Recent-Onset Altered Mental Status: Evaluation and Management.

Potential precipitating factors for the recent onset of altered mental status (AMS) include primary central nervous system insults, systemic infections, metabolic disturbances, toxin exposure, medications, chronic systemic diseases, and psychiatric conditions. Delirium is also an important manifestation of AMS, especially in older people who are hospitalized. Clinicians should identify and treat reversible causes of the AMS, some of which require urgent intervention to minimize morbidity and mortality. A history and physical examination guide diagnostic testing. Laboratory testing, chest radiography, and electrocardiography help diagnose infections, metabolic disturbances, toxins, and systemic conditions. Neuroimaging with computed tomography or magnetic resonance imaging should be performed when the initial evaluation does not identify a cause or raises concern for intracranial pathology. Lumbar puncture and electroencephalography are also important diagnostic tests in the evaluation of AMS. Patients at increased risk of AMS benefit from preventive measures. The underlying etiology determines the definitive treatment. When intervention is needed to control patient behaviors that threaten themselves or others, nonpharmacologic interventions are preferred to medications. Physical restraints should rarely be used and only for the shortest time possible. Medications should be used only when nonpharmacologic treatments are ineffective.

Development of a risk prediction nomogram for disposition of acute toxic exposure patients to intensive care unit.

Early risk stratification of acutely poisoned patients is essential to identify patients at high risk of intensive care unit (ICU) admission. We aimed to develop a prognostic model and risk-stratification nomogram based on the readily accessible clinical and laboratory predictors on admission for the probability of ICU admission in acutely poisoned patients. This retrospective cohort study included adult patients with acute toxic exposure to a drug or a chemical substance. Patients' demographic, toxicologic, clinical and laboratory data were collected. Among the 1260 eligible patients, 180 (14.3%) were admitted to the ICU. We developed a generalized prognostic model for predicting ICU admission in patients with acute poisoning. The predictors included the Glasgow coma scale, oxygen saturation, diastolic blood pressure, respiratory rate and blood bicarbonate concentration. The model displayed excellent discrimination and calibration (optimistic-adjusted area under the curve = 0.924 and optimistic-adjusted Hosmer and Lemeshow test = 0.922, respectively) when internally validated. Additionally, we developed prognostic models that determine ICU admission in patients with specific poisonings. Furthermore, we constructed risk-stratification nomograms that rank the probability of ICU admission in these patients. The developed risk-stratification nomograms help decision-making regarding ICU admission in acute poisonings. Future external validation in independent cohorts is necessary before clinical application.

Feasibility of physiologically based pharmacokinetic simulations for assessing pediatric patients after accidental drug ingestion: A case study of a 1.4-year-old girl who ingested alprazolam.

The accidental ingestion of drugs is a common concern, especially in the case of young children. A physiologically based pharmacokinetic (PBPK) model that implements the age-dependent size growth and ontogeny of organ functions can be used to predict the concentration-time profiles of drugs in the pediatric population. In this study, the feasibility of using a PBPK model for predicting the amount of drug accidentally swallowed by a child was assessed based on a case study in an infant. Alprazolam was the drug involved in the current case. The developed PBPK model of alprazolam was first evaluated using pharmacokinetic data obtained in healthy adult male volunteers. Then, it was adapted for application to virtual Japanese pediatric subjects having the same demographic information as the infant of interest. The pharmacokinetic data observed in the infant fell within the range of the 5th and 95th percentiles of the pharmacokinetic simulations after administration of 0.4 mg alprazolam (equivalent to one tablet) in the panel of virtual infants. PBPK simulations could provide estimates of the amount accidentally ingested by a child and also give mechanistic insights into the observed drug concentrations. The current study demonstrates the potential clinical utility of PBPK modeling.

How to interpret urine toxicology tests.

A 13-year-old girl presents to the emergency department for the second time with an unresponsive episode. She has a GCS (Glasgow Coma Scale) score of 11 on arrival and all other observations are normal. The story is unclear, but there are ongoing safeguarding concerns and the family are known to social services. All investigations are normal. After a period of observation on the ward, her GCS returns to normal and she appears well. Both on the first presentation and this presentation ingestion of a toxin was suspected. However, this was denied by the patient and urine toxicology screen was negative. Does this rule out toxin ingestion? Will this change your management?

