients have limited negotiating power; d) manufacturers attempt to maximise orphan drug prices within the constraints of domestic pricing and reimbursement policies; and e) substantial R&D costs need to be recouped from a small number of patients. Although these conditions apply to some orphan drugs, they do not apply to all orphan drugs. Indeed, the small number of patients treated with an orphan drug and the limited economic viability of orphan drugs can be questioned in a number of cases. Additionally, manufacturers have an incentive to game the system by artificially creating monopolistic market conditions. Given their high price for an often modest effectiveness, orphan drugs are unlikely to provide value for money. However, additional criteria are used to inform reimbursement decisions in some countries. These criteria may include: the seriousness of the disease; the availability of other therapies to treat the disease; and the cost to the patient if the medicine is not reimbursed. Therefore, the maximum cost per unit of outcome that a health care payer is willing to pay for a drug could be set higher for orphan drugs to which society attaches a high social value. There is a need for a transparent and evidence-based approach towards orphan drug pricing and reimbursement. Such an approach should be targeted at demonstrating the relative effectiveness, cost-effectiveness and economic viability of orphan drugs with a view to informing pricing and reimbursement decisions.

Implementation of a teaching programme to improve doctors' awareness of DVLA guidelines: a multicentre study.

PubMed

Maruthappu, Mahiben; Sykes, Mark; Green, Ben L; Watson, Robert; Gollop, Nicholas D; Shalhoub, Joseph; Ng, Ka Ying Bonnie

2017-02-01

Over half of the UK population holds a driver's licence. Driver and Vehicle Licensing Authority (DVLA) guidelines are available for conditions from most specialties. Despite this, no focused training occurs in the undergraduate or postgraduate setting. We evaluate the impact of a teaching programme to improve guideline awareness. A 25-point questionnaire was designed using the current DVLA guidelines. Five questions were included for the following fields: neurology, cardiology, drug and alcohol abuse, visual disorders and respiratory. This was distributed to doctors in training at five hospitals. Four weeks later, a single-session teaching programme was implemented. The questionnaire was redistributed. Preintervention and postintervention scores were compared using the Wilcoxon rank sum test. 139 preteaching and 144 post-teaching questionnaires were completed. Implementation of a single-session teaching programme significantly improved the knowledge of DVLA guidelines in all five areas explored. Median scores: neurology, preteaching 40%, post-teaching 100%, p<0.001; cardiology, 0%, 100%, p<0.001; drug and alcohol misuse, 0%, 100%, p<0.001; visual disorders, 40%, 100%, p<0.001; respiratory disorders, 20%, 100%, p<0.001; and overall, 28%, 92%, p<0.001. Knowledge of DVLA guidelines among our cohort was poor. Implementation of a single-session teaching programme can significantly improve guideline knowledge and awareness, serving as a cost-effective intervention. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Ability to monitor driving under the influence of marijuana among non-fatal motor-vehicle crashes: An evaluation of the Colorado electronic accident reporting system.

PubMed

Peterson, Alexis B; Sauber-Schatz, Erin K; Mack, Karin A

2018-06-01

As more states legalize medical/recreational marijuana use, it is important to determine if state motor-vehicle surveillance systems can effectively monitor and track driving under the influence (DUI) of marijuana. This study assessed Colorado's Department of Revenue motor-vehicle crash data system, Electronic Accident Reporting System (EARS), to monitor non-fatal crashes involving driving under the influence (DUI) of marijuana. Centers for Disease Control and Prevention guidelines on surveillance system evaluation were used to assess EARS' usefulness, flexibility, timeliness, simplicity, acceptability, and data quality. We assessed system components, interviewed key stakeholders, and analyzed completeness of Colorado statewide 2014 motor-vehicle crash records. EARS contains timely and complete data, but does not effectively monitor non-fatal motor-vehicle crashes related to DUI of marijuana. Information on biological sample type collected from drivers and toxicology results were not recorded into EARS; however, EARS is a flexible system that can incorporate new data without increasing surveillance system burden. States, including Colorado, could consider standardization of drug testing and mandatory reporting policies for drivers involved in motor-vehicle crashes and proactively address the narrow window of time for sample collection to improve DUI of marijuana surveillance. Practical applications: The evaluation of state motor-vehicle crash systems' ability to capture crashes involving drug impaired driving (DUID) is a critical first step for identifying frequency and risk factors for crashes related to DUID. Published by Elsevier Ltd.

Improving the Efficiency and Quality of the Value Assessment Process for Companion Diagnostic Tests: The Companion test Assessment Tool (CAT).

PubMed

Canestaro, William J; Pritchard, Daryl E; Garrison, Louis P; Dubois, Robert; Veenstra, David L

2015-08-01

Companion diagnostic tests (CDTs) have emerged as a vital technology in the effective use of an increasing number of targeted drug therapies. Although CDTs can offer a multitude of potential benefits, assessing their value within a health technology appraisal process can be challenging because of a complex array of factors that influence clinical and economic outcomes. To develop a user-friendly tool to assist managed care and other health care decision makers in screening companion tests and determining whether an intensive technology review is necessary and, if so, where the review should be focused to improve efficiency. First, we conducted a systematic literature review of CDT cost-effectiveness studies to identify value drivers. Second, we conducted key informant interviews with a diverse group of stakeholders to elicit feedback and solicit any additional value drivers and identify desirable attributes for an evidence review tool. A draft tool was developed based on this information that captured value drivers, usability features, and had a particular focus on practical use by nonexperts. Finally, the tool was pilot tested with test developers and managed care evidence evaluators to assess face-validity and usability. The tool was also evaluated using several diverse examples of existing companion diagnostics and refined accordingly. We identified 65 cost-effectiveness studies of companion diagnostic technologies. The following factors were most commonly identified as value drivers from our literature review: clinical validity of testing; efficacy, safety, and cost of baseline and alternative treatments; cost and mortality of health states; and biomarker prevalence and testing cost. Stakeholders identified the following additional factors that they believed influenced the overall value of a companion test: regulatory status, actionability, utility, and market penetration. These factors were used to maximize the efficiency of the evidence review process. Stakeholders also stated that a tool should be easy to use and time efficient. Cognitive interviews with stakeholders led to minor changes in the draft tool to improve usability and relevance. The final tool consisted of 4 sections: (1) eligibility for review (2 questions), (2) prioritization of review (3 questions), (3) clinical review (3 questions), and (4) economic review (5 questions). Although the evaluation of CDTs can be challenging because of limited evidence and the added complexity of incorporating a diagnostic test into drug treatment decisions, using a pragmatic tool to identify tests that do not need extensive evaluation may improve the efficiency and effectiveness of CDT value assessments.

The Standardized Field Sobriety Tests (SFST) and measures of cognitive functioning.

PubMed

Downey, Luke A; Hayley, Amie C; Porath-Waller, Amy J; Boorman, Martin; Stough, Con

2016-01-01

The Standardized Field Sobriety Tests (SFST) are utilised widely to assess fitness to drive when law enforcement suspects a driver's ability to drive is impaired, whether by drugs or alcohol. The SFST ostensibly achieve this through assessment of the level of drivers' cognitive and psychomotor impairment, although no studies have explicitly assessed the relatedness of cognitive ability and performance on the SFST. The current study aimed to assess the relationship between the three components of the SFST with a well validated computerised cognitive battery. A sub-set of 61 placebo condition participants comprised the sample, with 33 females and 28 males (mean age 25.45 years). Correlations between the individual SFST subscales 'Horizontal Gaze Nystagmus' (HGN), the 'One Leg Stand' (OLS) and the 'Walk and Turn' test (WAT) and Cognitive Drug Research (CDR) sub-scales of 'Quality of Working Memory', 'Power of Attention' and 'Continuity of Attention' were analysed using point-biserial correlation. Sixty participants were included for analyses. A weak-moderate positive (five subscales) and a moderate-strong negative (two subscales) association was noted between seven of the nine individual CDR subscales and the SFST subscale of the WAT test (all p<0.05). Individually, a moderate positive association was noted between the sub-scale 'Nystagmus lack of smooth pursuit' and 'digit vigilance reaction time' and 'choice reaction time; reaction time' (both p<0.05) and 'Nystagmus head move and/or jerk' and 'simple reaction time' (p<0.001). When assessed as a partially composite factor, a comparable association was also noted between the composite score of the SFST subscale 'Nystagmus head move and/or jerk' and both (a) simple and (b) digit vigilance reaction time (both p<0.05). No association was noted between any of the individual cognitive variables and the SFST subscale 'OLS', or between composite cognitive scores 'Quality of Working Memory', 'Power of Attention' and 'Continuity of Attention' and total SFST scores. Variation in some aspects of cognitive performance was found to be moderately and positively correlated with some individual aspects of the SFST; particularly among tasks which assess reaction time. Impairment of these cognitive processes can also contribute to the completion of complex tasks such as driving or the SFST. Complex behavioural tasks such as driving are often severely impaired due to intoxication, and thus in a practical sense, the SFST can still be considered a useful screening tool to identify drug or alcohol impaired drivers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Motor Vehicle Crashes, Medical Outcomes, and Hospital Charges Among Children Aged 1-12 Years - Crash Outcome Data Evaluation System, 11 States, 2005-2008.

PubMed

Sauber-Schatz, Erin K; Thomas, Andrea M; Cook, Lawrence J

2015-10-02

Motor vehicle crashes are a leading cause of death among children. Age- and size-appropriate restraint use is an effective way to prevent motor vehicle-related injuries and deaths. However, children are not always properly restrained while riding in a motor vehicle, and some are not restrained at all, which increases their risk for injury and death in a crash. 2005-2008. The Crash Outcome Data Evaluation System (CODES) is a multistate program facilitated by the National Highway Traffic Safety Administration to probabilistically link police crash reports and hospital databases for traffic safety analyses. Eleven participating states (Connecticut, Georgia, Kentucky, Maryland, Minnesota, Missouri, Nebraska, New York, Ohio, South Carolina, and Utah) submitted data to CODES during the reporting period. Descriptive analysis was used to describe drivers and child passengers involved in motor vehicle crashes and to summarize crash and medical outcomes. Odds ratios and 95% confidence intervals were used to compare a child passenger's likelihood of sustaining specific types of injuries by restraint status (optimal, suboptimal, or unrestrained) and seating location (front or back seat). Because of data constraints, optimal restraint use was defined as a car seat or booster seat use for children aged 1-7 years and seat belt use for children aged 8-12 years. Suboptimal restraint use was defined as seat belt use for children aged 1-7 years. Unrestrained was defined as no use of car seat, booster seat, or seat belt for children aged 1-12 years. Optimal restraint use in the back seat declined with child's age (1 year: 95.9%, 5 years: 95.4%, 7 years: 94.7%, 8 years: 77.4%, 10 years: 67.5%, 12 years: 54.7%). Child restraint use was associated with driver restraint use; 41.3% of children riding with unrestrained drivers also were unrestrained compared with 2.2% of children riding with restrained drivers. Child restraint use also was associated with impaired driving due to alcohol or drug use; 16.4% children riding with drivers suspected of alcohol or drug use were unrestrained compared with 2.9% of children riding with drivers not suspected of such use. Optimally restrained and suboptimally restrained children were less likely to sustain a traumatic brain injury than unrestrained children. The 90th percentile hospital charges for children aged 4-7 years who were in motor vehicle crashes were $1,630.00 and $1,958.00 for those optimally restrained in a back seat and front seat, respectively; $2,035.91 and $3,696.00 for those suboptimally restrained in a back seat and front seat, respectively; and $9,956.60 and $11,143.85 for those unrestrained in a back seat and front seat, respectively. Proper car seat, booster seat, and seat belt use among children in the back seat prevents injuries and deaths, as well as averts hospital charges. However, the number, severity, and cost of injuries among children in crashes who were not optimally restrained or who were seated in a front seat indicates the need for improvements in proper use of age- and size-appropriate car seats, booster seats, and seat belts in the back seat. Effective interventions for increasing proper child restraint use could be universally implemented by states and communities to prevent motor vehicle-related injuries among children and their resulting costs.

Biomedical HIV prevention including pre-exposure prophylaxis and opiate agonist therapy for women who inject drugs: State of research and future directions

PubMed Central

Page, Kimberly; Tsui, Judith; Maher, Lisa; Choopanya, Kachit; Vanichseni, Suphak; Mock, Philip A.; Celum, Connie; Martin, Michael

2015-01-01

Women who inject drugs are at higher risk of HIV compared to their male counterparts as a result of multiple factors including biological, behavioral and socio-structural, yet comparatively little effort has been invested in testing and delivering prevention methods that directly target this group. In this paper, we discuss the need for expanded prevention interventions for women who inject drugs, focusing on two safe, effective, and approved, yet underutilized biomedical prevention methods: opiate agonist therapy (OAT) and oral pre-exposure prophylaxis (PrEP). While both interventions are well researched they have not been well examined in the context of gender. We discuss the drivers of women injectors’ higher HIV risk, review the effectiveness of OAT and PrEP interventions among women, and explain why these new HIV prevention tools should be prioritized for women who inject drugs. There is substantial potential for impact of OAT and PrEP programs for women who inject drugs in the context of broader gender-responsive HIV prevention initiatives. While awaiting efficacy data on other biomedical approaches in the HIV prevention research ‘pipeline’, we propose that the scale up and implementation of these proven, safe, and effective interventions are needed now. PMID:25978484

Clinical trials in drug development: a minimalistic approach.

PubMed

Verweij, Jaap

2012-05-01

Drug development in oncology finds itself at the crossroad of unique opportunities and major challenges. The old paradigms should and can be replaced by a system that better matches the right patients to the right compounds and puts much more emphasis on the early stages of drug development. The clinical phases of drug development will no longer be split into phase I, II, and III studies, but rather into 'functional target pharmacology studies', followed by 'proof of concept studies'. The resulting development flow becomes Apollo-capsule shaped. Although randomized studies will still be needed for drugs using targets in the tumor environment, or for combinations of agents, drug registration might proceed without these if all of the following criteria are met in early development: availability of preclinical convincing evidence that the drug's target is the functional driver behind the disease phenotype, availability of a predictive biomarker that enables appropriate and actual patient selection in early pharmacology studies, a Response Evaluation Criteria In Solid Tumors (RECIST)-based single agent response rate of at least 50%, and/or a progression at first tumor assessment rate of 15% or less, a duration of absence of progression (stable disease) beyond doubt and considered clinically relevant, and no major safety concern. This set is not yet mature, but may be adapted over time. The concerns related to registering agents on the basis of small datasets can be adequately addressed by obligatory postmarketing hypothesis driven studies.

Systematic review of factors affecting pharmaceutical expenditures.

PubMed

Mousnad, Mohamed Awad; Shafie, Asrul Akmal; Ibrahim, Mohamed Izham

2014-06-01

To systematically identify the main factors contributing to the increase in pharmaceutical expenditures. A systematic search of published studies was conducted utilising major widely used electronic databases using the search terms 'factors,' 'financing,' 'pharmaceutical,' and 'expenditures.' To be included, the studies needed to: (1) measure at least one of the following outcomes: total growth in pharmaceutical expenditures, price growth or quantity growth; (2) mention a clear method for analysing the impact of factors affecting the increases in drug expenditures; (3) be written in English. Nonprimary articles that were published only as an abstract, a review, a commentary or a letter were excluded. From a total of 2039 studies, only 25 were included in the full review. The main determinant categories that were identified in the review were factors related to price, utilisation, therapeutic choice, demand and health care system. The major cost drivers were found to be changes in drug quantities and therapies as well as new drugs. It is important for policymakers to understand pharmaceutical spending trends and the factors that influence them in order to formulate effective cost containment strategies and design optimum drug policy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Scientific, economic, regulatory, and ethical challenges of bringing science-based pediatric nutrition products to the U.S. market and ensuring their availability for patients.

PubMed

Merritt, Russell J; Goldsmith, Arthur H

2014-11-01

Many nutrition products and related drugs are unavailable or not consistently available to clinicians despite a body of clinical data and experience supporting their use. Many of these can be related to drug shortages that have increased since 2009. In addition, there are potentially useful products that are not approved for a specific use or are no longer being manufactured. This review broadly examines the product availability gap from the perspectives of a clinician/former nutrition industry medical director and an economist. The process of pediatric nutrition product and related drug innovation, as well as its drivers and the steps involved in bringing a product to market, is first described. This is followed by an assessment of factors influencing product availability beyond the innovation process, including regulatory issues, manufacturing compliance, purchasing practices, and other factors related to drug and nutrition product pricing and reimbursement. Three pediatric case examples are reviewed and placed in the context of the prior review. Last, recent and future possible steps toward closing the product availability gap are discussed. © 2014 American Society for Parenteral and Enteral Nutrition.

