Lakartidningen. 2023 May 8;120:22152.

ABSTRACT

Reporting of suspected adverse drug reactions (ADRs), from healthcare professionals and from consumers, contributes to early detection of new safety risks with medicines. The reporting of adverse reactions has been working well during the pandemic but indicates at the same time a significant under-reporting (hidden statistics). The propensity to report clearly increases with enhanced communication. Consumer reports are an important complement to reports from health care professionals and contribute to valuable insights both within regulatory follow-up and research. Reporting of suspected ADRs is an important source that needs to be supplemented with other data sources for causality analysis. For reporting of suspected adverse reactions to continue to be a valuable tool in the search for new signals, we need to develop sustainable reporting systems and communication channels that meet our various needs in close cooperation between authorities and other actors.

PMID:37157880

Transpl Infect Dis. 2023 May 9:e14068. doi: 10.1111/tid.14068. Online ahead of print.

ABSTRACT

BACKGROUND: Left ventricular assist devices (LVAD) are a common strategy for management of end-stage heart failure. LVADs carry a risk of infection of the implanted device components, and skin flora are commonly implicated. Long-term antibiotics may be needed for management of deep device infection or recurrent superficial infections. In appropriately selected patients, dalbavancin can be a feasible option given its extended dosing interval.

METHODS: This is a retrospective, single-center review of patients presenting with an LVAD infection between January 2011 and November 2022, where management included the use of dalbavancin. Data regarding LVAD placement, details of index infection, dalbavancin use and outcomes was obtained from chart review, and documented in a RedCap database.

RESULTS: The mean time from LVAD placement to index infection was 131.6 weeks (standard deviation 87.2 weeks). The most common targeted organism was Corynebacterium striatum in six of 10 patients. Index infection presented as deep driveline infection in four patients and recurrent superficial driveline infection in three patients. Five patients had a concurrent bloodstream infection. Dalbavancin was discontinued in two patients due to breakthrough infection, with one patient requiring surgical intervention. No drug-related adverse events were noted.

CONCLUSION: Dalbavancin is an attractive option in the management of long-term LVAD infection in patients for whom alternative oral or parenteral antibiotics are not a feasible option. Additional studies are needed to determine the optimal dosing of dalbavancin in this setting, and to study adverse events and long-term outcomes of dalbavancin.

PMID:37159539 | DOI:10.1111/tid.14068

JAMA Netw Open. 2023 May 1;6(5):e2312443. doi: 10.1001/jamanetworkopen.2023.12443.

ABSTRACT

IMPORTANCE: Evidence of the clinical benefit of pharmacogenetics-informed treatment (PIT) with antidepressants is still limited. Especially for tricyclic antidepressants (TCAs), pharmacogenetics may be of interest because therapeutic plasma concentrations are well defined, identification of optimal dosing can be time consuming, and treatment is frequently accompanied by adverse effects.

OBJECTIVE: To determine whether PIT results in faster attainment of therapeutic TCA plasma concentrations compared with usual treatment in patients with unipolar major depressive disorder (MDD).

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial compared PIT with usual treatment among 111 patients at 4 centers in the Netherlands. Patients were treated with the TCAs nortriptyline, clomipramine, or imipramine, with clinical follow-up of 7 weeks. Patients were enrolled from June 1, 2018, to January 1, 2022. At inclusion, patients had unipolar nonpsychotic MDD (with a score of ≥19 on the 17-item Hamilton Rating Scale for Depression [HAMD-17]), were aged 18 to 65 years, and were eligible for TCA treatment. Main exclusion criteria were a bipolar or psychotic disorder, substance use disorder, pregnancy, interacting comedications, and concurrent use of psychotropic medications.

INTERVENTION: In the PIT group, the initial TCA dosage was based on CYP2D6 and CYP2C19 genotypes. The control group received usual treatment, which comprised the standard initial TCA dosage.