Hydrogen Sulfide Toxicity: Mechanism of Action, Clinical Presentation, and Countermeasure Development.

INTRODUCTION: Hydrogen sulfide (H2S) is found in various settings. Reports of chemical suicide, where individuals have combined readily available household chemicals to produce lethal concentrations of H2S, have demonstrated that H2S is easily produced. Governmental agencies have warned of potential threats of use of H2S for a chemical attack, but currently there are no FDA-approved antidotes for H2S. An ideal antidote would be one that is effective in small volume, readily available, safe, and chemically stable. In this paper we performed a review of the available literature on the mechanism of toxicity, clinical presentation, and development of countermeasures for H2S toxicity. DISCUSSION: In vivo, H2S undergoes an incomplete oxidation after an exposure. The remaining non-oxidized H2S is found in dissolved and combined forms. Dissolved forms such as H2S gas and sulfhydryl anion can diffuse between blood and tissue. The combined non-soluble forms are found as acid-labile sulfides and sulfhydrated proteins, which play a role in toxicity. Recent countermeasure development takes into account the toxicokinetics of H2S. Some countermeasures focus on binding free hydrogen sulfide (hydroxocobalamin, cobinamide); some have direct effects on the mitochondria (methylene blue), while others work by mitigating end organ damage by generating other substances such as nitric oxide (NaNO2). CONCLUSION: H2S exists in two main pools in vivo after exposure. While several countermeasures are being studied for H2S intoxication, a need exists for a small-volume, safe, highly effective antidote with a long shelf life to treat acute toxicity as well as prevent long-term effects of exposure.

Getting to Remission: Differentiating Residual Symptoms From Treatment Side Effects in Major Depressive Disorder.

Despite the availability of effective treatments for MDD, many individuals have difficulty achieving remission. Residual symptoms can be difficult to differentiate from treatment side effects. Through 2 comic-based case presentations, this CME activity depicts common clinical scenarios and provides evidence-based strategies for effectively identifying and managing residual symptoms of MDD.

relSCAN - A system for extracting chemical-induced disease relation from biomedical literature.

This paper proposes an effective and robust approach for Chemical-Induced Disease (CID) relation extraction from PubMed articles. The study was performed on the Chemical Disease Relation (CDR) task of BioCreative V track-3 corpus. The proposed system, named relSCAN, is an efficient CID relation extraction system with two phases to classify relation instances from the Co-occurrence and Non-Co-occurrence mention levels. We describe the case of chemical and disease mentions that occur in the same sentence as 'Co-occurrence', or as 'Non-Co-occurrence' otherwise. In the first phase, the relation instances are constructed on both mention levels. In the second phase, we employ a hybrid feature set to classify the relation instances at both of these mention levels using the combination of two Machine Learning (ML) classifiers (Support Vector Machine (SVM) and J48 Decision tree). This system is entirely corpus dependent and does not rely on information from external resources in order to boost its performance. We achieved good results, which are comparable with the other state-of-the-art CID relation extraction systems on the BioCreative V corpus. Furthermore, our system achieves the best performance on the Non-Co-occurrence mention level.

[About the safety of application of nasal decongestants in the practice of pediatricians]. / O bezopasnosti primeneniia nazal'nykh dekongestantov v pediatricheskoi praktike.

Undesirable effects of the application of the intransal vasoconstricting medications are a frequent occurrence in the pediatric practice. The objective of the present study was to evaluate the role of the intranasal vasoconstricting medications in the structure of the means and methods currently available for the treatment of toxicological pathologies based at a multi-field clinical hospital. The retrospective analysis of the medical histories of the patients admitted to the toxicological department and annual reports for the period from 2015 to 2016 was undertaken. The study has demonstrated that intoxication associated with the use of the intranasal vasoconstricting medications was the most common cause of hospitalization of the children in the toxicological departments. Intoxication of this origin accounted for 15-20% of the total number of toxicological pathologies among the children. The cases of intoxication are most frequently documented in the group of children at the age between 1 and 3 years. The risk of the undesirable serious complications is especially high after the application of naphazoline-based intranasal vasoconstricting medications (71.7-77.4% of all the cases of intoxication with these products). It is concluded that the use of intranasal vasoconstricting medications in the pediatric practice should be carried out under the strict control, with the naphazoline-based preparations being totally excluded from the application.

