Comparison of dispensed medications and forensic-toxicological findings to assess pharmacotherapy in the Swedish population 2006 to 2013.

PURPOSE: To investigate person-level agreement between medication exposure as predicted using the PRE2DUP (a prescription-based design to estimate continuous drug use) method and postmortem toxicological findings, in the Swedish population during the years 2006 to 2013. METHODS: Using the Swedish National Board of Forensic Medicine's toxicology database and the Swedish National Board of Health and Welfare's registries on causes of death, dispensed medications, and in-patient care, forensic-toxicological findings were compared with prescription-based estimates of drug use for 27 medications. We modeled expected drug-use periods with the PRE2DUP using an algorithm of demonstrated high validity that evaluates personal drug-purchasing patterns with consideration to possible stockpiling of drugs and package information. Excluding criteria included self-inflicted death and recent in-patient care. RESULTS: In data from 18 627 performed autopsies, as well as 10 160 instances of dispensed drug use, the agreement between PRE2DUP drug-use periods and forensic toxicology was, overall, moderate (Cohen's kappa: 0.56 [95% confidence interval {CI}: 0.55-0.57]) with a positive predictive value, or predicted adherence rate, of 46.0%. The group-level predicted adherence and agreement were highest for antidepressants, at 71.0% (Cohen's kappa: 0.74 [CI: 0.73-0.76]), and lowest for cardiovascular drugs, at 21.5% (Cohen's kappa: 0.33 [CI: 0.31-0.36]). Predicted recreational use (negative predictive value) was low for all investigated drugs (0.0%-1.4%). The biological half-life explained 29% (P = 0.003) of the variability of the false-positive rate. CONCLUSIONS: Measured agreement between PRE2DUP-based drug-use estimates and forensic-toxicological findings is dependent upon a number of factors, including true continuous drug use and postmortem detectability of the investigated drugs, as well as the occurrence of unconventional dosing and true non-adherence.

Nails in Forensic Toxicology: An Update.

BACKGROUND: The analysis of nails as a keratinized matrix to detect drugs or illicit substances has been increasingly used in forensic and clinical toxicology as a complementary test, especially for the specific characteristics of stably accumulating substances for long periods of time. This allows a retrospective investigation of chronic drug abuse, monitoring continuous drug or pharmaceutical use, reveal in utero drug exposure or environmental exposures. METHODS: We herein review the recent literature investigating drug incorporation mechanisms and drug detection in nails for forensic toxicological purposes. RESULTS: Mechanisms of drug incorporation have not yet been fully elucidated. However, some research has lately contributed to a better understanding of how substances are incorporated into nails, suggesting three potential mechanisms of drug incorporation: contamination from sweat, incorporation from nail bed and incorporation from germinal matrix. In addition, numerous methods dealing with the determination of drugs of abuse, medications and alcohol biomarkers in nails have been reported in studies over the years. The latter methods could find application in clinical and forensic toxicology. CONCLUSION: The studies herein reviewed point out how important it is to standardize and harmonize the methodologies (either pre-analytical or analytical) for nails analysis and the optimization of sampling as well as the development of proficiency testing programs and the determination of cut-off values.

Method Development in Forensic Toxicology.

BACKGROUND: In the field of forensic toxicology, the quality of analytical methods is of great importance to ensure the reliability of results and to avoid unjustified legal consequences. A key to high quality analytical methods is a thorough method development. METHODS: The presented article will provide an overview on the process of developing methods for forensic applications. RESULTS: This includes the definition of the method's purpose (e.g. qualitative vs quantitative) and the analytes to be included, choosing an appropriate sample matrix, setting up separation and detection systems as well as establishing a versatile sample preparation. CONCLUSION: Method development is concluded by an optimization process after which the new method is subject to method validation.

Overview of Forensic Toxicology, Yesterday, Today and in the Future.