MAIN OUTCOMES AND MEASURES: The primary outcome was days until attainment of a therapeutic TCA plasma concentration. Secondary outcomes were severity of depressive symptoms (measured by HAMD-17 scores) and frequency and severity of adverse effects (measured by Frequency, Intensity, and Burden of Side Effects Rating scores).

RESULTS: Of 125 patients randomized, 111 (mean [SD] age, 41.7 [13.3] years; 69 [62.2%] female) were included in the analysis; of those, 56 were in the PIT group and 55 were in the control group. The PIT group reached therapeutic concentrations faster than the control group (mean [SD], 17.3 [11.2] vs 22.0 [10.2] days; Kaplan-Meier χ21 = 4.30; P = .04). No significant difference in reduction of depressive symptoms was observed. Linear mixed-model analyses showed that the interaction between group and time differed for the frequency (F6,125 = 4.03; P = .001), severity (F6,114 = 3.10; P = .008), and burden (F6,112 = 2.56; P = .02) of adverse effects, suggesting that adverse effects decreased relatively more for those receiving PIT.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, PIT resulted in faster attainment of therapeutic TCA concentrations, with potentially fewer and less severe adverse effects. No effect on depressive symptoms was observed. These findings indicate that pharmacogenetics-informed dosing of TCAs can be safely applied and may be useful in personalizing treatment for patients with MDD.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03548675.

PMID:37155164 | PMC:PMC10167565 | DOI:10.1001/jamanetworkopen.2023.12443

Drug Des Devel Ther. 2023 May 1;17:1323-1327. doi: 10.2147/DDDT.S281626. eCollection 2023.

ABSTRACT

BACKGROUND: While dupilumab has shown efficacy in improving atopic dermatitis, few studies have assessed the long-term clinical data of dupilumab use in pediatric patients.

OBJECTIVE: In the present study, we reviewed the current literature to assess reported efficacies, side effects, and risks of using dupilumab to treat atopic dermatitis in pediatric populations.

METHODS: Using PRISMA guidelines, the authors searched PubMed/MEDLINE and Embase for studies related to dupilumab treatment for atopic dermatitis in pediatric patients aged 6-11 years old.

RESULTS: A total of 512 pediatric patients (ages 6-11) were included. Outcome measures assessed by EASI, SCORAD, P-NRS, IGA and C-DLQI showed significant improvements in scores from those observed at baseline to the last treatment of dupilumab. Most reported adverse effects on dupilumab were conjunctivitis and infection site reactions. All studies reported that dupilumab was well-tolerated.

LIMITATIONS: Limitations include the low number of studies available and observation periods of up to 16 weeks, which may be too short to evaluate the drug's effectiveness and occurrence of adverse effects. This also limits our knowledge on whether there are sustained benefits and/or diminished efficacy as well as long-term side effects.

CONCLUSION: Thus far, the data demonstrates dupilumab to be safe and effective in the management of moderate-to-severe atopic dermatitis in children aged 6-11 years. Future studies should evaluate long-term dupilumab use and sustained effects.

PMID:37152103 | PMC:PMC10162094 | DOI:10.2147/DDDT.S281626

Int J Infect Dis. 2023 May 5:S1201-9712(23)00550-7. doi: 10.1016/j.ijid.2023.05.002. Online ahead of print.

