Pharmaceutical Purchasing: a Review of the Landscape and Implications for Antidotal Therapies.

The management of the poisoned patient often requires the utilization of uncommonly used pharmaceutical interventions. These interventions can be associated with significant costs to both the patient and treating institution. Pharmaceutical supply shortages and issues with accessibility of antidotal therapies complicate the management of many toxic exposures. These challenges are an inherent property of the pharmaceutical purchasing infrastructure in the United States, which is a complicated network of public and private intra-institutional agreements. The cost and availability of any given therapy is dependent on the individual contracting agreements between the treating institution, payer, pharmacy benefit manager, manufacturer or wholesaler, and in some cases a specialty pharmacy. Small or remote hospitals may experience greater challenges related to insufficient patient volume to achieve predicable prescribing patterns of rare and expensive medications, necessitating consignment purchasing arrangements. Although pharmaceutical costs are the focus of recent legislative attention, these reforms are not expected to significantly alter the cost or availability of antidotal therapies.

Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors.

INTRODUCTION: Medications are compounded when a formulation of a medication is needed but not commercially available. Regulatory oversight of compounding is piecemeal and compounding errors have resulted in patient harm. We review compounding in the United States (US), including a history of compounding, a critique of current regulatory oversight, and a systematic review of compounding errors recorded in the literature. METHODS: We gathered reports of compounding errors occurring in the US from 1990 to 2020 from PubMed, Embase, several relevant conference abstracts, and the US Food and Drug Administration "Drug Alerts and Statements" repository. We categorized reports into errors of "contamination," suprapotency," and "subpotency." Errors were also subdivided by whether they resulted in morbidity and mortality. We reported demographic, medication, and outcome data where available. RESULTS: We screened 2155 reports and identified 63 errors. Twenty-one of 63 were errors of concentration, harming 36 patients. Twenty-seven of 63 were contamination errors, harming 1119 patients. Fifteen errors did not result in any identified harm. DISCUSSION: Compounding errors are attributed to contamination or concentration. Concentration errors predominantly result from compounding a prescription for a single patient, and disproportionately affect children. Contamination errors largely occur during bulk distribution of compounded medications for parenteral use, and affect more patients. The burden falls on the government, pharmacy industry, and medical providers to reduce the risk of patient harm caused by compounding errors. CONCLUSION: In the US, drug compounding is important in ensuring access to vital medications, but has the potential to cause patient harm without adequate safeguards.

Association of State-Level Opioid-Reduction Policies With Pediatric Opioid Poisoning.

Importance: Opioid-reduction policies have been enacted by US states to address the opioid epidemic. Evidence of an association between policy implementation and decreased rates of pediatric opioid poisoning provides further justification for expanded implementation of these policies. Objective: To examine the association of 3 state-level opioid-reduction policies with the rate of opioid poisoning in children and adolescents. Design, Setting, and Participants: This interrupted time series analysis used data from the National Poison Data System (NPDS), a database of poisoning information reported to poison control centers across the US. Individuals younger than 20 years who experienced poisoning associated with 1 or more prescription opioids from January 1, 2005, to November 30, 2017, were included. The analysis focused on 3 widespread policy interventions: the prescription drug monitoring program (PDMP), pain clinic legislation, and opioid prescribing guidelines. Data analysis was performed from January 30, 2020, to March 30, 2020. Exposures: Any opioid poisoning in individuals younger than 20 years that was reported to the NPDS. Main Outcomes and Measures: Opioid poisoning rates per million person-months before and after implementation of each of the 3 policies, overall and stratified by age (≤4 years, 5-9 years, 10-14 years, and 15-19 years). Results: A total of 338 476 opioid poisoning incidences in children and young adults were reported to the NPDS within the study period. Of this study population, the mean (SD) age was 9.74 (7.15) years, and 179 011 (52.9%) were female. The implementation of a PDMP was associated with a reduction in the monthly rate of opioid poisoning in children and adolescents (-0.07 per million person-months; 95% CI, -0.09 to -0.04) in the postimplementation period. This reduction was observed for all age groups except for the 10- to 14-year age group (-0.03 per million person-months; 95% CI, -0.05 to 0.00). Pain clinic legislation was associated with an immediate reduction in opioid poisoning (-6.22 per million person-months; 95% CI, -8.98 to -3.47). This association was statistically significant across all ages except for the 4 years or younger group. Analysis of the association of implementation of opioid prescribing guidelines was limited because of insufficient follow-up data and did not show an immediate or monthly change in the rate of opioid poisoning. Conclusions and Relevance: Results of this study suggest that certain state-level opioid-reduction policies were associated with decreases in pediatric opioid exposures across age groups. Further examination of the underlying mechanisms of these associations, including age group-specific outcomes, may expand and strengthen policies that reduce opioid poisoning, misuse, and overdoses in children and adolescents.

The Role and Promise of Artificial Intelligence in Medical Toxicology.

Artificial intelligence (AI) refers to machines or software that process information and interact with the world as understanding beings. Examples of AI in medicine include the automated reading of chest X-rays and the detection of heart dysrhythmias from wearables. A key promise of AI is its potential to apply logical reasoning at the scale of data too vast for the human mind to comprehend. This scaling up of logical reasoning may allow clinicians to bring the entire breadth of current medical knowledge to bear on each patient in real time. It may also unearth otherwise unreachable knowledge in the attempt to integrate knowledge and research across disciplines. In this review, we discuss two complementary aspects of artificial intelligence: deep learning and knowledge representation. Deep learning recognizes and predicts patterns. Knowledge representation structures and interprets those patterns or predictions. We frame this review around how deep learning and knowledge representation might expand the reach of Poison Control Centers and enhance syndromic surveillance from social media.

