Vaccine. 2024 May 31;42(15):3486-3492. doi: 10.1016/j.vaccine.2024.04.051. Epub 2024 May 3.

ABSTRACT

BACKGROUND: While safety of influenza vaccines is well-established, some studies have suggested potential associations between influenza vaccines and certain adverse events (AEs). This study examined the safety of the 2022-2023 influenza vaccines among U.S. adults ≥ 65 years.

METHODS: A self-controlled case series compared incidence rates of anaphylaxis, encephalitis/encephalomyelitis, Guillain-Barré Syndrome (GBS), and transverse myelitis following 2022-2023 seasonal influenza vaccinations (i.e., any, high-dose or adjuvanted) in risk and control intervals among Medicare beneficiaries ≥ 65 years. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) adjusted for event-dependent observation time and seasonality. Analyses also accounted for uncertainty from outcome misclassification where feasible. For AEs with any statistically significant associations, we stratified results by concomitant vaccination status.

RESULTS: Among 12.7 million vaccine recipients, we observed 76 anaphylaxis, 276 encephalitis/encephalomyelitis, 134 GBS and 75 transverse myelitis cases. Only rates of anaphylaxis were elevated in risk compared to control intervals. With all adjustments, an elevated, but non-statistically significant, anaphylaxis rate was observed following any (IRR: 2.40, 95% CI: 0.96-6.03), high-dose (IRR: 2.31, 95% CI: 0.67-7.91), and adjuvanted (IRR: 3.28, 95% CI: 0.71-15.08) influenza vaccination; anaphylaxis IRRs were 2.54 (95% CI: 0.49-13.05) and 1.64 (95% CI: 0.38-7.05) for persons with and without concomitant vaccination, respectively.

CONCLUSIONS: Rates of encephalitis/encephalomyelitis, GBS, or transverse myelitis were not elevated following 2022-2023 seasonal influenza vaccinations among U.S. adults ≥ 65 years. There was an increased rate of anaphylaxis following influenza vaccination that may have been influenced by concomitant vaccination.

PMID:38704258 | DOI:10.1016/j.vaccine.2024.04.051

Compr Psychiatry. 2024 Apr 15;133:152486. doi: 10.1016/j.comppsych.2024.152486. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine the long-term safety and tolerability of off-label high-dose serotonin reuptake inhibitors (OLHD-SRIs) in the treatment of obsessive-compulsive disorder (OCD).

METHODS: A retrospective longitudinal study was performed on 105 randomly selected outpatients diagnosed with OCD and were treated with OLHD-SRIs for at least 6 months. Patients received sertraline >200 mg/day, escitalopram >20 mg/day, fluvoxamine >300 mg/day, and fluoxetine >60 mg/day, combined with exposure and response prevention therapy. Patients were divided into three dosing groups: sertraline equivalent dose (SED) ≤ 200 mg/day (n = 26, 24.7%), 201-400 mg/day (n = 51, 48.5%) and 401-650 mg/day (n = 28, 26.6%). Safety and tolerability were assessed with an electrocardiogram, blood biochemistry, complete blood count, and side-effects monitoring.

RESULTS: SED ranged from 100 to 650 mg/day and the mean duration of OLHD-SRI treatment was 20.8 months. The most common side-effects reported were sexual dysfunction (n = 36, 34%), weight gain (n = 28, 27%), sedation (n = 27, 26%), hyperhidrosis (n = 20, 19%), and tremor (n = 11, 10%). Abnormal ECG was documented in one patient, and another patient experienced a first-time seizure, whereas elevated liver enzymes were seen in 4.8% of the sample (n = 5). None of the patients had serotonin syndrome or drug-induced liver injury. Side-effects did not differ among the three dosing groups.

CONCLUSION: OLHD-SRIs appear to be safe and well tolerated in OCD patients in SED ≤ 650 mg/day doses and the side-effects did not differ between the three dosing groups.

PMID:38703743 | DOI:10.1016/j.comppsych.2024.152486

Methods. 2024 Jun;226:164-175. doi: 10.1016/j.ymeth.2024.04.020. Epub 2024 May 1.