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay.

PubMed

Laporte, Aimée N; Ji, Jennifer X; Ma, Limin; Nielsen, Torsten O; Brodin, Bertha A

2016-06-07

Conventional cytotoxic therapies for synovial sarcoma provide limited benefit. Drugs specifically targeting the product of its driver translocation are currently unavailable, in part because the SS18-SSX oncoprotein functions via aberrant interactions within multiprotein complexes. Proximity ligation assay is a recently-developed method that assesses protein-protein interactions in situ. Here we report use of the proximity ligation assay to confirm the oncogenic association of SS18-SSX with its co-factor TLE1 in multiple human synovial sarcoma cell lines and in surgically-excised human tumor tissue. SS18-SSX/TLE1 interactions are disrupted by class I HDAC inhibitors and novel small molecule inhibitors. This assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known.

Personalized targeted therapy for esophageal squamous cell carcinoma

PubMed Central

Kang, Xiaozheng; Chen, Keneng; Li, Yicheng; Li, Jianying; D'Amico, Thomas A; Chen, Xiaoxin

2015-01-01

Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial. PMID:26167067

Road traffic accidents and self-reported Portuguese car driver's attitudes, behaviors, and opinions: Are they related?

PubMed

Bon de Sousa, Teresa; Santos, Carolina; Mateus, Ceu; Areal, Alain; Trigoso, Jose; Nunes, Carla

2016-10-02

This study aims to characterize Portuguese car drivers in terms of demographic characteristics, driving experience, and attitudes, opinions, and behaviors concerning road traffic safety. Furthermore, associations between these characteristics and self-reported involvement in a road traffic accident as a driver in the last 3 years were analyzed. A final goal was to develop a final predictive model of the risk of suffering a road traffic accident. A cross-sectional analytic study was developed, based on a convenience sample of 612 car drivers. A questionnaire was applied by trained interviewers, embracing various topics related to road safety such as driving under the influence of alcohol or drugs, phone use while driving, speeding, use of advanced driver assistance systems, and the transport infrastructure and environment (European Project SARTRE 4, Portuguese version). From the 52 initial questions, 19 variables were selected through principal component analysis. Then, and in addition to the usual descriptive measures, logistic binary regression models were used in order to describe associations and to develop a predictive model of being involved in a road traffic accident. Of the 612 car drivers, 37.3% (228) reported being involved in a road traffic accident with damage or injury in the past 3 years. In this group, the majority were male, older than 65, with no children, not employed, and living in an urban area. In the multivariate model, several factors were identified: being widowed (vs. single; odds ratio [OR] = 3.478, 95% confidence interval [95% CI], 1.159-10.434); living in a suburban area (vs. a rural area; OR = 5.023, 95% CI, 2.260-11.166); having been checked for alcohol once in the last 3 years (vs. not checked; OR = 3.124, 95% CI, 2.040-4,783); and seldom drinking an energetic beverage such as coffee when tired (vs. always do; OR = 6.822, 95% CI, 2.619-17.769) all suffered a higher risk of being involved in a car accident. The results obtained with regard to behavioral factors meet the majority of the risk factors associated with car accidents referred to in the literature. This study highlights the relation of relatively minor accidents (the majority with no injuries) with an urban (or semi-urban) context and involving older drivers. These accidents are not usually the focus of road safety literature (mainly death and serious health loss) but, in addition to the economic costs involved, they can have a huge impact on road safety (e.g., pedestrian). Specifically, the following interventions can be proposed: more detailed clinical examinations to identify real competencies to drive especially in older drivers (active aging can constitute a new challenge in road safety and new paradigms can arise) and education campaigns on how to cope with fatigue. Future studies in large samples and not based on self-reported behaviors should be developed.

The potential of targeting Ras proteins in lung cancer.

PubMed

McCormick, Frank

2015-04-01

The Ras pathway is a major driver in lung adenocarcinoma: over 75% of all cases harbor mutations that activate this pathway. While spectacular clinical successes have been achieved by targeting activated receptor tyrosine kinases in this pathway, little, if any, significant progress has been achieved targeting Ras proteins themselves or cancers driven by oncogenic Ras mutants. New approaches to drug discovery, new insights into Ras function, new ways of attacking undruggable proteins through RNA interference and new ways of harnessing the immune system could change this landscape in the relatively near future.

Deja Vu: EGF receptors drive resistance to BRAF inhibitors.

PubMed

Girotti, Maria Romina; Marais, Richard

2013-05-01

The promise of personalized medicine is upon us, and in some cancers, targeted therapies are rapidly becoming the mainstay of treatment for selected patients based on their molecular profile. The protein kinase BRAF is a driver oncogene in both thyroid cancer and melanoma, but while drugs that target BRAF and its downstream signaling pathway are effective in melanoma, they are ineffective in thyroid cancer. In this issue of Cancer Discovery, Montero-Conde and colleagues investigate why thyroid cancer is resistant to BRAF inhibitors despite the presence of BRAF mutation.

Robotics Offer Newfound Surgical Capabilities

NASA Technical Reports Server (NTRS)

2008-01-01

Barrett Technology Inc., of Cambridge, Massachusetts, completed three Phase II Small Business Innovation Research (SBIR) contracts with Johnson Space Center, during which the company developed and commercialized three core technologies: a robotic arm, a hand that functions atop the arm, and a motor driver to operate the robotics. Among many industry uses, recently, an adaptation of the arm has been cleared by the U.S. Food and Drug Administration (FDA) for use in a minimally invasive knee surgery procedure, where its precision control makes it ideal for inserting a very small implant.

Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing

PubMed Central

de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A.; Hur, Junguk

2018-01-01

The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree, clustering coefficient, and node strength, were used to identify new therapeutic applications within and beyond the anti-inflammatory context, as well as ADR risk for these drugs, helping to select better repurposing candidates. Based on these parameters, we identified naproxen, meloxicam, etodolac, tenoxicam, flufenamic acid, fenoprofen, and nabumetone as candidates for drug repurposing with lower ADR risk. This network-based analysis pipeline provides a novel way to explore the effects of drugs in a therapeutic space. PMID:29545755

Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing.

PubMed

de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A; Hur, Junguk

2018-01-01

The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree, clustering coefficient, and node strength, were used to identify new therapeutic applications within and beyond the anti-inflammatory context, as well as ADR risk for these drugs, helping to select better repurposing candidates. Based on these parameters, we identified naproxen, meloxicam, etodolac, tenoxicam, flufenamic acid, fenoprofen, and nabumetone as candidates for drug repurposing with lower ADR risk. This network-based analysis pipeline provides a novel way to explore the effects of drugs in a therapeutic space.

Prevalence of drug use during sex amongst MSM in Europe: Results from a multi-site bio-behavioural survey.

PubMed

Rosińska, Magdalena; Gios, Lorenzo; Nöstlinger, Christiana; Vanden Berghe, Wim; Marcus, Ulrich; Schink, Susanne; Sherriff, Nigel; Jones, Anna-Marie; Folch, Cinta; Dias, Sonia; Velicko, Inga; Mirandola, Massimo

2018-05-01

Substance use has been consistently reported to be more prevalent amongst Men who have Sex with Men (MSM) compared to the general population. Substance use, in particular polydrug use, has been found to be influenced by social and contextual factors and to increase the risk of unprotected intercourse among MSM. The objective of this analysis was to investigate the prevalence and predictors of drug use during a sexual encounter and to identify specific prevention needs. A multi-site bio-behavioural cross-sectional survey was implemented in 13 European cities, targeting MSM and using Time-Location Sampling and Respondent-Driven Sampling methods Multivariable multi-level logistic random-intercept model (random effect of study site) was estimated to identify factors associated with the use of alcohol, cannabis, party drugs, sexual performance enhancement drugs and chemsex drugs. Overall, 1261 (30.0%) participants reported drug use, and 436 of 3706 (11.8%) reported the use of two or more drugs during their last sexual encounter. By drug class, 966 (23.0%) reported using sexual performance enhancement drugs, 353 (8.4%) - party drugs, and 142 (3.4%) the use of chemsex drugs. Respondents who reported drug use were more frequently diagnosed with HIV (10.5% vs. 3.9%) before and with other STIs during the 12 months prior to the study (16.7% vs. 9.2%). The use of all the analysed substances was significantly associated with sexual encounter with more than one partner. Substance and polydrug use during sexual encounters occurred amongst sampled MSM across Europe although varying greatly between study sites. Different local social norms within MSM communities may be important contextual drivers of drug use, highlighting the need for innovative and multi-faceted prevention measures to reduce HIV/STI risk in the context of drug use. Copyright © 2018 Elsevier B.V. All rights reserved.

A decline in the prevalence of injecting drug users in Estonia, 2005–2009

PubMed Central

Uusküla, A; Rajaleid, K; Talu, A; Abel-Ollo, K; Des Jarlais, DC

2013-01-01

Aims and setting Descriptions of behavioural epidemics have received little attention compared with infectious disease epidemics in Eastern Europe. Here we report a study aimed at estimating trends in the prevalence of injection drug use between 2005 and 2009 in Estonia. Design and methods The number of injection drug users (IDUs) aged 15–44 each year between 2005 and 2009 was estimated using capture-recapture methodology based on 4 data sources (2 treatment data bases: drug abuse and non-fatal overdose treatment; criminal justice (drug related offences) and mortality (injection drug use related deaths) data). Poisson log-linear regression models were applied to the matched data, with interactions between data sources fitted to replicate the dependencies between the data sources. Linear regression was used to estimate average change over time. Findings there were 24305, 12292, 238, 545 records and 8100, 1655, 155, 545 individual IDUs identified in the four capture sources (Police, drug treatment, overdose, and death registry, accordingly) over the period 2005 – 2009. The estimated prevalence of IDUs among the population aged 15–44 declined from 2.7% (1.8–7.9%) in 2005 to 2.0% (1.4–5.0%) in 2008, and 0.9% (0.7–1.7%) in 2009. Regression analysis indicated an average reduction of over 1700 injectors per year. Conclusion While the capture-recapture method has known limitations, the results are consistent with other data from Estonia. Identifying the drivers of change in the prevalence of injection drug use warrants further research. PMID:23290632

Cannabis use: a perspective in relation to the proposed UK drug-driving legislation.

PubMed

Wolff, Kim; Johnston, Atholl

2014-01-01

With regard to THC (Δ(9)-tetrahydrocannabinol), the main psychoactive constituent identified in the plant Cannabis sativa L, several facts are indisputable. Cannabis remains the most commonly used drug in the UK among those who reported driving under the influence of illegal drugs in the previous 12 months. There is a significant dose-related decrement in driving performance following cannabis use; raised blood THC concentrations are significantly associated with increased traffic crash and death risk. When cannabis and alcohol are detected together, there is a greater risk to road safety than when either drug is used alone. Patterns of use are important when interpreting blood concentration data: Smoking infrequently a single cannabis cigarette leads to peak plasma THC concentrations (21-267 µg/L) causing acute intoxication. In habitual, daily users, plasma THC concentrations range from 1.0 to 11.0 µg/L and are maintained by sequestration of the drug from the tissues. These facts undoubtedly make setting thresholds for drug-driving legislation difficult but there is clearly a case for cannabis. Determining minimum blood THC concentrations at which a driver becomes sufficiently impaired to be unable to safely drive a vehicle is of particular concern given the increasing medicinal use of the drug. Internationally legislation for driving under the influence of drugs (DUID) is based on either a proof of impairment or a per se approach. For the latter this can be either zero-tolerance or based on concentration limits such as those used for alcohol. The different approaches are considered against current scientific evidence. Copyright © 2013 John Wiley & Sons, Ltd.

Assessing the economic value of avoiding hospital admissions by shifting the management of gram+ acute bacterial skin and skin-structure infections to an outpatient care setting.

PubMed

Ektare, V; Khachatryan, A; Xue, M; Dunne, M; Johnson, K; Stephens, J

2015-01-01

To estimate, from a US payer perspective, the cost offsets of treating gram positive acute bacterial skin and skin-structure infections (ABSSSI) with varied hospital length of stay (LOS) followed by outpatient care, as well as the cost implications of avoiding hospital admission. Economic drivers of care were estimated using a literature-based economic model incorporating inpatient and outpatient components. The model incorporated equal efficacy, adverse events (AE), resource use, and costs from literature. Costs of once- and twice-daily outpatient infusions to achieve a 14-day treatment were analyzed. Sensitivity analyses were performed. Costs were adjusted to 2015 US$. Total non-drug medical cost for treatment of ABSSSI entirely in the outpatient setting to avoid hospital admission was the lowest among all scenarios and ranged from $4039-$4924. Total non-drug cost for ABSSSI treated in the inpatient setting ranged from $9813 (3 days LOS) to $18,014 (7 days LOS). Inpatient vs outpatient cost breakdown was: 3 days inpatient ($6657)/11 days outpatient ($3156-$3877); 7 days inpatient ($15,017)/7 days outpatient ($2495-$2997). Sensitivity analyses revealed a key outpatient cost driver to be peripherally inserted central catheter (PICC) costs (average per patient cost of $873 for placement and $205 for complications). Drug and indirect costs were excluded and resource use was not differentiated by ABSSSI type. It was assumed that successful ABSSSI treatment takes up to 14 days per the product labels, and that once-daily and twice-daily antibiotics have equal efficacy. Shifting ABSSSI care to outpatient settings may result in medical cost savings greater than 53%. Typical outpatient scenarios represent 14-37% of total medical cost, with PICC accounting for 28-43% of the outpatient burden. The value of new ABSSSI therapies will be driven by eliminating the need for PICC line, reducing length of stay and the ability to completely avoid a hospital stay.

Key cost drivers of pharmaceutical clinical trials in the United States.

PubMed

Sertkaya, Aylin; Wong, Hui-Hsing; Jessup, Amber; Beleche, Trinidad

2016-04-01

The increasing cost of clinical research has significant implications for public health, as it affects drug companies' willingness to undertake clinical trials, which in turn limits patient access to novel treatments. Thus, gaining a better understanding of the key cost drivers of clinical research in the United States is important. The study which is based on a report prepared by Eastern Research Group, Inc., for the US Department of Health and Human Services, examined different factors, such as therapeutic area, patient recruitment, administrative staff, and clinical procedure expenditures, and their contribution to pharmaceutical clinical trial costs in the United States by clinical trial phase. The study used aggregate data from three proprietary databases on clinical trial costs provided by Medidata Solutions. We evaluated per-study costs across therapeutic areas by aggregating detailed (per patient and per site) cost information. We also compared average expenditures on cost drivers with the use of weighted mean and standard deviation statistics. Therapeutic area was an important determinant of clinical trial costs by phase. The average cost of a Phase 1 study conducted at a US site ranged from US$1.4 million (pain and anesthesia) to US$6.6 million (immunomodulation), including estimated site overhead and monitoring costs of the sponsoring organization. A Phase 2 study cost from US$7.0 million (cardiovascular) to US$19.6 million (hematology), whereas a Phase 3 study cost ranged from US$11.5 million (dermatology) to US$52.9 (pain and anesthesia) on average. Across all study phases and excluding estimated site overhead costs and costs for sponsors to monitor the study, the top three cost drivers of clinical trial expenditures were clinical procedure costs (15%-22% of total), administrative staff costs (11%-29% of total), and site monitoring costs (9%-14% of total). The data were from 2004 through 2012 and were not adjusted for inflation. Additionally, the databases used represented a convenience, that is, non-probability, sample and did not allow for statistically valid estimates of cost drivers. Finally, the data were from trials funded by the global pharmaceutical and biotechnology industry only. Hence, our study findings are limited to that segment. Therapeutic area being studied as well as number and types of clinical procedures involved were the key drivers of direct costs in Phase 1 through Phase 3 studies. Research shows that strategies exist for reducing the price tag of some of these major direct cost components. Therefore, to increase clinical trial efficiency and reduce costs, gaining a better understanding of the key direct cost drivers is an important step. © The Author(s) 2016.

Understanding the patient experience of cost-related non-adherence to prescription medications through typology development and application.