ABSTRACT

High-dose rifampicin (R) and isoniazid (H) are known to be safe but were not yet combined in a single regimen. TRIDORE (TRIple-DOse RE-treatment) is an ongoing pragmatic open-label multistage randomized clinical trial. The primary objective of this study is to determine whether a 6-month first-line regimen with triple-dose of both rifampicin and isoniazid (intervention arm; 6R3H3ZE) is non-inferior in terms of safety compared to a normal-dose regimen (6RHZE) in previously treated patients with rifampicin-susceptible (Rs) recurrent tuberculosis (TB). Between March 2021 and February 2022, 127 consenting patients were randomly assigned to either the intervention or control arm: 62 and 65 were treated with 6R3H3ZE and 6RHZE, respectively. Of 127, 111 (87.4%) were male and median age (IQR) was 37 (30-48) years. The median BMI at enrolment was 18.1 (16.3-19.7) kg/m2. Drug-related severe adverse events (grade 3-5) were significantly more frequent when 6R3H3ZE was used (5/62 vs 0/65, p=0.03, difference weighted for site 8%; (95%CI:1.0,14.3)). The study Data and Safety Monitoring Board (DSMB) recommended publishing our interim safety data analysis. We show that the combination of triple-dose rifampicin with triple-dose isoniazid in a retreatment regimen for patients with Rs-TB causes excess drug-related adverse events.

PMID:37150352 | DOI:10.1016/j.ijid.2023.05.002

Expert Rev Vaccines. 2023 Jan-Dec;22(1):440-446. doi: 10.1080/14760584.2023.2211668.

ABSTRACT

BACKGROUND: There is a high incidence and mortality rate in children with hematologic tumors (CHT), who are more prone to various infectious diseases. This study aims to clarify the real-world National Immunization Program (NIP) vaccination status of CHT before and after chemotherapy.

METHODS: Medical records, NIP vaccination data, and the Adverse Event Following Immunization (AEFI) of CHT who were admitted to the Children's Hospital, Zhejiang University School of Medicine, from 1 January 2011 to 1 December 2021 were completely collected.

RESULTS: A total of 2,874 CHT were included, and 1975 (68.7%) had vaccination records. Among the enrolled patients, the vaccination rate of all NIP vaccines was lower than 90% before diagnosis. Only 24.29% of CHT (410/1688) resumed vaccination after chemotherapy, and 69.02% (283/410) resumed vaccination more than 12 months after chemotherapy. No uncommon or serious side effects were reported.

CONCLUSION: The vaccination rate of CHT after chemotherapy was lower than that before the disease was diagnosed. It is necessary to provide more evidence-based support and formulate specific regimens to perfect the vaccination procedure after chemotherapy so as to improve the quality of life of CHT.

PMID:37148154 | DOI:10.1080/14760584.2023.2211668

Pharmacotherapy. 2023 May;43(5):358. doi: 10.1002/phar.2805. Epub 2023 May 5.

NO ABSTRACT

PMID:37143437 | DOI:10.1002/phar.2805

BMJ Case Rep. 2023 May 5;16(5):e251180. doi: 10.1136/bcr-2022-251180.

ABSTRACT

As COVID-19 vaccination becomes widely available and administered globally, there have been several reports of side effects attributed to the vaccine. This report highlights a patient who developed stroke 2 days following the administration of the COVID-19 vaccine, although its association remains uncertain. A man in his late 30s developed acute neurological symptoms 2 days after receiving the booster dose of the BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine. History and neurological examination suggested a posterior circulation stroke, which was confirmed by MRI, as a right-sided posterior inferior cerebellar artery stroke. Full workup did not suggest other causes of the stroke. Due to the patient's age and well-controlled risk factors, it was presumed to be a rare adverse effect of the vaccine. Medical management with aspirin, statin therapy and rehabilitation led to the improvement of symptoms and enabled ongoing restoration of function. Further cases of stroke following administration of COVID-19 vaccine have been documented in the literature, but the association is yet to be established.

PMID:37147105 | PMC:PMC10163425 | DOI:10.1136/bcr-2022-251180

BMJ. 2023 May 5;381:p1032. doi: 10.1136/bmj.p1032.

NO ABSTRACT

PMID:37146998 | DOI:10.1136/bmj.p1032

J Opioid Manag. 2023 May-Jun;19(3):257-271. doi: 10.5055/jom.2023.0781.

ABSTRACT

OBJECTIVE: To assess prescribing of tramadol among patients with contraindications and higher risks of adverse events in a large population of commercially insured and Medicare Advantage members.