ABSTRACT

Ensuring the safety and efficacy of chemical compounds is crucial in small-molecule drug development. In the later stages of drug development, toxic compounds pose a significant challenge, losing valuable resources and time. Early and accurate prediction of compound toxicity using deep learning models offers a promising solution to mitigate these risks during drug discovery. In this study, we present the development of several deep-learning models aimed at evaluating different types of compound toxicity, including acute toxicity, carcinogenicity, hERG_cardiotoxicity (the human ether-a-go-go related gene caused cardiotoxicity), hepatotoxicity, and mutagenicity. To address the inherent variations in data size, label type, and distribution across different types of toxicity, we employed diverse training strategies. Our first approach involved utilizing a graph convolutional network (GCN) regression model to predict acute toxicity, which achieved notable performance with Pearson R 0.76, 0.74, and 0.65 for intraperitoneal, intravenous, and oral administration routes, respectively. Furthermore, we trained multiple GCN binary classification models, each tailored to a specific type of toxicity. These models exhibited high area under the curve (AUC) scores, with an impressive AUC of 0.69, 0.77, 0.88, and 0.79 for predicting carcinogenicity, hERG_cardiotoxicity, mutagenicity, and hepatotoxicity, respectively. Additionally, we have used the approved drug dataset to determine the appropriate threshold value for the prediction score in model usage. We integrated these models into a virtual screening pipeline to assess their effectiveness in identifying potential low-toxicity drug candidates. Our findings indicate that this deep learning approach has the potential to significantly reduce the cost and risk associated with drug development by expediting the selection of compounds with low toxicity profiles. Therefore, the models developed in this study hold promise as critical tools for early drug candidate screening and selection.

PMID:38702021 | DOI:10.1016/j.ymeth.2024.04.020

J Med Internet Res. 2024 May 3;26:e48572. doi: 10.2196/48572.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADRs), which are the phenotypic manifestations of clinical drug toxicity in humans, are a major concern in precision clinical medicine. A comprehensive evaluation of ADRs is helpful for unbiased supervision of marketed drugs and for discovering new drugs with high success rates.

OBJECTIVE: In current practice, drug safety evaluation is often oversimplified to the occurrence or nonoccurrence of ADRs. Given the limitations of current qualitative methods, there is an urgent need for a quantitative evaluation model to improve pharmacovigilance and the accurate assessment of drug safety.

METHODS: In this study, we developed a mathematical model, namely the Adverse Drug Reaction Classification System (ADReCS) severity-grading model, for the quantitative characterization of ADR severity, a crucial feature for evaluating the impact of ADRs on human health. The model was constructed by mining millions of real-world historical adverse drug event reports. A new parameter called Severity_score was introduced to measure the severity of ADRs, and upper and lower score boundaries were determined for 5 severity grades.

RESULTS: The ADReCS severity-grading model exhibited excellent consistency (99.22%) with the expert-grading system, the Common Terminology Criteria for Adverse Events. Hence, we graded the severity of 6277 standard ADRs for 129,407 drug-ADR pairs. Moreover, we calculated the occurrence rates of 6272 distinct ADRs for 127,763 drug-ADR pairs in large patient populations by mining real-world medication prescriptions. With the quantitative features, we demonstrated example applications in systematically elucidating ADR mechanisms and thereby discovered a list of drugs with improper dosages.

CONCLUSIONS: In summary, this study represents the first comprehensive determination of both ADR severity grades and ADR frequencies. This endeavor establishes a strong foundation for future artificial intelligence applications in discovering new drugs with high efficacy and low toxicity. It also heralds a paradigm shift in clinical toxicity research, moving from qualitative description to quantitative evaluation.

PMID:38700923 | DOI:10.2196/48572

Expert Opin Drug Saf. 2024 May 3. doi: 10.1080/14740338.2024.2351451. Online ahead of print.

ABSTRACT

OBJECTIVE: Elagolix is approved for the treatment of moderate-to-severe pain associated with endometriosis. However, the long-term safety of elagolix in a large sample of real-world patients is unknown.

METHODS: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) reports were collected and analyzed for the first quarter of 2019 through the second quarter of 2023. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed in data mining to quantify the signals of elagolix-related adverse events (AEs).

