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Introduction: Neonates are very sensitive and vulnerable individuals. They require multiple medications during their stay in the Neonatal Intensive Care Unit (NICU), which can lead to pharmacological errors and Drug-related Problems (DRPs), like drug-drug interactions and adverse drug effects. Aim: To assess DRPs in the NICU to improve the quality of pharmaceutical care. Materials and Methods: This prospective observational study was conducted from June 2023 to August 2023 in a tertiary-level, well-equipped NICU at JNU Hospital, Jaipur, Rajasthan, India. All 61 neonates admitted to the NICU were included, except for those who were admitted for less than 24 hours and had not been prescribed any medications. All DRPs were documented using the Pharmaceutical Care Network Europe (PCNE V9.1). The problems related to DRPs, their causes, planned interventions, acceptance of interventions, and outcomes were assessed. The final analysis was conducted with the Statistical Package for Social Sciences (SPSS) software version 25.0. A p-value <0.05 was considered statistically significant. Results: A total of 61 newborns were enrolled, of which 34 (55.74%) were males. DRPs were present in 47 (77.05%) of the total 61 patients. The total number of DRPs identified was 98. The most common problems were 'unnecessary drug treatment' 63 (64.29%) cases and 'effect of drug treatment not optimal' 28 (28.57%) cases. The most common cause of DRPs was 'dose selection' 105 (62.87%) cases. The intervention was accepted in 96 (97.96%) of the DRPs, and the problem was totally resolved in 70.41% of the cases. However, the problem remained unsolved in 17.35% of DRPs, primarily due to the 'lack of cooperation from the prescriber' in 9.18% of cases. Conclusion: Unnecessary and ineffective treatments, along with inappropriate doses, are the major problems and causes of DRPs. The need for clinical pharmacologists in NICUs, along with planned interventions and their acceptance, could help address these issues and ultimately lead to improved quality of care. [ABSTRACT FROM AUTHOR]

Introduction: Neonates are very sensitive and vulnerable individuals. They require multiple medications during their stay in the Neonatal Intensive Care Unit (NICU), which can lead to pharmacological errors and Drug-related Problems (DRPs), like drug-drug interactions and adverse drug effects. Aim: To assess DRPs in the NICU to improve the quality of pharmaceutical care. Materials and Methods: This prospective observational study was conducted from June 2023 to August 2023 in a tertiary-level, well-equipped NICU at JNU Hospital, Jaipur, Rajasthan, India. All 61 neonates admitted to the NICU were included, except for those who were admitted for less than 24 hours and had not been prescribed any medications. All DRPs were documented using the Pharmaceutical Care Network Europe (PCNE V9.1). The problems related to DRPs, their causes, planned interventions, acceptance of interventions, and outcomes were assessed. The final analysis was conducted with the Statistical Package for Social Sciences (SPSS) software version 25.0. A p-value

Risperidone is a second-generation antipsychotic with common adverse effects, such as extrapyramidal symptoms, weight gain, hyperprolactinemia, and sedation. Angioedema, although generally considered to be uncommon, has previously been documented to occur following administration of some antipsychotics, including risperidone. This report describes a case of risperidone-induced angioedema in an older male patient.

Findings on the correlation between the use of antihypertensive medication and the risk of breast cancer (BC) have been inconsistent. We performed a two-sample Mendelian randomization (MR) using instrumental variables to proxy changes in gene expressions of antihypertensive medication targets to interrogate this. Genetic instruments for expression of antihypertensive drug target genes were identified with expression quantitative trait loci in blood, which should be associated with systolic blood pressure to proxy for the effect of antihypertensive drug. The association between genetic variants and BC risk were obtained from genome-wide association study summary statistics. The summary-based MR was employed to estimate the drug effects on BC risk. We further performed sensitivity analyses to confirm the discovered MR associations such as assessment of horizontal pleiotropy, colocalization, and multiple tissue enrichment analyses. The overall BC risk was only associated with SLC12A2 gene expression at a Bonferroni-corrected threshold. One standard deviation (SD) decrease of SLC12A2 gene expression in blood was associated with a decrease of 1.12 (95%CI, 0.80–1.58) mmHg of systolic blood pressure, but a 16% increased BC risk (odds ratio, 1.16, 95% confidential interval, 1.06–1.28). This signal was further observed for estrogen receptor positive (ER +) BC (1.17, 1.06–1.28). In addition, one SD decrease in expression of PDE1B in blood was associated with 7% decreased risk of ER + BC (0.93, 0.90–0.97). We detected no evidence of horizontal pleiotropy for these associations and the probability of the causal variants being shared between the gene expression and BC risk was 81.5, 40.5 and 66.8%, respectively. No significant association was observed between other target gene expressions and BC risk. Changes in expression of SLC12A2 and PDE1B mediated possibly via antihypertensive drugs may result in increased and decreased BC risk, respectively. [ABSTRACT FROM AUTHOR]

