Front Pharmacol. 2021 Aug 18;12:648805. doi: 10.3389/fphar.2021.648805. eCollection 2021.

ABSTRACT

A major challenge in drug development is safety and toxicity concerns due to drug side effects. One such side effect, drug-induced liver injury (DILI), is considered a primary factor in regulatory clearance. The Critical Assessment of Massive Data Analysis (CAMDA) 2020 CMap Drug Safety Challenge goal was to develop prediction models based on gene perturbation of six preselected cell-lines (CMap L1000), extended structural information (MOLD2), toxicity data (TOX21), and FDA reporting of adverse events (FAERS). Four types of DILI classes were targeted, including two clinically relevant scores and two control classifications, designed by the CAMDA organizers. The L1000 gene expression data had variable drug coverage across cell lines with only 247 out of 617 drugs in the study measured in all six cell types. We addressed this coverage issue by using Kru-Bor ranked merging to generate a singular drug expression signature across all six cell lines. These merged signatures were then narrowed down to the top and bottom 100, 250, 500, or 1,000 genes most perturbed by drug treatment. These signatures were subject to feature selection using Fisher's exact test to identify genes predictive of DILI status. Models based solely on expression signatures had varying results for clinical DILI subtypes with an accuracy ranging from 0.49 to 0.67 and Matthews Correlation Coefficient (MCC) values ranging from -0.03 to 0.1. Models built using FAERS, MOLD2, and TOX21 also had similar results in predicting clinical DILI scores with accuracy ranging from 0.56 to 0.67 with MCC scores ranging from 0.12 to 0.36. To incorporate these various data types with expression-based models, we utilized soft, hard, and weighted ensemble voting methods using the top three performing models for each DILI classification. These voting models achieved a balanced accuracy up to 0.54 and 0.60 for the clinically relevant DILI subtypes. Overall, from our experiment, traditional machine learning approaches may not be optimal as a classification method for the current data.

PMID:34483896 | PMC:PMC8416433 | DOI:10.3389/fphar.2021.648805

Ind Psychiatry J. 2021 Jan-Jun;30(1):113-117. doi: 10.4103/ipj.ipj_146_20. Epub 2021 Jun 17.

ABSTRACT

INTRODUCTION: Hyponatremia can be a common but often overlooked side effects of psychotropics drugs. Most patients with drug-induced hyponatremia are asymptomatic and diagnosis is made incidentally following routine blood tests.

OBJECTIVES: The aim of the study was to understand the pattern of hyponatremia in patients using selective serotonin reuptake inhibitors (SSRI) and serotonin dopamine antagonists (SDA).

MATERIALS AND METHODS: All inpatients and outpatients who were diagnosed with International Classification of Diseases-10 psychiatric disorders and undergoing treatment with SSRI, SDA, or combination of both for the same, were included in the study after simple random sampling, subject to inclusion and exclusion criteria.

STATISTICAL ANALYSIS USED: Categorical variables were observed as numbers and percentages. Continuous variables were evaluated as mean ± standard deviation. A Chi-square test was done to find the association between categorical variables. SPSS (IBM) version 21 was used for data analysis.

RESULTS: In 150 patients, we found hyponatremia in 17 patients (11.33%). About 66-75 age group patients had maximum found cases of hyponatremia (66.66%). About 20.31% of females found hyponatremia. Among SSRIs, 16% of individuals had hyponatremia whereas among SDA it was 6%. Patients who were taking both SSRIs and SDA total prevalence of hyponatremia was 12%.

CONCLUSIONS: Older age groups and females had higher chances of hyponatremia while taking SSRIs and SDAs. Among SSRIs, escitalopram had maximum percentage of hyponatremia, whereas fluvoxamine had minimum. Among SDAs, risperidone had maximum percentage, whereas quetiapine had minimum percentage of hyponatremia. Patients who were taking both fluoxetine + olanzapine or fluoxetine + risperidone had higher percentage of hyponatremia.

PMID:34483534 | PMC:PMC8395548 | DOI:10.4103/ipj.ipj_146_20

BMJ Open. 2021 Sep 3;11(9):e048000. doi: 10.1136/bmjopen-2020-048000.

ABSTRACT

OBJECTIVE: To examine sex differences in age-standardised rates (ASR) of overall and drug-specific drug poisoning deaths in Ireland between 2004 and 2017.