RESULTS: A total of 112 elagolix-induced AE signals were detected in 17 system organ classes (SOCs) that simultaneously met the thresholds of 4 algorithms. After removing the non-drug-related AE signals, we detected several AE signals such as hot flushes, bone pain, suicidal ideation, depression, and increased liver enzymes, which were known during the clinical trial phase. In addition to this, we detected several unexpected important adverse events that were not mentioned in the drug insert, including cystitis interstitial, parosmia, and epiploic appendagitis. The median onset time of elagolix-associated AEs was 28.5 days. The majority of cases occurred within 1 month after initiation of elagolix treatment.

CONCLUSION: Our study provides a comprehensive picture of the safety of elagolix in the post-marketing setting, while also identifying potential new AE signals. These findings emphasize the importance of continued monitoring of the potential risks of elagolix.

PMID:38700323 | DOI:10.1080/14740338.2024.2351451

Vet Rec. 2024 May 4;194(9):324. doi: 10.1002/vetr.4212.

NO ABSTRACT

PMID:38700205 | DOI:10.1002/vetr.4212

Lancet Child Adolesc Health. 2024 Jun;8(6):389-390. doi: 10.1016/S2352-4642(24)00106-8. Epub 2024 Apr 30.

NO ABSTRACT

PMID:38697176 | DOI:10.1016/S2352-4642(24)00106-8

Lancet Child Adolesc Health. 2024 Jun;8(6):422-432. doi: 10.1016/S2352-4642(24)00078-6. Epub 2024 Apr 30.

ABSTRACT

BACKGROUND: Rare and severe adverse events can occur in children with inflammatory bowel disease (IBD), and the relationship with disease or drug treatment is often uncertain. We aimed to establish a method of reporting adverse events of interest in children with IBD, allowing for estimates of incidence rates with comparison between different regions, and, if possible, to compare with published data on rates of adverse events in children overall.

METHODS: For this analysis, we used data from the Paediatric Inflammatory Bowel Disease Network for Safety, Efficacy and Treatment and Quality improvement of care (PIBD-SETQuality) Safety Registry, which collects data on multiple rare and severe adverse events in children younger than 19 years with IBD. Overall, the registry collected data on ten prespecified rare and severe adverse events in children with IBD, as established by a panel of paediatric IBD experts, via reports from paediatric gastroenterologists at participating hospitals between Nov 1, 2016, and March 31, 2023. Reporting physicians, who could only be paediatric gastroenterologists or IBD nurses reporting on behalf of paediatric gastroenterologists, were recruited through invitations sent to both national and international IBD networks and at conferences. Once per month, participating paediatric gastroenterologists received an email with an anonymous and unique link to an online survey asking them to report whether any of ten rare and severe adverse events had occurred in a patient in their paediatric-IBD population in the previous month. Prevalent or retrospective rare and severe adverse events were excluded, as were events occurring in children with an unconfirmed diagnosis of IBD or for whom inflammatory colitis was part of a monogenic immunodeficiency disorder. Duplicates and events that did not meet the definitions and criteria were excluded. Physicians could also report other, non-categorised adverse events if they considered them rare and severe. In case of no response, up to two reminders were sent for each per-month survey. Annual denominator data surveys were sent to obtain the total number of person-years for the estimation of incidence rates, which were calculated via Poisson regression models.

FINDINGS: Responses were gathered from 220 paediatric gastroenterologists from 167 centres. 121 centres were in Europe, 23 centres were in North America, 17 centres were in Asia, and six centres were in Oceania. Combined, the total population with paediatric IBD consisted of an estimated 30 193 children with 114 528 person-years of follow-up. 451 adverse events were initially reported. After excluding and reorganising adverse events, 402 were eligible; 261 (65%) were categorised and 141 (35%) were non-categorised. The most frequently reported adverse events were venous-thromboembolic events (n=66), renal failure (n=43), opportunistic infections (n=42), and cancer (n=33). Haemophagocytic lymphohistiocytosis (n=4) and liver failure (n=3) were the least frequently reported adverse events. Incidence rates per 10 000 person-years were 5·50 (95% CI 4·25-6·97) for venous-thromboembolic events, 3·75 (2·74-4·99) for renal failure, 3·67 (2·67-4·89) for opportunistic infection, and 2·88 (2·01-3·98) for cancer. Of 66 venous-thromboembolic events, 31 (47%) involved cerebral venous sinus thrombosis at an incidence rate of 2·71 (95% CI 1·86-3·77).