PubMed

Goldsmith, Laurie J; Kolhatkar, Ashra; Popowich, Dominic; Holbrook, Anne M; Morgan, Steven G; Law, Michael R

2017-12-01

Many patients report skipping doses, splitting pills, or not filling prescriptions due to out-of-pocket costs-a phenomenon known as cost-related non-adherence (CRNA). This study investigated CRNA from the patient's perspective, and, to our knowledge, is the first study to undertake a qualitative investigation of CRNA specifically. We report the results from 35 semi-structured interviews conducted in 2014-15 with adults in four Canadian cities across two provinces. We used framework analysis to develop a CRNA typology to characterize major factors in patients' CRNA decisions. Our typology identifies four major components: (1) the insurance reason driving the drug cost, (2) the individual's overall financial flexibility, (3) the burden of drug cost on the individual's budget, and (4) the importance of the drug from the individual's perspective. The first two components set the context for CRNA and the final two components are the drivers for the CRNA decision. We also found four major patterns in CRNA experiences: (1) CRNA in individuals with low financial flexibility occurred for all levels of drug importance and all but the lowest level of cost burden; (2) CRNA for high importance drugs only occurred when the drug cost had a high burden on an individual's budget; (3) CRNA in individuals with more financial flexibility primarily occurred in drugs with medium importance but high or very high cost burdens; and (4) CRNA for low importance drugs occurred at almost all levels of drug cost burden. Our study furthers the understanding of how numerous factors such as income, insurance, and individual preferences combine and interact to influence CRNA and suggests that policy interventions must be multi-faceted or encourage significant insurance redesign to reduce CRNA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Combination of a proteomics approach and reengineering of meso scale network models for prediction of mode-of-action for tyrosine kinase inhibitors.

PubMed

Balabanov, Stefan; Wilhelm, Thomas; Venz, Simone; Keller, Gunhild; Scharf, Christian; Pospisil, Heike; Braig, Melanie; Barett, Christine; Bokemeyer, Carsten; Walther, Reinhard; Brümmendorf, Tim H; Schuppert, Andreas

2013-01-01

In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is of highest relevance. Recent approaches for identification of MoA have employed various techniques for modeling of well defined signaling pathways including structural information, changes in phenotypic behavior of cells and gene expression patterns after drug treatment. However, efficient approaches focusing on proteome wide data for the identification of MoA including interference with mutations are underrepresented. As mutations are key drivers of drug resistance in molecularly targeted tumor therapies, efficient analysis and modeling of downstream effects of mutations on drug MoA is a key to efficient development of improved targeted anti-cancer drugs. Here we present a combination of a global proteome analysis, reengineering of network models and integration of apoptosis data used to infer the mode-of-action of various tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cell lines expressing wild type as well as TKI resistance conferring mutants of BCR-ABL. The inferred network models provide a tool to predict the main MoA of drugs as well as to grouping of drugs with known similar kinase inhibitory activity patterns in comparison to drugs with an additional MoA. We believe that our direct network reconstruction approach, demonstrated on proteomics data, can provide a complementary method to the established network reconstruction approaches for the preclinical modeling of the MoA of various types of targeted drugs in cancer treatment. Hence it may contribute to the more precise prediction of clinically relevant on- and off-target effects of TKIs.

Combination of a Proteomics Approach and Reengineering of Meso Scale Network Models for Prediction of Mode-of-Action for Tyrosine Kinase Inhibitors

PubMed Central

Balabanov, Stefan; Wilhelm, Thomas; Venz, Simone; Keller, Gunhild; Scharf, Christian; Pospisil, Heike; Braig, Melanie; Barett, Christine; Bokemeyer, Carsten; Walther, Reinhard

2013-01-01

In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is of highest relevance. Recent approaches for identification of MoA have employed various techniques for modeling of well defined signaling pathways including structural information, changes in phenotypic behavior of cells and gene expression patterns after drug treatment. However, efficient approaches focusing on proteome wide data for the identification of MoA including interference with mutations are underrepresented. As mutations are key drivers of drug resistance in molecularly targeted tumor therapies, efficient analysis and modeling of downstream effects of mutations on drug MoA is a key to efficient development of improved targeted anti-cancer drugs. Here we present a combination of a global proteome analysis, reengineering of network models and integration of apoptosis data used to infer the mode-of-action of various tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cell lines expressing wild type as well as TKI resistance conferring mutants of BCR-ABL. The inferred network models provide a tool to predict the main MoA of drugs as well as to grouping of drugs with known similar kinase inhibitory activity patterns in comparison to drugs with an additional MoA. We believe that our direct network reconstruction approach, demonstrated on proteomics data, can provide a complementary method to the established network reconstruction approaches for the preclinical modeling of the MoA of various types of targeted drugs in cancer treatment. Hence it may contribute to the more precise prediction of clinically relevant on- and off-target effects of TKIs. PMID:23326482

MADGiC: a model-based approach for identifying driver genes in cancer

PubMed Central

Korthauer, Keegan D.; Kendziorski, Christina

2015-01-01

Motivation: Identifying and prioritizing somatic mutations is an important and challenging area of cancer research that can provide new insights into gene function as well as new targets for drug development. Most methods for prioritizing mutations rely primarily on frequency-based criteria, where a gene is identified as having a driver mutation if it is altered in significantly more samples than expected according to a background model. Although useful, frequency-based methods are limited in that all mutations are treated equally. It is well known, however, that some mutations have no functional consequence, while others may have a major deleterious impact. The spatial pattern of mutations within a gene provides further insight into their functional consequence. Properly accounting for these factors improves both the power and accuracy of inference. Also important is an accurate background model. Results: Here, we develop a Model-based Approach for identifying Driver Genes in Cancer (termed MADGiC) that incorporates both frequency and functional impact criteria and accommodates a number of factors to improve the background model. Simulation studies demonstrate advantages of the approach, including a substantial increase in power over competing methods. Further advantages are illustrated in an analysis of ovarian and lung cancer data from The Cancer Genome Atlas (TCGA) project. Availability and implementation: R code to implement this method is available at http://www.biostat.wisc.edu/ kendzior/MADGiC/. Contact: kendzior@biostat.wisc.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25573922

Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer

PubMed Central

Qu, Sifeng; Ci, Xinpei; Xue, Hui; Dong, Xin; Hao, Jun; Lin, Dong; Clermont, Pier-Luc; Wu, Rebecca; Collins, Colin C; Gout, Peter W; Wang, Yuzhuo

2018-01-01

Background: Docetaxel used for first-line treatment of advanced prostate cancer (PCa) is only marginally effective. We previously showed, using the LTL-313H subrenal capsule patient-derived metastatic PCa xenograft model, that docetaxel combined with Aneustat (OMN54), a multivalent plant-derived therapeutic, led to marked synergistic tumour growth inhibition. Here, we investigated the effect of docetaxel+Aneustat on metastasis. Methods: C4-2 cells were incubated with docetaxel, Aneustat and docetaxel+Aneustat to assess effects on cell migration. The LTL-313H model, similarly treated, was analysed for effects on lung micro-metastasis and kidney invasion. The LTL-313H gene expression profile was compared with profiles of PCa patients (obtained from Oncomine) and subjected to IPA to determine involvement of cancer driver genes. Results: Docetaxel+Aneustat markedly inhibited C4-2 cell migration and LTL-313H lung micro-metastasis/kidney invasion. Oncomine analysis indicated that treatment with docetaxel+Aneustat was associated with improved patient outcome. The drug combination markedly downregulated expression of cancer driver genes such as FOXM1 (and FOXM1-target genes). FOXM1 overexpression reduced the anti-metastatic activity of docetaxel+Aneustat. Conclusions: Docetaxel+Aneustat can inhibit PCa tissue invasion and metastasis. This activity appears to be based on reduced expression of cancer driver genes such as FOXM1. Use of docetaxel+Aneustat may provide a new, more effective regimen for therapy of metastatic PCa. PMID:29381682

Tracking Progesterone Receptor-Mediated Actions in Breast Cancer

PubMed Central

Knutson, Todd P.; Lange, Carol A.

2014-01-01

Ovarian steroid hormones contribute to breast cancer initiation and progression primarily through the actions of their nuclear transcription factors, the estrogen receptor alpha (ERα) and progesterone receptors (PRs). These receptors are important drivers of the luminal A and B subtypes of breast cancer, where estrogen-blocking drugs have been effective endocrine therapies for patients with these tumors. However, many patients do not respond, or become resistant to treatment. When endocrine therapies fail, the luminal subtypes of breast cancer are more difficult to treat because these subtypes are among the most heterogeneous in terms of mutation diversity and gene expression profiles. Recent evidence suggests that progestin and PR actions may be important drivers of luminal breast cancers. Clinical trial data has demonstrated that hormone replacement therapy with progestins drives invasive breast cancer and results in greater mortality. PR transcriptional activity is dependent upon cross-talk with growth factor signaling pathways that alter PR phosphorylation, acetylation, or SUMOylation as mechanisms for regulating PR target gene selection required for increased cell proliferation and survival. Site-specific PR phosphorylation is the primary driver of gene-selective PR transcriptional activity. However, PR phosphorylation and heightened transcriptional activity is coupled to rapid PR protein degradation; the range of active PR detected in tumors is likely to be dynamic. Thus, PR target gene signatures may provide a more accurate means of tracking PR’s contribution to tumor progression rather than standard clinical protein-based (IHC) assays. Further development of antiprogestin therapies should be considered along side antiestrogens and aromatase inhibitors. PMID:24291072

Statistical implications of using moving violations to determine crash responsibility in young driver crashes

PubMed Central

Curry, Allison E.; Pfeiffer, Melissa R.; Myers, Rachel K.; Durbin, Dennis R.; Elliott, Michael R.

2014-01-01

Traditional methods for determining crash responsibility—most commonly moving violation citations—may not accurately characterize at-fault status among crash-involved drivers given that: (1) issuance may vary by factors that are independent of fault (e.g., driver age, gender), and (2) these methods do not capture driver behaviors that are not illegal but still indicative of fault. We examined the statistical implications of using moving violations to determine crash responsibility in young driver crashes by comparing it with a method based on crash-contributing driver actions. We selected all drivers in police-reported passenger-vehicle crashes (2010–2011) that involved a New Jersey driver <21 years old (79,485 drivers < age 21, 61,355 drivers ≥ age 21.) For each driver, crash responsibility was determined from the crash report using two alternative methods: (1) issuance of a moving violation citation; and (2) presence of a driver action (e.g., failure to yield, inattention). Overall, 18% of crash-involved drivers were issued a moving violation while 50% had a driver action. Only 32.2% of drivers with a driver action were cited for a moving violation. Further, the likelihood of being cited given the presence of a driver action was higher among certain driver subgroups—younger drivers, male drivers, and drivers in single-vehicle and more severe crashes. Specifically among young drivers, those driving at night, carrying peer passengers, and having a suspended or no license were more often cited. Conversely, fatally-injured drivers were almost never cited. We also demonstrated that using citation data may lead to statistical bias in the characterization of at-fault drivers and of quasi-induced exposure measures. Studies seeking to accurately determine crash responsibility should thoughtfully consider the potential sources of bias that may result from using legal culpability methods. For many studies, determining driver responsibility via the identification of driver actions may yield more accurate characterizations of at-fault drivers. PMID:24398139

Introduction to current and future protein therapeutics: a protein engineering perspective.

PubMed

Carter, Paul J

2011-05-15

Protein therapeutics and its enabling sister discipline, protein engineering, have emerged since the early 1980s. The first protein therapeutics were recombinant versions of natural proteins. Proteins purposefully modified to increase their clinical potential soon followed with enhancements derived from protein or glycoengineering, Fc fusion or conjugation to polyethylene glycol. Antibody-based drugs subsequently arose as the largest and fastest growing class of protein therapeutics. The rationale for developing better protein therapeutics with enhanced efficacy, greater safety, reduced immunogenicity or improved delivery comes from the convergence of clinical, scientific, technological and commercial drivers that have identified unmet needs and provided strategies to address them. Future protein drugs seem likely to be more extensively engineered to improve their performance, e.g., antibodies and Fc fusion proteins with enhanced effector functions or extended half-life. Two old concepts for improving antibodies, namely antibody-drug conjugates and bispecific antibodies, have advanced to the cusp of clinical success. As for newer protein therapeutic platform technologies, several engineered protein scaffolds are in early clinical development and offer differences and some potential advantages over antibodies. Copyright © 2011 Elsevier Inc. All rights reserved.

Introduction to current and future protein therapeutics: A protein engineering perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carter, Paul J., E-mail: pjc@gene.com

2011-05-15

Protein therapeutics and its enabling sister discipline, protein engineering, have emerged since the early 1980s. The first protein therapeutics were recombinant versions of natural proteins. Proteins purposefully modified to increase their clinical potential soon followed with enhancements derived from protein or glycoengineering, Fc fusion or conjugation to polyethylene glycol. Antibody-based drugs subsequently arose as the largest and fastest growing class of protein therapeutics. The rationale for developing better protein therapeutics with enhanced efficacy, greater safety, reduced immunogenicity or improved delivery comes from the convergence of clinical, scientific, technological and commercial drivers that have identified unmet needs and provided strategies tomore » address them. Future protein drugs seem likely to be more extensively engineered to improve their performance, e.g., antibodies and Fc fusion proteins with enhanced effector functions or extended half-life. Two old concepts for improving antibodies, namely antibody-drug conjugates and bispecific antibodies, have advanced to the cusp of clinical success. As for newer protein therapeutic platform technologies, several engineered protein scaffolds are in early clinical development and offer differences and some potential advantages over antibodies.« less

The influence of stimulants, sedatives, and fatigue on tunnel vision: risk factors for driving and piloting.

PubMed

Mills, K C; Spruill, S E; Kanne, R W; Parkman, K M; Zhang, Y

2001-01-01

A computerized task was used in two studies to examine the influence of stimulants, sedatives, and fatigue on single-target and divided-attention responses in different parts of the visual field. The drug effects were evaluated over time with repeated behavioral and subjective measures against ascending and descending drug levels. In the first study, 18 fully rested participants received placebo, alprazolam (0.5 mg), and dextroamphetamine (10 mg). Alprazolam impairs performance, whereas dextroamphetamine induces enhancement and tunnel vision. Study 2 exposed 32 participants to fatigue and no fatigue with a repeated-measures crossover design. Four independent groups subsequently received placebo, dextroamphetamine (10 mg), caffeine (250 mg), or alcohol (.07%). Under fatigue, stimulants have no performance-enhancing effects, whereas impairment from alcohol is severe. Under no fatigue, alcohol has a modest effect, caffeine has no effect, and dextroamphetamine significantly enhances divided-attention performance coincident with tunnel vision. Participants rate all drug effects more stimulating and less sedating while fatigued. Implications for transportation safety are discussed. Actual or potential applications of this research include driver and pilot training.

A Two-Year Study of Δ 9 Tetrahydrocannabinol Concentrations in Drivers; Part 2: Physiological Signs on Drug Recognition Expert (DRE) and non-DRE Examinations,.

PubMed

Declues, Kari; Perez, Shelli; Figueroa, Ariana

2018-03-01

Whole blood samples were examined for ∆ 9 -Tetrahydrocannabinol (THC) over 2 years in drivers suspected of driving under the influence. Part one of the study examined the link between [THC] and performance on field sobriety tests. This portion examined objective signs, eye examinations and physiological indicators; and their relationship to the presence of THC. Several objective signs were excellent indicators of the presence of THC: red eyes (94%), droopy eyelids (85.6%), affected speech (87.6%), tongue coating (96.2%), and odor of marijuana (82.4%). About 63.6% of THC positive subjects had dialted pupils (room light). THC positive subjects had either rebound dilation or hippus in 88.8% of cases. Pulse and blood pressure (BP) were evaluated to determine any correlation with [THC]. An increased pulse rate correlated well to the presence of THC (88.5%), but not [THC]. BP did not correlate to [THC] and was also a poor indicator of THC in the blood (50% high). © 2017 American Academy of Forensic Sciences.

Neuroblastoma pathogenesis: deregulation of embryonic neural crest development.