DESIGN: Repeated cross-sectional study.

SETTING: Drug poisoning deaths in Ireland.

PARTICIPANTS: National Drug-Related Deaths Index and pharmacy claims database (Primary Care Reimbursement Service-General Medical Services) data from 2004 to 2017.

OUTCOME MEASURES: The primary outcome was trends in drug poisoning death rates by sex. The secondary outcomes were trends in drug poisoning death rates involving (1) any CNS (Central Nervous System) depressants, (2) ≥2 CNS depressants and (3) specific drugs/drug classes (eg, prescription opioids, benzodiazepines, antidepressants, alcohol, cocaine and heroin) by sex. Joinpoint regression was used to examine trends, stratified by sex, in the ASR of drug poisoning deaths (2004-2017), change points over time and average annual percentage changes (AAPCs) with 95% CI.

RESULTS: Increased ASR for all drug poisoning deaths from 6.86 (95% CI 6.01 to 7.72) per 100 000 in 2004 to 8.08 (95% CI 7.25 to 8.91) per 100 000 in 2017 was mainly driven by increasing deaths among men (AAPC 2.6%, 95% CI 0.2 to 5.1), with no significant change observed among women. Deaths involving ≥2 CNS depressants increased for both men (AAPC 5.6%, 95% CI 2.4 to 8.8) and women (AAPC 4.0%, 95% CI 1.1 to 6.9). Drugs with the highest significant AAPC increases for men were cocaine (7.7%, 95% CI 2.2 to 13.6), benzodiazepines (7.2%, 95% CI 2.9 to 11.6), antidepressants (6.1%, 95% CI 2.4 to 10.0) and prescription opioids (3.5%, 95% CI 1.6 to 5.5). For women, the highest AAPC was for antidepressants (4.2%, 95% CI 0.2 to 8.3), benzodiazepines (3.3%, 95% CI 0.1 to 6.5) and prescription opioids (3.0%, 95% CI 0.7 to 5.3).

CONCLUSION: Drugs implicated in drug poisoning deaths vary by sex. Policy response should include prescription monitoring programmes and practical harm reduction information on polydrug use, especially CNS depressant drugs.

PMID:34479934 | DOI:10.1136/bmjopen-2020-048000

Paediatr Anaesth. 2021 Sep 3. doi: 10.1111/pan.14290. Online ahead of print.

ABSTRACT

BACKGROUND: Dexmedetomidine is utilized as a sedative agent for drug induced sleep cine magnetic resonance imaging studies due to its ability to mimic natural sleep and lack of respiratory depressant effects. The outcomes of dexmedetomidine sedation such as respiratory complications and unplanned admissions in obstructive sleep apnea patients undergoing these studies are currently unknown.

AIM: To describe the outcomes of dexmedetomidine sedation for outpatient drug induced sleep magnetic resonance imaging in pediatric patients with obstructive sleep apnea.

METHODS: This is a retrospective chart review conducted in pediatric patients with obstructive sleep apnea undergoing outpatient drug induced sleep ciné magnetic resonance imaging studies with dexmedetomidine sedation. Demographics, co-morbidities, polysomnography study results, vital signs, respiratory complications, airway interventions, successful completion of the scan and unplanned hospital admissions were measured.

MAIN RESULTS: We analyzed 337 patients aged 2 - 18 years (median age of 11 years). The imaging was completed with dexmedetomidine as the sole sedative agent in 61% (N=207) patients. Ketamine was administered as additional sedative agent in 36% (N=122) of the patients. There was no difference in sedation related adverse events and respiratory complications with regards to the severity of sleep apnea with the exception of mild desaturation episodes (SpO2 85-90%). Patients who received additional sedative agents had significantly longer recovery room stay [71.5 (44) vs 55 (39) minutes; 95% CI of difference (9-23 min), p < 0.001] and total periprocedural stay [164.5 (52) vs 138 (64) minutes; 95% CI of difference (17-35 min), p < 0.001].

CONCLUSIONS: Dexmedetomidine alone or along with ketamine provided acceptable sedation in majority of the patients with obstructive sleep apnea undergoing outpatient diagnostic sleep magnetic resonance imaging studies without significant respiratory adverse events regardless of the severity of sleep apnea. Sedation failure and unplanned admissions are rare and routine planned admission may not be required for this patient population.