BACKGROUND: The scope of forensic toxicology has been tremendously expanded over the past 50 years. From two general sections forensic toxicology can be further classified into 8-9 sections. METHODS: The most outstanding improvement in forensic toxicology is the changes brought by instrumental development. The field of forensic toxicology was revolutionized by the development of immunoassay and benchtop GC-MS in the 1980's and LC-MS-MS in 2000's. Detection of trace amounts of analytes has allowed the use of new specimens such as hair and oral fluids, along with blood and urine. Over a longer period of time, continuous efforts have been made to efficiently extract and separate drug and poison from biological fluids. International endeavors to develop high quality standards and guidelines for drugs and poisons in biological specimens and to promote them in order to increase reliability of laboratories are also part of the recent advancement of forensic toxicology. Interpretation of postmortem toxicology encompasses various factors including postmortem redistribution and stability. RESULTS: Considering the recent trend, the interpretation of toxicological results should account for autopsy findings, crime scene information, and related medical history. The fields of forensic toxicology will continuously develop to improve analysis of target analytes from various specimens, quality assurance program, and results interpretation. In addition, the development of analytical techniques will also contribute further advancement of forensic toxicology. CONCLUSION: The societies of forensic toxicologists, such as TIAFT, will play an important role for the advancement of forensic toxicology by collaborating and sharing ideas between toxicologists from both developed and developing countries.

Back to the Future - Part 2. Post-mortem assessment and evolutionary role of the bio-medicolegal sciences.

Part 2 of the review "Back to the Future" is dedicated to the evolutionary role of the bio-medicolegal sciences, reporting the historical profiles, the state of the art, and prospects for future development of the main related techniques and methods of the ancillary disciplines that have risen to the role of "autonomous" sciences, namely, Genetics and Genomics, Toxicology, Radiology, and Imaging, involved in historic synergy in the "post-mortem assessment," together with the mother discipline Legal Medicine, by way of its primary fundament, universally denominated as Forensic Pathology. The evolution of the scientific research and the increased accuracy of the various disciplines will be oriented towards the elaboration of an "algorithm," able to weigh the value of "evidence" placed at the disposal of the "justice system" as real truth and proof.

From Death to Death Certificate: What do the Dead say?

This is an overview of medicolegal death investigation and death certification. Postmortem toxicological analysis, particularly for ethanol and drugs of abuse, plays a large role in the forensic investigation of natural and unnatural deaths. Postmortem drug concentrations must be interpreted in light of the autopsy findings and circumstances. Interpretations of drug and ethanol concentrations are important for death certification, but they also may be important for other stakeholders such as police, attorneys, public health practitioners, and the next-of-kin.

Clinical Pharmacology in Denmark in 2016 - 40 Years with the Danish Society of Clinical Pharmacology and 20 Years as a Medical Speciality.

The Danish Society of Clinical Pharmacology was founded in 1976, and mainly thanks to the persistent efforts of the society, clinical pharmacology became an independent medical speciality in Denmark in 1996. Since then, clinical pharmacology has gone from strength to strength. In the Danish healthcare system, clinical pharmacology has established itself as an indispensible part of the efforts to promote the rational, safe and economic use of drugs. Clinical pharmacologists are active in drug committees both in hospitals and in the primary sector. All clinical pharmacology centres offer a local medicines information service. Some centres have established an adverse drug effect manager function. Only one centre offers a therapeutic drug monitoring service. Clinical pharmacologists are responsible for the toxicological advice at the Danish Poison Information Centre at Bispebjerg University Hospital in the Capital Region. The Department of Clinical Pharmacology at Aarhus University Hospital works closely together with forensic toxicologists and pathologists, covering issues regarding illicit substances, forensic pharmacology, post-mortem toxicology, expert testimony and research. Therapeutic geriatric and psychiatric teach-inns for specialist and junior doctors are among the newest initiatives organized by clinical pharmacologists. Clinical pharmacologists work also in the Danish Medicines Agency and in the Danish pharmaceutical industry, and the latter has in particular a great growth potential for creating new jobs and career opportunities for clinical pharmacologists. As of July 2016, the Danish Society of Clinical Pharmacology has 175 members, and 70 of these are specialists in clinical pharmacology corresponding to approximately 2.5 specialists per 1000 doctors (Denmark has in total 28,000 doctors) or approximately 12 specialists per one million inhabitants.

Biosampling strategies for emerging drugs of abuse: towards the future of toxicological and forensic analysis.

The term "new psychoactive substances" refers to emerging drugs of abuse whose chemical structure and psychoactive effects are similar to other already known compounds, often providing a "legal" alternative to internationally regulated drugs and mostly available via on-line retail sites. There are several categories of new psychoactive substances, such as synthetic cannabinoids, cathinone analogues, phenethylamines, tryptamines, and the need to identify and quantify an unprecedented and growing number of new compounds represents a unique challenge for toxicological and forensic analysis. The purpose of this review is to highlight biosampling, sample preparation and analysis of the most important classes of emerging drugs of abuse in biological matrices, focusing on alternatives to classical blood and urine "in tube" approach, still representing the standard routine for bioanalysis, despite inherent flaws regarding handling, stability and process feasibility. Chromatographic techniques coupled to mass spectrometry are usually exploited to identify and quantify new psychoactive substances; due to their high sensitivity and selectivity, it is possible to determine low concentrations not only in plasma and urine, but also in alternative matrices like dried blood spots, oral fluid, hair, other body fluids and tissues. Current literature on analytical methodologies applied to these samples is still limited and a more thorough validation is often required, including a comparison among the results obtained from conventional approaches and from innovative strategies, in order to determine their actual suitability.

