The Development of Practice Recommendations for Drug-Disease Interactions by Literature Review and Expert Opinion.

BACKGROUND: Drug-disease interactions negatively affect the benefit/risk ratio of drugs for specific populations. In these conditions drugs should be avoided, adjusted, or accompanied by extra monitoring. The motivation for many drug-disease interactions in the Summary of Product Characteristics (SmPC) is sometimes insufficiently supported by (accessible) evidence. As a consequence the translation of SmPC to clinical practice may lead to non-specific recommendations. For the translation of this information to the real world, it is necessary to evaluate the available knowledge about drug-disease interactions, and to formulate specific recommendations for prescribers and pharmacists. The aim of this paper is to describe a standardized method how to develop practice recommendations for drug-disease interactions by literature review and expert opinion. METHODS: The development of recommendations for drug-disease interactions will follow a six-step plan involving a multidisciplinary expert panel (1). The scope of the drug-disease interaction will be specified by defining the disease and by describing relevant effects of this drug-disease interaction. Drugs possibly involved in this drug-disease interaction are selected by checking the official product information, literature, and expert opinion (2). Evidence will be collected from the official product information, guidelines, handbooks, and primary literature (3). Study characteristics and outcomes will be evaluated and presented in standardized reports, including preliminary conclusions on the clinical relevance and practice recommendations (4). The multidisciplinary expert panel will discuss the reports and will either adopt or adjust the conclusions (5). Practice recommendations will be integrated in clinical decision support systems and published (6). The results of the evaluated drug-disease interactions will remain up-to-date by screening new risk information, periodic literature review, and (re)assessments initiated by health care providers. ACTIONABLE RECOMMENDATIONS: The practice recommendations will result in advices for specific DDSI. The content and considerations of these DDSIs will be published and implemented in all Clinical Decision Support Systems in the Netherlands. DISCUSSION: The recommendations result in professional guidance in the context of individual patient care. The professional will be supported in the decision making in concerning pharmacotherapy for the treatment of a medical problem, and the clinical risks of the proposed medication in combination with specific diseases.

Ocfentanil overdose fatality in the recreational drug scene.

This paper describes the first reported death involving ocfentanil, a potent synthetic opioid and structure analogue of fentanyl abused as a new psychoactive substance in the recreational drug scene. A 17-year-old man with a history of illegal substance abuse was found dead in his home after snorting a brown powder purchased over the internet with bitcoins. Acetaminophen, caffeine and ocfentanil were identified in the powder by gas chromatography mass spectrometry and reversed-phase liquid chromatography with diode array detector. Quantitation of ocfentanil in biological samples was performed using a target analysis based on liquid-liquid extraction and ultra performance liquid chromatography tandem mass spectrometry. In the femoral blood taken at the external body examination, the following concentrations were measured: ocfentanil 15.3µg/L, acetaminophen 45mg/L and caffeine 0.23mg/L. Tissues sampled at autopsy were analyzed to study the distribution of ocfentanil. The comprehensive systematic toxicological analysis on the post-mortem blood and tissue samples was negative for other compounds. Based on circumstantial evidence, autopsy findings and the results of the toxicological analysis, the medical examiner concluded that the cause of death was an acute intoxication with ocfentanil. The manner of death was assumed to be accidental after snorting the powder.

A vertebral artery dissection with basilar artery occlusion in a child.

This paper presents the case report of an 11-year-old boy with an acute dissection with thrombosis of the left vertebral artery and thrombosis of the basilar artery. The patient was treated with acute systemic thrombolysis, followed by intra-arterial thrombolysis, without any clinical improvement, showing left hemiplegia, bilateral clonus, hyperreflexia, and impaired consciousness. MRI indicated persistent thrombosis of the arteria basilaris with edema and ischemia of the right brainstem. Heparinization for 72 hours, followed by a two-week LMWH treatment and subsequent oral warfarin therapy, resulted in a lasting improvement of the symptoms. Vertebral artery dissection after minor trauma is rare in children. While acute basilar artery occlusion as a complication is even more infrequent, it is potentially fatal, which means that prompt diagnosis and treatment are imperative. The lack of class I recommendation guidelines for children regarding treatment of vertebral artery dissection and basilar artery occlusion means that initial and follow-up management both require a multidisciplinary approach to coordinate emergency, critical care, interventional radiology, and child neurology services.

History of an abusive head trauma including a lucid interval and a retinal hemorrhage is most likely false.

A lucid interval (LI) is the period of time between regaining consciousness after a short period of unconsciousness, resulting from a head injury and deteriorating after the onset of neurologic signs and symptoms caused by that injury. The incentive for this study was the case of a father who left his 14-week-old infant with the nanny in whose custody the infant had collapsed. The nanny denied involvement in the injury, and the father became a suspect. Of 47 abusive head trauma (AHT) cases, 8 were found to have an LI in the past. The history of the cases were thoroughly analyzed and compared with evidence in the literature. An LI is not compatible with an inertial brain injury. Shaking has either an immediate effect or no effect, which means that an LI occurs only in pure impact or blunt injuries. When "shaking lesions" are found including a retinal hemorrhage while the history mentions an LI, the story most likely is false, regardless of whether the perpetrator confesses. The finding of an LI may change the assessment of an AHT case. Lucid interval is a valuable variable in the diagnostic accuracy of an AHT.

Delta-storage pool disease as a mimic of abusive head trauma in a 7-month-old baby: a case report.