DESIGN: We performed a cross-sectional analysis evaluating tramadol utilization in patients with higher risk of adverse outcomes.

SETTING: This study utilized 2016-2017 data from the Optum Clinformatics Data Mart.

PATIENTS AND PARTICIPANTS: Patients with at least one tramadol prescription without a cancer or sickle cell diagnosis during the study period.

MAIN OUTCOME MEASURES: We first determined if tramadol was prescribed among patients with contraindications or risk factors for adverse outcomes. We then determined if patient demographic or clinical factors were associated with the use of tramadol in these higher-risk scenarios using multivariable logistic regression models.

RESULTS: Among patients with at least one prescription for tramadol, 19.66 percent (99 percent CI: 19.57-19.75) concurrently received an interacting cytochrome P450 isoenzyme medication, 19.24 percent (99 percent CI: 19.15-19.33) concurrently received a serotonergic medication, and 7.93 percent (99 percent CI: 7.88-8.00) concurrently received a benzodiazepine. Additionally, 1.59 percent (99 percent CI: 1.56-1.61) of patients who received tramadol also had a seizure disorder, while 0.55 percent (99 percent CI: 0.53-0.56) of patients were under the age of 18. Overall, nearly one in three patients (31.17 percent) received tramadol in the presence of at least one of these risks (99 percent CI: 31.06-31.27).

CONCLUSION: Almost one in three patients prescribed tramadol had a clinically significant drug interaction or contraindication for use, suggesting that prescribers often disregard these concerns. Real-world studies are needed to better understand the likelihood of harms associated with the use of tramadol in these contexts.

PMID:37145928 | DOI:10.5055/jom.2023.0781

WMJ. 2023 May;122(2):143-145.

ABSTRACT

INTRODUCTION: Benztropine is an anticholinergic drug used as a therapy for Parkinson's disease and treatment for extrapyramidal side effects. While tardive dyskinesia is an involuntary movement disorder that often occurs gradually after long-term use of medications, it does not commonly present acutely.

CASE PRESENTATION: A 31-year-old White woman experiencing psychosis presented with spontaneous, acute-onset dyskinesia induced with the withdrawal of benztropine. She had been followed in our academic outpatient clinic for medication management and intermittent psychotherapy.

DISCUSSION: The pathophysiology of tardive dyskinesia is not fully understood, but several hypotheses exist, including the involvement of changes in basal ganglia neuronal systems. To our knowledge, this is the first case report to document acute-onset dyskinesia associated with the withdrawal of benztropine.

CONCLUSION: his case report, which describes an atypical response to discontinuing benztropine, might offer the scientific community potential clues to better understand the pathophysiology of tardive dyskinesia.

PMID:37141483

Eur Rev Med Pharmacol Sci. 2023 Apr;27(8):3545-3551. doi: 10.26355/eurrev_202304_32128.

ABSTRACT

OBJECTIVE: Obesity is a global public health problem with rapidly increasing prevalence in many countries, including Turkey, and different treatment modalities have been used. This study aimed to compare the effect of intragastric botulinum toxin A (BTA) injection and BTA injection combined with low-dose liraglutide in patients with obesity.

PATIENTS AND METHODS: Records of 701 patients (female/male, 660:41; mean age, 45.6 ± 6.2 years) who received an intragastric injection of BTA for weight loss between November 2019 and May 2020 were reviewed retrospectively. The patients were divided into the BTA group, which included patients who received BTA injection alone, and BTA + liraglutide, which included those who used liraglutide after BTA injection. The demographic characteristics and comorbid diseases of the patients and follow-up results 6 months after the procedure were evaluated.

RESULTS: In the comparison of the 3-month and 6-month weights of the patients, weight measurements were significantly lower in the BTA + liraglutide group than in the BTA group (p < 0.001 and p < 0.001, respectively). Adverse effects were observed in 212 (30.2%) of the study participants, of which 25% were observed in the BTA group and 31.8% in the BTA + liraglutide group, with no significant difference.