Adverse drug reaction are defined as "harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product". In France, adverse effects due to medicines are reported to the French National Agency of Medicines (ANSM) by the healthcare professionals or consumers. The objective of this study was to implement a tool that facilitates the utilization of ANSM reports by synthesizing information to effectively inform prescribers and users. We focused on 3 psychotropic classes: antidepressants, antipsychotics and anxiolytics. We extracted relevant data from the ANSM website through a webscraping process, based on the names of molecules in these 3 classes: antidepressants, antipsychotics, and anxiolytics. We implemented a web interface with R Shiny that provides three panels: (i) a presentation of the active ingredient with the fewest reports for a selected adverse effect category, (ii) the adverse reactions for a selected active ingredient ranked in descending order, and (iii) a comparison of two active ingredients where, for each adverse effect, the active ingredient with the fewest reported adverse drug events (ADEs) is displayed. Our application allows for synthesizing information to effectively inform prescribers and users. In the ANSM existing interface, molecules can only be viewed one by one, and the ratio needs to be calculated manually, making it difficult to compare molecules. It is important to note that this is not a prescription assistance device but rather for informational purposes. In the future, the application may be expanded to include other categories of molecules. Finally, the indicators provided by our tool could be compared to those from other pharmacovigilance databases. [ABSTRACT FROM AUTHOR]

Introduction Serotonin syndrome and neuroleptic malignant syndrome are caused by 2 distinct pathologies; however, the clinical presentation associated with both syndromes share many features. Methods We describe a 56-year-old male patient who presented to our facility with seizures, leukocytosis, fevers, extremity hyperreflexia, and signs of autonomic dysfunction as evidenced by cardiovascular instability. The patient was noted to be taking vortioxetine, trazodone, lamotrigine, lurasidone, and carbidopa-levodopa as outpatient medications for his depression, an unspecified mood disorder, and Parkinson disease. Following a robust workup and failure of other therapies, all serotonergic and dopaminergic medications were held, and the patient was tried on cyproheptadine for serotonin syndrome, which led to the cessation of fevers. Bromocriptine was added to the regimen, which led to the resolution of the remainder of the patient’s symptoms. Results The overlapping symptomatology of several key diagnostic criteria for both serotonin syndrome and neuroleptic malignant syndrome as well as their nature as diagnoses of exclusion require an evaluation of the patient’s aggregate improvement following targeted pharmacologic strategies for both syndromes. The efficacy of both cyproheptadine and bromocriptine when administered concomitantly support the concurrent pathologies. Discussion Clinicians at the bedside must be cognizant of the potential for clinically relevant drug-drug interactions that may present with overlapping pathologies.

Background of the study: Depression is a prevalent mental disorder characterized by various symptoms, including low mood, lack of pleasure, changes in appetite and sleep, and difficulty concentrating. Antidepressants are commonly used to manage depression as well as other related disorders, such as anxiety and somatoform disorders. This study aimed to investigate the adverse drug effects experienced by adult patients who were using antidepressants at Chitwan Medical College Teaching Hospital in Nepal. Methods: This study was a retro-prospective, observational study consisting of 117 adult patients under antidepressant medication. The adverse drug profile for the patients was collected using an antidepressant side effect checklist developed by the NHS foundation trust. Statistical analysis was performed using SPSS version 20. Result: The study group consisted of adult patients using antidepressants at Chitwan Medical College Teaching Hospital, Chitwan, Nepal. The mean age of the group was 40.9 ± 12.8, with 63.2% females and 36.7% males. The most common conditions for which antidepressants were prescribed were depression (49.5%), anxiety disorder (31.6%), and somatoform disorder (13.6%). Amitriptyline was the most commonly used medication in monotherapy (64.1%), followed by escitalopram and sertraline. Dry mouth, weight gain, drowsiness, blurred vision, problems with sexual function, and an increase in appetite were the most commonly reported adverse effects. The incidence of certain adverse effects was higher in the multiple therapy group than in the monotherapy group (p < 0.05). Conclusion: The incidence of adverse drug effects is high in patients taking antidepressants, especially those receiving multiple medications. Educating patients about common side effects and prescribing monotherapy whenever possible are crucial in reducing the incidence.

Azoles are frequently used to treat systemic mycoses but have been associated with a number of adverse effects of the skin and skin appendages. Herein we describe two cases of chronic paronychia in pediatric patients receiving fluconazole for coccidioidomycosis. Their clinical characteristics are described, and the literature reviewed.

Posaconazole therapy may lead to increased serum estradiol levels and development of gynecomastia. Early detection by endocrine hormone measurements may help preventing gynecomastia.

CBS deficient individuals undergoing betaine supplementation without sufficient dietary methionine restriction can develop severe hypermethioninemia and brain edema. Brain edema has also been observed in individuals with severe hypermethioninemia without concomitant betaine supplementation. We systematically evaluated reports from 11 published and 4 unpublished patients with CBS deficiency and from additional four cases of encephalopathy in association with elevated methionine. We conclude that, while betaine supplementation does greatly exacerbate methionine accumulation, the primary agent causing brain edema is methionine rather than betaine. Clinical signs of increased intracranial pressure have not been seen in patients with plasma methionine levels below 559 μmol/L but occurred in one patient whose levels did not knowingly exceed 972 μmol/L at the time of manifestation. While levels below 500 μmol/L can be deemed safe it appears that brain edema can develop with plasma methionine levels close to 1000 μmol/L. Patients with CBS deficiency on betaine supplementation need to be regularly monitored for concordance with their dietary plan and for plasma methionine concentrations. Recurrent methionine levels above 500 μmol/L should alert clinicians to check for clinical signs and symptoms of brain edema and review dietary methionine intake. Levels approaching 1000 μmol/L do increase the risk of complications and levels exceeding 1000 μmol/L, despite best dietetic efforts, should be acutely addressed by reducing the prescribed betaine dose.