A seven-month-old baby was admitted to a hospital emergency department after collapsing suddenly while staying with his nanny. The baby displayed classic symptoms of shaken baby syndrome, including subdural haemorrhage, cytotoxic cerebral oedema, and bilateral retinal hemorrhages. Child protection services were informed, but both the parents and the nanny denied any involvement. In the subsequent weeks, the baby developed three other episodes of new subdural bleeding and a medico-legal investigation was started into the origin of the repeated subdural bleeding. Eventually, platelet aggregation tests and electron microscopy diagnosed a delta-storage pool disease; that is, a haemostatic disorder involving dense granules of the platelets. Initial minor blunt trauma may have resulted in subdural bleeding, while subsequent retinal haemorrhage could have been facilitated by the underlying haemostatic disorder. Delta-storage pool disease should be considered as a possible mimic of abusive head trauma similar to other rare conditions such as Menkes disease and type 1 glutaric aciduria.

Confessed abusive blunt head trauma.

It is generally accepted that terms referring to specific craniocerebral injury mechanisms must be replaced by the more general term abusive head trauma (AHT). Although blunt impact trauma remains an essential part of AHT, it has received far less attention in the literature than shaken-impact injuries. The current article presents 19 confessed cases of a series of 47 highly suspected AHT cases. Of these, 13 were confessed shaken-impact cases, and the other 6 confessed blunt trauma cases. There were no significant differences in the appearance of subdural hematoma, which was present in each case. Retinal hemorrhage, which was present in 10 of the 13 shaken-impact cases in which an ophthalmologic examination was conducted, occurred in 2 of the 6 blunt trauma cases. In 1 case, retinal hemorrhage probably had of metabolic origin. Skull fractures with an overlying subgaleal hematoma and a subdural hematoma below the fracture side were found in 5 of the blunt trauma cases but was also seen in the 2 shaken-impact cases with a skull fracture. The most important finding was a lucid interval (LI) in 3 blunt AHT cases. An LI does not seem to occur in shaking injuries because of the immediate and persistent effect of brain damage that such injuries involve. Therefore, LI makes it important to conduct a detailed investigation of the clinical course in time in suspected AHT cases.

Forensic emergency medicine: old wine in new barrels.

Emergency and forensic physicians may find themselves sometimes on the same medical battleground but with different primary aims and hence often ignore or do not recognize each other's needs. The emergency physician interacts with law enforcement agencies with greater frequency than any other hospital physician and hence needs expertise with legal issues. Awareness of the forensic relevance of certain medical observations by emergency physicians, knowledge of emergency medicine methodology and techniques and of resuscitation-related injuries by forensic physicians may lead to a higher standard in both forensic and emergency medicine, a better serving of the criminal justice system, and most importantly safeguarding the rights of victims of criminal assault. It is this achievable mutual symbiosis that we would like to refer to as the concept of 'forensic emergency medicine'.

Suicidal death after injection of a castor bean extract (Ricinus communis L.).

The castor bean plant (Ricinus communis L.) or wonder tree is cultivated in many countries as an ornamental annual plant in gardens. The highest concentration of the lectin ricin is present in the seeds and pods. Ricin is considered as one of the most toxic natural poisons. Ricinine is a piperidine alkaloidal toxin present in castor bean and is described as a biomarker for the exposure to ricin. A case report is presented of a 49-year-old man who committed suicide by intravenous and subcutaneous injection of a castor bean extract. He was brought to the emergency department 24 h after injecting himself. On admission, the patient was conscious and he presented with a history of nausea, vomiting, diarrhoea, dyspnoea, vertigo and muscular pain. Despite symptomatic and supportive intensive care, the man died 9 h after admission due to multiorgan failure. A body external examination was performed. Blood, urine, vitreous humour and the castor bean extract were submitted to the laboratory for toxicological analysis. The identification of ricinine in the extract was performed by solid phase extraction in combination with full-scan gas chromatography/mass spectrometry, high-performance liquid chromatography with photodiode array detection and liquid chromatography/mass spectrometry operated in the full-scan mode, respectively. An extraction procedure with Oasis HLB solid phase extraction cartridges was applied. Chromatography was achieved using a Symmetry C18 column using a gradient mode with 0.15% formic acid and 0.15% formic acid in acetonitrile as mobile phase. Exposure to the castor bean extract was confirmed by identification of the biomarker ricinine in blood, urine and vitreous humour using solid phase extraction and liquid chromatography tandem mass spectrometry with electro spray source in positive ionization mode. Multiple reaction monitoring was used for specific detection. To the authors' knowledge, it is the first time that ricinine has been identified in vitreous humour in a case of castor bean poisoning. Based on the clinical symptoms and the results of the toxicological analysis, we concluded that death was caused by intoxication with plant toxins originated from R. communis L.

The concept of forensic emergency medicine as illustrated by an unusual complication of pulmonary artery catheterization.

Forensic pathologists are regularly confronted with emergency and invasive medical procedures performed on critically ill or traumatized patients. Basic knowledge of such procedures and their possible complications is therefore mandatory in medico-legal practice. In this article, we describe a very unusual complication of pulmonary artery catheterization: through-and-through perforation of the carotid artery, initially without hemodynamic consequence. Death resulted from an aggravation of the preexisting cerebral edema (secondary to a craniocerebral trauma). The misplacement of the pulmonary artery catheter was clinically missed because the guidewire was initially deflected on the cervical spine towards the subclavian vein where the catheter--by chance--entered the circulatory system and followed its normal route further. The forensic importance of leaving all invasive medical devices in situ on a deceased person when a medico-legal autopsy is to be expected and the mutual interaction between emergency and forensic medicine (forensic emergency medicine) are discussed.