PMID:34478206 | DOI:10.1111/pan.14290

Clin Cosmet Investig Dermatol. 2021 Aug 27;14:1125-1129. doi: 10.2147/CCID.S330354. eCollection 2021.

ABSTRACT

Reports of immune-related adverse events caused by programmed cell death protein-1 inhibitor are becoming increasingly frequent. Herein, we report the first case of pemphigus herpetiformis-type drug reaction presented after the treatment of tislelizumab (6 cycles) in a primary non-small cell lung carcinoma patient. A 56-year-old Chinese man was referred to our department for pruritic annulare erythema and blister for two weeks. Histological finding revealed blister formation in the epidermis and eosinophilic infiltration in the blister fluid. Direct immunofluorescence showed intercellular deposition of IgG and C3 within the lower part of epidermis. Serum anti-intercellular antibodies were positive at 1:100 dilution. Based on history and clinicopathological correlation, herpetiformis-type drug-induced pemphigus was diagnosed, which was possibly be induced by tislelizumab. To the best to our knowledge, there is no report of pemphigus herpetiformis-type drug-induced reaction associated with programmed cell death protein-1 inhibitor treatment.

PMID:34475771 | PMC:PMC8407525 | DOI:10.2147/CCID.S330354

Clin Pharmacol Ther. 2021 Sep 2. doi: 10.1002/cpt.2411. Online ahead of print.

ABSTRACT

The relevance of biological therapies for an increasing number of conditions is on the rise. Following the expiry of the initial period of market exclusivity, many of these successful therapies have seen the arrival of biosimilars on the market. The clear identification of the precise medicine responsible for an adverse drug reaction (ADR) report is an important element for pharmacovigilance, allowing timely detection of potential product-specific safety signals. We looked at the identifiability of biologicals up to the level of commercial product name in ADR reports received from European clinical practice between 2011 and December 2019. A good level of identification (91.5%) was observed overall, but at the same time a downward trend was observed in the last 5 years. This reduction in the level of identifiability of biological products (originators and biosimilars) at the commercial name level in general was driven by 5 widely used substances, while the identification of all other biologics stayed consistent over time (at over 90%). We observed that those 5 substances were used mostly within oncology. The introduction of the first biosimilar in the market did not appear to affect their identifiability. These results show that although the general level of identification at the commercial product name level in ADRs in Europe is robust and generally stable over time, decreasing trends can be down to a few commonly used substances which need to be monitored to reverse the trend.

PMID:34472087 | DOI:10.1002/cpt.2411

Indian Pediatr. 2021 Aug 15;58(8):753-755.

ABSTRACT

OBJECTIVES: To assess the adverse effects of propranolol therapy in infantile hemangioma.

METHODS: An ambispective study was conducted from August 2011 to December 2019. In retrospective arm all children managed for infantile hemangioma with propranolol were included and case records were assessed for adverse reactions. In prospective arm the adverse reactions were identified on the basis of predefined criteria.

RESULTS: A total of 514 patients (358 retrospective records) were included. A majority, 378 (73.5%) patients had an excellent response, 75 (14.5%) had partial response and 61 (11.8 %) had no response. A total of 82 (15.9%) patients experienced at least one adverse effect. Diarrhea with weight loss (27, 32.9%) and irritability with decreased sleep (21, 25.6%) were the most common adverse effects. The adverse effects in 22 (4.2%) cases lead to the discontinuation of propranolol. Younger age, low body weight and early onset were risk factors for development of severe adverse reactions.

CONCLUSIONS: Young children with low body weight were at higher risk for adverse effects of propranolol.

PMID:34465658

J Patient Saf. 2021 Aug 30. doi: 10.1097/PTS.0000000000000889. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to estimate the frequency of hospital adverse events (AEs) and explore the rate of AEs over time, and across and within hospital populations.

METHODS: Validated search terms were run in MEDLINE and EMBASE; gray literature and references of included studies were also searched. Studies of any design or language providing an estimate of AEs within the hospital were eligible. Studies were excluded if they only provided an estimate for a specific AE, a subgroup of hospital patients or children. Data were abstracted in duplicate using a standardized data abstraction form. Study quality was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis estimated the occurrence of hospital AEs, and meta-regression explored the association between hospital AEs, and patient and hospital characteristics.