Aripiprazole is an atypical antipsychotic drug that is mainly transformed by the hepatic enzymes CYP2D6 and CYP3A4. Dose adjustment is recommended for CYP2D6-poor metabolizers. Aripiprazole is generally well tolerated by most adult patients, but occasionally adverse effects can occur in some individuals resulting in the drug being withdrawn. Recent studies suggested that other genes involved in drug metabolism, transport, and elimination can be related to the efficacy and safety of drug therapy. This study aimed to evaluate the differences in genetic variants between patients who tolerated the therapy well and those who experienced adverse effects leading to withdrawing the drug. The genetic profiling of 20 genes was performed using MassARRAY technology. No differences between both groups in the ABCB1, COMT, CYP2D6, CYP3A4, and CYP3A5 polymorphisms were found. Unexpectedly, we observed a higher frequency of homozygous CYP1A21F/*1F (78% vs. 45%) and CYP2B6*1/*1 (80% vs. 45%) as well as the frequency of CYP1A2 ultra-rapid metabolizes in the group with adverse effects. Moreover, a combined homozygous status (CYP1A2*1F/*1F/CYP2B6*1/*1) has been exclusively identified in patients with adverse effects. To date, there are no findings about the possible role of CYP1A2 and CYP2B6 enzymes in aripiprazole metabolism. Thus, our preliminary data suggest that the CYP1A2*F and/or CYP2B6*1 alleles may contribute to the adverse effects of aripiprazole. Therefore, further studies on larger sample sizes are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Rising antibiotic use is a serious threat to the success of therapy in dentistry for bacterial resistance and side effects to the patients. The dentist community in Albania prescribing too many antibiotics. This survey assesses the mode of antibiotic use among Albanian dentists, with appropriate dosage and regimen, and antibiotic stewardship and their knowledge of relevant guidelines. Material and Methods: This survey study was conducted among 180 Albanian dentists. The questionnaire was distributed through e-mail addresses found in the database of the Faculty of Dental Medicine, University of Medicine of Tirana. We assessed 180 dentists out of which 154 (85.56%) completed the entire questionnaire. Results: There were 24,870 prescriptions in adult patients from 154 dentists for a period of six months with an average of 1,243 prescriptions per week. The most used antibiotics were fixed combinations of amoxicillin–clavulanic acid (67.43%) and azithromycin (39.3%) for allergic patients to beta-lactams. The results for antibiotic stewardship were incorrect in 37.01% of total providers, and gastrointestinal disorders were reported as side effects. Conclusion: This survey conducted among Albanian dentists shows a different trend of using antibiotics than in other countries. To tackle the current antibiotic resistance, dentists must be an important part of the antimicrobial stewardship program of the Public Health Institution in Albania to change individual behavior.

Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) is a rare and potentially life-threatening condition. Symptoms typically manifest two to eight weeks after exposure to an offending agent, such as anticonvulsants and antibiotics. Clinical features include fever, morbilliform rash, eosinophilia, lymphadenopathy, and, in severe cases, multiorgan dysfunction, including interstitial nephritis, hepatitis, and pneumonitis. This case report discusses a 55-year-old female who developed DRESS syndrome while being treated for a urinary tract infection with trimethoprim/sulfamethoxazole (TMP/SMX). Presenting with fever, dysuria, flank pain, and a widespread non-pruritic maculopapular rash, her lab results were remarkable for eosinophilia, while the urinalysis revealed mild hematuria. Computed tomography imaging ruled out nephrolithiasis and acute pyelonephritis, leading to the diagnosis of DRESS syndrome. Management focused on discontinuing TMP/SMX and initiating systemic glucocorticoids. The patient responded well to treatment and was discharged on hospital day two with prescriptions for topical and oral steroids, famotidine, and diphenhydramine. The patient was provided with follow-up instructions and return precautions. Drug reaction with eosinophilia and systemic symptoms poses unique diagnostic challenges due to its similarity to other cutaneous reactions and the delay between drug exposure and symptom onset. Early recognition and intervention are vital for preventing severe complications. Given its potential for multiorgan dysfunction and poor patient outcomes, healthcare providers must be vigilant when evaluating patients presenting with fever and rash. Comprehensive history taking and accurate reconciliation of active and recent medications are necessary to make the diagnosis. Immediate discontinuation of the offending agent is essential, while supportive care and topical or systemic glucocorticoids remain the treatment standards., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Memorial Healthcare System issued approval N/A. Informed consent is waived for case reports with 3 or less patients. Patient consent form has been filled out and signed by the patient and is available upon request. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Szczepanek et al.)

Risperidone is a second-generation antipsychotic with common adverse effects, such as extrapyramidal symptoms, weight gain, hyperprolactinemia, and sedation. Angioedema, although generally considered to be uncommon, has previously been documented to occur following administration of some antipsychotics, including risperidone. This report describes a case of risperidone-induced angioedema in an older male patient., (© 2024 AAPP. The Mental Health Clinician is a publication of the American Association of Psychiatric Pharmacists.)