PubMed

Tomolonis, Julie A; Agarwal, Saurabh; Shohet, Jason M

2018-05-01

Neuroblastoma (NB) is an aggressive pediatric cancer that originates from neural crest tissues of the sympathetic nervous system. NB is highly heterogeneous both from a clinical and a molecular perspective. Clinically, this cancer represents a wide range of phenotypes ranging from spontaneous regression of 4S disease to unremitting treatment-refractory progression and death of high-risk metastatic disease. At a cellular level, the heterogeneous behavior of NB likely arises from an arrest and deregulation of normal neural crest development. In the present review, we summarize our current knowledge of neural crest development as it relates to pathways promoting 'stemness' and how deregulation may contribute to the development of tumor-initiating CSCs. There is an emerging consensus that such tumor subpopulations contribute to the evolution of drug resistance, metastasis and relapse in other equally aggressive malignancies. As relapsed, refractory disease remains the primary cause of death for neuroblastoma, the identification and targeting of CSCs or other primary drivers of tumor progression remains a critical, clinically significant goal for neuroblastoma. We will critically review recent and past evidence in the literature supporting the concept of CSCs as drivers of neuroblastoma pathogenesis.

Nature and Nurture: What Determines Tumor Metabolic Phenotypes?

PubMed

Mayers, Jared R; Vander Heiden, Matthew G

2017-06-15

Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein. These differences in amino acid metabolism translate into distinct pathway dependencies, as genetic disruption of the enzymes responsible for utilization of BCAA nitrogen limits the growth of lung tumors, but not pancreatic tumors. These data argue that some cancer metabolic phenotypes are defined by cancer tissue-of-origin and environment and that these features constrain the influence of genetic mutations on metabolism. A better understanding of the factors defining tumor nutrient utilization could be exploited to help improve cancer therapy. Cancer Res; 77(12); 3131-4. ©2017 AACR . ©2017 American Association for Cancer Research.

Tissue-specific tumorigenesis – Context matters

PubMed Central

Schneider, Günter; Schmidt-Supprian, Marc; Rad, Roland; Saur, Dieter

2018-01-01

Preface How can we treat cancer more effectively? Traditionally, tumours from the same anatomical site are treated as one tumour entity. This concept has been challenged by recent breakthroughs in cancer genomics and translational research enabling molecular tumour profiling. The identification and validation of cancer drivers, which are shared between different tumour types, spurred the new paradigm to target driver pathways across anatomical sites by off-label drug use, or within so called “basket or umbrella trials”, which are designed to test whether molecular alterations in one tumour entity can be extrapolated to all others. However, recent clinical and preclinical studies suggest that there are tissue- and cell type-specific differences in tumourigenesis and the organization of oncogenic signalling pathways. In this Opinion article, we focus on the molecular, cellular, systemic and environmental determinants of organ-specific tumourigenesis and mechanisms of context-specific oncogenic signalling outputs. Investigation, recognition and in-depth biological understanding of these differences will be vital for the design of next-generation clinical trials and the implementation of molecularly-guided cancer therapies in the future. PMID:28256574

Genetic Correction of SOD1 Mutant iPSCs Reveals ERK and JNK Activated AP1 as a Driver of Neurodegeneration in Amyotrophic Lateral Sclerosis.

PubMed

Bhinge, Akshay; Namboori, Seema C; Zhang, Xiaoyu; VanDongen, Antonius M J; Stanton, Lawrence W

2017-04-11

Although mutations in several genes with diverse functions have been known to cause amyotrophic lateral sclerosis (ALS), it is unknown to what extent causal mutations impinge on common pathways that drive motor neuron (MN)-specific neurodegeneration. In this study, we combined induced pluripotent stem cells-based disease modeling with genome engineering and deep RNA sequencing to identify pathways dysregulated by mutant SOD1 in human MNs. Gene expression profiling and pathway analysis followed by pharmacological screening identified activated ERK and JNK signaling as key drivers of neurodegeneration in mutant SOD1 MNs. The AP1 complex member JUN, an ERK/JNK downstream target, was observed to be highly expressed in MNs compared with non-MNs, providing a mechanistic insight into the specific degeneration of MNs. Importantly, investigations of mutant FUS MNs identified activated p38 and ERK, indicating that network perturbations induced by ALS-causing mutations converge partly on a few specific pathways that are drug responsive and provide immense therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Economic consequences of legal and illegal drugs: The case of social costs in Belgium.

PubMed

Lievens, Delfine; Vander Laenen, Freya; Verhaeghe, Nick; Putman, Koen; Pauwels, Lieven; Hardyns, Wim; Annemans, Lieven

2017-06-01

Legal and illegal drugs impose a considerable burden to the individual and to society. The misuse of addictive substances results in healthcare and law enforcement costs, loss of productivity and reduced quality of life. A social cost study was conducted to estimate the substance-attributable costs of alcohol, tobacco, illegal drugs and psychoactive medication to Belgian society in 2012. The cost-of-illness framework with prevalence-based and human capital approach was applied. Three cost components were considered: direct, indirect and intangible costs related to substance misuse. The direct and indirect cost of addictive substances was estimated at 4.6 billion euros in Belgium (419 euros per capita or 1.19% of the GDP) and more than 515,000 healthy years are lost due to substance misuse. The Belgian social cost study reaffirms that alcohol and tobacco impose the highest cost to society compared to illegal drugs. Health problems are the main driver of the social cost of legal drugs. Law enforcement expenditure exceed the healthcare costs but only in the case of illegal drugs. Estimating social costs of addictive substances is complex because it is difficult to determine to what extent the societal harm is caused by substances. It can be argued that social cost studies take only a 'snapshot' of the monetary consequences of substance misuse. Nevertheless, the current study offers the most comprehensive analysis thus far of the social costs of substance misuse in Belgium. Copyright © 2017 Elsevier B.V. All rights reserved.

A Qualitative Approach to a Better Understanding of the Problems Underlying Drug Shortages, as Viewed from Belgian, French and the European Union’s Perspectives

PubMed Central

Prokop, Anna; Pilc, Andrzej

2015-01-01

The problem of drug shortages has been reported worldwide, gaining prominence in multiple domains and several countries in recent years. The aim of the study was to analyze, characterise and assess this problem in Belgium and France, while also adopting a wider perspective from the European Union. A qualitative methodological approach was employed, including semi-structured interviews with the representatives of respective national health authorities, pharmaceutical companies and wholesalers, as well as hospital and community pharmacists. The research was conducted in early 2014. Four themes, which were identified through the interviews, were addressed in the paper, i.e. a) defining drug shortages, b) their dynamics and perception, c) their determinants, d) the role of the European and national institutions in coping with the problem. Three groups of determinants of drug shortages were identified throughout this study: manufacturing problems, distribution and supply problems, and problems related to economic aspects. Currently, the Member States of the European Union are striving to resolve the problem very much on their own, although a far more focused and dedicated collaboration may well prove instrumental in coping with drug shortages throughout Europe more effectively. To the best of the authors’ knowledge, this is the first qualitative study to investigate the characteristics, key determinants, and the problem drivers of drug shortages, focusing on this particular group of countries, while also adopting the European Union’s perspective. PMID:25942432

Open source machine-learning algorithms for the prediction of optimal cancer drug therapies.

PubMed

Huang, Cai; Mezencev, Roman; McDonald, John F; Vannberg, Fredrik

2017-01-01

Precision medicine is a rapidly growing area of modern medical science and open source machine-learning codes promise to be a critical component for the successful development of standardized and automated analysis of patient data. One important goal of precision cancer medicine is the accurate prediction of optimal drug therapies from the genomic profiles of individual patient tumors. We introduce here an open source software platform that employs a highly versatile support vector machine (SVM) algorithm combined with a standard recursive feature elimination (RFE) approach to predict personalized drug responses from gene expression profiles. Drug specific models were built using gene expression and drug response data from the National Cancer Institute panel of 60 human cancer cell lines (NCI-60). The models are highly accurate in predicting the drug responsiveness of a variety of cancer cell lines including those comprising the recent NCI-DREAM Challenge. We demonstrate that predictive accuracy is optimized when the learning dataset utilizes all probe-set expression values from a diversity of cancer cell types without pre-filtering for genes generally considered to be "drivers" of cancer onset/progression. Application of our models to publically available ovarian cancer (OC) patient gene expression datasets generated predictions consistent with observed responses previously reported in the literature. By making our algorithm "open source", we hope to facilitate its testing in a variety of cancer types and contexts leading to community-driven improvements and refinements in subsequent applications.

Japan-Specific Key Regulatory Aspects for Development of New Biopharmaceutical Drug Products.

PubMed

Desai, Kashappa Goud; Obayashi, Hirokazu; Colandene, James D; Nesta, Douglas P

2018-03-28

Japan represents the third largest pharmaceutical market in the world. Developing a new biopharmaceutical drug product for the Japanese market is a top business priority for global pharmaceutical companies while aligning with ethical drivers to treat more patients in need. Understanding Japan-specific key regulatory requirements is essential to achieve successful approvals. Understanding the full context of Japan-specific regulatory requirements/expectations is challenging to global pharmaceutical companies due to differences in language and culture. This article summarizes key Japan-specific regulatory aspects/requirements/expectations applicable to new drug development, approval, and postapproval phases. Formulation excipients should meet Japan compendial requirements with respect to the type of excipient, excipient grade, and excipient concentration. Preclinical safety assessments needed to support clinical phases I, II, and III development are summarized. Japanese regulatory authorities have taken appropriate steps to consider foreign clinical data, thereby enabling accelerated drug development and approval in Japan. Other important topics summarized in this article include: Japan new drug application-specific bracketing strategies for critical and noncritical aspects of the manufacturing process, regulatory requirements related to stability studies, release specifications and testing methods, standard processes involved in pre and postapproval inspections, management of postapproval changes, and Japan regulatory authority's consultation services available to global pharmaceutical companies. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Concordance of IHC, FISH and RT-PCR for EML4-ALK rearrangements.

PubMed

Teixidó, Cristina; Karachaliou, Niki; Peg, Vicente; Gimenez-Capitan, Ana; Rosell, Rafael

2014-04-01

The echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) has emerged as the second most important driver oncogene in lung cancer and the first targetable fusion oncokinase to be identified in 4-6% of lung adenocarcinomas. Crizotinib, along with a diagnostic test-the Vysis ALK Break Apart fluorescence in situ hybridization (FISH) Probe Kit-is approved for the treatment of ALK positive advanced non-small cell lung cancer (NSCLC). However, the success of a targeted drug is critically dependent on a sensitive and specific screening assay to detect the molecular drug target. In our experience, reverse transcription polymerase chain reaction (RT-PCR)-based detection of EML4-ALK is a more sensitive and reliable approach compared to FISH and immunohistochemistry (IHC). Although ALK FISH is clinically validated, the assay can be technically challenging and other diagnostic modalities, including IHC and RT-PCR should be further explored.

Comparative physiology of mice and rats: radiometric measurement of vascular parameters in rodent tissues.

PubMed

Boswell, C Andrew; Mundo, Eduardo E; Ulufatu, Sheila; Bumbaca, Daniela; Cahaya, Hendry S; Majidy, Nicholas; Van Hoy, Marjie; Schweiger, Michelle G; Fielder, Paul J; Prabhu, Saileta; Khawli, Leslie A

2014-05-05

A solid understanding of physiology is beneficial in optimizing drug delivery and in the development of clinically predictive models of drug disposition kinetics. Although an abundance of data exists in the literature, it is often confounded by the use of various experimental methods and a lack of consensus in values from different sources. To help address this deficiency, we sought to directly compare three important vascular parameters at the tissue level using the same experimental approach in both mice and rats. Interstitial volume, vascular volume, and blood flow were radiometrically measured in selected harvested tissues of both species by extracellular marker infusion, red blood cell labeling, and rubidium chloride bolus distribution, respectively. The latter two parameters were further compared by whole-body autoradiographic imaging. An overall good interspecies agreement was observed for interstitial volume and blood flow on a weight-normalized basis in most tissues. In contrast, the measured vascular volumes of most rat tissues were higher than for mouse. Mice and rats, the two most commonly utilized rodent species in translational drug development, should not be considered as interchangeable in terms of vascular volume per gram of tissue. This will be particularly critical in biodistribution studies of drugs, as the amount of drug in the residual blood of tissues is often not negligible, especially for biologic drugs (e.g., antibodies) having long circulation half-lives. Physiologically based models of drug pharmacokinetics and/or pharmacodynamics also rely on accurate knowledge of biological parameters in tissues. For tissue parameters with poor interspecies agreement, the significance and possible drivers are discussed.

French Health Technology Assessment of Antineoplastic Drugs Indicated in the Treatment of Solid Tumours: Perspective for Future Trends.

PubMed

Chouaid, Christos; Borget, Isabelle; Braun, Eric; Bazil, Marie-Laure; Schaetz, Dominique; Rémuzat, Cécile; Toumi, Mondher

2016-08-01

France is one of the European countries that spend the most on oncology drugs. To keep pharmaceutical expenditure under control, Health Authorities highly scrutinize market access of costly medicines. To assess current and future trends in French health technology assessment (HTA) of antineoplastic drugs indicated in the treatment of solid tumours. A review of the SMR and ASMR drivers of the Transparency Committee (CT) opinions issued for antineoplastic drugs indicated in the treatment of solid tumours and approved between 2009 and 2014 was performed to assess current trends in French health technology assessment (HTA), complemented by an expert board consultation to capture the critical issues on the future of antineoplastic drugs HTA. Thirty-one drugs indicated for the treatment of solid tumours were identified (77 % targeted therapies). Initial CT assessments were available for 26 drugs. Four key items in the CT assessment were identified: 1) Clinical trial methodology; 2) Acceptance of progression-free survival (PFS) as a valuable endpoint; 3) Transferability of clinical trials in clinical practice; 4) Unpredictability of CT decisions. Experts raised the important development of personalised medicines in oncology and key challenges for oncology products to generate information expected from HTA perspective. The French system remains committed to its values and philosophy (access of all innovations for everybody) which are threatened by the increasing launch of innovative therapies and budget constraint. Both HTA decision framework evolution and revision of the current pricing process should be considered in France to cope with these new challenges.

A systematic review of cost-effectiveness analyses of drugs for postmenopausal osteoporosis.

PubMed

Hiligsmann, Mickaël; Evers, Silvia M; Ben Sedrine, Wafa; Kanis, John A; Ramaekers, Bram; Reginster, Jean-Yves; Silverman, Stuart; Wyers, Caroline E; Boonen, Annelies

2015-03-01

Given the limited availability of healthcare resources and the recent introduction of new anti-osteoporosis drugs, the interest in the cost effectiveness of drugs in postmenopausal osteoporosis remains and even increases. This study aims to identify all recent economic evaluations on drugs for postmenopausal osteoporosis, to critically appraise the reporting quality, and to summarize the results. A literature search using Medline, the National Health Service Economic Evaluation database and the Cost-Effectiveness Analysis Registry was undertaken to identify original articles published between January 1, 2008 and December 31, 2013. Studies that assessed cost effectiveness of drugs in postmenopausal osteoporosis were included. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement was used to assess the quality of reporting of these articles. Of 1,794 articles identified, 39 studies fulfilled the inclusion criteria. They were conducted in 14 different countries and nine active interventions were assessed. When compared with no treatment, active osteoporotic drugs were generally cost effective in postmenopausal women aged over 60-65 years with low bone mass, especially those with prior vertebral fractures. Key drivers of cost effectiveness included individual fracture risk, medication adherence, selected comparators and country-specific analyses. Quality of reporting varied between studies with an average score of 17.9 out of 24 (range 7-21.5). This review found a substantial number of published cost-effectiveness analyses of drugs in osteoporosis in the last 6 years. Results and critical appraisal of these articles can help decision makers when prioritizing health interventions and can inform the development of future economic evaluations.

Traffic Safety Facts, 2001: Young Drivers.

ERIC Educational Resources Information Center

National Highway Traffic Safety Administration (DOT), Washington, DC.

This document provides statistical information on U.S. traffic accidents involving young drivers. Data tables include: (1) driver fatalities and drivers involved in fatal crashes among drivers 15 to 20 years old, 1991-2001; (2) drivers involved in fatal crashes and driver involvement rates by age group, 2001; (3) drivers 15 to 20 years old…

Young Drivers. Traffic Safety Facts, 2000.

ERIC Educational Resources Information Center

National Highway Traffic Safety Administration (DOT), Washington, DC.

