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In mammals, the skin acts as a barrier to prevent harmful environmental stimuli from entering the circulation. CYP450s are involved in drug biotransformation, exogenous and endogenous substrate metabolism, and maintaining the normal physiological function of the skin, as well as facilitating homeostasis of the internal environment. The expression pattern of CYP450s in the skin is tissue-specific and thus differs from the liver and other organs. The development of skin topical medications, and knowledge of the toxicity and side effects of these medications require a detailed understanding of the expression and function of skin-specific CYP450s. Thus, we summarized the expression of CYP450s in the skin, their function in endogenous metabolic physiology, aberrant CYP450 expression in skin diseases and the influence of environmental variables and medications. This information will serve as a crucial foundation for future studies on the skin, as well as for the design and development of new drugs for skin diseases including topical medications.
The properties that might influence the sequestration of aflatoxin B1 (AfB1) were examined. Laser-diffraction, particle-size analysis (LDPSA) indicated that the particle size of the smectite influences the amount of AfB1 adsorbed. Effective adsorbent smectites disperse well under combined sodium hexametaphosphate solution and ultrasonic agitation. Particle size explained 66% of the variability for most of the samples investigated in an ‘as-received’ state. One effective adsorbent smectite was especially well aggregated and required additional physical dispersion, thus raising the correlation to 73%. Transmission electron microscope (TEM) images show typical smectites and reveal the very diverse morphology of smectites in bentonites. Thin, cloud-like smectite, in TEM images, related positively to AfB1-adsorption capacity. Particles that often fold and are usually ∼0.5 µm across seem to be optimal. The selection of criteria for evaluating these smectites provides a scientific basis for their selection to obtain reliable performance. Particle size is of particular importance as outlined below, and use of LDPSA makes it possible to perform the analysis efficiently and with precision.
It has been estimated that 11% of United States ED patients have substance use disorder. One urban ED estimated that nearly 7% of visits were due to illicit drug use. In a large statewide review of ED visits, alcohol use disorder was more prevalent in rural settings while opioid use disorder was more prevalent in urban settings. Substance use leads to harmful outcomes such as acute injuries, overdose, and medical complications. Forensic laboratory data offers some insight on which drugs are commonly used in US cities. (Ethanol is not included in these reports, but is used ubiquitously and considered to be the most commonly used intoxicating drug.) Opioids, sympathomimetics, cannabinoids, and sedatives classes predominate in all US cities, although there is some regional variation of the specific drugs used among cities. In Baltimore, for example, the top four drugs identified are cocaine, fentanyl, heroin, and tramadol; in Phoenix, the top four are cannabis, fentanyl, heroin, and methamphetamines.
New product development processes need to be compliant to regulatory requirements, and this chapter highlights the salient processes and quality systems to put into place to achieve success. Project management is made simple with specific tools provided here. Customer feedback is channeled into specific product characteristics, and the right tools are shown in this chapter. The biopharma industry has statistics showing less than 10% of starting compounds succeed in reaching market approval, and this chapter explains what causes these failures. The key issues that have repeatedly caused failure during device and diagnostic product development are also pointed out. Ethical decisions have to be made during product development as shown in this chapter. Outsourcing is a real option due to the availability of many contract research and manufacturing organizations, and judicious use of this option is discussed in this chapter. Key milestones that reduce risk and show transition from early stage to preclinical prototype stages are reviewed here. Does the popular concept of minimum viable product in software development apply in biomedicine prototyping? Other similar questions that help the reader understand pitfalls and best practices are answered here.
Medicolegal experts often struggled to discern whether a suspicious death was caused by poisoning or natural causes, particularly during cholera epidemics, and faced difficulties in detecting traces of poison in cadavers. Changing understandings of the absorption of poisons in the body and the advent of new techniques, including the Marsh apparatus test, presented possibilities for demonstrative evidence of poisoning and revealed the dangers of flawed forensic expertise. Some doctors, scientists, jurists, writers, and other commentators issued warnings about the high sensitivity of the Marsh test, the possibility of numerous sources of contamination, and the problem of incompetent practitioners operating beyond the bounds of their knowledge and training. Nonetheless, the prevalence and nature of poisonings shifted over the course of the nineteenth century, largely in response to the evolution of scientific knowledge. However, public battles over the state of scientific and medical knowledge in poisoning trials raised concerns that the very means by which forensic doctors sought to establish their authority might undermine it.
