Hypervitaminosis A-induced premature closure of epiphyses (physeal obliteration) in humans and calves (hyena disease): a historical review of the human and veterinary literature

Vitamin A toxicity in the infant, which now occurs rarely from dietary overdosage, was recognized in the 1940s as painful periostitis with rare progression to premature closure of the lower limb epiphyses. Decades later, most cases of vitamin A-induced premature epiphyseal closure (physeal obliteration) occur in pediatric dermatologic patients given vitamin A analogues. This phenomenon resembles a strange disease discovered in more recent years in calves with closed epiphyses of the hind limbs, known as hyena disease. This was a mystery until proved to be caused by vitamin A toxicity from enriched grain that causes the calves to have short hind limbs that resemble those of a hyena and gait disturbance. This historical review links the human and veterinary literature in terms of vitamin A-induced epiphyseal closure using a case report format of a 16-month-old human infant with closed knee epiphyses and gait disturbance that is reminiscent of hyena disease seen in calves. In honor of Dr. David H. Baker (1959–1982)     

First-Line Vasopressor and Mortality Rates in ED Patients with Acute Drug Overdose

IntroductionWhile emergency department (ED) visits for acute drug overdose are at an all-time high, the importance of vasopressors to treat circulatory shock in this patient population remains unclear. This study investigated the association between first-line vasopressor and mortality, for both push-dose and infusion, in this patient population.MethodsFrom a prospective cohort of consecutive ED patients with drug overdose at two urban teaching centers over 5 years, we performed a secondary data analysis of patients with circulatory shock, defined as hypotension requiring either vasopressors, high-dose insulin euglycemia therapy, or both. The first-line vasopressor (push-dose and infusion) was analyzed for associations with the primary outcome (in-hospital mortality) and secondary outcomes (24-hour mortality, ICU LOS). Subgroup analysis of beta-/calcium-channel blocker overdose was performed to evaluate impact of antidotal therapies. Data analysis included multivariable regression.ResultsFifty-five patients with circulatory shock were analyzed, in whom there was 20% 24-hour mortality, 42% in-hospital mortality, 730-minute mean vasopressor duration, and 53.4-hour median ICU LOS. On multivariable analysis, there was significantly decreased adjusted odds of in-hospital mortality with first-line push-dose phenylephrine (aOR 0.06, CI 0.01–0.55), and significantly increased adjusted odds of in-hospital mortality with first-line push-dose epinephrine (aOR 60.8, CI 6.1–608). Of the first-line infusions, norepinephrine had the lowest odds of in-hospital mortality (aOR 0.80, CI 0.2–3.1).ConclusionsIn ED patients with undifferentiated drug overdose and circulatory shock, the first-line vasopressor is associated with in-hospital mortality. First-line push-dose phenylephrine was associated with the lowest odds of in-hospital mortality. Future randomized studies are warranted for validation.     

The ecology of overdose mortality in Philadelphia

Fatal drug overdose represents a significant public health threat in Philadelphia, but substantial variation exists across its communities. This study uses negative binomial longitudinal regression to model ZIP code overdose fatalities over a seven-year period. Model covariates indicate that structural inequality, police arrest activity, and features of the built environment are associated with increased mortality across ZIP codes. Additionally, fatalities are spatially concentrated in select geographies of the city. These findings emphasize the pertinence of community ecological features in the production of stratified within-city health outcomes, and inform the geographic distribution of harm reduction interventions.     

Reducing the toll of opioid overdose deaths in Australia

Opioid overdose mortality among young adults in Australia has increased consistently over the past several decades. Among Australian adults aged 15-44 years, the number of these deaths has increased from six in 1964 to 600 in 1997. The rate (per million adults in this age group) increased 55-fold, from 1.3 in 1964 to 71.5 in 1997. The proportion of all deaths in adults in this age group caused by opioid overdose increased from 0.1% in 1964 to 7.3% in 1997. The magnitude of the increase makes it unlikely to be an artefact of changes in diagnosis, especially as similar increases have also been observed in other countries. These trends are also consistent with historical information which indicates that illicit heroin use first came to police attention in Sydney and Melbourne in the late 1960s. There is an urgent need to implement and evaluate a variety of measures to reduce the unacceptable toll of opioid overdose deaths among young Australians. These include: peer education about the risks of polydrug use and overdose after resuming opioid use after periods of abstinence, and attracting more dependent users into opioid maintenance treatment. Measures are also needed to improve responses to overdose by encouraging witnesses to call ambulances, training drug users in CPR, and trialling distribution of the opiate antagonist naloxone to users at high risk of overdose.     

