Cureus. 2022 Aug 8;14(8):e27778. doi: 10.7759/cureus.27778. eCollection 2022 Aug.

ABSTRACT

Dasatinib is a second-generation BCR-ABL tyrosine kinase inhibitor (TKI) that is approved for the treatment of chronic myeloid leukemia (CML), a myeloproliferative disorder seen commonly in adults over the age of 50. Dasatinib is superior in tolerance and efficacy to first-generation TKIs such as imatinib, given its ability to target mutation products that are resistant to first-generation TKIs. One of the common side effects of dasatinib includes pleural effusion which can be seen in up to 25% of patients on treatment. These effusions are predominantly exudative; however, they tend to resolve upon discontinuation of the drug. While infrequent, chylous effusions have been reported with the use of dasatinib; they tend to resolve following discontinuation of the drug. We present a case of a patient who was treated with dasatinib and developed a chylous effusion which was refractory to the discontinuation of the medication. Our patient was switched to imatinib and since his first episode, he has had multiple reaccumulation requiring thoracentesis, all of which have revealed chylous pleural fluid as per fluid analysis. We present this case to highlight a rare adverse effect of dasatinib which, via an unknown mechanism, can potentially lead to irreversible damage to the lymphatic duct resulting in recurrent chylous effusions.

PMID:36106302 | PMC:PMC9450929 | DOI:10.7759/cureus.27778

Cureus. 2022 Sep 5;14(9):e28798. doi: 10.7759/cureus.28798. eCollection 2022 Sep.

ABSTRACT

Drug-induced liver injury (DILI) is a frequent cause of liver toxicity. We describe the case of a 32-year-old male patient without any relevant past medical history or medication use. In the past two months, he was engaged in weightlifting exercises and consumed androgenic-anabolic steroids to enhance his exercise routine. The patient initially experienced choluria and acholia for two weeks, followed by itching for two days, which led him to present to the emergency room. His laboratory results revealed cytocholestasis. He was admitted for investigations and after excluding other causes of liver injury, the diagnosis of DILI related to the consumption of androgenic-anabolic steroids was made. This case report highlights the perils of using performance-enhancing substances such as androgenic-anabolic steroids, which may lead to severe side effects like DILI.

PMID:36105900 | PMC:PMC9444045 | DOI:10.7759/cureus.28798

Integr Med Rep. 2022 Aug 1;1(1):157-163. doi: 10.1089/imr.2022.0070. Epub 2022 Aug 26.

ABSTRACT

BACKGROUND: Opioid use disorder (OUD) remains a major public health concern. Despite the use of medications for OUD such as buprenorphine, the current gold-standard treatment, relapse in the context of increased craving remains common. Cannabidiol (CBD) has been shown to reduce cue-induced craving in individuals with OUD, but among those who were not receiving any buprenorphine treatment. This small proof-of-concept open-label study sought to evaluate the effect of CBD on cue-induced craving among individuals with OUD who were being actively treated with buprenorphine.

METHODS: Participants (n = 5) received CBD (Epidiolex®) 600 mg once daily for 3 consecutive days in an open-label manner. Primary outcome was cue-induced craving measured on a visual analog scale of 0 to 10, calculated as the difference in craving in response to drug-related versus neutral cues. The cue-reactivity paradigm was performed at baseline before CBD administration, and was repeated after 3 days of CBD. Secondary outcomes included scores on depression, anxiety, pain, opioid withdrawal, and side effects.

RESULTS: All participants were actively taking buprenorphine for an average of 37.8 months (range 1-120 months). Cue-induced craving was significantly lower after CBD dosing compared with baseline (0.4 vs. 3.2, paired t-test, p = 0.0046). No significant changes in scores for depression, anxiety, pain, or opioid withdrawal were noted. CBD was well tolerated, although one participant experienced moderate sedation; otherwise, no other adverse effects were reported.