Rising antibiotic use is a serious threat to the success of therapy in dentistry for bacterial resistance and side effects to the patients. The dentist community in Albania prescribing too many antibiotics. This survey assesses the mode of antibiotic use among Albanian dentists, with appropriate dosage and regimen, and antibiotic stewardship and their knowledge of relevant guidelines. Material and Methods: This survey study was conducted among 180 Albanian dentists. The questionnaire was distributed through e-mail addresses found in the database of the Faculty of Dental Medicine, University of Medicine of Tirana. We assessed 180 dentists out of which 154 (85.56%) completed the entire questionnaire. Results: There were 24,870 prescriptions in adult patients from 154 dentists for a period of six months with an average of 1,243 prescriptions per week. The most used antibiotics were fixed combinations of amoxicillin–clavulanic acid (67.43%) and azithromycin (39.3%) for allergic patients to beta-lactams. The results for antibiotic stewardship were incorrect in 37.01% of total providers, and gastrointestinal disorders were reported as side effects. Conclusion: This survey conducted among Albanian dentists shows a different trend of using antibiotics than in other countries. To tackle the current antibiotic resistance, dentists must be an important part of the antimicrobial stewardship program of the Public Health Institution in Albania to change individual behavior. [ABSTRACT FROM AUTHOR]

ObjectiveTenofovir disoproxil fumarate is a commonly used antiretroviral drug, but risk factors for tenofovir (TFV)-associated kidney disease are not fully understood. We used intensive pharmacokinetic studies in a cohort of HIV-infected women on TFV-based therapy to study the relationship between TFV exposure and subsequent kidney function.DesignThis is a nested study within the Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-infected women. Participants on TFV-based therapy underwent 24-h intensive pharmacokinetic sampling after witnessed dose. Kidney function was measured over the succeeding 7 years by serum creatinine [estimated glomerular filtration rate calculated by serum creatinine (eGFRcr)].MethodsMultivariable linear mixed models evaluated the relationship of baseline TFV area under the-time concentration curves (AUCs) with subsequent changes in kidney function. Covariates included age, diabetes, hypertension, race, BMI, ritonavir use, duration of TFV exposure, current CD4 cell count, and HIV viral load.ResultsOf the 105 participants, persons within the highest baseline TFV AUC tertile had significantly lower eGFRcr compared with those in the lowest tertile (mean ± standard error: 80 ± 4.3 vs. 104 ± 2.5 ml/min per 1.73 m, P

Objectives: Although Gross hematuria in patients receiving anticoagulants is not very common, it is one of the most common reasons of consulting with urologists. It is recommended to investigate urinary tract malignancies but simultaneous approach to anticoagulation and hematuria so as the optimum balance could be attained, is not clearly defined in the literature yet. We aim to answer pitfalls of hematuria management in anticoagulant receiving patients in this manuscript. Materials and methods: In a prospective case control study during 2017–2019, we observed and collected the data of patients receiving anticoagulant therapy and suffered from gross hematuria with coagulation parameters in prophylactic or therapeutic range in an academic hospital affiliated to Tehran University of Medical Sciences. SPSS 24th version was used for descriptive analysis of collected data. Results: Sixty-six patients encountered hematuria while receiving anticoagulant therapy. Although hematuria was more common in male patients, its recurrence was higher in female patients. It started mostly in first 72 h of therapy and was anticoagulant-dose dependent. Degree of hematuria was mostly mild or moderate by visual estimation and controlled easily by holding the anticoagulant therapy for less than 2 days. Anti-platelet therapy, urinary catheterization and patient's activity did not have any effect on re-bleeding rate. Conclusion: Considering the fact that ruling out the urinary tract malignancy is mandatory in these patients, moderate and severe hematuria can be controlled simply by short term holding the anticoagulant therapy while continuing antiplatelet therapy albeit there is possibility to continue them in mild cases. Removing urinary catheters and decreasing the patient's mobility are not recommended. In order to decrease the recurrence of hematuria, re-establishing anticoagulation with LMWH and non-Vitamin D dependent oral agents rather than continuing Heparin and Warfarin might be helpful. [ABSTRACT FROM AUTHOR]

Abstract Posaconazole therapy may lead to increased serum estradiol levels and development of gynecomastia. Early detection by endocrine hormone measurements may help preventing gynecomastia.

Abstract CBS deficient individuals undergoing betaine supplementation without sufficient dietary methionine restriction can develop severe hypermethioninemia and brain edema. Brain edema has also been observed in individuals with severe hypermethioninemia without concomitant betaine supplementation. We systematically evaluated reports from 11 published and 4 unpublished patients with CBS deficiency and from additional four cases of encephalopathy in association with elevated methionine. We conclude that, while betaine supplementation does greatly exacerbate methionine accumulation, the primary agent causing brain edema is methionine rather than betaine. Clinical signs of increased intracranial pressure have not been seen in patients with plasma methionine levels below 559 μmol/L but occurred in one patient whose levels did not knowingly exceed 972 μmol/L at the time of manifestation. While levels below 500 μmol/L can be deemed safe it appears that brain edema can develop with plasma methionine levels close to 1000 μmol/L. Patients with CBS deficiency on betaine supplementation need to be regularly monitored for concordance with their dietary plan and for plasma methionine concentrations. Recurrent methionine levels above 500 μmol/L should alert clinicians to check for clinical signs and symptoms of brain edema and review dietary methionine intake. Levels approaching 1000 μmol/L do increase the risk of complications and levels exceeding 1000 μmol/L, despite best dietetic efforts, should be acutely addressed by reducing the prescribed betaine dose.