INTERPRETATION: The PIBD-SETQuality Safety Registry enabled us to identify incidence rates of rare and severe adverse events in children with IBD. Our findings can guide physicians and enhance awareness of the incidence of adverse events in children with IBD that are considered to be rare.

FUNDING: EU Horizon 2020 Research and Innovation Programme.

PMID:38697175 | DOI:10.1016/S2352-4642(24)00078-6

Eur J Hosp Pharm. 2024 May 2:ejhpharm-2023-004023. doi: 10.1136/ejhpharm-2023-004023. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to assess and compare the occurrence of 3-HIT in people living with HIV (PLWH) and seronegative patients. Additionally, the study investigated whether HIV infection could serve as a predictor of the presence of 3-HIT.

METHODS: A cross-sectional study was conducted between December 2022 and January 2023 to compare PLWH with a group of seronegative patients with chronic diseases attending an outpatient hospital pharmacy service. The 3-HIT concept encompasses the simultaneous presence of non-adherence to concomitant treatment (NAC), drug-drug interactions (DDIs), and high pharmacotherapeutic complexity in polymedicated patients. The assessment of 3-HIT compliance included NAC, evaluated using both the Morisky-Green questionnaire and electronic pharmacy dispensing records. DDIs were analysed using the Liverpool University and Micromedex databases. Pharmacotherapeutic complexity was measured using the Medication Regimen Complexity Index (MRCI) tool. Logistic regression analysis was performed to identify independent factors related to 3-HIT. Additionally, an explanatory logistic model was created to investigate whether HIV infection, along with other adjustment variables, could predict compliance with the 3-HIT concept.

RESULTS: The study included 145 patients: 75 PLWH and 70 seronegative patients. The median age was 40 versus 39 years, respectively (p=0.22). Seronegative patients exhibited a higher prevalence of NAC (p<0.01). HIV infection was identified as a protective factor in the context of DDIs (p<0.01). Male sex (p<0.01) and age (p=0.01) were identified as being associated with an MRCI ≥11.25 points. A higher prevalence of 3-HIT was observed in seronegative patients (18.7% vs 48.6%, p<0.01). However, the developed regression model identified HIV infection as a risk factor associated with an increased likelihood of 3-HIT (OR 4.00, 95% CI 1.88 to 8.52, p<0.01).

CONCLUSIONS: The 3-HIT concept exhibited a high prevalence among seronegative patients with chronic diseases, with HIV infection identified as a predicted risk factor for NAC and the development of 3-HIT.

PMID:38697803 | DOI:10.1136/ejhpharm-2023-004023

Drug Ther Bull. 2024 May 2:dtb-2024-000029. doi: 10.1136/dtb.2024.000029. Online ahead of print.

NO ABSTRACT

PMID:38697797 | DOI:10.1136/dtb.2024.000029

Drug Ther Bull. 2024 May 2:dtb-2024-000030. doi: 10.1136/dtb.2024.000030. Online ahead of print.

NO ABSTRACT

PMID:38697796 | DOI:10.1136/dtb.2024.000030

BMC Cancer. 2024 May 2;24(1):552. doi: 10.1186/s12885-024-12291-w.

ABSTRACT

BACKGROUND: Patients with hematological malignancies often require multidrug therapy using a variety of antineoplastic agents and supportive care medications. This increases the risk of drug-related problems (DRPs). Determining DRPs in patients hospitalized in hematology services is important for patients to achieve their drug treatment goals and prevent adverse effects. This study aims to identify DRPs by the clinical pharmacist in the multidisciplinary team in patients hospitalized in the hematology service of a university hospital in Turkey.

METHODS: This study was conducted prospectively between December 2022 and May 2023 in the hematology service of Suleyman Demirel University Research and Application Hospital in Isparta, Turkey. DRPs were determined using the Pharmaceutical Care Network Europe (PCNE) 9.1 Turkish version.