CONCLUSIONS: Given the high risk for bias in a small uncontrolled open label study such as this, results must be interpreted with caution. A larger adequately powered trial with a suitable control group is needed to confirm the finding that CBD may help to reduce cue-induced craving among individuals with OUD currently on buprenorphine treatment. Research should further evaluate whether adjunctive use of CBD can improve clinical outcomes for individuals with OUD maintained on buprenorphine. ClinicalTrials.gov (NCT04192370).

PMID:36105269 | PMC:PMC9462449 | DOI:10.1089/imr.2022.0070

BMC Health Serv Res. 2022 Sep 14;22(1):1157. doi: 10.1186/s12913-022-08505-1.

ABSTRACT

BACKGROUND: The incidence of drug-related problems (DRPs) has caused serious health hazards and economic burdens among polymedicine patients. Effective communication between clinical pharmacists and physicians has a significant impact on reducing DRPs, but the evidence is poor. This study aimed to explore the impact of communication between clinical pharmacists and physicians on reducing DRPs.

METHODS: A semistructured interview was conducted to explore the communication mode between clinical pharmacists and physicians based on the interprofessional approach of the shared decision-making model and relational coordination theory. A randomized controlled trial (RCT) was used to explore the effects of communication intervention on reducing DRPs. Logistic regression analysis was used to identify the influencing factors of communication.

RESULTS: The mode of communication is driven by clinical pharmacists between clinical pharmacists and physicians and selectively based on different DRP types. Normally, the communication contents only cover two (33.8%) types of DRP contents or fewer (35.1%). The communication time averaged 5.8 minutes. The communication way is predominantly face-to-face (91.3%), but telephone or other online means (such as WeChat) may be preferred for urgent tasks or long physical distances. Among the 367 participants, 44 patients had DRPs. The RCT results indicated a significant difference in DRP incidence between the control group and the intervention group after the communication intervention (p = 0.02), and the incidence of DRPs in the intervention group was significantly reduced (15.6% vs. 0.07%). Regression analysis showed that communication time had a negative impact on DRP incidence (OR = 13.22, p < 0.001).

CONCLUSION: The communication mode based on the interprofessional approach of the shared decision-making between clinical pharmacists and physicians in medication decision-making could significantly reduce the incidence of DRPs, and the length of communication time is a significant factor. The longer the communication time is, the fewer DRPs that occur.

TRIAL REGISTRATION: This trial was approved by the ethics committee of The First Affiliated Hospital of Medical College of Xinjiang Shihezi University Hospital (kj2020-087-03) and registered in the China clinical trial registry (https://www.chictr.org.cn , number ChiCTR2000035321 date: 08/08/2020).

PMID:36104805 | DOI:10.1186/s12913-022-08505-1

Rheumatol Int. 2022 Sep 14. doi: 10.1007/s00296-022-05201-5. Online ahead of print.

ABSTRACT

Colchicine is increasingly used as the number of potential indications expands. However, it also has a narrow therapeutic index that is associated with bothersome to severe side effects. When concomitantly use with medications inhibiting its metabolism, higher plasma levels will result and increase likelihood of colchicine toxicity. We conducted a cohort study using electronic health records comparing encounters with colchicine plus a macrolide and colchicine with an antibiotic non-macrolide. We assessed the relationship between the two groups using adjusted multivariate logistic regression models and the risk of rhabdomyolysis, pancytopenia, muscular weakness, heart failure, acute hepatic failure and death. 12670 patients on colchicine plus an antibiotic non-macrolide were compared to 2199 patients exposed to colchicine plus a macrolide. Patients exposed to colchicine and a macrolide were majority men (n = 1329, 60.4%) and white (n = 1485, 67.5%) in their late sixties (mean age in years 68.4, SD 15.6). Heart failure was more frequent in the colchicine plus a macrolide cohort (n = 402, 18.3%) vs the colchicine non-macrolide one (n = 1153, 9.1%) (p < 0.0001) and also had a higher mortality rate [(85 (3.87%) vs 289 (2.28%), p < 0.0001 macrolides vs non-macrolides cohorts, respectively]. When the sample was limited to individuals exposed to either clarithromycin or erythromycin and colchicine, the adjusted OR for acute hepatic failure was 2.47 (95% CI 1.04-5.91) and 2.06 for death (95% CI 1.07-3.97). There is a significant increase in the risk of hepatic failure and mortality when colchicine is concomitantly administered with a macrolide. Colchicine should not be used concomitantly with these antibiotics or should be temporarily discontinued to avoid toxic levels of colchicine.