CONCLUSIONS: The intragastric injection of BTA combined with liraglutide is a safe method that provides more effective weight loss than BTA alone, which is minimally invasive without any serious adverse effects.

PMID:37140305 | DOI:10.26355/eurrev_202304_32128

Eur Rev Med Pharmacol Sci. 2023 Apr;27(8):3322-3335. doi: 10.26355/eurrev_202304_32103.

ABSTRACT

OBJECTIVE: Drug and substance abuse remains a major medical problem globally. Alcohol consumption, particularly heavy drinking, is an important risk factor for many health problems and is a major contributor to the global burden of disease. Vitamin C has proven to be defensive against toxic substances and provides antioxidant and cytoprotective activity to hepatocytes. The aim of this study was to investigate vitamin C as a potential ameliorating agent against hepatotoxicity among alcohol abusers.

PATIENTS AND METHODS: This study was a cross-sectional study that included eighty male hospitalized alcohol abusers and twenty healthy people as a control group. Alcohol abusers received standard treatment plus vitamin C. Total protein, albumin, total Bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and 8-hydroxhguanosine (8-OHdG) were investigated.

RESULTS: This study reported that, in the alcohol abuser group, there was a significant increase in the total protein, bilirubin, AST, ALT, ALP, TBARS, SOD and 8-OHdG; on the other hand, there was a significant decrease in albumin, GSH and CAT compared with the control group. The alcohol abuser group treated with vitamin C showed a significant decrease in total protein, bilirubin, AST, ALT, ALP, TBARS, SOD and 8-OHdG; on the other hand, there was a significant increase in albumin, GSH and CAT compared with the control group.

CONCLUSIONS: This study's findings suggest that alcohol abuse induces significant alterations in various hepatic biochemical parameters and oxidative stress and that vitamin C has a partial protective role in countering alcohol abuse-induced hepatotoxicity. Using vitamin C as an adjunctive supplement to standard treatment may be helpful in minimizing the toxic side effects of alcohol abuse.

PMID:37140282 | DOI:10.26355/eurrev_202304_32103

PeerJ. 2023 Apr 28;11:e15277. doi: 10.7717/peerj.15277. eCollection 2023.

ABSTRACT

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) produces unwanted side-effects that are mainly caused by chemotherapeutic drugs in the treatment of gastrointestinal (GI) cancers, and these effects have not been systematically summarized. The aim of this article was to provide a comprehensive overview of the side-effects of HIPEC for GI cancers and propose practical strategies for adverse event management.

METHODOLOGY: PubMed, Web of Science, and the Cochrane Library were systematically searched for side-effects of HIPEC in GI cancers prior to October 20, 2022. A total of 79 articles were included in this review.

RESULTS: Adverse events, such as enterocutaneous digestive fistulas, GI tract perforation, neutropenia, postoperative bleeding, ventricular tachycardia, hyperglycemia, hypocalcemia, renal impairment, encapsulating peritoneal sclerosis, scrotal ulceration, and sarcopenia were described, and their clinical management was discussed. These side-effects involve the digestive, hematopoietic, circulatory, metabolic, and urinary systems. Effective methods for adverse event management included an expert multidisciplinary team, replacing chemotherapy drugs, using Chinese medicine, and careful preoperative assessments.

CONCLUSION: The side-effects of HIPEC are frequent and can be minimized by several effective methods. This study proposes practical strategies for adverse event management of HIPEC to assist physicians in choosing the optimal treatment method.

PMID:37138820 | PMC:PMC10150720 | DOI:10.7717/peerj.15277

Pharmazie. 2023 Apr 15;78(1):17-19. doi: 10.1691/ph.2023.2541.