RESULTS: This study included 140 patients. Older age, longer hospital stay, presence of acute lymphoblastic leukemia, presence of comorbidities, higher number of medications used, and polypharmacy rate were statistically significantly higher in the DRP group than in the non-DRP group (p < 0.05). According to multivariate logistic regression analysis, the probability of DRP in patients with polypharmacy was statistically significant 7.921 times (95% CI: 3.033-20.689) higher than in patients without polypharmacy (p < 0.001).Every 5-day increase in the length of hospital stay increased the likelihood of DRP at a statistically significant level (OR = 1.476, 95% CI: 1.125-1.938 p = 0.005). In this study, at least one DRP was detected in 69 (49.3%) patients and the total number of DRPs was 152. Possible or actual adverse drug events (96.7%) were the most common DRPs. The most important cause of DRPs was drug choice (94.7%), and the highest frequency within its subcategories was the combination of inappropriate drugs (93.4%).

CONCLUSIONS: This study shows the importance of including a clinical pharmacist in a multidisciplinary team in identifying and preventing DRPs in the hematology service.

PMID:38698336 | DOI:10.1186/s12885-024-12291-w

Front Pharmacol. 2024 Apr 17;15:1322473. doi: 10.3389/fphar.2024.1322473. eCollection 2024.

ABSTRACT

CONTEXT: Cabozantinib combined with immune checkpoint inhibitors (ICIs) has brought a new therapeutic effect for the medical treatment of renal cell carcinoma (RCC).

OBJECTIVES: We performed a meta-analysis of randomized controlled trials and single-arm trials to evaluate the efficacy and safety of cabozantinib plus ICIs in RCC.

METHODS: We extracted data from PubMed, Cochrane, Medline and Embase databases, and rated literature quality through Cochrane risk of bias tool and MINORS. RevMan5.3 software was used to analyze the results of randomized controlled trials and single-arm trials.

RESULTS: A total of 7 studies were included. Treatment with cabozantinib plus ICIs improved PFS [HR 0.75, (95%CI: 0.52, 1.08), p = 0.12] and the OS [HR 0.80, (95%CI: 0.60, 1.07), p = 0.13] in randomized controlled trials. Meanwhile, the result of the ORR in randomized controlled trials was [risk ratio (RR) 1.37, (95%CI: 1.21, 1.54), p < 0.00001] and in single-arm trials was [risk difference (RD) 0.49, (95%CI: 0.26, 0.71), p < 0.0001].

CONCLUSION: Cabozantinib plus ICIs prolonged the PFS and OS, and improved ORR in patients with RCC. Our recommendation is to use cabozantinib plus ICIs to treat advanced RCC, and to continuous monitor and manage the drug-related adverse events.

SYSTEMATIC REVIEW REGISTRATION: identifier CRD42023455878.

PMID:38694912 | PMC:PMC11061414 | DOI:10.3389/fphar.2024.1322473

Ann Med Surg (Lond). 2024 Mar 4;86(5):3029-3035. doi: 10.1097/MS9.0000000000001878. eCollection 2024 May.

ABSTRACT

INTRODUCTION AND IMPORTANCE: Brentuximab vedotin (BV) is an anti-CD30 antibody approved for various cancers, including refractory Hodgkin lymphoma (HL), anaplastic large-cell lymphoma (ALCL) among others. In general, BV has been found to be well-tolerated, with the most frequently reported side effects being peripheral neuropathy and neutropenia. BV-induced pneumonitis is extremely rare. To the best of our knowledge, this is the sixth reported instance of BV-induced lung toxicity.

CASE PRESENTATION: This case presents a female patient in her forties diagnosed with cutaneous T-cell lymphoma undergoing BV treatment. She developed acute hypoxic respiratory failure, ultimately, underwent a diagnostic evaluation including a computed tomography (CT) scan, which showed bilateral airspace consolidations and ground-glass opacities, suggestive of organizing pneumonia and diffuse alveolar damage. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy ruled out infection, and pulmonary lymphoma and confirmed the diagnosis of BV-induced pneumonitis. The patient had significant clinical improvement after stopping the offending agent, and starting steroids, with optimal clinical recovery at 8 weeks follow-up.