This document provides statistical information on U.S. traffic accidents involving young drivers. Data tables include: (1) driver fatalities and drivers involved in fatal crashes among drivers 15 to 20 years old, 1990-2000; (2) drivers involved in fatal crashes and driver involvement rates by age group, 2000; (3) drivers 15 to 20 years old…

Gender Effects in Young Road Users on Road Safety Attitudes, Behaviors and Risk Perception

PubMed Central

Cordellieri, Pierluigi; Baralla, Francesca; Ferlazzo, Fabio; Sgalla, Roberto; Piccardi, Laura; Giannini, Anna Maria

2016-01-01

In the present study, we investigated gender-related effects on road safety attitudes in 2681 young drivers (1458 males, 54.4%; aged 18–22) who filled out several scales assessing attitudes toward road safety issues, driving behavior in specific hypothetical situations, accident risk perception, and concerns about such a risk. We focused only on young drivers to better understand the role of gender in road safety attitudes in a period of life in which risky behaviors are widespread for males and females. Indeed, there is still no agreement as to the nature of these gender differences. According to some authors, the effects of gender on being involved in a crash due to driving skills are either non-existent or largely explained by differences in alcohol consumption. In our study, we found gender differences in road safety attitudes (i.e., “negative attitude toward traffic rules and risky driving”; “negative attitude toward drugs and alcohol” and “tolerance toward speeding”) and in driver behavior (i.e., “errors in inattentive driving” and “driving violations”). This result is consistent in all drivers coming from nine different European countries. Our analyses yielded an important finding concerning risk perception. The results indicate that the level of risk perception during driving is the same for males and females. However, these two groups differ in the level of concern about this risk, with males being less concerned about the risk of a road accident. This suggests that the main difference between these two groups is not strictly related to judgment of the perceived risk probability but rather to the level of concern experienced about the consequences of the risk. This difference between risk perception and worry could explain differences in the frequency of car accidents in the two groups. The present findings may provide new insights for the development of gender-based prevention programs. PMID:27729877

[Occupational stress situation analysis of different types of train drivers].

PubMed

Zhou, Wenhui; Gu, Guizhen; Wu, Hui; Yu, Shanfa

2014-11-01

To analyze the status of occupational stress in different types of train drivers. By using cluster sampling method, a cross-sectional study was conducted in 1 339 train drivers (including 289 passenger train drivers, 637 freight trains drivers, 339 passenger shunting train drivers, and 74 high speed rail drivers) from a Railway Bureau depot. The survey included individual factors, occupational stress factors, stress response factors and stress mitigating factors. The occupational stress factors, stress response factors and mitigating factors were measured by the revised effort-reward imbalance (ERI) model questionnaires and occupational stress measurement scale. By using the method of covariance analysized the difference of occupational stress factors of all types train drivers, the method of Stepwise regression was used to analyze the effection (R(2)) of occupational stress factors and stress mitigating factors on stress response factors. Covariance analysis as covariates in age, education level, length of service and marital status showed that the scores of ERI (1.58 ± 0.05), extrinsic effort (19.88 ± 0.44), rewards (23.43 ± 0.43), intrinsic effort (17.86 ± 0.36), physical environment (5.70 ± 0.22), social support (30.51 ± 0.88) and daily tension (10.27 ± 0.38 ) of high speed rail drivers were higher than other drivers (F values were 6.06, 11.32, 7.05, 13.25, 5.20, 9.48 and 6.14 respectively, P < 0.01), but the scores of emotional balance (4.15 ± 0.31) and positive emotion (2.06 ± 0.20) were lower than other drives (P < 0.01);the scores of psychological needs (10.48 ± 0.18), emotional balance (4.88 ± 0.16) and positive emotion (2.63 ± 0.10) of passenger train drivers were higher than other drivers (F values were 4.33 and 5.50 respectively, P < 0.01). The descending rank of the effect value on occupational stress factors and mitigating factors to depressive symptoms of train drivers was high speed rail drivers (R(2) = 0.64), passenger train drivers (R(2) = 0.44), passenger shunting train drivers (R(2) = 0.39), freight trains drivers (R(2) = 0.38); job satisfaction of train drivers was high speed rail drivers (R(2) = 0.68), passenger train drivers (R(2) = 0.62), freight trains drivers (R(2) = 0.43), passenger shunting train drivers(R(2) = 0.38); to daily tension of train drivers was high speed rail drivers (R(2) = 0.54), passenger train drivers (R(2) = 0.37), passenger shunting train drivers (R(2) = 0.33), freight trains drivers (R(2) = 0.30); emotional balance of train drivers was high speed rail drivers (R(2) = 0.47), passenger train drivers (R(2) = 0.43), passenger shunting train drivers (R(2) = 0.33), freight trains drivers(R(2) = 0.31). ERI, psychological needs, work responsibilities, job roles, work conflict, and physical environment were important occupational stress factors of train drivers; social support was pivotal mitigating factors; different train drivers had different occupational stress status, high speed rail drivers were the highest, and freight trains drivers passenger train drivers or passenger shunting train drivers were the lowest.

Safer Vehicles for People and the Planet: Letter to the Editor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wenzel, Thomas P; Wenzel, Thomas P; Ross, Marc

Letter to the Editors from Leonard Evans, Bloomfield Hills, MI: Single-vehicle crashes, which account for half of occupant fatalities, are not mentioned in 'Safer Vehicles for People and the Planet', by Thomas P. Wenzel and Marc Ross (March-April). Simple physics shows that in such crashes risk declines as vehicle mass increases. The authors write 'driving imported luxury cars carries extremely low risk, for reasons that are not obvious'. The reasons are obvious--the cars are purchased by low-risk drivers. If they swapped vehicles with drivers of sports cars (which have high risk), the risks would stick with the drivers, not themore » vehicles. The article reflects the American belief that death on our roads can be substantially reduced by making vehicles in which it is safer to crash. From 1979 through 2002, Great Britain, Canada and Australia reduced fatalities by an average of 49 percent, compared with 16 percent in the U.S. Accumulating the differences over this time shows that by merely matching the safety performance of these other countries, about 200,000 fewer Americans would have died. These trends continue. In 2006 the U.S. recorded 42,642 traffic deaths, a modest 22 percent decline from our all-time high. Sweden recorded 445, a reduction of 66 percent from their all-time high. The obsessive focus on vehicles rather than on countermeasures that scientific research shows substantially reduce risk is at the core of our dramatic safety failure. The only way to substantially reduce deaths is to reduce the risk of crashing, not to make it safer to crash. The response from Drs. Wenzel and Ross: Of course Dr. Evans is correct in stating that driver behavior influences crash risk. In our article we made clear that our estimates of risk include how well a vehicle/driver combination avoids a crash, as well as how crash-worthy a vehicle (and robust a driver) is once a crash occurs. We also analyzed two variables that can account for driver behavior: the fraction of all driver fatalities that are young men, and a 'bad driver' rating that combines information about the current crash (drug or alcohol involvement, driving without a license, or reckless driving) as well as the operator's driving record for the previous three years. For example, the high risks of sports cars, and the low risks of minivans, are clearly influenced by who drives these types of vehicles (36 percent young males and 0.77 bad driver rating for sports cars, vs. 4 percent and 0.21 for minivans; the average values for all types of cars are 20 percent and 0.50). On the other hand, we were surprised to find that the imported luxury cars, with the lowest risks, have only average drivers (21 percent young males, 0.57 bad driver rating). That is the basis for our conclusion that the design of imported luxury vehicles, or at least specific safety features on them, overcome risky behavior taken by their drivers. The safety of vehicles has greatly improved over the years. In our studies we have found several examples of models that greatly reduced their risks over time; for example, the Ford Focus has a much better risk to its drivers (118) than the Ford Escort it replaced (148). Our data indicate that more young males drive the Focus (21 percent) than the Escort (15 percent), and that Focus drivers are perhaps slightly more risky (0.50 vs. 0.44 bad driver rating). Clearly vehicle design does not play as small a role in vehicle safety as Dr. Evans suggests. Dr. Evans asserts that we ignore single-vehicle crashes and that simple physics dictates that vehicle mass provides safety in single-vehicle crashes. By itself, additional vehicle mass does provide some protection from rapid deceleration in crashes with a movable object, particularly for an unbelted occupant. However, when it comes to vehicle safety, our research by vehicle model indicates that there is essentially no relationship between car mass and risk, even in frontal crashes. In his own papers, Dr. Evans appears to admit that it is not clear whether mass, or size (specifically crush space) is inherent to vehicle safety. Additional research indicates that it is not size per se that protects in two-vehicle crashes, but how well the stiff structures on the vehicles are aligned. The auto manufacturing industry has voluntarily made design changes to their pickup trucks to increase the likelihood that truck and car bumpers will interact in a frontal crash, reducing the aggressivity of pickup trucks in recent years. Regarding the differences in experiences between the U.S. and other countries, it is important to keep in mind that the U.S. vehicle fleet is fairly unique; about half of U.S. vehicles are light duty trucks (pickups, SUVs and minivans), which many studies have shown are dangerous to other road users.« less

An Approach to Mitigate Particle Formation on the Dilution of a Monoclonal Antibody Drug Product in an IV Administration Fluid.

PubMed

Zheng, Songyan; Adams, Monica; Mantri, Rao V

2016-03-01

To support dose reduction, low dose of a monoclonal antibody (mAb) was required to be administered via IV infusion at a concentration of 0.1 mg/mL. To achieve the target protein concentration, the infusion solution was prepared by diluting the drug product containing 10-mg/mL mAb with normal saline, a 0.9% sodium chloride injection solution. However, particles were observed in the diluted solution. Particle formation must be avoided to administer the low dose using the existing drug product. To mitigate the particle formation, an unconventional compounding approach was used. With this approach, a stabilizing vehicle containing polysorbate-80 was added to saline before drug-product dilution to maintain suitable surfactant level to prevent precipitation of the mAb. In this way, use of the stabilizing vehicle to support low doses ensured suitable quality across a wider range of mAb concentrations, thereby allowing additional flexibility to the clinical trial. Such an approach may be useful for broader application in early-stage clinical trials where there is an uncertainty regarding doses or the need to revise to lower doses based on clinical observations or other drivers. Copyright © 2016. Published by Elsevier Inc.

Drivers of bacterial genomes plasticity and roles they play in pathogen virulence, persistence and drug resistance.

PubMed

Patel, Seema

2016-11-01

Despite the advent of next-generation sequencing (NGS) technologies, sophisticated data analysis and drug development efforts, bacterial drug resistance persists and is escalating in magnitude. To better control the pathogens, a thorough understanding of their genomic architecture and dynamics is vital. Bacterial genome is extremely complex, a mosaic of numerous co-operating and antagonizing components, altruistic and self-interested entities, behavior of which are predictable and conserved to some extent, yet largely dictated by an array of variables. In this regard, mobile genetic elements (MGE), DNA repair systems, post-segregation killing systems, toxin-antitoxin (TA) systems, restriction-modification (RM) systems etc. are dominant agents and horizontal gene transfer (HGT), gene redundancy, epigenetics, phase and antigenic variation etc. processes shape the genome. By illegitimate recombinations, deletions, insertions, duplications, amplifications, inversions, conversions, translocations, modification of intergenic regions and other alterations, bacterial genome is modified to tackle stressors like drugs, and host immune effectors. Over the years, thousands of studies have investigated this aspect and mammoth amount of insights have been accumulated. This review strives to distillate the existing information, formulate hypotheses and to suggest directions, that might contribute towards improved mitigation of the vicious pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

The evolving landscape of therapeutic drug development for hepatocellular carcinoma.

PubMed

Chong, Dawn Qingqing; Tan, Iain Beehuat; Choo, Su-Pin; Toh, Han Chong

2013-11-01

Currently, only one drug, sorafenib, is FDA approved for the treatment of advanced hepatocellular carcinoma (HCC), achieving modest objective response rates while still conferring an overall survival benefit. Unlike other solid tumors, no oncogenic addiction loops have been validated as clinically actionable targets in HCC. Outcomes of HCC could potentially be improved if critical molecular subclasses with distinct therapeutic vulnerabilities can be identified, biomarkers that predict recurrence or progression early can be determined and key epigenetic, genetic or microenvironment drivers that determine best response to a specific targeting treatment can be uncovered. Our group and others have examined the molecular heterogeneity of hepatocellular carcinoma. We have developed a panel of patient derived xenograft models to enable focused pre-clinical drug development of rationally designed therapies in specific molecular subgroups. We observed unique patterns, including synergies, of drug activity across our molecularly diverse HCC xenografts, pointing to specific therapeutic vulnerabilities for individual tumors. These efforts inform clinical trial designs and catalyze therapeutic development. It also argues for efficient strategic allocation of patients into appropriate enriched clinical trials. Here, we will discuss some of the recent important therapeutic studies in advanced HCC and also some of the potential strategies to optimize clinical therapeutic development moving forward. Copyright © 2013 Elsevier Inc. All rights reserved.

Staphylococcus aureus disease and drug resistance in resource-limited countries in south and east Asia.

PubMed

Nickerson, Emma K; West, T Eoin; Day, Nicholas P; Peacock, Sharon J

2009-02-01

By contrast with high-income countries, Staphylococcus aureus disease ranks low on the public-health agenda in low-income countries. We undertook a literature review of S aureus disease in resource-limited countries in south and east Asia, and found that its neglected status as a developing world pathogen does not equate with low rates of disease. The incidence of the disease seems to be highest in neonates, its range of clinical manifestations is as broad as that seen in other settings, and the mortality rate associated with serious S aureus infection, such as bacteraemia, is as high as 50%. The prevalence of meticillin-resistant S aureus (MRSA) infection across much of resource-limited Asia is largely unknown. Antibiotic drugs are readily and widely available from pharmacists in most parts of Asia, where ease of purchase and frequent self-medication are likely to be major drivers in the emergence of drug resistance. In our global culture, the epidemiology of important drug-resistant pathogens in resource-limited countries is inextricably linked with the health of both developing and developed communities. An initiative is needed to raise the profile of S aureus disease in developing countries, and to define a programme of research to find practical solutions to the health-care challenges posed by this important global pathogen.

Benzodiazepines, opioids and driving: an overview of the experimental research.

PubMed

Leung, Stefanie Y

2011-05-01

Road crashes contribute significantly to the total burden of injury in Australia, with the risk of injury being associated with the presence of drugs and/or alcohol in the driver's blood. Increasingly, some of the most commonly detected drugs include prescription medicines, the most notable of these being benzodiazepines and opioids. However, there is a paucity of experimental research into the effects of prescribed psychoactive drugs on driving behaviours. This paper provides an overview of experimental studies investigating the effects of prescribed doses of benzodiazepines and opioids on driving ability, and points to future directions for research. There is growing epidemiological evidence linking the therapeutic use of benzodiazepines and opioids to an increased crash risk. However, the current experimental literature remains unclear. Limitations to study methodologies have resulted in inconsistent findings. Limited experimental evidence exists to inform policy and guidelines regarding fitness-to-drive for patients taking prescribed benzodiazepines and opioids. Further experimental research is required to elucidate the effects of these medications on driving, under varying conditions and in different medical contexts. This will ensure that doctors prescribing benzodiazepines and opioids are well informed, and can appropriately advise patients of the risks associated with driving whilst taking these medications. © 2011 Australasian Professional Society on Alcohol and other Drugs.

Implementing Genome-Driven Oncology

PubMed Central

Hyman, David M.; Taylor, Barry S.; Baselga, José

2017-01-01

Early successes in identifying and targeting individual oncogenic drivers, together with the increasing feasibility of sequencing tumor genomes, have brought forth the promise of genome-driven oncology care. As we expand the breadth and depth of genomic analyses, the biological and clinical complexity of its implementation will be unparalleled. Challenges include target credentialing and validation, implementing drug combinations, clinical trial designs, targeting tumor heterogeneity, and deploying technologies beyond DNA sequencing, among others. We review how contemporary approaches are tackling these challenges and will ultimately serve as an engine for biological discovery and increase our insight into cancer and its treatment. PMID:28187282

The tough decisions that no one wants to make.

PubMed

Taylor, Joe; Jacobs, Michael

2003-01-01

This article examines prescription drug benefit plan trends: past, current, short-term future and long-term future. It includes a brief discussion of each cost trend and its drivers, then asks the question, "What can be done to protect the pharmacy benefit budget, yet provide what is needed?" from three perspectives: (1) business, (2) stakeholders (management, human resource groups, physicians, employees) and (3) patients (employees and dependents). The article discusses therapeutic guidelines, physician education, reimbursement issues, distribution channels and the impact of business decisions on employees, dependents, stockholders, shareholder value, management, human resources and decision makers' own careers.