[The comprehensive investigation of the new psychoactive substances].

This article was designed to discuss the issues related to ensuring the methodological uniformity of investigations of the novel psychoactive substances based on the system of the newly established specialized laboratories. The authors propose the methodological approaches to the implementation of comprehensive chemical and pharmacological research including chemical, biological, and sociological studies. The main specific features of these approaches are the use of laboratory animals and the automation of in vivo experiments. Also, we discuss the use of the concrete results of the computational experiments designed to elucidate the parameters responsible for the chemical similarity of psychoactive substances. The mechanisms of their action are considered. The special emphasis is placed on the necessity of close cooperation between scientific and expert communities with a view to accumulation of the data on the newly developed and potentially harmful psychoactive substances as a basis for the efficacious prevention of their illegal trafficking.

Los peritajes médicos en la Valencia bajomedieval: los casos de envenenamiento / Medical expert reports in the Valencia of the late Middle Ages: cases of poisoning

En las últimas décadas del siglo XIII, en pleno proceso de configuración del nuevo Reino de Valencia y de su medicalización, se vislumbró por parte de las autoridades y de los ciudadanos el papel que podían desarrollar los médicos para esclarecer muertes violentas. Fue el problema del posible envenenamiento de un individuo la primera circunstancia que obligó a los jueces a recurrir a los médicos, pues éstos podían con su conocimiento experto contribuir a dilucidar la verdad. Por eso se les pidió incluso el uso de la disección post mortem, si era necesario. En realidad, los médicos fueron conscientes de sus limitaciones en este campo y de que debían actuar con cautela (AU)

During the last decades of the 13th century, in the midst of the shaping and medicalization of the new Kingdom of Valencia, the authorities and citizens envisaged the role that physicians could have in clarifying violent deaths. The first circumstance that compelled judges to resort to physicians was the possible poisoning of an individual, given that they could contribute to elucidating the truth with their expert knowledge. They were even requested to use post-mortem dissection if necessary for this purpose. In reality, physicians were conscious of their limitations in this field and the need for them to act with caution (AU)

[Research Progress on Forensic Toxicology of Z-drugs].

The Z-drugs (zolpidem, zopiclone, and zaleplon), as the innovative hypnotics, have an improvement over the traditional benzodiazepines in the management of insomnia. Z-drugs have significant hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. As benzodiazepines, Z-drugs exert their effects through increasing the transmission of γ-aminobutyric acid. Z-drugs overdose are less likely to be fatal, more likely would result in poisoning. Z-drugs can be detected in blood, urine, saliva, and other postmortem specimens through liquid chromatography-mass spectrometry techniques. Zolpidem and zaleplon exhibit significant postmortem redistribution. Z-drugs have improved pharmacokinetic profiles, but incidence of neuropsychiatric sequelae, poisoning, and death may prove to be similar to the other hypnotics. This review focuses on the pharmacology and toxicology of Z-drugs with respect to their adverse effect profile and toxicity and toxicology data in the field of forensic medicine.

Research Progress on Forensic Toxicology of Z-drugs / 法医学杂志

The Z-drugs (zolpidem, zopiclone, and zaleplon), as the innovative hypnotics, have an improvement over the traditional benzodiazepines in the management of insomnia. Z-drugs have significant hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. As benzodiazepines, Z-drugs exert their effects through increasing the transmission of γ-aminobutyric acid. Z-drugs overdose are less likely to be fatal, more likely would result in poisoning. Z-drugs can be detected in blood, urine, saliva, and other postmortem specimens through liquid chromatography-mass spectrometry techniques. Zolpidem and zaleplon exhibit significant postmortem redistribution. Z-drugs have improved pharmacokinetic profiles, but incidence of neuropsychiatric sequelae, poisoning, and death may prove to be similar to the other hypnotics. This review focuses on the pharmacology and toxicology of Z-drugs with respect to their adverse effect profile and toxicity and toxicology data in the field of forensic medicine.