CLINICAL DISCUSSION: Drug-related pneumonitis poses a significant concern in the management of cancer patients. Numerous chemotherapeutic agents, such as bleomycin, cyclophosphamide, methotrexate, thalidomide, and others, have been associated with pulmonary-related toxicities. These adverse effects primarily stem from direct toxicity or immunosuppression-related infections. Less commonly, immune-mediated injury may occur.

CONCLUSION: Physicians must have a high index of suspicion for BV-induced pneumonitis, hence, early recognition with subsequent holding of the causative agent, initiation of immunosuppression with steroids, and occasionally steroid-sparing medications, prevent an otherwise fatal outcome.

PMID:38694384 | PMC:PMC11060267 | DOI:10.1097/MS9.0000000000001878

Farm Hosp. 2024 Apr 30:S1130-6343(24)00041-2. doi: 10.1016/j.farma.2024.03.004. Online ahead of print.

ABSTRACT

INTRODUCTION: Intensive care units (ICUs) pose challenges in managing critically ill patients with polypharmacy, potentially leading to adverse drug reactions (ADRs), particularly in the elderly.

OBJECTIVE: To evaluate whether the severity and clinical prognosis scores used in ICUs correlate with the prediction of ADRs in aged patients admitted to an ICU.

METHODS: A cohort study was conducted in a Brazilian University Hospital ICU. APACHE II and SAPS 3 assessed clinical prognosis, while GerontoNet ADR Risk Score and BADRI evaluated ADR risk at ICU admission. Severity of the patients' clinical conditions was evaluated daily based on the SOFA score. ADR screening was performed daily through the identification of ADR triggers.

RESULTS: 1295 triggers were identified (median 30 per patient, IQR=28), with 15 suspected ADRs. No correlation was observed between patient severity and ADRs at admission (p=0.26), during hospitalization (p=0.91), or at follow-up (p=0.77). There was also no association between death and ADRs (p=0.28) or worse prognosis and ADRs (p>0.05). Higher BADRI scores correlated with more ADRs (p=0.001).

CONCLUSIONS: These data suggest that employing the severity and clinical prognosis scores used in ICUs is not sufficient to direct active pharmacovigilance efforts, which are therefore indicated for critically ill patients.

PMID:38693001 | DOI:10.1016/j.farma.2024.03.004

Folia Med (Plovdiv). 2024 Apr 30;66(2):161-170. doi: 10.3897/folmed.66.e117783.

ABSTRACT

Inappropriate polypharmacy is a common occurrence in elderly patients, resulting in increased adverse drug reactions, nonadherence, and increased healthcare costs. Medication review and deprescribing are the primary strategies described in the literature for dealing with problematic polypharmacy. To effectively carry out the medication review, various tools have been developed. These tools can support medication review in a variety of ways. Some tools include a list of medications requiring detailed attention, while others guide medical professionals with principles and algorithms for reviewing and prescribing medicines. A third category of tools focuses on tracking and identifying symptoms that may be due to drug-related problems.

PMID:38690810 | DOI:10.3897/folmed.66.e117783

Cureus. 2024 Mar 31;16(3):e57341. doi: 10.7759/cureus.57341. eCollection 2024 Mar.

ABSTRACT

Clozapine is an effective medication for treatment-resistant schizophrenia, and it has been associated with well-documented side effects that limit its use. Clozapine-induced hepatotoxicity is a less-known complication of clozapine therapy. The literature is unclear about the psychopharmacologic options available following clozapine cessation on account of liver toxicity. We present a patient with clinical symptomatology in keeping with clozapine-induced hepatotoxicity who achieved full recovery following clozapine cessation and conservative medical management. Her psychiatric symptomatology was successfully managed with oral olanzapine augmented with haloperidol without recurrence of psychosis or liver toxicity.

PMID:38690462 | PMC:PMC11060696 | DOI:10.7759/cureus.57341

Natl J Maxillofac Surg. 2024 Jan-Apr;15(1):151-153. doi: 10.4103/njms.njms_128_22. Epub 2024 Mar 19.