The Use of Drugs to Reduce Hearing Loss Following Acute Acoustic Trauma

DTIC Science & Technology

2013-10-15

Src and Ebselen were put into solution using DMSO. Both EDTA and DMSO have anti- oxidant /anti-inflammatory properties. As a result the SOW was modified...P re ss ur e (d B S P L) Driver Pressure (psi) diaphragm: Grafit Clear Acetate Thickness d=0.003 in. -600 -400 -200 0 200 400 600 800 0 50 100 150...A m pl itu de ms -100 0 100 200 300 400 500 600 700 0 0.5 1 1.5 2 Figure 2. Peak pressure of the incident shock wave at the entrance of the 36

Occupational Fatalities Among Driver/Sales Workers and Truck Drivers in the United States, 2003–2008

PubMed Central

Chen, Guang X.; Amandus, Harlan E.; Wu, Nan

2015-01-01

Background This study provides a national profile of occupational fatalities among truck drivers and driver-sales workers. Methods Data from the 2003–2008 Census of Fatal Occupational Injuries were used. Cases were extracted specifically for occupational subcategories included in the Driver/Sales Workers and Truck Drivers occupational category: Driver/Sales Workers, Heavy and Tractor-Trailer Truck Drivers, and Light Truck or Delivery Services Drivers. Results In 2003–2008, the group Driver/Sales Workers and Truck Drivers had 5,568 occupational fatalities, representing 17% of all occupational fatalities in the United States. The majority of these fatalities were in the subgroup Heavy and Tractor-Trailer Truck Drivers (85%) and due to transportation incidents (80%). Older and male drivers had higher fatality rates than their counterparts. Conclusions Findings suggest a need for targeted interventions to reduce highway fatalities among heavy truck drivers. Better employment data are needed to separate the three occupational subcategories by worker characteristic and employment history for use in research and prevention efforts. PMID:24811905

In Patients With Cirrhosis, Driving Simulator Performance Is Associated With Real-life Driving.

PubMed

Lauridsen, Mette M; Thacker, Leroy R; White, Melanie B; Unser, Ariel; Sterling, Richard K; Stravitz, Richard T; Matherly, Scott; Puri, Puneet; Sanyal, Arun J; Gavis, Edith A; Luketic, Velimir; Siddiqui, Muhammad S; Heuman, Douglas M; Fuchs, Michael; Bajaj, Jasmohan S

2016-05-01

Minimal hepatic encephalopathy (MHE) has been linked to higher real-life rates of automobile crashes and poor performance in driving simulation studies, but the link between driving simulator performance and real-life automobile crashes has not been clearly established. Furthermore, not all patients with MHE are unsafe drivers, but it is unclear how to distinguish them from unsafe drivers. We investigated the link between performance on driving simulators and real-life automobile accidents and traffic violations. We also aimed to identify features of unsafe drivers with cirrhosis and evaluated changes in simulated driving skills and MHE status after 1 year. We performed a study of outpatients with cirrhosis (n = 205; median 55 years old; median model for end-stage liver disease score, 9.5; none with overt hepatic encephalopathy or alcohol or illicit drug use within previous 6 months) seen at the Virginia Commonwealth University and McGuire Veterans Administration Medical Center, from November 2008 through April 2014. All participants were given paper-pencil tests to diagnose MHE (98 had MHE; 48%), and 163 patients completed a standardized driving simulation. Data were collected on traffic violations and automobile accidents from the Virginia Department of Motor Vehicles and from participants' self-assessments when they entered the study, and from 73 participants 1 year later. Participants also completed a questionnaire about alcohol use and cessation patterns. The driving simulator measured crashes, run-time, road center and edge excursions, and illegal turns during navigation; before and after each driving simulation session, patients were asked to rate their overall driving skills. Drivers were classified as safe or unsafe based on crashes and violations reported on official driving records; simulation results were compared with real-life driving records. Multivariable regression analyses of real-life crashes and violations was performed using data on demographics, cirrhosis details, MHE status, and alcohol cessation patterns, at baseline and at 1 year. Drivers categorized as unsafe had more crashes and made more illegal turns on the driving simulator than drivers categorized as safe; a higher proportion of subjects with MHE were categorized as unsafe drivers at baseline (16%) than subjects without MHE (7%; P = .02), and at 1-year follow-up (18% vs 0%; P = .02). Alcohol cessation within <1 year and illegal turns during simulator navigation tasks were associated with real-life automobile crashes and MHE in regression analysis; road edge excursions in the simulator were associated with real-life traffic violations. Personal assessment of driving skills improved after each simulation episode. In a study of 205 patients with cirrhosis, we associated results from driving simulation tests with real-life driving records and MHE. Traffic safety counseling should focus on patients with cirrhosis who recently quit consuming alcohol and perform poorly on driving simulation. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Driving fatigue in professional drivers: a survey of truck and taxi drivers.

PubMed

Meng, Fanxing; Li, Shuling; Cao, Lingzhi; Li, Musen; Peng, Qijia; Wang, Chunhui; Zhang, Wei

2015-01-01

Fatigue among truck drivers has been studied extensively; however, less is known regarding the fatigue experience of taxi drivers in heavily populated metropolitan areas. This study aimed to compare the differences and similarities between truck and taxi driver fatigue to provide implications for the fatigue management and education of professional drivers. A sample of 274 truck drivers and 286 taxi drivers in Beijing was surveyed via a questionnaire, which included items regarding work characteristics, fatigue experience, accident information, attitude toward fatigue, and methods of counteracting fatigue. Driver fatigue was prevalent among professional drivers, and it was even more serious for taxi drivers. Taxi drivers reported more frequent fatigue experiences and were involved in more accidents. Among the contributing factors to fatigue, prolonged driving time was the most important factor identified by both driver groups. Importantly, the reason for the engagement in prolonged driving was neither due to the lack of awareness concerning the serious outcome of fatigue driving nor because of their poor detection of fatigue. The most probable reason was the optimism bias, as a result of which these professional drivers thought that fatigue was more serious for other drivers than for themselves, and they thought that they were effective in counteracting the effect of fatigue on their driving performance. Moreover, truck drivers tended to employ methods that require stopping to counteract fatigue, whereas taxi drivers preferred methods that were simultaneous with driving. Although both driver groups considered taking a nap as one of the most effective means to address fatigue, this method was not commonly used. Interestingly, these drivers were aware that the methods they frequently used were not the most effective means to counteract fatigue. This study provides knowledge on truck and taxi drivers' characteristics in fatigue experience, fatigue attitude, and fatigue countermeasures, and these findings have practical implications for the fatigue management and education of professional drivers.

National reported patterns of driver cell phone use in the United States.

PubMed

Braitman, Keli A; McCartt, Anne T

2010-12-01

To obtain detailed information on patterns of driver cell phone use, including how often drivers talk and text, the extent to which they use hands-free devices, and knowledge of and reaction to state cell phone laws. Telephone surveys were conducted with 1219 drivers in the 48 contiguous U.S. states and the District of Columbia, using random samples of landline and cell phone numbers. Forty percent of drivers reported talking on phones at least a few times per week. The percentages were highest for males (49%) and drivers ages 25-29 (66%). The percentage of drivers who reported never talking on phones was higher in states with all-driver bans on handheld phone use (44%) than in states without a ban applying to all drivers (30%). The percentage of drivers who talk on phones and always talk hands-free was higher in states with all-driver handheld phone bans (22%) than where such bans are not in effect (13%). Thirteen percent of drivers reported some texting while driving, and this percentage was highest among drivers ages 18-24 (43%). Twelve percent of drivers in states with all-driver texting bans reported texting while driving, compared with 14 percent in states with no texting ban. Among drivers ages 18-24, the percentages were 45 and 48 percent, respectively. Most drivers reported talking on phones while driving, even though earlier surveys have found that most people think this behavior should be banned. Fewer drivers overall reported texting, but the frequency of texting was higher among young drivers. Laws banning handheld phone use seem to discourage some drivers from talking on any type of phone and motivate some drivers to talk hands-free. Laws banning texting while driving have little effect on the reported frequency of texting while driving in any age group.

Examination of Supplemental Driver Training and Online Basic Driver Education

DOT National Transportation Integrated Search

2012-06-01

This report describes supplemental driver training programs and online basic driver education. It coves supplemental driver training that : focused on knowledge and skills beyond those normally found in traditional driver education delivered in the U...

76 FR 61136 - Agency Information Collection Activities; New Information Collection Request: Commercial Driver...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-03

...,'' submissions; 75 minutes for paper and 70 minutes for electronic Driver Survey and Job Descriptive Index from... paper Driver Survey and Job Descriptive Index x 75 minutes per driver / 60 minutes + 200 CMV drivers completing paper Driver Survey and Job Descriptive Index x 70 minutes per driver / 60 minutes = 26,466 hours...

77 FR 15182 - Agency Information Collection Activities; New Information Collection Request: Commercial Driver...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-14

... Descriptive Index from the Follow-Up Survey submission; and 10 minutes for the Form MCSA-5865, ``Fleet... + 800 CMV drivers completing paper Driver Survey and Job Descriptive Index x 75 minutes per driver/ 60 minutes + 200 CMV drivers completing paper Driver Survey and Job Descriptive Index x 70 minutes per driver...

Characteristics of Single Vehicle Crashes with a Teen Driver in South Carolina, 2005-2008.

PubMed

Shults, Ruth A; Bergen, Gwen; Smith, Tracy J; Cook, Larry; Kindelberger, John; West, Bethany

2017-09-22

Teens' crash risk is highest in the first years of independent driving. Circumstances surrounding fatal crashes have been widely documented, but less is known about factors related to nonfatal teen driver crashes. This study describes single vehicle nonfatal crashes involving the youngest teen drivers (15-17 years), compares these crashes to single vehicle nonfatal crashes among adult drivers (35-44 years) and examines factors related to nonfatal injury producing crashes for teen drivers. Police crash data linked to hospital inpatient and emergency department data for 2005-2008 from the South Carolina Crash Outcomes Data Evaluation System (CODES) were analyzed. Nonfatal, single vehicle crashes involving passenger vehicles occurring on public roadways for teen (15-17 years) drivers were compared with those for adult (35-44 years) drivers on temporal patterns and crash risk factors per licensed driver and per vehicle miles traveled. Vehicle miles traveled by age group was estimated using data from the 2009 National Household Travel Survey. Multivariable log-linear regression analysis was conducted for teen driver crashes to determine which characteristics were related to crashes resulting in a minor/moderate injury or serious injury to at least one vehicle occupant. Compared with adult drivers, teen drivers in South Carolina had 2.5 times the single vehicle nonfatal crash rate per licensed driver and 11 times the rate per vehicle mile traveled. Teen drivers were nearly twice as likely to be speeding at the time of the crash compared with adult drivers. Teen driver crashes per licensed driver were highest during the afternoon hours of 3:00-5:59 pm and crashes per mile driven were highest during the nighttime hours of 9:00-11:59 pm. In 66% of the teen driver crashes, the driver was the only occupant. Crashes were twice as likely to result in serious injury when teen passengers were present than when the teen driver was alone. When teen drivers crashed while transporting teen passengers, the passengers were >5 times more likely to all be restrained if the teen driver was restrained. Crashes in which the teen driver was unrestrained were 80% more likely to result in minor/moderate injury and 6 times more likely to result in serious injury compared with crashes in which the teen driver was restrained. Despite the reductions in teen driver crashes associated with Graduated Driver Licensing (GDL), South Carolina's teen driver crash rates remain substantially higher than those for adult drivers. Established risk factors for fatal teen driver crashes, including restraint nonuse, transporting teen passengers, and speeding also increase the risk of nonfatal injury in single vehicle crashes. As South Carolina examines strategies to further reduce teen driver crashes and associated injuries, the state could consider updating its GDL passenger restriction to either none or one passenger <21years and dropping the passenger restriction exemption for trips to and from school. Surveillance systems such as CODES that link crash data with health outcome data provide needed information to more fully understand the circumstances and consequences of teen driver nonfatal crashes and evaluate the effectiveness of strategies to improve teen driver safety. Published by Elsevier Ltd.

The relationship between observed signs of impairment and THC concentration in oral fluid.

PubMed

Fierro, Inmaculada; González-Luque, Juan Carlos; Alvarez, F Javier

2014-11-01

Studies have shown that cannabis intake increases the risk of traffic accidents. Controlled experiments support these findings and have shown a positive dose-effect relationship. In this retrospective cross-sectional study of data from a roadside survey, we investigated whether a police officer's judgment regarding signs of impairment is related to the concentration of delta-9-tetrahydrocannabinol (THC) in the oral fluid (OF). We investigated 2,632 cases from a representative sample of 3,302 Spanish drivers: 253 drivers positive for THC only, 32 positive for THC and ethanol, 201 with only ethanol detected in their breath, and 2,146 drivers who tested negative for ethanol in breath and drugs in OF. Recorded data comprised breath alcohol concentrations, THC concentrations in the OF, and the 31 observed signs of impairment. Subject groups were compared using the chi-square test, and logistic regression was used to examine the risk of being categorized as exhibiting signs of impairment. A relationship was found between the OF THC concentration and some observed signs of impairment. Eye signs were noticeable from a THC concentration >3.0 ng/ml in OF, and >25 ng/ml was related to behavior, facial expression, and speech signs. Alcohol and THC contribute to impairment independently and, when taken simultaneously, the effects are comparable to the sum of the effects when consumed separately. The observation of signs of impairment due to cannabis occurs in an OF concentration-related manner but, as a clinical test, OF has low sensitivity and specificity in a random roadside survey. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Drivers Are More Physically Active Than Non-Drivers in Older Adults.

PubMed

Amagasa, Shiho; Fukushima, Noritoshi; Kikuchi, Hiroyuki; Takamiya, Tomoko; Odagiri, Yuko; Oka, Koichiro; Inoue, Shigeru

2018-05-28

Car use has been identified as sedentary behavior, although it may enhance mobility, particularly in the older population. This cross-sectional study aimed to compare the time spent in objectively determined sedentary behavior (SB) and physical activity (PA) between older drivers and non-drivers. Four hundred and fifty Japanese older adults (74.3 ± 2.9 years) who had valid accelerometer data were included. They were asked to respond to a questionnaire and wear an accelerometer (HJA-350IT, Omron Healthcare) on their waist for 7 consecutive days in 2015. To compare activity time between drivers and non-drivers, we calculated estimated means using analysis of covariance, adjusting for sociodemographic, physical, and psychological factors and accelerometer wear time. Compared to non-drivers, drivers engaged in more light-intensity PA (LPA) (drivers: 325.0 vs. non-drivers: 289.0 min/day) and moderate-to-vigorous PA (drivers: 37.5 vs. non-drivers: 30.0 min/day) and less SB (drivers: 493.4 vs. non-drivers: 535.9 min/day) (all p < 0.05). After stratification by age, sex, and residential area, larger effect of driving on PA time was found in older-older adults, in men, and in rural residents. Older drivers were found to be more physically active than non-drivers, suggesting more access to outdoor activities or expanding social network.

Idaho Driver Education Instructional Guide. Revised.

ERIC Educational Resources Information Center

Idaho State Dept. of Education, Boise.

This driver education instructional safety guide is organized in three sections: Driver Education; Motorcycle Education; and Driver Education for the Handicapped. The driver education section contains 10 units dealing with the following topics: parent orientation; student orientation; basic control skills; driver performance; driving regulations;…

Effects of Defensive Vehicle Handling on Novice Driver Safety : Phase 3. Data Analysis and Results

DOT National Transportation Integrated Search

2010-09-01

This project evaluates the effectiveness of a multistage driver education program for Montanas young : drivers. A total of 347 teenaged drivers who had completed high school driver education agreed to participate. : These drivers were randomly spl...

A cost effectiveness study of eribulin versus standard single-agent cytotoxic chemotherapy for women with previously treated metastatic breast cancer.

PubMed

Lopes, Gilberto; Glück, Stefan; Avancha, Kiran; Montero, Alberto J

2013-01-01

Eribulin was FDA approved in 2012 as a treatment for patients with MBC who have previously received at least two prior chemotherapy regimens. The aim of this analysis was to assess the cost effectiveness of eribulin versus the three most commonly utilized drugs (TPC) in the EMBRACE trial: vinorelbine, gemcitabine, and capecitabine (X); and to other branded FDA approved drugs: ixabepilone (I), liposomal-doxorubicin (D), and nab-paclitaxel. We created a decision-analytical and a Markov model using clinical data from the EMBRACE trial. Health utilities were derived from the published literature. Costs for drug acquisition, physician visits, and laboratory tests were obtained from Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2012 USD. Life-years saved (LY), quality-adjusted life years (QALY), and incremental cost effectiveness ratio (ICER) were calculated. Eribulin added 0.208 LY and 0.119 QALY with an incremental cost over TPC of $25,458, and therefore an ICER of $213,742 per QALY. The main drivers of the model were drug cost, PFS, OS, and health utility values. The results of the model were robust in sensitivity analyses. Relative to I, D, A, and X, the ICER for eribulin was $76,823, $109,283, $129,773, and $167,267, respectively. Even with a more contemporary willingness-to-pay threshold of approximately $120,000 per QALY, eribulin was not found to be cost effective in the treatment of MBC relative to TPC; relative to some more expensive branded drugs, eribulin appears to be cost effective.