PMID:36104598 | DOI:10.1007/s00296-022-05201-5

J Med Toxicol. 2022 Oct;18(4):311-320. doi: 10.1007/s13181-022-00906-2. Epub 2022 Sep 12.

ABSTRACT

INTRODUCTION: Pharmacovigilance (PV) has proven to detect post-marketing adverse drug events (ADE). Previous research used the natural language processing (NLP) tool to extract unstructured texts relevant to ADEs. However, texts without context reduce the efficiency of such algorithms. Our objective was to develop and validate an innovative NLP tool, aTarantula, using a context-aware machine-learning algorithm to detect existing ADEs from social media using an aggregated lexicon.

METHOD: aTarantula utilized FastText embeddings and an aggregated lexicon to extract contextual data from three patient forums (i.e., MedHelp, MedsChat, and PatientInfo) taking warfarin. The lexicon used warfarin package inserts and synonyms of warfarin ADEs from UMLS and FAERS databases. Data was stored on SQLite and then refined and manually checked by three clinical pharmacists for validation.

RESULTS: Multiple organ systems where the most frequent ADE were reported at 1.50%, followed by CNS side effects at 1.19%. Lymphatic system ADEs were the least common side effect reported at 0.09%. The overall Spearman rank correlation coefficient between patient-reported data from the forums and FAERS was 0.19. As determined by pharmacist validation, aTarantula had a sensitivity of 84.2% and a specificity of 98%. Three clinical pharmacists manually validated our results. Finally, we created an aggregated lexicon for mining ADEs from social media.

CONCLUSION: We successfully developed aTarantula, a machine-learning algorithmn based on artificial intelligence to extract warfarin-related ADEs from online social discussion forums automatically. Our study shows that it is feasible to use aTarantula to detect ADEs. Future researchers can validate aTarantula on the diverse dataset.

PMID:36097239 | DOI:10.1007/s13181-022-00906-2

Eur J Hosp Pharm. 2022 Sep 13:ejhpharm-2022-003424. doi: 10.1136/ejhpharm-2022-003424. Online ahead of print.

ABSTRACT

OBJECTIVE: Drug-induced sleepiness is a frequent cause of emergency department (ED) visits for frail patients. The aim of this study was to assess the impact of anticholinergic burden on 90-day revisitation risk for frail patients who visit the ED due to drug-induced sleepiness.

METHODS: This was a retrospective study in which patients treated at a fragility care area of an ED who sought consultation for drug-associated sleepiness from June 2020 to June 2021 were included. To evaluate the 90-day revisitation risk factors, a multivariate analysis was performed, including those factors with a p<0.200 from a previous univariate model. A Cox regression model was performed to assess the impact of a high burden on the time until 90-day ED revisitation.

RESULTS: One hundred and forty-eight patients were included (mean age 80.7±12.3 years). The median number of drugs that patients were currently on at emergency admission was eight (range 2-19), while at hospital discharge it was nine (range 2-20), with the median number of central nervous system (CNS) depressant drugs on admission being three (range 1-6). Thirty-five (23.6%) patients revisited the ED 90 days after discharge for sleepiness or agitation. In the multivariate model, a significant association was observed between a high anticholinergic burden during treatment at discharge (OR 3.74, 95% CI 1.36 to 9.71), chronic kidney disease (OR 2.87, 95% CI 1.19 to 6.81), and the risk of 90-day revisitation. Patients with high anticholinergic burden had a shorter time to revisit than those with medium or low anticholinergic burden (HR 1.96, 95% CI 1.05 to 3.99).