Azoles are frequently used to treat systemic mycoses but have been associated with a number of adverse effects of the skin and skin appendages. Herein we describe two cases of chronic paronychia in pediatric patients receiving fluconazole for coccidioidomycosis. Their clinical characteristics are described, and the literature reviewed., Competing Interests: Nathan B. Price, MD: Consulted for DSM-Firmenich; no relevant conflict of interest to disclose. Emily S. Cormack, PharmD: nothing to disclose. Kathryn R. Matthias, PharmD: nothing to disclose. Kareem W. Shehab, MD: nothing to disclose., (© 2024 Published by Elsevier Ltd.)

Toxic epidermal necrolysis is a rare, life-threatening skin disease with no consensus on adjunctive treatment, particularly in pediatric patients. We present the case of a 13-year-old previously healthy patient with drug-associated toxic epidermal necrolysis who experienced significantly shortened length of hospital stay and duration of symptoms compared with published literature when treated with 2 doses of etanercept 50 mg during 5 days. [ABSTRACT FROM AUTHOR]

Local anesthetic agents play a key role in the treatment and prevention of pain in children. Although generally safe and effective, as with any pharmacologic agent, adverse effects may occur with the administration of these medications. Systemic absorption or inadvertent systemic injection during bolus dosing or continuous infusion can result in local anesthetic systemic toxicity with life-threatening neurological and cardiac complications. The following article reviews the pharmacology of local anesthetic agents, outlines previous reports of systemic toxicity during regional anesthesia, and discusses prevention and treatment algorithms. [ABSTRACT FROM AUTHOR]

OBJECTIVE Metronidazole is recommended as a first-line treatment of necrotizing enterocolitis (NEC) in neonates. Metronidazole-associated neurotoxicity has been reported, but long-term neurodevelopmental effects in neonates have not been explored. The primary objective was to evaluate the relationship of cumulative metronidazole dose with each Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) composite score in neonates with NEC. Secondary objectives included comparison of seizure rates, mean Bayley-III scores, and neurodevelopmental impairment defined as 2 of 3 Bayley-III composite scores = 79 or 1 score = 70 between the metronidazole exposed and non-exposed groups METHODS This multisite, retrospective cohort study compared infants with a birth weight < 1500 grams between January 1, 2011, and December 31, 2016, who developed stage 2 or greater NEC or spontaneous intestinal perforation and were followed up at a developmental clinic visit at approximately 1 year of age. Patients were excluded if admitted >72 hours of life, had congenital neurodevelopmental anomalies, hypoxic ischemic encephalopathy, grade III or IV intraventricular hemorrhage, or seizures prior to treatment of NEC. Included patients were stratified into 2 groups based on metronidazole exposure versus no metronidazole. Data were assessed using descriptive and inferential statistical techniques, using SAS 9.4. RESULTS Forty-one patients were included. Seven patients received metronidazole and 34 patients were in the non-metronidazole group. The only statistical difference noted between groups was for gestational age, with the non-exposed group being more premature. There was no statistical difference in Bayley-III scores, seizure rates, or neurodevelopmental impairment between groups. CONCLUSION No differences in neurodevelopmental outcomes were found between those with and without metronidazole exposure. Further studies are needed to validate our results. [ABSTRACT FROM AUTHOR]

Toxicity related to acetaminophen is most encountered with the acute ingestion of large doses. However, toxicity may also result from chronic ingestion, even when recommended doses are administered over a prolonged period of time. We present the case of a 20-month-old female toddler who received therapeutic recommended doses of acetaminophen (oral or intravenous) following multiple surgical interventions for treatment of a tracheo-esophageal fistula following ingestion of a button battery. The potential role of chronic acetaminophen administration in the etiology of hepatoxicity is discussed and prevention strategies are presented. [ABSTRACT FROM AUTHOR]

OBJECTIVE Our objective was to determine the incidence and risk factors for intravenous acetazolamideassociated acute kidney injury (AKI). METHODS We utilized a retrospective cohort study including patients <19 years of age initiated on intravenous acetazolamide while admitted to an ICU. Data collection included patient demographics, clinical variables, acetazolamide dosing, and serum creatinine (SCr) values. Incidence of AKI was assessed per Kidney Disease Improving Global Outcomes criteria. Descriptive statistical analysis and ordinal logistic regression analysis were performed to determine the incidence of AKI and variables associated with AKI. RESULTS A total of 868 patients met study criteria (male 55.8%, median age 0.66 years [IQR 0.19, 3.0 years]). Intravenous acetazolamide was administered at 5.1 ± 2.8 mg/kg/dose for a median of 4 doses (IQR 2, 6). Median baseline SCr was 0.28 mg/dL (IQR 0.22, 0.37), corresponding to a creatinine clearance of 115 ± 55 mL/min/1.73 m2. Acute kidney injury occurred in 26.8% (n = 233) of patients (stage I = 20.1%, stage II = 3.7%, stage III 3.1%), and no patients received renal replacement therapy. An ordinal logistic regression model identified an increased odds of AKI with cyclosporine, ethacrynic acid, and piperacillin-tazobactam administration. CONCLUSIONS Acute kidney injury occurs frequently in critically ill pediatric patients receiving intravenous acetazolamide. [ABSTRACT FROM AUTHOR]