ABSTRACT

While fluconazole use is generally considered safe and well-tolerated, there has been an increasing number of reports regarding several adverse events. Therefore, the present study aimed to present a unique case in which photobiomodulation therapy (PBMT) was employed to manage bullous erythema multiforme lesions secondary to fluconazole intake. A 32-year-old female patient sought emergency dental care due to painful orofacial lesions that had developed two days after oral fluconazole use for recurrent vulvovaginal candidiasis. Given the acute clinical features, a diagnosis of bullous erythema multiforme secondary to fluconazole was established. Prednisone 20 mg was then prescribed for five days, and fluconazole intake was immediately discontinued. As the initial treatment strategies failed to show improvement in the clinical condition, three PBMT sessions were proposed every other day. Within seven days, almost complete wound healing was observed, and any pain complaints were no longer present. The resolution of orofacial lesions within a short period suggests that PBMT could be a promising tool for managing drug-induced bullous erythema multiforme. However, more studies are needed to confirm this statement.

PMID:38690232 | PMC:PMC11057598 | DOI:10.4103/njms.njms_128_22

Toxicol Appl Pharmacol. 2024 Apr 28:116945. doi: 10.1016/j.taap.2024.116945. Online ahead of print.

ABSTRACT

Cytochrome P450 enzymes (CYPs) play a crucial role in the metabolism and synthesis of various compound classes. While drug-metabolizing CYP enzymes are frequently investigated as anti-targets, the inhibition of CYP enzymes involved in adrenal steroidogenesis is not well studied. The steroidogenic enzyme CYP17A1 is a dual-function enzyme catalyzing hydroxylase and lyase reactions relevant for the biosynthesis of adrenal glucocorticoids and androgens. Inhibition of CYP17A1-hydroxylase leads to pseudohyperaldosteronism with subsequent excessive mineralocorticoid receptor activation, hypertension and hypokalemia. In contrast, specific inhibition of the lyase function might be beneficial for the treatment of prostate cancer by decreasing adrenal androgen levels. This study combined in silico and in vitro methods to identify drugs inhibiting CYP17A1. The most potent CYP17A1 inhibitors identified are serdemetan, mocetinostat, nolatrexed, liarozole, and talarozole. While some of these drugs are currently under investigation for the treatment of various cancers, their potential for the treatment of prostate cancer is yet to be explored. The DrugBank database was screened for CYP17A1 inhibitors, to increase the awareness for the risk of drug-induced pseudohyperaldosteronism and to highlight drugs so far unknown for their potential to cause side effects resulting from CYP17A1 inhibition.

PMID:38688424 | DOI:10.1016/j.taap.2024.116945

JCO Clin Cancer Inform. 2024 Apr;8:e2300151. doi: 10.1200/CCI.23.00151.

ABSTRACT

PURPOSE: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet their use is associated with immune-related adverse events (irAEs). Estimating the prevalence and patient impact of these irAEs in the real-world data setting is critical for characterizing the benefit/risk profile of ICI therapies beyond the clinical trial population. Diagnosis codes, such as International Classification of Diseases codes, do not comprehensively illustrate a patient's care journey and offer no insight into drug-irAE causality. This study aims to capture the relationship between ICIs and irAEs more accurately by using augmented curation (AC), a natural language processing-based innovation, on unstructured data in electronic health records.

METHODS: In a cohort of 9,290 patients treated with ICIs at Mayo Clinic from 2005 to 2021, we compared the prevalence of irAEs using diagnosis codes and AC models, which classify drug-irAE pairs in clinical notes with implied textual causality. Four illustrative irAEs with high patient impact-myocarditis, encephalitis, pneumonitis, and severe cutaneous adverse reactions, abbreviated as MEPS-were analyzed using corticosteroid administration and ICI discontinuation as proxies of severity.

RESULTS: For MEPS, only 70% (n = 118) of patients found by AC were also identified by diagnosis codes. Using AC models, patients with MEPS received corticosteroids for their respective irAE 82% of the time and permanently discontinued the ICI because of the irAE 35.9% (n = 115) of the time.

CONCLUSION: Overall, AC models enabled more accurate identification and assessment of patient impact of ICI-induced irAEs not found using diagnosis codes, demonstrating a novel and more efficient strategy to assess real-world clinical outcomes in patients treated with ICIs.

PMID:38687915 | DOI:10.1200/CCI.23.00151