Antimalarial and cytotoxic drugs on COVID-19 and the cardiovascular burden: Literature review and lessons to be learned.

BACKGROUND: The world is witnessing an unprecedented crisis with Coronavirus disease 2019 (COVID-19). It is important to accurately analyze the available evidence to provide correct clinical guidance for optimal patient care. We aim to discuss current clinical evidence regarding chloroquine, hydroxychloroquine, azithromycin, remdesivir, and the cardiovascular burden of COVID-19. METHODS: A literature review was performed using PubMed and Google Scholar. Additional clinical trials were identified through the "TrialsTracker" project. RESULTS: We found conflicting evidence of chloroquine, hydroxychloroquine plus azithromycin, and remdesivir in COVID-19 despite promising early reports of in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2. Some of the current studies have demonstrated adverse drug reactions to chloroquine and hydroxychloroquine + azithromycin. Widespread systemic inflammation and procoagulant/hypercoagulable state, including thrombotic microangiopathy, endothelial dysfunction, bleeding disorder, and thrombosis are increasingly being witnessed in COVID-19. Evidence of cardiac injury and stroke is mostly reported in hospitalized patients; however, large specialized studies that focus on cardiac or neuropathology are lacking. DISCUSSION: There is no convincing clinical evidence of chloroquine, hydroxychloroquine with or without azithromycin, and remdesivir use in COVID-19. As evidence of systemic inflammation is rapidly unfolding, there is a dire need to maximize our resources to find the best possible solutions to the current crisis while conclusive evidence from clinical trials emerges.

DigChem: Identification of disease-gene-chemical relationships from Medline abstracts.

Chemicals interact with genes in the process of disease development and treatment. Although much biomedical research has been performed to understand relationships among genes, chemicals, and diseases, which have been reported in biomedical articles in Medline, there are few studies that extract disease-gene-chemical relationships from biomedical literature at a PubMed scale. In this study, we propose a deep learning model based on bidirectional long short-term memory to identify the evidence sentences of relationships among genes, chemicals, and diseases from Medline abstracts. Then, we develop the search engine DigChem to enable disease-gene-chemical relationship searches for 35,124 genes, 56,382 chemicals, and 5,675 diseases. We show that the identified relationships are reliable by comparing them with manual curation and existing databases. DigChem is available at http://gcancer.org/digchem.

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.

Causes of Death After Nonfatal Opioid Overdose.

Importance: A recent increase in patients presenting with nonfatal opioid overdoses has focused clinical attention on characterizing their risks of premature mortality. Objective: To describe all-cause mortality rates, selected cause-specific mortality rates, and standardized mortality rate ratios (SMRs) of adults during their first year after nonfatal opioid overdose. Design, Setting, and Participants: This US national longitudinal study assesses a cohort of patients aged 18 to 64 years who were Medicaid beneficiaries and experienced nonfatal opioid overdoses. The Medicaid data set included the years 2001 through 2007. Death record information was obtained from the National Death Index. Data analysis occurred from October 2017 to January 2018. Main Outcomes and Measures: Crude mortality rates per 100 000 person-years were determined in the first year after nonfatal opioid overdose. Standardized mortality rate ratios (SMR) were estimated for all-cause and selected cause-specific mortality standardized to the general population with respect to age, sex, and race/ethnicity. Results: The primary cohort included 76 325 adults and 66 736 person-years of follow-up. During the first year after nonfatal opioid overdose, there were 5194 deaths, the crude death rate was 778.3 per 10 000 person-years, and the all-cause SMR was 24.2 (95% CI, 23.6-24.9). The most common immediate causes of death were substance use-associated diseases (26.2%), diseases of the circulatory system (13.2%), and cancer (10.3%). For every cause examined, SMRs were significantly elevated, especially with respect to drug use-associated diseases (SMR, 132.1; 95% CI, 125.6-140.0), HIV (SMR, 45.9; 95% CI, 39.5-53.0), chronic respiratory diseases (SMR, 41.1; 95% CI, 36.0-46.8), viral hepatitis (SMR, 30.6; 95% CI, 22.9-40.2), and suicide (SMR, 25.9; 95% CI, 22.6-29.6), particularly including suicide among females (SMR, 47.9; 95% CI, 39.8-52.3). Conclusions and Relevance: In a US national cohort of adults who had experienced a nonfatal opioid overdose, a marked excess of deaths was attributable to a wide range of substance use-associated, mental health, and medical conditions, underscoring the importance of closely coordinating the substance use, mental health, and medical care of this patient population.

[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.

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.

Trimetazidine in conditions other than coronary disease, old drug, new tricks?

Trimetazidine (TMZ) has traditionally been used as an anti-ischemic drug for coronary artery disease by selectively inhibiting the mitochondrial long-chain 3-ketoacyl-CoA thiolase. Recently, new applications for this therapy have been investigated. This article reviews alternative uses for TMZ in non-coronary artery diseases, such as non-ischemic cardiomyopathy, sepsis, myocardial dysfunction induced by anti-cancer drugs, diabetic cardiomyopathy and contrast-induced nephropathy.

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.

Chemical photoallergy: photobiochemical mechanisms, classification, and risk assessments.

Chemical photosensitivity can be elicited by exposure of the skin to various pharmaceutical substances, foods, cosmetics and other environmental chemicals, followed by exposure to sunlight. There are at least three types of chemical photosensitivity, i.e., photoirritancy (narrowly defined as phototoxicity), photogenotoxicity and photoallergenicity, and their clinical characteristics and mechanisms are quite different. Concerns about chemical photoallergy is increasing, and various studies have been made to clarify the photobiochemical characteristics of photoallergens and the mechanisms involved. Various methodologies, including in silico prediction models, photochemical assay systems, and in vitro phototoxicity prediction tools, have been developed to predict the photoallergenic potential of chemicals over the past few years. The aim of this manuscript is to review the clinical characteristics, pathogenetic mechanisms and photobiochemical features of photoallergens, with special emphasis on the current status about development of screening systems for predicting photoallergenic potential of chemicals.

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.