OBJECTIVE Ceftriaxone and cefotaxime are appealing options for the treatment of neonatal infections. Guidelines recommend cefotaxime as the cephalosporin of choice in neonates because of ceftriaxone's potential to cause hyperbilirubinemia. Unfortunately, due to cefotaxime discontinuation, providers must choose between alternative antibiotics. Clinicians at our institution adopted a protocol allowing for the utilization of cefepime and ceftriaxone for the management of neonatal sepsis. The objective of this study was to compare the incidence of hyperbilirubinemia between ceftriaxone and cefotaxime in the treatment of neonatal infections beyond the first 14 days of life. METHODS This was a retrospective chart review of patients receiving ceftriaxone or cefotaxime for the treatment of neonatal infections. Patients were 15 to 30 days old at the time of antimicrobial administration and received at least 1 dose of ceftriaxone or cefotaxime during hospital admission. Patient characteristics and bilirubin levels were compared between ceftriaxone and cefotaxime. RESULTS The analysis included 88 patients. There was no statistically significant difference between groups in age, gestational age, weight, and baseline total calcium and bilirubin levels. Normal baseline bilirubin levels increased to an abnormal level after antibiotic administration in 2 patients in the cefotaxime group and 1 patient in the ceftriaxone group. The median number of doses of cefotaxime and ceftriaxone were 3 and 2, respectively. CONCLUSION Patients who received a short-term course of ceftriaxone did not have a higher likelihood of developing hyperbilirubinemia compared with those who received a short-term course of cefotaxime during their hospital stay. [ABSTRACT FROM AUTHOR]

Objective: The objective was to determine the incidence of leukocytosis associated with carbamazepine, lamotrigine, and phenobarbital. Data sources: A comprehensive literature review was conducted with the assistance of a medical reference librarian on PubMed, MEDLINE, Embase, and Google Scholar through June 2023 using the following search terminology: "leukocytosis/chemically induced"[MeSH Terms] AND ("Anticonvulsants"[MeSH Terms] OR ("Anticonvulsants"[Pharmacological Action] OR "Anticonvulsants"[MeSH Terms] OR "Anticonvulsants"[All Fields] OR "anticonvulsant"[All Fields] OR "anticonvulsion"[All Fields] OR "anticonvulsive"[All Fields] OR "anticonvulsives"[All Fields]) OR ("Anticonvulsants"[Pharmacological Action] OR "Anticonvulsants"[MeSH Terms] OR "Anticonvulsants"[All Fields] OR "antiepileptic"[All Fields] OR "antiepileptics"[All Fields])). Study selection and data extraction: Thirteen reports were included from 64 potential results of our literature review following the application of inclusion and exclusion criteria: 7 of the reports involved carbamazepine, 4 of the reports involved lamotrigine, and 2 of the reports involved phenobarbital. Data synthesis: Drug-induced leukocytosis is commonly a diagnosis of exclusion and is a phenomenon that has numerous ramifications to patients and clinicians at the bedside, including mandating a full infectious evaluation, the identification of confounding variables, and the eventual discontinuation of the offending agent. Despite several medications and medication classes possessing this adverse drug effect, an evaluation of the specific clinical presentation and management strategies for drug-induced leukocytosis associated with anticonvulsant medications has not been elucidated in the literature. Conclusions: Clinicians should be judicious when evaluating leukocytosis in patients on potentially precipitating medications, including carbamazepine, lamotrigine, and phenobarbital., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Oseltamivir is a neuraminidase inhibitor that is labeled for prophylaxis and treatment of influenza. We describe a previously healthy 4-month-old infant who tested positive for influenza A and was started on oseltamivir. One hour after receiving his first dose of oseltamivir, the infant had a diaphoretic episode and appeared grey and clammy. The infant was subsequently seen by the primary care physician and referred for admission to the hospital. Approximately 40 minutes after the second dose of oseltamivir in the hospital, the infant's heart rate rose to greater than 300 bpm. An electrocardiogram was suggestive of supraventricular tachycardia. At the time of the event, the infant received 2 doses of adenosine, and oseltamivir was discontinued prior to transfer to a tertiary facility for a higher level of care. [ABSTRACT FROM AUTHOR]

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We describe an 11-year-old female who presented with severe hypersomnolence after receiving 1 week of modest doses of clobazam (CLB). In reviewing the above case, we considered that the hypersomnolence could be related to a pharmacodynamic, pharmacokinetic, or pharmacogenomic issue associated with CLB or to a combination of these factors. Although serum concentrations of CLB and its active metabolite are sensitive to factors that affect cytochrome-dependent metabolism, drug-drug interactions were omitted as a cause of the hypersomnolence. Subsequent DNA analysis of the cytochrome P450 2C19 gene revealed the patient as *2/*2 genotype with poor metabolizer enzyme activity. Because genetic testing of all patients treated with CLB is currently not practical, CLB dose/concentration ratios and pharmacokinetic drug-drug interaction impact models may be indicated. Genetic testing should be considered when an adverse effect suggests the possibility of a polymorphism important to drug metabolism. [ABSTRACT FROM AUTHOR]

