Orphan drugs: the question of products liability

Orphan drugs, essential for the treatment of persons with rare diseases, generally are unprofitable for manufacturers to develop and market. While congressional and administrative efforts to promote the development of orphan drugs have met with modest success, application of products liability doctrine to orphan drug sponsors could subvert those efforts. This Note describes the provisions of the Orphan Drug Act and analyzes products liability law with respect to orphan drug litigation. It argues that the goals of tort law support the imposition of liability for design defect, failure to warn and negligence in testing. Finally, the Note acknowledges that liability costs create disincentives for orphan drug development and suggests mechanisms for reducing manufacturers' liability concerns.     

葡萄牙治理毒品危害的去刑法化改革：绩效与借鉴

葡萄牙毒品使用的去刑法化改革带来了一系列的变化,而其本源在于观念的变革,即由对毒品的“零容忍”趋向于注重政策实效性的务实主义的转变.改革取得了显著的成效,同时也引发了国际社会的广泛关注甚至效仿.尽管葡萄牙模式的可持续性及可复制性仍有待于时间的进一步检验,但其观念更新基础上的多层级治理体系的建构,无疑为有效抑制日益泛滥的毒品消费提供了有价值的路径探索.     

Skeletal muscle as an alternative specimen for alcohol and drug analysis

In a random group of medical examiner cases, muscle tissue, as well as blood and vitreous humor, was analyzed for ethyl alcohol, and the results were compared. When the blood concentration was greater than 0.10 g/dL, the muscle to blood ratio was 1.00 or less (average 0.94), and when the blood concentration was less than 0.10 g/dL, this ratio was greater than 1.00 (average 1.48). The author proposes that this ratio is dependent upon the time course of absorption and distribution, as has been observed for vitreous humor, but with a more rapid equilibration. Muscle tissue was also analyzed in another group of cases found to be positive for one or more drugs in blood. The concentrations of the drugs in muscle varied from none detected to 6.5 times those in blood and seemed to be dependent on the time course between ingestion and death, as well as on the nature of the drug. For most common basic drugs, the ratios were often near unity. Muscle is proposed as a useful alternative specimen to postmortem blood.     

Anaphylaxis After the Injection of Buprenorphine

Cause of death rulings in cases when the concentration of a drug or drugs is higher than observed following therapeutic use are generally straightforward “drug deaths.” However, when toxicology testing identifies drug concentrations consistent with therapeutic use or detects no drugs at all, then the cause of death determination is more complicated. Given the rapidity and protean manifestations of anaphylaxis, it should be considered in deaths where no other cause of death is apparent in a suspected drug death. This article reports two cases where an anaphylactic reaction was observed following either the actual or alleged use of therapeutic formulations of buprenorphine intravenously.     

Lifting the cover on drug courts: evaluation findings and policy concerns

Drug treatment courts emerged in 1989 as a court-based solution to an enormous increase of drug-related arrests. Since their inception, drug treatment courts have been subject to empirical and process evaluations to provide quantitative and qualitative data regarding their effectiveness. This article reviews the extant literature on the effectiveness of drug treatment courts and discusses findings regarding various components of the criminal justice system. It is argued that based on empirical evaluation findings, drug treatment courts have achieved success in lowering rates of recidivism among drug offenders, despite problematic methodological and analytical concerns. This article also presents key components and agents of drug treatment courts and discusses their impact and relevance to policy creation and adaptation. It is suggested that when combined with empirical evaluations, process evaluations provide great insight into the drug-treatment-court dynamic. This article concludes with a discussion of the implications of drug treatment courts for justice policy.     

Evidence for bias in hair testing and procedures to correct bias

A number of in vitro experiments show that different hair samples incorporate differing amounts of drugs under identical conditions. Incorporation of cocaine and morphine tends to be correlated with race, in that the hair of African American females incorporates higher concentrations of cocaine than does the hair of Caucasian males or females. Extrapolation of these data into populations has been fraught with difficulties because the dosages of drugs and their use patterns are unknown. Cosmetic treatments and hygiene alter drug binding, which must be considered in comparing populations because cosmetic treatments are often group dependent. Four reasons are proposed that account for the uptake and retention of drugs by hair and that may differ among groups: (1) permeability and other characteristics of the hair due to genetic influences, (2) cosmetic hair treatments and hair care habits (which may be culturally influenced), (3) drug removal during personal hygiene, and (4) manner and route of drug administration which can affect passive exposure to residual drugs in the environment. The data supporting bias in hair testing are reviewed and methods are proposed that use either the uptake of dyes or the incorporation of drug homologs to reduce bias.     