Stingray envenomation is a marine injury suffered by ocean goers throughout the world. No prospective studies exist on the various outcomes associated with these injuries.
Study Objective:
The aim of this study was to perform a prospective, observational study of human stingray injuries to determine the natural history, acute and subacute complications, prevalence of medical evaluation, and categories of medical treatment.
Methods:
This study prospectively studied a population of subjects who were injured by stingrays at Seal Beach, California (USA) from July 2012 through September 2016 and did not immediately seek emergency department evaluation. Subjects described their initial injury and provided information on their symptoms, medical evaluations, and medical treatment for the injury at one week and one month after the injury. This information was reported as descriptive statistics.
Results:
A total of 393 participants were enrolled in the study; 313 (80%) of those completed the one-week follow-up interview and 279 (71%) participants completed both the one-week and one-month follow-up interviews. Overall, 234 (75%) injuries occurred to the foot. One hundred sixty-three (52%) patients had complete resolution of their pain within one week and 261 (94%) had either complete resolution or improvement of pain by one month. Sixty-eight (22%) subjects reported being evaluated by a physician and a total of 49 (17%) subjects reported antibiotic treatment for their wound. None of the subjects required parenteral antibiotics or hospital admission.
Conclusion:
The majority of stingray victims recover from stingray injury without requiring antibiotics. A subset of subjects will have on-going wound pain after one month. The need for parenteral antibiotics or hospital admission is rare.
1. A systematic approach is needed for the assessment of a patient who has taken an overdose, and it should follow standard resuscitation algorithms.
2. Symptoms of drug overdose can produce a constellation of symptoms known as a ‘toxidrome’, knowledge of which aids identification and management when the specific drug is unknown.
3. Mixed overdose of multiple agents is common, and each agent may potentiate and prolong the effects of others.
4. Medications administered in the treatment of an overdose should be used judiciously. They too can potentiate some of the toxic effects.
5. Early engagement from both the psychiatric and the drug and alcohol liaison teams can aid step down from the intensive care unit.
Americium is a man-made metal produced in very small quantities in nuclear reactors. Americium-241 is one of the radioactive isotopes of americium and has commercial applications, including use in smoke detectors. This is a case report of an occupational inhalation of americium-241, treated with both effective external decontamination and the use of diethylenetriamine pentaacetate to promote decorporation. This experience is significant because of the potential for americium or similar radionuclides to be used in “dirty” bombs or other radiological dispersion devices to cause large-scale radioactive contamination.
Acquired methemoglobinemia (MetHb) is an uncommon presentation of cyanosis in the pediatric emergency department (ED), making its diagnosis and management a clinical challenge. Through this case series we hope to improve clinician ability to recognize the potential for MetHb in pediatric ED patients and to avoid overlooking this important cause of cyanosis.
Methods
This was a case series using a health records review, investigating patients diagnosed with MetHb at our pediatric ED during 2007–2018. We included only cases with methemoglobin saturation ≥5%.
Results
Ten patients were diagnosed with MetHb in our pediatric ED during the study period. Five had an underlying hematologic disease who received a pharmacologic trigger known to induce MetHb as well (four dapsone, one rasburicase). The other five patients were previously healthy, who presented with a clinical picture of hemolytic anemia, all of whom were diagnosed with previously unknown glucose-6-phosphate dehydrogenase (G6PD) deficiency. Two of the patients received methylene blue, and five patients needed packed red blood cells. All of the patients survived the acute MetHb episode.