A 2-year-old Caucasian boy with tuberous sclerosis complex presented to the emergency department with lethargy and new onset myoclonias. Pancreatitis, thrombocytopenia, and coagulopathy associated to a decreased level of consciousness were diagnosed. Valproic acid had been initiated 13 months before and had been slowly increased to a dose of approximately 38 mg/kg/day. All the symptoms resolved after discontinuation of the medication. The clinical presentation of this child highlights that valproic acidrelated pancreatitis can present with decreased level of consciousness without associated gastrointestinal symptoms. Adverse drug reactions associated with valproic acid can lead to damage of multiple organs and may prove fatal if not promptly recognized and managed. ABBREVIATIONS ADR, adverse drug reaction; AED, antiepileptic drug; INR, international normalized ratio; VPA, valproic acid. [ABSTRACT FROM AUTHOR]

Background: Class 1C antiarrhythmic drugs (AADs) are effective first‐line agents for atrial fibrillation (AF) treatment. However, these agents commonly are avoided in patients with known coronary artery disease (CAD), due to known increased risk in the postmyocardial infarction population. Whether 1C AADs are safe in patients with CAD but without clinical ischemia or infarct is unknown. Reduced coronary flow capacity (CFC) on positron emission tomography (PET) reliably identifies myocardial regions supplied by vessels with CAD causing flow limitation. Objective: To assess whether treatment with 1C AADs increases mortality in patients without known CAD but with CFC indicating significantly reduced coronary blood flow. Methods: In this pilot study, we compared patients with AF and left ventricular ejection fraction ≥50% who were treated with 1C AADs to age‐matched AF patients without 1C AAD treatment. No patient had clinically evident CAD (ie, reversible perfusion defect, known ≥70% epicardial lesion, percutaneous coronary intervention, coronary artery bypass grafting, or myocardial infarction). All patients had PET‐based quantification of stress myocardial blood flow and CFC. Death was assessed by clinical follow‐up and social security death index search. Results: A total of 78 patients with 1C AAD exposure were matched to 78 controls. Over a mean follow‐up of 2.0 years, the groups had similar survival (P =.54). Among patients with CFC indicating the presence of occult CAD (ie, reduced CFC involving ≥50% of myocardium), 1C‐treated patients had survival similar to (P =.44) those not treated with 1C agents. Conclusions: In a limited population of AF patients with preserved left ventricle function and PET‐CFC indicating occult CAD, treatment with 1C AADs appears not to increase mortality. A larger study would be required to confidently assess the safety of these drugs in this context. [ABSTRACT FROM AUTHOR]

Hydroxyurea is a chemotherapeutic agent used for myeloproliferative disorders and sickle cell anemia that is well known to cause painful mucocutaneous ulcers, typically involving the legs or mouth. However, genital ulcerations due to hydroxyurea therapy are a rare, and likely underrecognized, adverse effect with only a few cases reported in the literature to date. Ulcers of the lower legs caused by hydroxyurea are associated with a diagnostic delay, and this is likely exacerbated in cases of genital ulceration due to a lack of awareness. Herein we present two cases of painful genital ulceration in patients on hydroxyurea therapy. In the first Case, an 87 year-old male with polycythemia vera developed an ulcer on the scrotum, which was assessed initially through virtual visits during the COVID-19 pandemic, and was refractory to topical and oral antibiotic treatments. The second case was a 79 year-old male with essential thrombocythemia and a history of persistent leg ulcers who developed erosions of the glans penis. Both patients experienced complete resolution within weeks of discontinuing hydroxyurea therapy. In conclusion, genital ulcers and erosions induced by hydroxyrea may be underrecognized in clinical practice, but if identified, withdrawal of hydroxyurea leads to quick resolution of these lesions and the associated pain. [ABSTRACT FROM AUTHOR]

Background: The integration of medical and dental records is gaining significance over the past 2 decades. However, few studies have evaluated the opinions of practicing dentists on patient medical histories. Questions remain on dentists' information needs; their perception of the reliability of patient-reported medical history; satisfaction with the available information and the methods to gather this information; and their attitudes to other options, such as a health information exchange (HIE) network, to collect patient medical history., Objective: This study aims to determine Indiana dentists' information needs regarding patients' medical information and their opinions about accessing it via an HIE., Methods: We administered a web-based survey to Indiana Dental Association members to assess their current medical information-retrieval approaches, the information critical for dental care, and their willingness to access or share information via an HIE. We used descriptive statistics to summarize survey results and multivariable regression to examine the associations between survey respondents' characteristics and responses., Results: Of the 161 respondents (161/2148, 7.5% response rate), 99.5% (n=160) respondents considered patients' medical histories essential to confirm no contraindications, including allergies or the need for antibiotic prophylaxis during dental care and other adverse drug events. The critical information required were medical conditions or diagnosis, current medications, and allergies, which were gathered from patient reports. Furthermore, 88.2% (n=142) of respondents considered patient-reported histories reliable; however, they experienced challenges obtaining information from patients and physicians. Additionally, 70.2% (n=113) of respondents, especially those who currently access an HIE or electronic health record, were willing to use an HIE to access or share their patient's information, and 91.3% (n=147) shared varying interests in such a service. However, usability, data accuracy, data safety, and cost are the driving factors in adopting an HIE., Conclusions: Patients' medical histories are essential for dentists to optimize dental care, especially for those with chronic conditions. In addition, most dentists are interested in using an HIE to access patient medical histories. The findings from this study can provide an alternative option for improving communications between dental and medical professionals and help the health information technology system or tool developers identify critical requirements for more user-friendly designs., (©Shuning Li, Grace Gomez Felix Gomez, Huiping Xu, Anushri Singh Rajapuri, Brian E Dixon, Thankam Thyvalikakath. Originally published in JMIR Formative Research (https://formative.jmir.org), 11.01.2024.)