Comparative investigations on the uptake of basic substances into the human keratinocyte cell line HaCaT--a model for the uptake of xenobiotics into the keratinocytes of the hair follicle

The human cell line HaCaT was used to study drug uptake by keratinocytes as an in-vitro model to elucidate drug incorporation into anagen hair follicle. The basic drugs under investigation were taken up very rapidly resulting in a concentration plateau in the keratinocytes which was dependent on the drug concentration in the cell culture medium. The results obtained for HaCaT clearly demonstrated the existence of a partition-equilibrium between the extracellular and intracellular drug concentrations. Only small amounts of the offered drugs were taken up and remarkable differences were observed showing a decreasing uptake for imipramine > haloperidol > cocaine/benzoylecgonine. Total protein content in the culture medium was 3.5 +/- 0.3 mg/mL and the protein binding of the drugs to the foetal serum proteins was found to be negligible in the experiments. Overall, the in vitro findings were consistent with previous observations for in vivo drug incorporation into hair. In particular, an explanation was found for the correlation between the AUC-value and hair concentration observed in animal studies as well as for the generally low drug concentrations in non-pigmented hair.     

Toxicological Findings in Fatal Motor Vehicle Collisions in Ontario,Canada: A One‐Year Study

Drug‐impaired driving is a complex area of forensic toxicology due in part to limited data concerning the type of drugs involved and the concentrations detected. This study analyzed toxicological findings in drivers from fatal motor vehicle collisions (FMVCs) in Ontario, Canada, over a one‐year period using a standardized protocol. Of the 229 cases included in the study, 56% were positive for alcohol and/or drugs. After alcohol, cannabis was the most frequently encountered substance (27%), followed by benzodiazepines (17%) and antidepressants (17%). There were differences in drugs detected by age but no marked difference in drugs detected between single and multiple FMVC's. Not all drugs detected were considered impairing either due to drug type, concentration or case history. The findings indicate the importance of comprehensive drug testing in FMVCs and highlight the need to consider a variety of factors, in addition to drug type and concentration, when assessing the role of drugs in driving impairment.     

Drug Contamination of U.S. Paper Currency and Forensic Relevance of Canine Alert to Paper Currency: A Critical Review of the Scientific Literature

Several studies have reported on wide‐spread contamination of U.S. paper currency with cocaine and to a lesser extent other illicit drugs. Canines are trained and employed to search for and alert to drugs. Canine alert to currency has been used as evidence that currency has been directly involved in illicit drug trafficking to justify currency seizure and forfeiture. This assertion, particularly when the only evidence is based upon canine alert, has been challenged in the courts considering that most currency in circulation is contaminated with cocaine. Comprehensive review of the scientific literature establishes that (i) 67–100% of circulated U.S. currency is contaminated with cocaine ranging from a few nanograms to over one milligram/bill (ii) various biological and environmental parameters impact canine alert to drugs. It is concluded that canine alert to U.S. currency is not sufficiently reliable to determine that currency was directly used in an illicit drug transaction.     

Civilian Health and Medical Program of the Uniformed Services (CHAMPUS); clarification of the CHAMPUS exclusion of unproven drugs, devices and medical treatments and procedures--DoD. Final rule

This final rule clarifies the CHAMPUS exclusion of unproven drugs, devices and medical treatments and procedures and describes the process that the Office of CHAMPUS follows in determining when such drugs, devices, treatments and procedures have moved from the status of unproven to the position of proven medical effectiveness. This clarification is necessary to ensure the CHAMPUS beneficiary and provider population understand the process the Office of CHAMPUS (OCHAMPUS) follows prior to endorsement by CHAMPUS of a new emerging medical technology, drug, or device for which the safety and efficacy have been proven.     