Conclusion
Acquired MetHb in the pediatric ED is a rare but important cause of cyanosis. Diagnosis and management of acute, acquired MetHb in the ED requires a high level of suspicion, and a background knowledge of the common precipitants and underlying conditions associated with this condition. We hope this case series will help ED physicians to consider MetHb in pediatric patients presenting with cyanosis and persistent hypoxia. Exposure to known precipitants (e.g., medications and foods), particularly in the setting of active treatment for malignancy or with symptoms of hemolytic anemia should further increase suspicion.
Introduction: Patients who present to the Emergency Department (ED) with a drug overdose often require long periods of monitoring. After their initial assessment and stabilization, they spend a significant amount of time in a high cost acute care bed in the ED for monitoring until they are medically cleared for psychiatric care or to be discharged. The shift length at this ED is a maximum of 8 hours; meaning any patients staying over 8 hours must be handed over between physicians, increasing the chance of medical errors. The objective of this study is to examine the total ED length of stay (LOS) of this patient group after physician initial assessment (PIA) to determine if there is there justification for the creation of a toxicology observation or short-stay unit for these patients. Methods: A single-centre, blinded retrospective chart review was conducted examining all adult patients presenting to the ED at an urban academic tertiary care centre with a drug overdose in 2018. Variables examined include: Disposition (home, admitted to acute care setting, admitted to non-acute care setting), time from PIA to disposition and total length of stay from PIA to discharge home or admission to hospital. The primary outcome is total length of stay in the ED after PIA.M Results: A total of 1006 patients presenting with an overdose were included. A total of 388 patients were admitted with 44% (172) having an ED LOS greater than 8 hours and 36% (138) staying 8 hours after PIA. The median [IQR] LOS in the ED for all patients was 343 minutes [191-565] while the median [IQR] time to PIA was 37 minutes [15-97]. The majority of these patients (54%) were discharged with no consulting services involved, 23% received a consult to psychiatry, 22% were consulted to internal medicine and 5% of patients were consulted to Critical Care Medicine. Conclusion: This demonstrates patients presenting to the ED with an overdose are seen in the ED by a physician quickly, however many stay in the department over 5 hours from their initial assessment in a monitored setting. While a majority of these patients are able to go home, 44% of admitted patients wait greater than 8 hours in the ED on monitors. The creation of a toxicology observation unit would be helpful for this population to increase patient safety and ease ED bed congestion.
Evaluate the relationship between naloxone dose (initial and cumulative) and opioid toxicity reversal and adverse events in undifferentiated and presumed fentanyl/ultra-potent opioid overdoses.
Methods
We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings (1972 to 2018). We included interventional, observational, and case studies/series reporting on naloxone dose and opioid toxicity reversal or adverse events in people >12 years old.
Results
A total of 174 studies (110 case reports/series, 57 observational, 7 interventional) with 26,660 subjects (median age 35 years; 74% male). Heterogeneity precluded meta-analysis. Where reported, we abstracted naloxone dose and proportion of patients with toxicity reversal. Among patients with presumed exposure to fentanyl/ultra-potent opioids, 56.9% (617/1,085) responded to an initial naloxone dose ≤0.4 mg compared with 80.2% (170/212) of heroin users, and 30.4% (7/23) responded to an initial naloxone dose >0.4 mg compared with 59.1% (1,434/2,428) of heroin users. Among patients who responded, median cumulative naloxone doses were higher for presumed fentanyl/ultra-potent opioids than heroin overdoses in North America, both before 2015 (fentanyl/ultra-potent opioids: 1.8 mg [interquartile interval {IQI}, 1.0, 4.0]; heroin: 0.8 mg [IQI, 0.4, 0.8]) and after 2015 (fentanyl/ultra-potent opioids: 3.4 mg [IQI, 3.0, 4.1]); heroin: 2 mg [IQI, 1.4, 2.0]). Where adverse events were reported, 11% (490/4,414) of subjects experienced withdrawal. Variable reporting, heterogeneity and poor-quality studies limit conclusions.