RESULTS: A total of 45,426 unique references were identified; 1,265 full-texts were reviewed and 94 studies representing 590 million admissions from 25 countries from 1961 to 2014 were included. The incidence of hospital AEs was 8.6 per 100 patient admissions (95% confidence interval [CI], 8.3 to 8.9; I2 = 100%, P < 0.001). Half of the AEs were preventable (52.6%), and a third resulted in moderate/significant harm (39.7%). The most evaluated AEs were surgical AEs, drug-related AEs, and nosocomial infections. The occurrence of AEs increased by year (95% CI, -0.05 to -0.04; P < 0.001) and patient age (95% CI = -0.15 to -0.14; P < 0.001), and varied by country income level and study characteristics. Patient sex, hospital type, hospital service, and geographical location were not associated with AEs.

CONCLUSIONS: Hospital AEs are common, and reported rates are increasing in the literature. Given the increase in AEs over time, hospitals should reinvest in improving hospital safety with a focus on interventions targeted toward the more than half of AEs that are preventable.

PMID:34469915 | DOI:10.1097/PTS.0000000000000889

AMIA Annu Symp Proc. 2021 May 17;2021:420-429. eCollection 2021.

ABSTRACT

Adverse drug events (ADEs) are unexpected incidents caused by the administration of a drug or medication. To identify and extract these events, we require information about not just the drug itself but attributes describing the drug (e.g., strength, dosage), the reason why the drug was initially prescribed, and any adverse reaction to the drug. This paper explores the relationship between a drug and its associated attributes using relation extraction techniques. We explore three approaches: a rule-based approach, a deep learning-based approach, and a contextualized language model-based approach. We evaluate our system on the n2c2-2018 ADE extraction dataset. Our experimental results demonstrate that the contextualized language model-based approach outperformed other models overall and obtain the state-of-the-art performance in ADE extraction with a Precision of 0.93, Recall of 0.96, and an F1 score of 0.94; however, for certain relation types, the rule-based approach obtained a higher Precision and Recall than either learning approach.

PMID:34457157 | PMC:PMC8378605

AMIA Annu Symp Proc. 2021 May 17;2021:180-189. eCollection 2021.

ABSTRACT

We assessed the scalability of pharmacological signal detection use case from a single-site CDW to a large aggregated clinical data warehouse (single-site database with 754,214 distinct patient IDs vs. multisite database with 49.8M). We aimed to explore whether a larger clinical dataset would provide clearer signals for secondary analyses such as detecting the known relationship between prednisone and weight. We found significant weight gain rate using the single-site data but not from using aggregated data (0.0104 kg/day, p<0.0001 vs. -0.050 kg/day, p<.0001). This rate was also found more consistently across 30 age and gender subgroups using the single-site data than in the aggregated data (26 vs. 18 significant weight gain findings). Contrary to our expectations, analyses of much larger aggregated clinical datasets did not yield stronger signals. Researchers must check the underlying model assumptions and account for greater heterogeneity when analyzing aggregated multisite data to ensure reliable findings.

PMID:34457132 | PMC:PMC8378643

Malawi Med J. 2020 Dec;32(4):229-231. doi: 10.4314/mmj.v32i4.9.

ABSTRACT

Acute ataxia in children is a rare clinical syndrome usually caused by an infectious, post-infectious, or toxin-related aetiology. Although infrequent, acute ataxia can be related to more common diseases and treatments in Southern African countries including side effects of efavirenz-based anti-retroviral therapy (ART) for HIV or the post-malaria neurologic syndrome (PMNS) after infection with falciparum malaria. We describe a case from Lilongwe, Malawi of a 16-year-old HIV-positive patient with viral load suppression who presented with acute ataxia, confusion, and diplopia. Although he was on efavirenz-based ART for many years, his dose was increased 6 weeks prior, and he was treated for uncomplicated falciparum malaria 5 weeks prior with resolution of symptoms. Studies including cerebrospinal fluid analyses were normal, and he had rapid improvement of symptoms following discontinuation of efavirenz-based ART. Several case series have described supratherapeutic levels of efavirenz leading to acute ataxia as well as the self-limiting PMNS after non-complicated falciparum malaria. Though rare, recognition of efavirenz and PMNS as causes of ataxia is important to inform prompt treatment for HIV patients with acute ataxia in Malawi and other similar settings.