A review on symptoms, treatments protocols, and proteomic profile in sulfur mustard-exposed victims.

Sulfur mustard (SM) as an alkylating and vesicating agent was used for 100 years as a chemical weapon. SM as bi-functional mustard can attacks and alkylates lots of biomolecules. Different cellular mechanism and molecular pathways are responsible for damages to body tissues. Such as DNA damages, oxidative stress, Apoptosis, and inflammation. Sulfur mustard penetrated body organs and induces long term eye, skin, lung, gastrointestinal, urogenital damages and can cause carcinogenic and mutagenic consequences. Currently there is no definitive treatment protocol for SM exposed patients. The goal of treatment is relieving the symptoms with fast healing rate and retrieval of damaged tissues to normal function and appearance in short period of time. Evaluation of proteomics profile in SM-exposed victims has been performed in animal model and human patients. These studies revealed that different protein were involved in the patients with SM damages to skin and lungs. Apolipoprotein A1, type I cytokeratins K14, K16 and K17, S100 calcium-binding protein A8, α1 haptoglobin isoforms, Amyloid A1, albumin, haptoglobin, and keratin isoforms, immunoglobulin kappa chain are defined expressed proteins in the damaged tissues.

Pica in Pregnancy: An Unusual Presentation.

BACKGROUND: Pica is common in pregnancy and is often felt to be benign. The following case of severe pica presenting without anemia is unusual in its presentation, laboratory findings, and treatment. CASE: A 31-year-old multiparous woman at 37 0/7 weeks of gestation presented with esophagitis and gastritis secondary to laundry detergent consumption. She had borderline anemia (hemoglobin of 11 g/dL and hematocrit of 37%, mean corpuscular volume 80%) but was severely iron-deficient (serum ferritin 7 micrograms/dL). Parenteral iron infusion was associated with dramatic resolution of her cravings within 36 hours of treatment. CONCLUSION: Pica may be related to deficient iron stores in the absence of anemia and can result in serious morbidity. Parenteral iron may be associated with rapid pica resolution in symptomatic pregnant patients.

"Visually impaired elderly patient ingests pill desiccant, leading to acute hypoxic respiratory failure requiring intubation".

BACKGROUND: A significant percentage of elderly patients suffer from both polypharmacy and visual impairment. This combination can increase the risk of an adverse event related to medication. This case highlights an unusual, but potentially deadly, medication adverse event. CASE PRESENTATION: A 77-year-old male, visually impaired, ingested a pill desiccant, believing it was the ampicillin/sulbactam tablet he was prescribed for an infected diabetic foot ulcer. He presented to the emergency room with inability to swallow, and imaging revealed the pill desiccant lodged in his upper esophagus. He developed respiratory distress due to aspiration of secretions, necessitating intubation both to protect his airway and for an esophagogastroduodenoscopy (EGD). During EGD the desiccant was pushed into the stomach due to an inability to remove it without causing harm. Patient self-extubated the following day and per family and patient's wishes was not re-intubated. The patient suffered no further complications directly related to the desiccant, but he died several days later from respiratory failure. CONCLUSIONS: This case highlights a concerning medication patient safety issue for visually impaired geriatric patients.

Formulas for Calculated Osmolarity and Osmolal Gap: A Study of Diagnostic Accuracy.