Conclusions
Practitioners have used higher initial doses, and in some cases higher cumulative naloxone doses to reverse toxicity due to presumed fentanyl/ultra-potent opioid exposure compared with other opioids. High-quality comparative naloxone dosing studies assessing effectiveness and safety are needed.
Although alcohol withdrawal is common, the recognition of benzodiazepine-resistant alcohol withdrawal is a relatively new concept. To provide a framework for both literature review and future research, we assessed clinicians’ personal definition of resistant alcohol withdrawal.
Method
We developed a cross-sectional web-based survey. Administrators from collaborating toxicology and emergency medicine associations deployed the survey directly to their respective memberships. Only physicians, pharmacists, and other clinicians routinely treating alcohol withdrawal were eligible to participate. Respondents selected their preferred definition among the three most common author sources – JB Hack, NJ Benedict, D Hughes – or provided their own. Additional criteria to define resistant alcohol withdrawal were explored.
Results
384 individuals answered the survey. Respondents were mostly attending physicians (79%), in full-time practice (90%), in emergency medicine (70%), and from North America (90%). The majority (64%) described resistant alcohol withdrawal as a high benzodiazepine dosage. Seizures (26%) and persistent tachycardia (16%) were also main characteristics. The median dose to describe high benzodiazepine dose (n = 146) was 40 mg per hour of diazepam equivalents (IQR 20–50). Available definitions were ranked equally as the preferred one: Hack (27%); Benedict (28%); Hughes (28%).
Conclusion
Our results did not identify one single preferred definition for resistant alcohol withdrawal even though a high total dose of benzodiazepine is a major component. Hourly requirements of 40 mg of diazepam equivalents or more emerged as a possible threshold. These findings serve as a base to explore consensus guidelines or future research.
Approximately 50,000 patients per year present at emergency departments (EDs) because of carbon monoxide (CO) intoxication. The hypothesis of this study was that the half-life of CO and the regression period of complaints could be reduced more rapidly by applying oxygen with the Continuous Positive Airway Pressure (CPAP) modality using a non-invasive mechanical ventilator.
Methods:
The patients were divided into Group 1 and Group 2 in terms of the treatment method applied. Patients in Group 1 received FiO2 1.0 15 l/minute oxygen at room temperature for at least 30 minutes with a non-rebreather mask. Patients in Group 2 received FiO2 1.0 oxygen at 12 cmH2O pressure with non-invasive mechanical ventilation for at least 30 minutes with an oronasal mask in the CPAP modality.
Results:
The median values (interquartile range) of carboxyhemoglobin (COHb) levels at zero and 30 minutes of patients were 19% (8) and 14% (6) in Group 1 and 22% (8) and nine percent (3) in Group 2; a median difference of six percent (2) was detected in Group 1 and of 13% (4) in Group 2 in the first 30 minutes (P <.001). When the symptoms of the patients were examined, the median values of Group 1 and Group 2 at zero minutes were both eight units and at 30 minutes were five and three units, respectively. A decrease of five units was determined in the median of Group 2 in the first 30 minutes, and a decrease of two units in the median of Group 1 (P <.001).
Conclusion:
The use of CPAP was determined to more rapidly reduce COHb level as opposed to high-flow oxygen therapy. It is also thought that it may enable earlier discharge by reducing the duration of the emergency follow-up since it provides a faster improvement in the symptoms of the patients.
In recent years it has become apparent that the novel properties of nanomaterials may predispose them to a hitherto unknown potential for toxicity. A number of recent toxicological studies of nanomaterials exist, but these appear to be fragmented and often contradictory. Such discrepancies may be, at least in part, due to poor description of the nanomaterial or incomplete characterization, including failure to recognise impurities, surface modifications or other important physicochemical aspects of the nanomaterial. Herew em ake a casef or the importance of good quality, well-characterized nanomaterials for future toxicological studies, combined with reliable synthesis protocols, and we present our efforts to generate such materials. The model system for which we present results is TiO2 nanoparticles, currently used in a variety of commercial products.