PMID:34457209 | PMC:PMC8364792 | DOI:10.4314/mmj.v32i4.9

Optom Vis Sci. 2021 Aug 1;98(8):881-885. doi: 10.1097/OPX.0000000000001749.

ABSTRACT

SIGNIFICANCE: In this report, the authors present a case of a 63-year-old man with recurrent pseudophakic cystoid macular edema. Macular edema was refractory to the treatments with periocular corticosteroid injection and topical anti-inflammatory medications. It was treated with subconjunctival bevacizumab (2.5 mg) injections.

PURPOSE: The purpose of this report was to demonstrate the efficacy and safety of repeated injections of subconjunctival bevacizumab in pseudophakic cystoid macular edema.

CASE REPORT: A 63-year-old White man presented with ongoing blurred vision in his left eye 4 months after a complicated cataract surgery. Despite the administration of sub-Tenon triamcinolone in the first-month visit because of cystoid macular edema and the use of topical steroid and nonsteroidal anti-inflammatory medications during the 4 months, there was no change in his vision. The first subconjunctival bevacizumab injection was performed 16 weeks after cataract surgery. The best-corrected visual acuity was significantly improved, and central retinal thickness dramatically decreased after the first injection. Macular edema reoccurred 26 and 46 weeks after cataract surgery. At these relapses, repeated subconjunctival injections of bevacizumab were influential in resolving macular edema and restoration of vision, even in the chronic phase. After 6 months, visual acuity (20/20) and central retinal thickness (274 μm) were stable after four total injections. No drug-related adverse events were observed during the follow-up period.

CONCLUSIONS: The repeated subconjunctival injections of bevacizumab were effective and well tolerated in pseudophakic cystoid macular edema. Subconjunctival bevacizumab may be a safe alternative to intravitreal applications in patients with pseudophakic cystoid macular edema.

PMID:34460450 | DOI:10.1097/OPX.0000000000001749

Trials. 2021 Aug 28;22(1):570. doi: 10.1186/s13063-021-05478-0.

ABSTRACT

BACKGROUND AND AIM: Globally, the ongoing pursuit in exploring an effective drug to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has not met with significant success to date. Indian traditional medicines, especially polyherbal formulations like Nilavembu Kudineer (NVK) and Kaba Sura Kudineer (KSK) of the Siddha system of medicine, have been used as public health interventions for controlling viral epidemics like dengue and Chikungunya. These traditional therapies have been found safe, effective, and widely accepted. The current study evaluates the comparative efficacy of NVK and KSK as opposed to the placebo, in the management of mild to moderate COVID-19 disease.

METHODS: The study was a double-blind, placebo-controlled comparative clinical trial, with the primary objective of determining the efficacy of KSK and NVK. Patients (n=125) diagnosed with mild to moderate COVID-19 symptoms were enrolled in the study over a period of 4 months (Aug 2020-Dec 2020). Participants were randomized into 3 arms; placebo-decaffeinated tea in Arm I, NVK in Arm II, and KSK in Arm III. Each arm received 60 ml of the respective treatment twice a day, post morning and evening meals, along with standard allopathy treatment for a maximum of 10 days. The main outcome measures of the study were the reduction in SARS-CoV-2 viral load, hospital stay, and time taken by the patients to become asymptomatic from symptomatic. Efficacy assessments included clinical symptoms (fever, cough, and breathlessness) each day and real-time reverse transcription-polymerase chain reaction (RT-PCR), liver function test (LFT), renal function test (RFT), and electrolytes and electrocardiogram (ECG) at baseline (day 0) and days 3, 6, and 10. Post-treatment, participants were followed up for 30 days via phone for adverse effects if any. Effects of drugs on inflammatory markers (IL6) at the end of treatment were also recorded. Adverse events (AE) were monitored throughout the study.