ABSTRACT

The current conflict between Russia and Ukraine increased concerns in the German population of a release of radioactive substances, e.g.radioactive iodine. A high dose of potassium iodide (PI) may prevent accumulation of radioactive iodine in the thyroid gland. Therefore, the German government keeps a sufficient quantity of PI in stock for public supply in case of an emergency. We investigated ambulatory drug dispensing rates of PI and found that the total dispensing of PI (statutory health insurance (SHI), private health insurance (PHI), and overthe-counter (OTC)) increased by 106% from February to March 2022. Changes in PI dispensing were mainly due to an increase in OTC sales, where PI as an antidote showed a sevenfold increase from around 930 packages (February 2022) to 6,500 packages (March 2022), while SHI and PHI dispensing remained relatively low. Furthermore, we investigated whether these changes in dispensing raised the number of suspected adverse drug reactions (ADR). We found no increase of ADR reports related to the use of PI-containing medicinal products between February and September 2022, neither in our national pharmacovigilance nor in the European EudraVigilance database. The data suggest that the mere possibility of a nuclear disaster in Ukraine raised the demand of PI in Germany. Thus, timely and proactive information and reassurance of the public of supply reliability by the Government in a case of a nuclear emergency could be helpful in preventing potential drug shortages and unfounded concern.

PMID:37138408 | DOI:10.1691/ph.2023.2541

JHEP Rep. 2023 Mar 7;5(6):100719. doi: 10.1016/j.jhepr.2023.100719. eCollection 2023 Jun.

ABSTRACT

BACKGROUND & AIMS: Immune checkpoint inhibitors (ICIs) have changed the landscape of cancer therapy. Liver toxicity occurs in up to 25% of patients treated with ICIs. The aim of our study was to describe the different clinical patterns of ICI-induced hepatitis and to assess their outcome.

METHODS: We conducted a retrospective observational study of patients with checkpoint inhibitor-induced liver injury (CHILI) discussed in multidisciplinary meetings between December 2018 and March 2022 in three French centres specialised in ICI toxicity management (Montpellier, Toulouse, Lyon). The hepatitis clinical pattern was analysed by the ratio of serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) (R value = (ALT/ULN)/(ALP/ULN)) for characterisation as cholestatic (R ≤2), hepatocellular (R ≥5), or mixed (2 <R <5).

RESULTS: We included 117 patients with CHILI. The clinical pattern was hepatocellular in 38.5%, cholestatic in 36.8%, and mixed in 24.8% of patients. High-grade hepatitis severity (grade ≥3 according to the Common Terminology Criteria for Adverse Events system) was significantly associated with the hepatocellular hepatitis (p <0.05). No cases of severe acute hepatitis were reported. Liver biopsy was performed in 41.9% of patients: granulomatous lesions, endothelitis, or lymphocytic cholangitis were described. Biliary stenosis occurred in eight patients (6.8%) and was significantly more frequent in the cholestatic clinical pattern (p < 0.001). Steroids alone were mainly administered to patients with a hepatocellular clinical pattern (26.5%), and ursodeoxycholic acid was more frequently used in the cholestatic pattern (19.7%) than in the hepatocellular or mixed clinical pattern (p <0.001). Seventeen patients improved without any treatment. Among the 51 patients (43.6%) rechallenged with ICIs, 12 (23.5%) developed CHILI recurrence.

CONCLUSIONS: This large cohort indicates the different clinical patterns of ICI-induced liver injury and highlights that the cholestatic and hepatocellular patterns are the most frequent with different outcomes.

IMPACT AND IMPLICATIONS: ICIs can induce hepatitis. In this retrospective series, we report 117 cases of ICI-induced hepatitis, mostly grades 3 and 4. We find a similar distribution of the different patterns of hepatitis. ICI could be resumed without systematic recurrence of hepatitis.

PMID:37138674 | PMC:PMC10149360 | DOI:10.1016/j.jhepr.2023.100719

Rev Med Suisse. 2023 Apr 19;19(823):746-751. doi: 10.53738/REVMED.2023.19.823.746.