Scientific Authors in a Changing World of Scholarly Communication: What Does the Future Hold?

Scholarly communication in science, technology, and medicine has been organized around journal-based scientific publishing for the past 350 years. Scientific publishing has unique business models and includes stakeholders with conflicting interests-publishers, funders, libraries, and scholars who create, curate, and consume the literature. Massive growth and change in scholarly communication, coinciding with digitalization, have amplified stresses inherent in traditional scientific publishing, as evidenced by overwhelmed editors and reviewers, increased retraction rates, emergence of pseudo-journals, strained library budgets, and debates about the metrics of academic recognition for scholarly achievements. Simultaneously, several open access models are gaining traction and online technologies offer opportunities to augment traditional tasks of scientific publishing, develop integrated discovery services, and establish global and equitable scholarly communication through crowdsourcing, software development, big data management, and machine learning. These rapidly evolving developments raise financial, legal, and ethical dilemmas that require solutions, while successful strategies are difficult to predict. Key challenges and trends are reviewed from the authors' perspective about how to engage the scholarly community in this multifaceted process.

Differentiating Delirium From Sedative/Hypnotic-Related Iatrogenic Withdrawal Syndrome: Lack of Specificity in Pediatric Critical Care Assessment Tools.

OBJECTIVES: To identify available assessment tools for sedative/hypnotic iatrogenic withdrawal syndrome and delirium in PICU patients, the evidence supporting their use, and describe areas of overlap between the components of these tools and the symptoms of anticholinergic burden in children. DATA SOURCES: Studies were identified using PubMed and EMBASE from the earliest available date until July 3, 2016, using a combination of MeSH terms "delirium," "substance withdrawal syndrome," and key words "opioids," "benzodiazepines," "critical illness," "ICU," and "intensive care." Review article references were also searched. STUDY SELECTION: Human studies reporting assessment of delirium or iatrogenic withdrawal syndrome in children 0-18 years undergoing critical care. Non-English language, exclusively adult, and neonatal intensive care studies were excluded. DATA EXTRACTION: References cataloged by study type, population, and screening process. DATA SYNTHESIS: Iatrogenic withdrawal syndrome and delirium are both prevalent in the PICU population. Commonly used scales for delirium and iatrogenic withdrawal syndrome assess signs and symptoms in the motor, behavior, and state domains, and exhibit considerable overlap. In addition, signs and symptoms of an anticholinergic toxidrome (a risk associated with some common PICU medications) overlap with components of these scales, specifically in motor, cardiovascular, and psychiatric domains. CONCLUSIONS: Although important studies have demonstrated apparent high prevalence of iatrogenic withdrawal syndrome and delirium in the PICU population, the overlap in these scoring systems presents potential difficulty in distinguishing syndromes, both clinically and for research purposes.

A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment.

The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is "probably carcinogenic to humans" (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC's assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies. Two of the Panels (animal bioassay and genetic toxicology) also provided a critique of the IARC position with respect to conclusions made in these areas. The incidences of neoplasms in the animal bioassays were found not to be associated with glyphosate exposure on the basis that they lacked statistical strength, were inconsistent across studies, lacked dose-response relationships, were not associated with preneoplasia, and/or were not plausible from a mechanistic perspective. The overall weight of evidence from the genetic toxicology data supports a conclusion that glyphosate (including GBFs and AMPA) does not pose a genotoxic hazard and therefore, should not be considered support for the classification of glyphosate as a genotoxic carcinogen. The assessment of the epidemiological data found that the data do not support a causal relationship between glyphosate exposure and non-Hodgkin's lymphoma while the data were judged to be too sparse to assess a potential relationship between glyphosate exposure and multiple myeloma. As a result, following the review of the totality of the evidence, the Panels concluded that the data do not support IARC's conclusion that glyphosate is a "probable human carcinogen" and, consistent with previous regulatory assessments, further concluded that glyphosate is unlikely to pose a carcinogenic risk to humans.

Ocular irrigant alternatives in pediatric emergency medicine.

Minimizing pain and discomfort is an important consideration in pediatric ocular decontamination. The pH of an irrigant solution plays a significant role in its tolerability, because a solution with a pH that is too low or too high may cause edema and discomfort to the conjunctiva. We reviewed several available ocular irrigation solutions with respect to their chemical composition, pH, and cost efficiency. Currently, the irrigation solution of first choice for most ocular decontaminations in the pediatric emergency department (ED) is 0.9 % saline solution or normal saline (NS), which has a pH range between 4.5 and 6.0. Alternative ocular irrigant solutions available include Lactated Ringers solution (LR), which has a pH range between 6.2 and 7.5, buffered NS with pH adjusted to 7.4 with sodium bicarbonate, and Balanced Salt Solution Plus (BSS Plus), which has a pH of 7.4. Of these alternative solutions, all except BSS Plus are comparable in cost efficiency to NS. The use of more pH neutral solutions such as LR, NS with bicarbonate buffer, or BSS Plus may decrease ocular pain and irritation associated with copious irrigation, and may improve tolerance of ocular decontamination by a child.