RESULTS: The results revealed that when compared to patients in the placebo arm, those in NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and the time taken to become symptomatic from asymptomatic. Out of 125 COVID-19 patients recruited, 120 completed the study; two from the placebo group developed severe symptoms and were shifted to the intensive care unit (ICU) and three patients from Arms II and III withdrew from the study. The mean age of females (n=60) and males (n=60) enrolled was between 40.2 and 44.3 years, respectively. Results were more promising for all the patients in NVK and KSK arms as all enrolled participants (100%) under this group got discharged by day 6 as compared to only 42.5% (n=17) from the placebo group on that day. The hospital stay time for patients in Arm I was significantly longer (mean [SD]=8.4 [2.0] days) as compared to the Arms II and III (mean [SD]=4.7 [1.5] and 4.2 [1.5] days, respectively (Kruskal-Wallis test, P=0.0001). Patients in the three groups took a significantly different number of days to become asymptomatic. While Arm II and III patients took mean of 2.5 and 1.7 days, respectively, Arm I, patients took a mean of 4.2 days (Kruskal-Wallis test, P=0.0001). In all, two adverse events were recorded, one for vomiting and one for diarrhea lasting a day in Arm I and Arm II, respectively. The mean value of interleukin-6 (IL6) was significantly different in comparison to the placebo-decaffeinated tea arm (NVK=2.6 and KSK=2.2, placebo=4.0, P=0.02). The other blood biochemical parameters like C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and D-dimer that were analyzed at the baseline and at the time of discharge from the hospital, were not significantly different in the three arms.

CONCLUSION: NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and time taken for patients to become asymptomatic from symptomatic, when compared to the placebo (decaffeinated tea). The primary outcome measures of the KSK arm were significantly better than those in the NVK arm.

PMID:34454572 | DOI:10.1186/s13063-021-05478-0

Res Social Adm Pharm. 2021 Aug 25:S1551-7411(21)00315-6. doi: 10.1016/j.sapharm.2021.08.011. Online ahead of print.

ABSTRACT

BACKGROUND: Patients are often exposed to contradictory information about pharmaceutical products from various types of advertising. For example, direct-to-consumer advertising (DTCA) tend to emphasize a drug's benefits, while drug injury advertising emphasizes the worst side effects. Regarding DTCA as a drug information source, many researchers in pharmacy field focus on investigating the misinformation in DTCA and corrective advertising. However, no prior research has examined the effects of such contradictory advertising messages on patients' prescription medicine-related beliefs and medication adherence. This is a significant gap in the research literature on pharmaceutical advertising effects and medication adherence.

OBJECTIVE: This is aimed to examine how exposure to DTCA and drug injury advertising would influence patients' chronic accessibility of drug-related beliefs and their medication adherence behavior.

METHODS: An online survey was conducted with a sample of 213 patients taking prescription blood thinners.

RESULTS: The findings from this study did not support the predicted relationship between exposure to DTCA and consumers' drug-related belief accessibility or their medication adherence. However, this study found a significant interaction effect of exposure to DTCA and exposure to drug injury ads on patients' medication adherence. The analysis results demonstrate that, for those who were exposed to drug injury ads, a significant negative relationship emerged between DTCA exposure and medication adherence.

CONCLUSION: This study provides important empirical evidence of a negative interaction effect of exposure to DTCA and drug injury ads on patients' medication adherence, which demonstrates that the influence of DTCA and drug injury ad exposures on patients' medication adherence is not independent, separate process but an interactive process. A communication campaign with corrective advertising could alleviate the negative interaction effect of exposure to contradictory information from different types of pharmaceutical ads on patients' medication adherence.

PMID:34454872 | DOI:10.1016/j.sapharm.2021.08.011

Brief Bioinform. 2021 Aug 27:bbab347. doi: 10.1093/bib/bbab347. Online ahead of print.

ABSTRACT

Continuous evaluation of drug safety is needed following approval to determine adverse events (AEs) in patient populations with diverse backgrounds. Spontaneous reporting systems are an important source of information for the detection of AEs not identified in clinical trials and for safety assessments that reflect the real-world use of drugs in specific populations and clinical settings. The use of spontaneous reporting systems is expected to detect drug-related AEs early after the launch of a new drug. Spontaneous reporting systems do not contain data on the total number of patients that use a drug; therefore, signal detection by disproportionality analysis, focusing on differences in the ratio of AE reports, is frequently used. In recent years, new analyses have been devised, including signal detection methods focused on the difference in the time to onset of an AE, methods that consider the patient background and those that identify drug-drug interactions. However, unlike commonly used statistics, the results of these analyses are open to misinterpretation if the method and the characteristics of the spontaneous reporting system cannot be evaluated properly. Therefore, this review describes signal detection using data mining, considering traditional methods and the latest knowledge, and their limitations.