Exposure to particles and nitrogen dioxide among taxi, bus and lorry drivers.

PubMed

Lewné, Marie; Nise, Gun; Lind, Marie-Louise; Gustavsson, Per

2006-03-01

The aims of this study have been to investigate the occurrence of systematic differences in the personal exposure to motor exhaust between different groups of taxi, bus and lorry drivers, and to study if these are influenced by the choice of exposure indicator. We used one indicator of the gaseous phase, nitrogen dioxide (NO(2)), and one of the particle phase (measured by DataRAM), of the exhausts. A total of 121 drivers were included in the study: 39 taxi drivers, 42 bus drivers and 40 lorry drivers. Personal measurements were performed during one working day. Nitrogen dioxide was measured with passive diffusive samplers and particles with Data-RAM, a logging instrument using nephelometric monitoring. The instrument measures particles between 0.1 and 10 microm in size. The average exposure to NO(2) for lorry drivers was 68 microg/m(3); for bus drivers 60 microg/m(3) and for taxi drivers 48 microg/m(3). For particles the exposure was 57 microg/m(3) for lorry drivers, 44 microg/m(3) for bus drivers and 26 microg/m(3) for taxi drivers. The result remained unchanged when exposures were adjusted for variation in urban background levels of NO(2) and particulate matter with an aerodynamic diameter <10 microm (PM(10)). Lorry drivers experienced the highest exposure and taxi drivers the lowest with bus drivers in an intermediate position, regardless of whether NO(2) or particles were used as exposure indicator. The levels of both NO(2) and particles were higher for bus drivers in the city than for them driving in the suburbs. Using diesel or petrol as a fuel for taxis had no influence on the exposure for the drivers, indicating that the taxi drivers' exposure mainly depends on exhaust from surrounding traffic.

The effect of cannabis compared with alcohol on driving.

PubMed

Sewell, R Andrew; Poling, James; Sofuoglu, Mehmet

2009-01-01

The prevalence of both alcohol and cannabis use and the high morbidity associated with motor vehicle crashes has lead to a plethora of research on the link between the two. Drunk drivers are involved in 25% of motor vehicle fatalities, and many accidents involve drivers who test positive for cannabis. Cannabis and alcohol acutely impair several driving-related skills in a dose-related fashion, but the effects of cannabis vary more between individuals than they do with alcohol because of tolerance, differences in smoking technique, and different absorptions of Delta(9)-tetrahydrocannabinol (THC), the active ingredient in marijuana. Detrimental effects of cannabis use vary in a dose-related fashion, and are more pronounced with highly automatic driving functions than with more complex tasks that require conscious control, whereas alcohol produces an opposite pattern of impairment. Because of both this and an increased awareness that they are impaired, marijuana smokers tend to compensate effectively while driving by utilizing a variety of behavioral strategies. Combining marijuana with alcohol eliminates the ability to use such strategies effectively, however, and results in impairment even at doses which would be insignificant were they of either drug alone. Epidemiological studies have been inconclusive regarding whether cannabis use causes an increased risk of accidents; in contrast, unanimity exists that alcohol use increases crash risk. Furthermore, the risk from driving under the influence of both alcohol and cannabis is greater than the risk of driving under the influence of either alone. Future research should focus on resolving contradictions posed by previous studies, and patients who smoke cannabis should be counseled to wait several hours before driving, and avoid combining the two drugs.

Neurocognitive Correlates in Driving Under the Influence of Cannabis.

PubMed

Busardò, Francesco P; Pellegrini, Manuela; Klein, Julia; di Luca, Natale M

2017-01-01

Delta (9)-tetrahydrocannabinol (THC) is the main psychoactive compound in cannabis and is frequently identified in blood samples from apprehended drivers suspected for driving under the influence of drugs. Changing social norms towards cannabis and higher acceptability towards the drug emphasize the need for in-depth understanding of the acute neurocognitive and psychomotor effects caused by cannabis and how these effects are correlated to driving skills and performance. In this review, PubMed, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE and Google Scholar databases were used to identify and select publications up to January 2017 dealing with acute and chronic neurocognitive effects induced by cannabis and ability to drive. Thirty-six publications were selected for this review. The studies conducted were experimental, using simulators or on-road studies and brain imaging (structural and functional) to better understand the acute and chronic effects on cognitive functions comprised in the short and long-term fitness to drive after cannabis consumption. In a case-crossover self-report study a significant odds ratio increase was found for driving- related injury after combined exposure to cannabis and alcohol compared to cannabis alone (OR of 10.9 and 5.8 respectively). Both, experimental and epidemiological studies have revealed that THC affects negatively both, psychomotor skills and cognitive functions. Studies of the acute effects of cannabis on driving have shown that drivers under the influence of this substance are impaired. Indeed, driving under the influence of cannabis doubles or triples the risk of a crash. Specifically, cannabis use impairs critical-tracking tasks, increases lane weaving, decreases reaction time, and divided attention. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Musashi RNA-Binding Proteins as Cancer Drivers and Novel Therapeutic Targets.

PubMed

Kudinov, Alexander E; Karanicolas, John; Golemis, Erica A; Boumber, Yanis

2017-05-01

Aberrant gene expression that drives human cancer can arise from epigenetic dysregulation. Although much attention has focused on altered activity of transcription factors and chromatin-modulating proteins, proteins that act posttranscriptionally can potently affect expression of oncogenic signaling proteins. The RNA-binding proteins (RBP) Musashi-1 (MSI1) and Musashi-2 (MSI2) are emerging as regulators of multiple critical biological processes relevant to cancer initiation, progression, and drug resistance. Following identification of Musashi as a regulator of progenitor cell identity in Drosophila , the human Musashi proteins were initially linked to control of maintenance of hematopoietic stem cells, then stem cell compartments for additional cell types. More recently, the Musashi proteins were found to be overexpressed and prognostic of outcome in numerous cancer types, including colorectal, lung, and pancreatic cancers; glioblastoma; and several leukemias. MSI1 and MSI2 bind and regulate the mRNA stability and translation of proteins operating in essential oncogenic signaling pathways, including NUMB/Notch, PTEN/mTOR, TGFβ/SMAD3, MYC, cMET, and others. On the basis of these activities, MSI proteins maintain cancer stem cell populations and regulate cancer invasion, metastasis, and development of more aggressive cancer phenotypes, including drug resistance. Although RBPs are viewed as difficult therapeutic targets, initial efforts to develop MSI-specific inhibitors are promising, and RNA interference-based approaches to inhibiting these proteins have had promising outcomes in preclinical studies. In the interim, understanding the function of these translational regulators may yield insight into the relationship between mRNA expression and protein expression in tumors, guiding tumor-profiling analysis. This review provides a current overview of Musashi as a cancer driver and novel therapeutic target. Clin Cancer Res; 23(9); 2143-53. ©2017 AACR . ©2017 American Association for Cancer Research.

Human rights and access to hepatitis C treatment for people who inject drugs.

PubMed

Wolfe, D; Luhmann, N; Harris, M; Momenghalibaf, A; Albers, E; Byrne, J; Swan, T

2015-11-01

People who inject drugs (PWID) achieve adherence to and outcomes from hepatitis C virus (HCV) treatment comparable to other patients. Nonetheless, this population has been excluded from treatment by regulation or practice. Approval of safer and more effective oral HCV medicines should offer greater treatment options for PWID, although high medicine prices have led to continued treatment rationing and exclusion in developed countries. In middle-income countries (MICS), treatment is largely unavailable and unaffordable for most PWID. Human rights analysis, with its emphasis on the universal and interconnected nature of the economic, social and political spheres, offers a useful framework for HCV treatment reform. Using peer-reviewed and grey literature, as well as community case reports, we discuss barriers to treatment, correlate these barriers to rights violations, and highlight examples of community advocacy to increase treatment for PWID. Structural drivers of lack of treatment access for PWID include stigma in health settings; drug use status as a criterion for treatment exclusion; requirements for fees or registration by name as a drug user prior to treatment initiation; and incarceration/detention in prisons and rehabilitation centers where treatment is unavailable. High medicine prices force further exclusion of PWID, with cost containment masked as concern about treatment adherence. These barriers correlate to multiple rights violations, including of the rights to privacy; non-discrimination; health; freedom of information; fair trial; and freedom from cruel, inhuman and degrading treatment. Needed reforms include decriminalization of drug use, possession of drugs and drug injecting equipment; removal of exclusionary or discriminatory treatment protocols; approaches to strengthen links between health providers and increase participation of PWID in treatment design and implementation; and measures to increase transparency in government/pharmaceutical company negotiations and reduce treatment price. Copyright © 2015. Published by Elsevier B.V.

Legislating thresholds for drug trafficking: a policy development case study from New South Wales, Australia.

PubMed

Hughes, Caitlin Elizabeth; Ritter, Alison; Cowdery, Nicholas

2014-09-01

Legal thresholds are used in many parts of the world to define the quantity of illicit drugs over which possession is deemed "trafficking" as opposed to "possession for personal use". There is limited knowledge about why or how such laws were developed. In this study we analyse the policy processes underpinning the introduction and expansion of the drug trafficking legal threshold system in New South Wales (NSW), Australia. A critical legal and historical analysis was undertaken sourcing data from legislation, Parliamentary Hansard debates, government inquiries, police reports and research. A timeline of policy developments was constructed from 1970 until 2013 outlining key steps including threshold introduction (1970), expansion (1985), and wholesale revision (1988). We then critically analysed the drivers of each step and the roles played by formal policy actors, public opinion, research/data and the drug trafficking problem. We find evidence that while justified as a necessary tool for effective law enforcement of drug trafficking, their introduction largely preceded overt police calls for reform or actual increases in drug trafficking. Moreover, while the expansion from one to four thresholds had the intent of differentiating small from large scale traffickers, the quantities employed were based on government assumptions which led to "manifest problems" and the revision in 1988 of over 100 different quantities. Despite the revisions, there has remained no further formal review and new quantities for "legal highs" continue to be added based on assumption and an uncertain evidence-base. The development of legal thresholds for drug trafficking in NSW has been arbitrary and messy. That the arbitrariness persists from 1970 until the present day makes it hard to conclude the thresholds have been well designed. Our narrative provides a platform for future policy reform. Copyright © 2014 Elsevier B.V. All rights reserved.

A microcosting study of immunogenicity and tumour necrosis factor alpha inhibitor drug level tests for therapeutic drug monitoring in clinical practice.

PubMed

Jani, Meghna; Gavan, Sean; Chinoy, Hector; Dixon, William G; Harrison, Beverley; Moran, Andrew; Barton, Anne; Payne, Katherine

2016-12-01

To identify and quantify resource required and associated costs for implementing TNF-α inhibitor (TNFi) drug level and anti-drug antibody (ADAb) tests in UK rheumatology practice. A microcosting study, assuming the UK National Health Service perspective, identified the direct medical costs associated with providing TNFi drug level and ADAb testing in clinical practice. Resource use and costs per patient were identified via four stages: identification of a patient pathway with resource implications; estimation of the resources required; identification of the cost per unit of resource (2015 prices); and calculation of the total costs per patient. Univariate and multiway sensitivity analyses were performed using the variation in resource use and unit costs. Total costs for TNFi drug level and concurrent ADAb testing, assessed using ELISAs on trough serum levels, were £152.52/patient (range: £147.68-159.24) if 40 patient samples were tested simultaneously. For the base-case analysis, the pre-testing phase incurred the highest costs, which included booking an additional appointment to acquire trough blood samples. The additional appointment was the key driver of costs per patient (67% of the total cost), and labour accounted for 10% and consumables 23% of the total costs. Performing ELISAs once per patient (rather than in duplicate) reduced the total costs to £133.78/patient. This microcosting study is the first assessing the cost of TNFi drug level and ADAb testing. The results could be used in subsequent cost-effectiveness analyses of TNFi pharmacological tests to target treatments and inform future policy recommendations. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Drug Testing in Oral Fluid

PubMed Central

Drummer, Olaf H

2006-01-01

Over the last decade there have been considerable developments in the use of oral fluid (saliva) for drug testing. Oral fluid can provide a quick and non-invasive specimen for drug testing. However, its collection may be thwarted by lack of available fluid due to a range of physiological factors, including drug use itself. Food and techniques designed to stimulate production of oral fluid can also affect the concentration of drugs. Current applications are mainly focused on drugs of abuse testing in employees at workplaces where drug use has safety implications, in drivers of vehicles at the roadside and in other situations where drug impairment is suspected. Testing has included alcohol (ethanol) and a range of clinical tests eg antibodies to HIV, therapeutic drugs and steroids. Its main application has been for testing for drugs of abuse such as the amphetamines, cocaine and metabolites, opioids such as morphine, methadone and heroin, and for cannabis. Oral fluid concentrations of basic drugs such as the amphetamines, cocaine and some opioids are similar or higher than those in plasma. Tetrahydrocannabinol (THC), the major species present from cannabis use, displays similar concentrations in oral fluid compared to blood in the elimination phase. However, there is significant local absorption of the drug in the oral cavity which increases the concentrations for a period after use of drug. Depot effects occur for other drugs introduced into the body that allow local absorption, such as smoking of tobacco (nicotine), cocaine, amphetamines, or use of sub-lingual buprenorphine. Screening techniques are usually an adaptation of those used in other specimens, with an emphasis on the parent drug since this is usually the dominant species present in oral fluid. Confirmatory techniques are largely based on mass spectrometry (MS) with an emphasis on Liquid Chromatography-Mass Spectrometry (LC-MS), due to low sample volumes and the low detection limits required. Drug testing outside laboratory environments has become widespread and provides presumptive results within minutes of collection of specimens. This review focuses on the developments, particularly over the last 10 years, and outlines the roles and applications of testing for drugs in oral fluid, describes the difficulties associated with this form of testing and illustrates applications of oral fluid testing for specific drugs. PMID:17268583

Drinking driver and traffic safety project. Volume 2, Probabilities for drinking drivers

DOT National Transportation Integrated Search

1973-10-01

This is the second volume of a final report of a four-year study of drinking drivers. It includes a brief description of a prediction model developed from over 4000 cases, including drinking drivers, recidivist drinking drivers and drivers license ap...

German taxi drivers' experiences and expressions of driving anger: Are the driving anger scale and the driving anger expression inventory valid measures?

PubMed

Brandenburg, Stefan; Oehl, Michael; Seigies, Kristin

2017-11-17

The objective of this article was 2-fold: firstly, we wanted to examine whether the original Driving Anger Scale (DAS) and the original Driving Anger Expression Inventory (DAX) apply to German professional taxi drivers because these scales have previously been given to professional and particularly to nonprofessional drivers in different countries. Secondly, we wanted to examine possible differences in driving anger experience and expression between professional German taxi drivers and nonprofessional German drivers. We applied German versions of the DAS, the DAX, and the State-Trait Anger Expression Inventory (STAXI) to a sample of 138 professional German taxi drivers. We then compared their ratings to the ratings of a sample of 1,136 nonprofessional German drivers (Oehl and Brandenburg n.d. ). Regarding our first objective, confirmatory factor analysis shows that the model fit of the DAS is better for nonprofessional drivers than for professional drivers. The DAX applies neither to professional nor to nonprofessional German drivers properly. Consequently, we suggest modified shorter versions of both scales for professional drivers. The STAXI applies to both professional and nonprofessional drivers. With respect to our second objective, we show that professional drivers experience significantly less driving anger than nonprofessional drivers, but they express more driving anger. We conclude that the STAXI can be applied to professional German taxi drivers. In contrast, for the DAS and the DAX we found particular shorter versions for professional taxi drivers. Especially for the DAX, most statements were too strong for German drivers to agree to. They do not show behaviors related to driving anger expression as they are described in the DAX. These problems with the original American DAX items are in line with several other studies in different countries. Future investigations should examine whether (professional) drivers from further countries express their anger as proposed by the DAX. In addition, professional drivers experience less driving anger (DAS) and less general trait anger (STAXI) than nonprofessional drivers, but they report more driving anger expression (DAX) and more current general state anger (STAXI). Subsequent studies should therefore focus on different types of anger within the group of professional drivers.