Natural or deliberate outbreak in Pakistan: how to prevent or detect and trace its origin: biosecurity, surveillance, forensics.

Over the last few decades biosecurity and biosafety have emerged as a prominent public health concern due to some high-profile accidents. Effective strategies to deal with the outbreak, whether deliberate or non-deliberate requires a multidisciplinary approach and coordinated decision-making by various state departments such as health, forensics, agriculture, environment, intelligence, law and enforcement, etc. In a dynamic global environment and the overwhelming asymmetric threats from the non-state actors, it is of utmost importance to understand the biosecurity issues and initiate a coordinated global effort to cope with biosecurity and biosafety breaches and develop an as effective response mechanism. An attractive choice for the terrorists, state enemies and non-state actors is the use of biological weapons. An unwanted incident may not only bring chaos to the people, but also can inflict severe economic damage industrially and locally as was in the notorious foot-and-mouth disease outbreak. Because of special geopolitical compulsion, Pakistan is one of the hot spots where special action needs to be taken. The current review focuses on the various approaches, technologies that can be used to alleviate the chances of biosafety and biosecurity incident and emphasizes the role of modern technology that can be used in this regard.

Sumisión química en casos de presuntos delitos contra la libertad sexual analizados en el Instituto Nacional de Toxicología y Ciencias Forenses (Departamento de Madrid) durante los años 2010, 2011 y 2012 / Alleged drug-facilitated sexual assault cases analyzed at the National Institute of Toxicology and Forensic Science (Madrid Department) during the years 2010, 2011 and 2012

Introducción. La sumisión química en relación con los delitos contra la libertad sexual se puede aplicar tanto a los casos de administración subrepticia de determinadas sustancias, como a los casos oportunistas por una mayor vulnerabilidad de la víctima debido al consumo voluntario de las mismas. Material y métodos. Se ha realizado un estudio descriptivo retrospectivo de los casos de agresiones sexuales relacionados con el consumo de sustancias químicas, remitidos durante los años 2010, 2011 y 2012 al Departamento de Madrid del Instituto Nacional de Toxicología y Ciencias Forenses. Se ha recogido información en relación con el perfil de la víctima, el tipo de muestras biológicas remitidas y los resultados toxicológicos. Resultados. De los 306 casos de agresión o abuso sexual remitidos, 107 han cumplido los criterios de inclusión. El perfil de la víctima es el de una mujer española o latinoamericana joven (edad media: 25,9 años), que admite consumo de alcohol previo al episodio, y que sufre de amnesia total o parcial de los hechos. Las muestras remitidas han sido sangre (27,1%), orina (14%) o ambas (57%). El análisis toxicológico ha sido positivo en el 87,9% de los casos, y las sustancias identificadas han sido etanol (61,7%), fármacos (40,2%, fundamentalmente benzodiacepinas) y drogas ilícitas (27,1%, fundamentalmente cocaína), solas o en combinación. Conclusiones. El estudio refleja la necesidad de trabajar en prevención e información de potenciales víctimas y personal sanitario, que una temprana y adecuada toma de muestras son factores claves a la hora de confirmar el diagnóstico, y que las sustancias detectadas, lícitas e ilícitas, pertenecen a un patrón de consumo frecuente en nuestra sociedad (AU)

Introduction. Drug-facilitated sexual assault crimes can be applied in cases of covert administration of certain substances, as well as cases in which the victim voluntarily consumes these same substances. Materials and methods. This study describes retrospectively cases of sexual assault related to the consumption of chemical substances. They were reported to the Madrid Department of the National Institute of Toxicology and Forensic Sciences during 2010, 2011 and 2012. We collected information related to the victim's profile, the type of biological samples given and the results of the toxicological analysis. Results. Out of 306 cases of sexual assault or abuse referred, 107 have met the inclusion criteria. The victim's profile is of a young Spanish or Latin-American woman (mean age: 25.9 years) who admits to consuming alcohol prior to the episode and suffering from total or partial amnesia with regard to the facts. The given samples were blood (27.1%), urine (14%) or both (57%). Toxicological analysis was positive in 87.9% of cases and the substances identified were ethanol (61.7%), pharmaceuticals (40.2%, mainly benzodiazepines), and illicit drugs (27.1%, primarily cocaine) either alone or in combination. Conclusions. This study reflects the requirement to work in prevention and training of potential victims and healthcare personnel, proves that an early and adequate collection of samples are key factors to confirm the diagnosis and identifies that detected licit or illicit substances belong to a frequent consumption pattern (AU)