PMID:34453158 | DOI:10.1093/bib/bbab347

Reg Anesth Pain Med. 2021 Aug 27:rapm-2021-103095. doi: 10.1136/rapm-2021-103095. Online ahead of print.

NO ABSTRACT

PMID:34452982 | DOI:10.1136/rapm-2021-103095

Int J Environ Res Public Health. 2021 Aug 13;18(16):8572. doi: 10.3390/ijerph18168572.

ABSTRACT

There are various trigger tools for detecting adverse drug events (ADEs), however, a drug-related emergency department (ED) visit trigger tool (DrEDTT) has not yet been developed. We aimed to develop and validate a DrEDTT with a multi-center cohort. In this cross-sectional study, we developed the DrEDTT consisting of 28 triggers through a comprehensive literature review and three phase expert group discussion. Next, we evaluated the performance of the DrEDTT by applying it to relevant medical records retrieved from four hospitals from January 2016 to June 2016. Two experts performed an in-depth chart review of a 25% of random sample of trigger flagged and unflagged ED visits and a true ADE was determined through causality assessment. Among 66,564 patients who visited the ED for reasons other than traffic accident and trauma during the study period, at least one trigger was found in 21,268 (32.0%) patients. A total of 959 true ADE cases (5.8%) were identified from a randomly selected 25% of ED visit cases. The overall positive predictive value was 14.0% (range: 8.3-66.7%). Sensitivity and specificity of DrEDTT were 77.7% and 70.4%, respectively. In conclusion, this newly developed trigger tool might be helpful to detect ADE-related ED visits.

PMID:34444320 | PMC:PMC8391800 | DOI:10.3390/ijerph18168572

Medicina (Kaunas). 2021 Jul 30;57(8):782. doi: 10.3390/medicina57080782.

ABSTRACT

The most widely used medications in dentistry are local anesthetics (LA), especially lidocaine, and the number of recorded adverse allergic responses, particularly of hazardous responses, is quite low. However, allergic reactions can range from moderate to life-threatening, requiring rapid diagnosis and treatment. This article serves as a review to provide information on LA, their adverse reactions, causes, and management.

PMID:34440986 | PMC:PMC8399637 | DOI:10.3390/medicina57080782

Acad Emerg Med. 2021 Aug 27. doi: 10.1111/acem.14382. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of single-dose ketamine infusion in adults with sickle cell disease who presented with acute sickle vaso-occlusive crisis.

DESIGN: Parallel-group, prospective, randomized, double-blinded, pragmatic trial MAIN OUTCOME MEASURE: Participants were randomized to receive either a single dose of ketamine or morphine, infused over 30 min. Primary outcome was mean difference in the numerical pain rating score (NPRS) over two hours. NPRS was recorded every 30 min for a maximum of 180 min and secondary outcomes were cumulative dose of opioids, ED length of stay, hospital admission, change in vital signs, and drug-related side effects. Authors performed the analysis using intention-to-treat principle.

RESULT: 278 adults with sickle cell disease and presented with acute sickle vaso-occlusive crisis participated in this trial. 138 were allocated to the ketamine group. Mean numerical pain rating score over 2 h was 5•7 (2•13 SD) and 5•6 (1•90 SD) in the ketamine and morphine groups. Ketamine group received significantly lower cumulative doses of morphine during ED stay (mean 4•5 mg; 4•6 SD) than of the morphine group (mean 8•5 mg; 7•55 SD). Both groups had similar rates of hospital admission. 6•3% in Ketamine group has drug-related side effects, compared to 2•2% in the morphine group.

CONCLUSION: Early use of ketamine in adults with VOC resulted in a meaningful reduction in pain scores over a 2-h period and reduced the cumulative morphine dose in the ED with no significant drug-related side effects in the ketamine treated group.

PMID:34449939 | DOI:10.1111/acem.14382

Reg Anesth Pain Med. 2021 Aug 26:rapm-2021-103092. doi: 10.1136/rapm-2021-103092. Online ahead of print.

NO ABSTRACT

PMID:34446543 | DOI:10.1136/rapm-2021-103092