CONCLUSIONS: Patients with pharmacological sleepiness and a high anticholinergic burden in their chronic treatment carry a greater risk of revisitation to EDs, and should be considered candidates for specific interventions after visiting these units.

PMID:36100370 | DOI:10.1136/ejhpharm-2022-003424

Drug Ther Bull. 2022 Sep 13:dtb-2022-000051. doi: 10.1136/dtb.2022.000051. Online ahead of print.

ABSTRACT

The BNF is jointly published by the Royal Pharmaceutical Society and BMJ. BNF is published in print twice a year and interim updates are issued and published monthly in the digital versions. The following summary provides a brief description of some recent key changes that have been made to BNF content.

PMID:36100360 | DOI:10.1136/dtb.2022.000051

PLoS Negl Trop Dis. 2022 Sep 12;16(9):e0010680. doi: 10.1371/journal.pntd.0010680. eCollection 2022 Sep.

ABSTRACT

BACKGROUND: To manage the deleterious effects of parasitic infections such as lymphatic filariasis (LF) and schistosomiasis among school children, most countries including Ghana make use of mass drug administration (MDA). Although MDA has proven effective in reducing worm burden, unfortunately adverse drug effects (ADEs) post-MDA are derailing the gains and also remain poorly monitored. The study assessed incidence and factors associated with ADEs among students following a school-based mass de-worming exercise involving administration of Praziquantel (PZQT) and Albendazole (ADZ) against LF and SCH at Komenda-Edina-Eguafo-Abirem (KEEA) Municipal.

METHODOLOGY: After fulfilling all ethical obligations, a total of 598 students aged 5-20 years who received PZQT or ADZ monotherapy or a combination of the two (PZQT + ADZ) as part of the mass de-worming exercise were recruited through quota and random sampling. Bodyweight and height of students were measured and body mass index (BMI) calculated. Students were orally interviewed to obtain information such as age, sex, intake of diet before taking drugs. Subsequently, students were monitored over 24 hours post-MDA for cases of ADEs. Descriptive statistics and logistic regression analysis using SPSS version 26 was used to describe data collected and to determine associations between incidence of ADEs and predictor variables.

PRINCIPAL FINDINGS: Out of the 598 students, 243 (40.64%) represented by 124 males (51.03%) and 119 females (48.97%) with mean (SD) age of 13.43 (2.74) years experienced one or more forms of ADE. In decreasing order, the detected ADEs included headache (64.6%), Abdominal pain (48.6%), fever (30.0%), diarrhea (21.4%) and itching (12.8%). Multivariable statistical analysis showed that age 5-9 years (OR: 2.01, p = 0.041) and underweight (OR: 2.02, p = 0.038) were associated with incidence of ADEs. Compared with students who received combination therapy, students who received ADZ only (OR: 0.05, p < 0.001) and PZQT only (OR: 0.26, p < 0.001) had low cases of ADEs. Gender and diet intake before MDA were not associated with ADE incidence.

CONCLUSION: ADE incidence was common among students in the KEEA municipality. Age, underweight, and double dosing were associated with increase in ADE incidence, while gender and food intake were not associated with increase in ADE incidence. The Disease Control Unit of the Ghana Health Service should incorporate stringent ADE monitoring in post-MDA surveillance in the National MDA program in order to be able to detect, manage and report ADEs to inform planning for future MDA programs. Such initiatives will help not only in improving effectiveness of MDA programs but also identify high risk groups and exact strategies to reduce negative influence of ADE on MDA coverage and anthelminthic drug compliance.

PMID:36094964 | PMC:PMC9499283 | DOI:10.1371/journal.pntd.0010680

Ann Neurol. 2022 Sep 12. doi: 10.1002/ana.26503. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the safety, tolerability, pharmacokinetics, and immunogenicity of elezanumab (ABT-555), a fully human monoclonal antibody (mAb) directed against Repulsive Guidance Molecule A (RGMa), in healthy and multiple sclerosis (MS) study participants.