Complex land use and cover trajectories in the northern Choco bioregion of Colombia

NASA Astrophysics Data System (ADS)

Santos, Carolina

The Choco bioregion in Northwestern Colombia is a lowland rain forest and hotspot of biodiversity. Significant land use and cover change (LUCC) is occurring throughout the region driven by global markets, illicit drug production, and civil unrest. The dominant land cover conversion is from primary forest to African Palm plantations, mediated and modified by complex combinations of social and biophysical drivers. This research combined a remote sensing based methodology to monitor LUCC in the region with an analytical approach for evaluating the possible trajectories of LUCC in a complex biological, socio-economical, and political environment. Synoptic LUCC models were developed using textural classification derived from Synthetic Aperture Radar (SAR) images for the period 1995 to 2010. LUCC models along with empirical social and spatial biophysical drivers were used to project historical land use trajectories. DINAMICA EGO a complex systems based spatial analytical framework was adopted as the platform to model land use change. The RADAR backscatter was able to capture areas were forest has been converted to African Oil Palm Plantations. However, an in depth characterization of the LUC dynamics was problematic given the spectral and spatial limitations of the sensor combined with the lack of ground data. The results of the LUC model suggest that under the current socio-political conditions African oil palm plantations will continue to expand toward forested areas into the territories traditionally inhabited by Afro-Colombians and Indigenous populations. Insecure land tenure appears as a main driver of the transformation in close association with the conditions created by the armed conflict, and the drug traffic. The rate of the transformation appears to slow down in the period after 2007. However, according to the model by 2020 most of the area inhabited by ethnic groups will be transform to AOP. This study contributes towards the understanding of land use change in the context of social conflict. Although, it is recognized that conflicts impact the land--use and land-cover, few studies have address the linkages between particular circumstances and events in the conflict and the consequences for the land. As resource conflicts spread around the globe a better understanding of how it impacts the land and the people is paramount.

Simulator training with a forward collision warning system: effects on driver-system interactions and driver trust.

PubMed

Koustanaï, Arnaud; Cavallo, Viola; Delhomme, Patricia; Mas, Arnaud

2012-10-01

The study addressed the role of familiarization on a driving simulator with a forward collision warning (FCW) and investigated its impact on driver behavior. Drivers need a good understanding of how an FCW system functions to trust it and use it properly. Theoretical and empirical data suggest that exploring the capacities and limitations of the FCW during the learning period improves operating knowledge and leads to increased driver trust in the system and better driver-system interactions.The authors tested this hypothesis by comparing groups of drivers differing in FCW familiarity. During the familiarization phase, familiarized drivers were trained on the simulator using the FCW, unfamiliarized drivers simply read an FCW manual, and control drivers had no contact with the FCW. During the test, drivers drove the simulator and had to interact with traffic; both familiarized and unfamiliarized drivers used the FCW, whereas controls did not. Simulator familiarization improved driver understanding of FCW operation. Driver-system interactions were more effective: Familiarized drivers had no collisions, longer time headways, and better reactions in most situations. Familiarization increased trust in the FCW but did not raise system acceptance. Familiarization on the simulator had a positive effect on driver-system interactions and on trust in the system. The limitations of the familiarization method are discussed in relation to the driving simulator methodology. Practicing on a driving simulator with driving-assistance systems could facilitate their use during real driving.

Comparison of visual status of Iranian military and commercial drivers.

PubMed

Ghasemi, Mohammad; Hoseini Yazdi, Seyed Hosein; Heravian, Javad; Jafarzadehpur, Ebrahim; Rezaee, Maryam

2015-04-01

There is no legal requirement for Iranian military truck drivers to undergo regular visual checkups as compared to commercial truck drivers. This study aimed to evaluate the impact of drivers' visual checkups by comparing the visual function of Iranian military and commercial truck drivers. In this comparative cross-sectional study, two hundred military and 200 commercial truck drivers were recruited and their Visual Acuity (VA), Visual Field (VF), color vision and Contrast Sensitivity (CS) were assessed and compared using the Snellen chart, confrontation screening method, D15 test and Pelli-Robson letter chart, respectively. A questionnaire regarding driving exposure and history of motor-vehicle crashes (MVCs) was also filled by drivers. Results were analyzed using an independent samples t-test, one-way ANOVA (assessing difference in number of MVCs across different age groups), chi-square test and Pearson correlation at statistical significance level of P < 0.05. Mean age was 41.6 ± 9.2 for the military truck drivers and 43.4 ± 10.9 for commercial truck drivers (P > 0.05). No significant difference between military and commercial drivers was found in terms of driving experience, number of MVCs, binocular VA, frequency of color vision defects and CS scores. In contrast, the last ocular examination was significantly earlier in military drivers than commercial drivers (P < 0.001). In addition, 4% of military drivers did not meet the national standards to drive as opposed to 2% of commercial drivers. There was a significant but weak correlation between binocular VA and age (r = 0.175, P < 0.001). However, CS showed a significantly moderate correlation with age (r = -0.488, P < 0.001). The absence of legal requirement for regular eye examination in military drivers caused the incompetent drivers to be missed in contrast to commercial drivers. The need for scientific revision of VA standard for Iranian drivers is also discussed. The CS measurement in visual checkups of older drivers deserves to be investigated more thoroughly.

Critical older driver errors in a national sample of serious U.S. crashes.

PubMed

Cicchino, Jessica B; McCartt, Anne T

2015-07-01

Older drivers are at increased risk of crash involvement per mile traveled. The purpose of this study was to examine older driver errors in serious crashes to determine which errors are most prevalent. The National Highway Traffic Safety Administration's National Motor Vehicle Crash Causation Survey collected in-depth, on-scene data for a nationally representative sample of 5470 U.S. police-reported passenger vehicle crashes during 2005-2007 for which emergency medical services were dispatched. There were 620 crashes involving 647 drivers aged 70 and older, representing 250,504 crash-involved older drivers. The proportion of various critical errors made by drivers aged 70 and older were compared with those made by drivers aged 35-54. Driver error was the critical reason for 97% of crashes involving older drivers. Among older drivers who made critical errors, the most common were inadequate surveillance (33%) and misjudgment of the length of a gap between vehicles or of another vehicle's speed, illegal maneuvers, medical events, and daydreaming (6% each). Inadequate surveillance (33% vs. 22%) and gap or speed misjudgment errors (6% vs. 3%) were more prevalent among older drivers than middle-aged drivers. Seventy-one percent of older drivers' inadequate surveillance errors were due to looking and not seeing another vehicle or failing to see a traffic control rather than failing to look, compared with 40% of inadequate surveillance errors among middle-aged drivers. About two-thirds (66%) of older drivers' inadequate surveillance errors and 77% of their gap or speed misjudgment errors were made when turning left at intersections. When older drivers traveled off the edge of the road or traveled over the lane line, this was most commonly due to non-performance errors such as medical events (51% and 44%, respectively), whereas middle-aged drivers were involved in these crash types for other reasons. Gap or speed misjudgment errors and inadequate surveillance errors were significantly more prevalent among female older drivers than among female middle-aged drivers, but the prevalence of these errors did not differ significantly between older and middle-aged male drivers. These errors comprised 51% of errors among older female drivers but only 31% among older male drivers. Efforts to reduce older driver crash involvements should focus on diminishing the likelihood of the most common driver errors. Countermeasures that simplify or remove the need to make left turns across traffic such as roundabouts, protected left turn signals, and diverging diamond intersection designs could decrease the frequency of inadequate surveillance and gap or speed misjudgment errors. In the future, vehicle-to-vehicle and vehicle-to-infrastructure communications may also help protect older drivers from these errors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toward the establishment of standardized in vitro tests for lipid-based formulations. 2. The effect of bile salt concentration and drug loading on the performance of type I, II, IIIA, IIIB, and IV formulations during in vitro digestion.

PubMed

Williams, Hywel D; Anby, Mette U; Sassene, Philip; Kleberg, Karen; Bakala-N'Goma, Jean-Claude; Calderone, Marilyn; Jannin, Vincent; Igonin, Annabel; Partheil, Anette; Marchaud, Delphine; Jule, Eduardo; Vertommen, Jan; Maio, Mario; Blundell, Ross; Benameur, Hassan; Carrière, Frédéric; Müllertz, Anette; Pouton, Colin W; Porter, Christopher J H

2012-11-05

The LFCS Consortium was established to develop standardized in vitro tests for lipid-based formulations (LBFs) and to examine the utility of these tests to probe the fundamental mechanisms that underlie LBF performance. In this publication, the impact of bile salt (sodium taurodeoxycholate, NaTDC) concentration and drug loading on the ability of a range of representative LBFs to generate and sustain drug solubilization and supersaturation during in vitro digestion testing has been explored and a common driver of the potential for drug precipitation identified. Danazol was used as a model poorly water-soluble drug throughout. In general, increasing NaTDC concentrations increased the digestion of the most lipophilic LBFs and promoted lipid (and drug) trafficking from poorly dispersed oil phases to the aqueous colloidal phase (AP(DIGEST)). High NaTDC concentrations showed some capacity to reduce drug precipitation, although, at NaTDC concentrations ≥3 mM, NaTDC effects on either digestion or drug solubilization were modest. In contrast, increasing drug load had a marked impact on drug solubilization. For LBFs containing long-chain lipids, drug precipitation was limited even at drug loads approaching saturation in the formulation and concentrations of solubilized drug in AP(DIGEST) increased with increased drug load. For LBFs containing medium-chain lipids, however, significant precipitation was evident, especially at higher drug loads. Across all formulations a remarkably consistent trend emerged such that the likelihood of precipitation was almost entirely dependent on the maximum supersaturation ratio (SR(M)) attained on initiation of digestion. SR(M) defines the supersaturation "pressure" in the system and is calculated from the maximum attainable concentration in the AP(DIGEST) (assuming zero precipitation), divided by the solubility of the drug in the colloidal phases formed post digestion. For LBFs where phase separation of oil phases did not occur, a threshold value for SR(M) was evident, regardless of formulation composition and drug solubilization reduced markedly above SR(M) > 2.5. The threshold SR(M) may prove to be an effective tool in discriminating between LBFs based on performance.

Meanings and vulnerability to HIV/AIDS among long-distance truck drivers in Brazil.

PubMed

Magno, Laio; Castellanos, Marcelo Eduardo Pfeiffer

2016-12-22

To understand the meanings assigned by long-distance truck drivers to HIV/AIDS and its transmission and prevention, bearing in mind different contexts of vulnerability. Qualitative research with 22 truck drivers. Semi-structured interviews and participant observation were conducted in highways of the state of Bahia in 2013. We selected male truck drivers, with one year or more of work experience in long-distance routes. We carried out the thematic analysis of the interviews, to identify different contexts of vulnerability. The results showed that the insertion of truck drivers in contexts of high social vulnerability (poor working conditions, violence on the roads, and use of alcohol and other drugs) along with the advances in access and effectiveness of treatment for AIDS promote a reduced perception of the risk and severity of this disease. In addition, the notion of "risk group" and the symbolic division between "home space" (protected) and "street space" (unprotected) intensified a restricted and specific use of condoms, guided by the opposition between "woman of the street" (unknown women, prostitutes, among others) and "woman of the house" (wives, girlfriends). The meanings assigned by truckers to AIDS incorporated elements of recent transformations of the expanded social context, such as the development of health technologies (especially anti-retroviral drugs) and the guarantee of free access to treatment in the Brazilian public health system; but also incorporated old elements of social vulnerability context - such as the poor working conditions on Brazilian highways. Compreender os significados atribuídos pelos caminhoneiros de rota longa ao HIV/aids e à sua transmissão e prevenção, tendo em vista diferentes contextos de vulnerabilidade. Pesquisa qualitativa com 22 caminhoneiros. Foram realizadas entrevistas semi-estruturadas e observação participante em rodovias do estado da Bahia em 2013. Foram selecionados caminhoneiros do sexo masculino, com um ano ou mais de experiência de trabalho em rotas de longa distância. Realizou-se análise temática das entrevistas, orientada para identificação de diferentes contextos de vulnerabilidade. Os resultados mostraram que a inserção dos caminhoneiros em contextos de alta vulnerabilidade social (más condições de trabalho, violência nas estradas e uso de álcool e outras drogas) e os avanços no acesso e efetividade do tratamento para aids favorecem a minimização da percepção de risco e gravidade dessa doença. Além disso, a noção de "grupo de risco" e a divisão simbólica entre "espaço da casa" (protegido) e "espaço da rua" (desprotegido) intensificaram um uso restrito e específico do preservativo, orientado pela oposição entre "mulher do mundo" (desconhecidas, prostitutas, entre outros) e "mulher de casa" (esposas, namoradas). Os significados atribuídos pelos caminhoneiros à aids incorporaram elementos de transformações recentes do contexto social ampliado, como o desenvolvimento de tecnologias em saúde (com destaque para os antirretrovirais) e a garantia de acesso gratuito ao tratamento no sistema público de saúde no Brasil; mas também incorporaram antigos elementos do contexto de vulnerabilidade social - a exemplo das más condições de trabalho nas estradas brasileiras.

Turning movements, vehicle offsets and ageing drivers driving behaviour at channelized and unchannelized intersections.

PubMed

Choi, Jaisung; Tay, Richard; Kim, Sangyoup; Jeong, Seungwon

2017-11-01

Ageing drivers experience a higher risk of intersection crashes because of their decrease in driving efficiency, including the decline in cognitive ability, head and neck flexibility, and visual acuity. Although several studies have been conducted to examine the factors associated with ageing driver crashes at intersections, little research has been conducted to examine the differences in the factors related to ageing drivers' turning paths and intersection geometric features. This study aims to improve the safety of ageing drivers at intersections by identifying the maneuvers that are risky for them and tracking their turning movements at selected intersections. We find that ageing drivers experience more crashes at intersections than younger drivers, especially crashes involving turning movements. Furthermore, ageing drivers experience more crashes at unchannelized intersections compared to channelized intersections. In addition, this study finds that ageing drivers exhibit greater and more inconsistent offsets during turning movements compared to those of younger drivers at both channelized and unchannelized intersections. Ageing drivers also tend to make relatively sharper or tighter turns than younger drivers. Hence, transportation engineers and road safety professionals should consider appropriate countermeasures to reduce the risks of crashes involving ageing drivers at intersections. Copyright © 2017 Elsevier Ltd. All rights reserved.

The implications of regional and national demographic projections for future GMS costs in Ireland through to 2026.

PubMed

Conway, Aisling; Kenneally, Martin; Woods, Noel; Thummel, Andreas; Ryan, Marie

2014-10-21

As the health services in Ireland have become more resource-constrained, pressure has increased to reduce public spending on community drug schemes such as General Medical Services (GMS) drug prescribing and to understand current and future trends in prescribing. The GMS scheme covers approximately 37% of the Irish population in 2011 and entitles them, inter alia, to free prescription drugs and appliances. This paper projects the effects of future changes in population, coverage, claims rates and average claims cost on GMS costs in Ireland. Data on GMS coverage, claims rates and average cost per claim are drawn from the Primary Care Reimbursement Service (PCRS) and combined with Central Statistics Office (CSO) (Regional and National Population Projections through to 2026). A Monte Carlo Model is used to simulate the effects of demographic change (by region, age, gender, coverage, claims rates and average claims cost) will have on GMS prescribing costs in 2016, 2021 and 2026 under different scenarios. The Population of Ireland is projected to grow by 32% between 2007 and 2026 and by 96% for the over 70s. The Eastern region is estimated to grow by 3% over the lifetime of the projections at the expense of most other regions. The Monte Carlo simulations project that females will be a bigger driver of GMS costs than males. Midlands region will be the most expensive of the eight old health board regions. Those aged 70 and over and children under 11 will be significant drivers of GMS costs with the impending demographic changes. Overall GMS medicines costs are projected to rise to €1.9bn by 2026. Ireland's population will experience rapid growth over the next decade. Population growth coupled with an aging population will result in an increase in coverage rates, thus the projected increase in overall prescribing costs. Our projections and simulations map the likely evolution of GMS cost, given existing policies and demographic trends. These costs can be contained by government policy initiatives.