ABSTRACT

Despite the effectiveness of osteoporosis treatments, fear of side effects reduces both their prescription by doctors, and their acceptance by patients. The most common side effects are benign and transient, such as flu-like symptoms after zoledronate infusion, or nausea and dizziness after teriparatide introduction. On the other hand, the dreaded osteonecrosis of the jaw is very rare and associated with known risk factors. Only vertebral fractures after stopping denosumab make this treatment a matter for experienced practitioners. Therefore, knowing the side effects of prescribed treatments and explaining them to patients is essential to promote adherence.

PMID:37133954 | DOI:10.53738/REVMED.2023.19.823.746

AMIA Annu Symp Proc. 2023 Apr 29;2022:1163-1172. eCollection 2022.

ABSTRACT

Adverse event reports (AER) are widely used for post-market drug safety surveillance and drug repurposing, with the assumption that drugs with similar side-effects may have similar therapeutic effects also. In this study, we used distributed representations of drugs derived from the Food and Drug Administration (FDA) AER system using aer2vec, a method of representing AER, with drug embeddings emerging from a neural network trained to predict the probability of adverse drug effects given observed drugs. We combined these representations with molecular features to predict permeability of the blood-brain barrier to drugs, a prerequisite to their application to treat conditions of the central nervous system. Across multiple machine learning classifiers, the addition of distributed representations improved performance over prior methods using drug-drug similarity estimates derived from discrete representations of AER system data. Embedding-based approaches outperformed those using discrete statistics, with improvements in absolute AUC of 5% and 9%, corresponding to improvements of 9% and 13% over performance with molecular features only. Performance was retained when reducing embedding dimensions from 500 to 6, indicating that they are neither attributable to overfitting, nor to a difference in the number of trainable parameters. These results indicate that aer2vec distributed representations carry information that is valuable for drug repurposing.

PMID:37128462 | PMC:PMC10148361

AMIA Annu Symp Proc. 2023 Apr 29;2022:596-605. eCollection 2022.

ABSTRACT

Post-market drug surveillance monitors new and evolving treatments for their effectiveness and safety in real-world conditions. A large amount of drug safety surveillance data is captured by spontaneous reporting systems such as the FAERS. Developing automated methods to identify actionable safety signals from these databases is an active area of research. In this paper, we propose two novel network representation learning methods (HARE and T-HARE) for signal detection that jointly utilize association information between drugs and medical outcomes from the FAERS and ancestral information in medical ontologies. We evaluate these methods using two publicly available reference datasets, EU-ADR and OMOP corpus. Experimental results showed that the proposed methods significantly outper-formed standard methodologies based on disproportionality metrics and the existing state-of-the-art aer2vec method with statistically significant improvements on both EU-ADR and OMOP datasets. Through quantitative and qualitative analysis, we demonstrate the potential of the proposed methods for effective signal detection.

PMID:37128452 | PMC:PMC10148317

AMIA Annu Symp Proc. 2023 Apr 29;2022:1227-1236. eCollection 2022.

ABSTRACT

Remdesivir has been widely used for the treatment of Coronavirus (COVID) in hospitalized patients, but its nephrotoxicity is still under investigation1. Given the paucity of knowledge regarding the mechanism and optimal treatment of the development of acute kidney injury (AKI) in the setting of COVID, we analyzed the role of remdesivir and built multifactorial causal models of COVID-AKI by applying causal discovery machine learning techniques. Risk factors of COVID-AKI and renal function measures were represented in a temporal sequence using longitudinal data from EHR. Our models successfully recreated known causal pathways to changes in renal function and interactions with each other and examined the consistency of high-level causal relationships over a 4-day course of remdesivir. Results indicated a need for assessment of renal function on day 2 and 3 use of remdesivir, while uncovering that remdesivir may pose less risk to AKI than existing conditions of chronic kidney disease.

PMID:37128413 | PMC:PMC10148284