Parents and Drugs

This article examines three hypotheses about the relationship between attachment to parents and children's drug use when parents are perceived by their children as having used drugs. Hirschi's hypothesis that attachment to parents inhibits delinquency regardless of parental behavior is rejected in favor of hypotheses that predict variation in that relationship. In contrast to attachment to straight parents, attachment to drug-using parents does not inhibit drug use significantly and there are occasional hints at reversals in the relationships.     

Clocapramine-related fatality. Postmortem drug levels in multiple psychoactive drug poisoning

A suicide caused by ingestion of multiple psychoactive drugs is reported. A 42-year-old man with a history of psychosis was found dead in a blood pool in his room. The forensic autopsy revealed two stab wounds on his chest. However, these wounds could not explain the cause of death. Eighty-six tablets were found in his stomach. Four psychoactive drugs; clocapramine (CC), chlorpromazine (CP), promethazine (PM) and clotiazepam (CT) were detected in blood and tissues. The concentrations of CC, CP, PM and CT in the femoral vein (FV) blood were 0.39, 0.61, 1.23 and 0.09 microg/ml, respectively. The cause and manner of death were attributed to suicidal multiple psychoactive drug poisoning.Postmortem drug redistribution showed great site-dependent variations with the lowest level in the FV blood. Remarkable variations were observed in CC, CP and PM, but not in CT compared to other three drugs. The variations were dependent on the volume of distribution (Vd) of the drugs. Our human case has demonstrated drugs with higher Vd values showed higher degree of postmortem redistribution of the drug and vice versa.     

The dynamics of illicit drugs production: Future sources and threats

This paper examines the opportunities for illicit drugs production which arise out of the economic, political and social conditions of some countries. These drivers can help us to understand the geographical pattern of global drugs sources and assist in the process of identifying those parts of the world in which new production opportunities are arising. It was found that there is not a homogenous set of risks which contributes to drugs production. Instead, the particular contexts which are conductive to drug production activities varies for different drug types. This has influenced the different patterns of drugs production for highly refined, organic drugs, such as cocaine and heroin, compared to synthetic drugs. The nature of developments which could trigger new areas of drug production are discussed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Drug Prevention and the DARE Programme in Britain

An increasing interest in drug prevention has led to the growth in various programmes, most of which have been imported from the United States. The programmes receiving the most acclaim are the so-called resistance training programmes, of which Drug Abuse Resistance Education (DARE) is the most widely used whether in America or elsewhere. It has also been surrounded by controversy. Resistance training programmes are given to schoolchildren, the aim of which is to teach them skills to resist pressure to take drugs. DARE has recently been introduced in Britain in Nottinghamshire; another similar programme, Chemical Abuse Resolution Lies in Education (Project Charlie), operates in Hackney, London. The aim of this paper is to review the data on the effectiveness of these programmes. The conclusion is that drug resistance programmes have had a mixed response in the US, but that Project Charlie has had reasonable success in London and that DARE in Nottinghamshire needs a long-term evaluation to determine its effectiveness. Such an evaluation could have an impact on drugs prevention policy over the next decade.     

Post-mortem toxicology

Studies examining post-mortem processes are difficult to conduct since changes will have already occurred when the body arrives at the mortuary. While control of collection site for blood can minimize changes in concentration it is very difficult to conduct experiments in humans aimed at understanding the mechanisms and determining the extent of such changes. The use of appropriate animal models can be useful in this regard providing the species and conditions are carefully chosen. Pharmacokinetic studies in humans are also very useful for understanding the changes in drug concentration with time in blood (and other fluids) and also for improving our understanding of drug effects. Unfortunately, doses of illicit drugs that can be given are relatively low to guarantee safety hence extrapolations are made to real life situations. Individual case studies can be useful to describe an unusual or particularly interesting circumstances but little useful information can be obtained when trying to ascertain the role of competing factors, e.g. role of individual drugs when multiple drugs are present, varying toxicity between route of administration, and the role of age or natural disease when drugs are also present. Epidemiological approaches by reviewing large numbers of related cases are the most powerful tool to obtain this information. All of these studies need to operate under the ethical and legal framework appropriate for a jurisdiction. This paper discusses the relative merits of scientific approaches to research in post-mortem toxicology and provides guidance on the most appropriate techniques for future studies.     