Drug-related deaths between 2002 and 2013 with accent to methadone and benzodiazepines

AimThe aim of the study is to assess the trends of overdose and drug related fatalities in the Republic of Macedonia during the 11 years.Material and methodsCross-sectional retrospective survey and reviewed of postmortem toxicological analyses which examined fatal poisonings with illegal drugs in years 2002–2013. Information about gender, age, drug consumption, reported years were analyzed. Narcotics were confirmed with toxicological semi quantitative fluorescence polarization immunoassay (FPIA) in urine (range 250–4000 ng/ml).ResultsTotal of 165 deaths were observed. Out of them 145 (87.9%) were male. There is statistical significant differences between male and female DRD due to age (Mann–Whitney U Test = 925, Z = −2626, p = 0.0087). For p < 0.05 there is significant differences between genders due to cause of overdose (Pearson Chi-square = 9743, df = 4, p = 0.0449). DRD among male were mainly because of overdose due to heroin in 80 (51.17%) cases followed by DRD due to combination of methadone and BZD in 25 (11.72%) cases. Out of all DRD cases 50 (30.3%) are related to polydrug use. For p < 0.01 there is a significant differences between analyzed age groups due to cause of overdose (Pearson Chi-square = 33,886, df = 12, p = 0.0007).ConclusionsDeath cause analysis reveals the difficulties in determining the role of substitution drugs, as many other factors may be involved. The findings also highlight the importance of further enhancing treatment interventions for benzodiazepine misuse among patients on methadone substitution treatment.     

Outcomes of patients resuscitated from cardiac arrest in the setting of drug overdose

ObjectivesTo compare the attributes and clinical outcomes of patients with cardiac arrest in the setting of drug overdose (OD) to patients with cardiac arrest from non-drug related etiologies.MethodsWe utilized a US inpatient cardiac arrest registry used to study targeted temperature management (TTM) to identify patients with cardiac arrest in the setting of drug overdose between 2005 and 2013. Data regarding the cardiac arrest, resuscitation interventions, use of post-arrest TTM, urine drug screen, survival, and neurologic outcome were examined. These results were compared to patients suffering cardiac arrest from other causes during the same time period using Wilcoxon rank-sum tests for continuous variables and chi-square tests on categorical variables.ResultsApproximately 2.5% (64/2584) of cardiac arrests occurred in the setting of drug overdose. Patients in the OD cohort were younger, more likely to be male, and more likely to have an out-of-hospital cardiac arrest that was unwitnessed with no bystander CPR and from a non-shockable rhythm. However, the patients in the OD cohort had similar rates of survival and good neurologic outcomes (Cerebral Performance Category 1–2) compared to non-OD patients. A fraction of initially resuscitated patients in each group (8% in OD cohort vs. 15% in non-OD cohort, p = ns) did not receive post-arrest TTM due to prompt awakening following resuscitation.ConclusionsPatients resuscitated from cardiac arrest in the setting of drug OD have neurologic and survival outcomes comparable to non-OD patients despite lower rates of bystander CPR, shockable rhythms, and witnessed arrest.     

Evaluation of dexmedetomidine therapy for sedation in patients with toxicological events at an academic medical center

Introduction. Although clinical use of dexmedetomidine (DEX), an alpha₂-adrenergic receptor agonist, has increased, its role in patients admitted to intensive care units secondary to toxicological sequelae has not been well established. Objectives. The primary objective of this study was to describe clinical and adverse effects observed in poisoned patients receiving DEX for sedation. Methods. This was an observational case series with retrospective chart review of poisoned patients who received DEX for sedation at an academic medical center. The primary endpoint was incidence of adverse effects of DEX therapy including bradycardia, hypotension, seizures, and arrhythmias. For comparison, vital signs were collected hourly for the 5 h preceding the DEX therapy and every hour during DEX therapy until the therapy ended. Additional endpoints included therapy duration; time within target Richmond Agitation Sedation Score (RASS); and concomitant sedation, analgesia, and vasopressor requirements. Results. Twenty-two patients were included. Median initial and median DEX infusion rates were similar to the commonly used rates for sedation. Median heart rate was lower during the therapy (82 vs. 93 beats/minute, p < 0.05). Median systolic blood pressure before and during therapy was similar (111 vs. 109 mmHg, p = 0.745). Five patients experienced an adverse effect per study definitions during therapy. No additional adverse effects were noted. Median time within target RASS and duration of therapy was 6.5 and 44.5 h, respectively. Seventeen patients (77%) had concomitant use of other sedation and/or analgesia with four (23%) of these patients requiring additional agents after DEX initiation. Seven patients (32%) had concomitant vasopressor support with four (57%) of these patients requiring vasopressor support after DEX initiation. Conclusion. Common adverse effects of DEX were noted in this study. The requirement for vasopressor support during therapy warrants further investigation into the safety of DEX in poisoned patients. Larger, comparative studies need to be performed before the use of DEX can be routinely recommended in poisoned patients.