BACKGROUND: The osmolal gap has been used for decades to screen for exposure to toxic alcohols. However, several issues may affect its reliability. We aimed to develop equations to calculate osmolarity with improved performance when used to screen for intoxication to toxic alcohols. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 7,525 patients undergoing simultaneous measurements of osmolality, sodium, potassium, urea, glucose, and ethanol or undergoing similar measurements performed within 30 minutes of a measurement of toxic alcohol levels at a single tertiary-care center from April 2001 to June 2016. Patients with detectable toxic alcohols were excluded. INDEX TEST: Equations to calculate osmolarity using multiple linear regression. OUTCOMES: The performance of new equations compared with published equations developed to calculate osmolarity, and to diagnose toxic alcohol intoxications more accurately. RESULTS: We obtained 7,525 measurements, including 100 with undetectable toxic alcohols. Among them, 3,875 had undetectable and 3,650 had detectable ethanol levels. In the entire cohort, the best equation to calculate osmolarity was 2.006×Na + 1.228×Urea + 1.387×Glucose + 1.207×Ethanol (values in mmol/L, R2=0.96). A simplified equation, 2.0×Na + 1.2×Urea + 1.4×Glucose + 1.2×Ethanol, had a similar R2 with 95% of osmolal gap values between -10.9 and 13.8. In patients with undetectable ethanol concentrations, the range of 95% of osmolal gap values was narrower than previous published formulas, and in patients with detectable ethanol concentrations, the range was narrower or similar. We performed a subanalysis of 138 cases for which both the toxic alcohol concentration could be measured and the osmolal gap could be calculated. Our simplified equation had superior diagnostic accuracy for toxic alcohol exposure. LIMITATIONS: Single center, no external validation, limited number of cases with detectable toxic alcohols. CONCLUSIONS: In a large cohort, coefficients from regression analyses estimating the contribution of glucose, urea, and ethanol were higher than 1.0. Our simplified formula to precisely calculate osmolarity yielded improved diagnostic accuracy for suspected toxic alcohol exposures than previously published formulas.

Severe Self-Inflicted Acute Ocular Siderosis Caused by an Iron Tablet in the Conjunctival Fornix.

We present the case of a female patient who grinded a ferrous sulfate tablet and placed it at the conjunctival fornix of her left eye. She rapidly developed severe ocular siderosis, with profoundly decreased visual acuity, corneal opacities, cataract, retinal degeneration and ultimately phthisis bulbi. To our knowledge, this is the first report on the consequences of application of an iron tablet on the conjunctiva.

Concurrent Hemoperfusion and Hemodialysis in Patients with Acute Pesticide Intoxication.

BACKGROUND: Water soluble and insoluble chemicals in the pesticide formulation may be eliminated more effectively in time if hemodialysis (HD) and hemoperfusion (HP) are performed concurrently. AIM: This study is aimed at evaluating the efficacy of concurrent HP and HD in patients with acute pesticide intoxication. METHODS: Between January 2011 and December 2012, we used HP and HD consecutively (HP-HD group, 347 cases), and then during the next 2 years (January 2013 to December 2014), we used concurrent HP and HD (HPD group, 383 cases). We compared the clinical outcomes between the 2 groups. RESULTS: The mortality was higher in the HP-HD group than in the HPD group: (48.1 vs. 20.9%) for the overall mortality and (81.8 vs. 57.9%) for the paraquat (bipyridylium) mortality (p < 0.001). In multiple logistic analyses, age (p = 0.013), ingested volume (p < 0.001), and HP-HD (p = 0.014) were significant risk factors for mortality in the paraquat ingested group. CONCLUSION: Concurrent HP and HD would be an effective and safe treatment for patients with acute pesticide intoxication, in particular, paraquat intoxication.

Pediatric Ingestions: Emergency Department Management.

Pediatric ingestions present a common challenge for emergency clinicians. Each year, more than 50,000 children aged less than 5 years present to emergency departments with concern for unintentional medication exposure, and nearly half of all calls to poison centers are for children aged less than 6 years. Ingestion of magnetic objects and button batteries has also become an increasing source of morbidity and mortality. Although fatal pediatric ingestions are rare, the prescription medications most responsible for injury and fatality in children include opioids, sedative/hypnotics, and cardiovascular drugs. Evidence regarding the evaluation and management of common pediatric ingestions is comprised largely of case reports and retrospective studies. This issue provides a review of these studies as well as consensus guidelines addressing the initial resuscitation, diagnosis, and treatment of common pediatric ingestions. Also discussed are current recommendations for decontamination, administration of antidotes for specific toxins, and management of ingested foreign bodies.