Drug use in India: Historical traditions and current problems

By all accounts, drug abuse in India — as elsewhere around the world — is reaching near epidemic proportions. Although India has been a world producer of legal drugs for pharmaceutical markets, it also has an ancient tradition of using drugs in daily activities and ceremonial rituals. Only in recent years has this historically drug‐rich country developed a drug abuse problem. Because of its history of tolerance of drug use in culturally sanctioned activities, India offers a rich site for investigating the conditions that foster responsible and irresponsible use of drugs. Global efforts at crop reduction, interdiction, and criminal sanctions continue to be disappointing at best. A more realistic approach may be to identify factors that make drugs particularly alluring to some segments of the population and not to others. This approach emphasized responsible conduct in drug‐rich environments rather than depending on the increasingly unlikely eradication of the supply.     

PATTERNS OF DRUG USE,DRUG TRAFFICKING,AND OTHER DELINQUENCY AMONG INNER-CITY ADOLESCENT MALES IN WASHINGTON,D.C.*

This paper examines (1) the relationship between drug involvement among inner-city youths and the commission of other kinds of crime, (2) the role of drug use in crime commission, (3) the connection between crime and drug procurement, and (4) the factors that distinguish between individuals as a function of (a) levels of involvement in drug trafficking and (b) drug usage and criminal activity. Drug use and trafficking were both related to other criminal activities; the type of drug involvement was related to the type of crimes reported. The heaviest users were significantly more likely than nonusers to commit property crimes and drug traffickers were significantly more likely to commit crimes against persons than were respondents who did not sell drugs. Adolescents who used and sold drugs were the most likely to commit crimes against persons and property, and at the greatest rate. Still, for every type of crime reported in the past year, only a minority of offenders reported ever using drugs while committing the crime or said that they committed any type of crime in order to obtain drugs or money to obtain drugs. Most youths appear to commit crime for reasons completely independent of drugs.     

Detection of antidepressant and antipsychotic drugs in human hair

The presence of therapeutic drugs and their metabolites in the hair of psychiatric patients was investigated using gas chromatography (GC)-mass spectroscopy (MS)-electron ionization (EI) and GC-MS-chemical ionization (CI). In hair samples tested from 35 subjects, carbamazepine, amitriptyline, doxepin, trihexyphenidyl, chlorpromazine, chlorprothixene, trifluoperazine, clozapine and haloperidol were detected, with maximal concentrations of 22.5, 57.7, 183.3, 15.6, 68.2, 30.0, 36.8, 59.2 and 20.1 ng/mg of hair sample, respectively. Chlorpromazine and clozapine concentrations in the hair were found to be dependent on the dosage used and their correlation coefficients were 0.8047 (P<0.001, n=16) and 0.7097 (P<0.001, n=16), respectively. Segmental analysis demonstrated that there was a correlation between the history of subject's drug exposure and the distribution of drug along the hair shaft. Our results also show that drug analysis in hair may provide useful information about drug treatment and the history of usage, and that drugs can be detected in normally kept hair for at least 16 months after intake.     

The problem of interviewing drug addicts in custody: A study of interrogative suggestibility and compliance

Abstract

The interrogation of drug addicts in custody presents a problem. The reliability of confessions made either under the influence of drugs or during drug withdrawal may be adversely affected. This study explores the effect of drug use and drug withdrawal on interrogative suggestibility and compliance. These two psychological factors are relevant to erroneous testimony. The interrogative suggestibility and compliance of heroin addicts on an inpatient drug unit were measured on opiates, whilst withdrawing from opiates and drug free. The interrogative suggestibility and compliance of the group of subjects as a whole did not differ significantly in these three conditions. However the results did suggest that a subgroup of vulnerable individuals may have been more suggestible when under the influence of opiates. Further work is needed to clarify these results and to aid professionals assessing fitness for interview and cases of retracted confessions.