Misoprostol is widely used for the medical management of incomplete abortion. Few serious adverse events have been reported, so it is considered a safe drug. We present a case of a 40-year-old woman in which misoprostol preceded coronary artery spasm. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether use of contemporary protease inhibitors pose a similar risk of chronic kidney disease (CKD) as use of older protease inhibitors.Methods: Participants in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study were followed up until the earliest occurrence of CKD, the last visit plus 6 months, or 1 February 2016. Adjusted Poisson regression was used to assess associations between CKD and the use of ritonavir-boosted atazanavir (ATV/r) or ritonavir-boosted darunavir (DRV/r).Results: The incidence of CKD (10.0/1000 person-years of follow-up; 95% confidence interval, 9.5-10.4/1000 person-years of follow-up) increased gradually with increasing exposure to ATV/r, but the relation was less clear for DRV/r. After adjustment, only exposure to ATV/r (adjusted incidence rate ratio, 1.4; 95% confidence interval, 1.2-1.6), but not exposure to DRV/r (1.0; .8-1.3), remained significantly associated with CKD.Conclusion: While DRV/r use was not significantly associated with CKD an increasing incidence with longer ATV/r use was confirmed. [ABSTRACT FROM AUTHOR]

OBJECTIVE The objective of this survey was to assess the current use of continuous infusion propofol in PICUs across the United States and Canada. METHODS A list of institutions with PICU beds/units was identified through the residency directories available on the American Society of Health-Systems Pharmacists (ASHP) and Canadian Society of Hospital Pharmacists (CHSP) Web sites. A REDCap questionnaire was sent to each identified institution's program director via email. An initial reminder email was sent out 2 weeks later and a second reminder email was sent 4 weeks after the initial request. The survey was closed at 6 weeks. RESULTS A total of 514 emails were sent to residency program directors, and 50 pharmacists responded to the survey. Of the pharmacists that did respond, 27 (54%) reported using propofol while 23 (46%) did not. Of those that did not, 43.5% reported the FDA boxed warning as the primary reason. Thirty-seven percent of respondents using propofol felt comfortable using a maximum infusion rate of 200 mcg/kg/min. Twentynine percent, 25%, and 33% of those who responded as using propofol felt comfortable using this agent for a maximum duration of 24, 48, and 72 hours, respectively. The majority of respondents using propofol did not have a case of propofol-related infusion syndrome. CONCLUSIONS Despite the FDA warning, propofol is used as a continuous infusion (with variable limitations) by a majority of pharmacists in North America. Self-reported incidence of propofol-related infusion syndrome (PRIS) remains low. [ABSTRACT FROM AUTHOR]

• We design a weighted online recurrent extreme learning machine based method to identify ADE mentions from biomedical texts. • We propose a character-level embedding with a modified OR-ELM to capture morphological features. • We evaluate the impact of five well-known segments to encode multi-word mentions. • The proposed method outperforms the state-of-the-art ones on the ADE corpus. Automatic extraction of adverse drug effect (ADE) mentions from biomedical texts is a challenging research problem that has attracted significant attention from the pharmacovigilance and biomedical text mining communities. Indeed, deep learning based methods have recently been employed to solve this issue with great success. However, they fail to effectively identify the boundary of mentions. In this paper, we propose a weighted online recurrent extreme learning machine (WOR-ELM) based method to overcome this drawback. The proposed method for ADE mentions extraction from biomedical texts is divided into two stages: span detection and ADE mentions classification. At the first stage, we identify the boundary of the mentions irrespective of their types with a WOR-ELM in a given sentence. At the second stage, another WOR-ELM is used to classify the identified mentions to the appropriate type. Both stages use the concatenation of character-level and word-level embeddings as features. The character-level embedding is obtained using a modified online recurrent extreme learning machine, whereas the word-level embedding is obtained from a pre-trained model. Several experiments were carried out on a well-known ADE corpus to evaluate the effectiveness and demonstrate the usefulness of the proposed method. The obtained results show that our method achieves an F-score of 87.5%, which outperforms the current state-of-the-art methods. Our research results indicate that the proposed method for adverse drug effect mentions extraction from text can significantly improve performance over existing methods. Our experiments show the effectiveness of incorporating word-level and character level embeddings as features for WOR-ELM. They also illustrate the benefits of using IOU segment to represent ADE mentions. [ABSTRACT FROM AUTHOR]