METHODS: The single-center, first-in-human, single ascending dose (SAD) study evaluated elezanumab (50mg-1600mg IV and 150mg SC) in 47 healthy men and women. The multi-center multiple ascending dose (MAD; NCT02601885) study evaluated elezanumab (150mg, 600mg, and 1800mg) in 20 adult men and women with MS, receiving either maintenance or no immunomodulatory treatment.

RESULTS: No pattern of study drug-related adverse events were identified for either the SAD or MAD elezanumab regimens. Across both studies, the Tmax occurred within 4 hours of elezanumab IV infusion, and the harmonic mean of t1/2 ranged between 18.6-67.7 days. Following multiple dosings, elezanumab Cmax , AUC, and Ctrough increased dose-proportionally and resulted in dose-dependent increases in elezanumab CSF concentrations. Elezanumab CSF penetration was 0.1-0.4% across both studies with CSF levels of free RGMa decreased by over 40%. Changes in CSF IL-10 and free RGMa demonstrated dose/exposure-dependence.

INTERPRETATION: The elezanumab pharmacokinetic profile supports monthly, or bi-monthly, administration of up to 1800mg with the option of a loading dose of 3600mg. Elezanumab partitioning into CSF is within the range expected for mAbs. Reduced CSF levels of free RGMa levels demonstrate central nervous system target binding of elezanumab with an apparent maximal effect at 1800mg IV. Exposure-associated increases in CSF IL-10, an anti-inflammatory cytokine with neuroprotective/neurorestorative properties, support potential pathway modulation in MS participants. This article is protected by copyright. All rights reserved.

PMID:36093738 | DOI:10.1002/ana.26503

Front Med (Lausanne). 2022 Aug 24;9:949520. doi: 10.3389/fmed.2022.949520. eCollection 2022.

ABSTRACT

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening immunologic reactions. Prior studies using electronic health records, registries or reporting databases are often limited in sample size or lack clinical details. We reviewed diverse detailed case reports published over four decades.

METHODS: Stevens-Johnson syndrome and toxic epidermal necrolysis-related case reports were identified from the MEDLINE database between 1980 and 2020. Each report was classified by severity (i.e., SJS, TEN, or SJS-TEN overlap) after being considered a "probable" or "definite" SJS/TEN case. The demographics, preconditions, culprit agents, clinical course, and mortality of the cases were analyzed across the disease severity.

RESULTS: Among 1,059 "probable" or "definite" cases, there were 381 (36.0%) SJS, 602 (56.8%) TEN, and 76 (7.2%) SJS-TEN overlap cases, with a mortality rate of 6.3%, 24.4%, and 21.1%, respectively. Over one-third of cases had immunocompromised conditions preceding onset, including cancer (n = 194,18.3%), autoimmune diseases (n = 97, 9.2%), and human immunodeficiency virus (HIV) (n = 52, 4.9%). During the acute phase of the reaction, 843 (79.5%) cases reported mucous membrane involvement and 210 (19.8%) involved visceral organs. Most cases were drug-induced (n = 957, 90.3%). A total of 379 drug culprits were reported; the most frequently reported drug were antibiotics (n = 285, 26.9%), followed by anticonvulsants (n = 196, 18.5%), analgesics/anesthetics (n = 126, 11.9%), and antineoplastics (n = 120, 11.3%). 127 (12.0%) cases reported non-drug culprits, including infections (n = 68, 6.4%), of which 44 were associated with a mycoplasma pneumoniae infection and radiotherapy (n = 27, 2.5%).

CONCLUSION: An expansive list of potential causative agents were identified from a large set of literature-reported SJS/TEN cases, which warrant future investigation to understand risk factors and clinical manifestations of SJS/TEN in different populations.

PMID:36091694 | PMC:PMC9449801 | DOI:10.3389/fmed.2022.949520

Front Cell Neurosci. 2022 Aug 24;16:941031. doi: 10.3389/fncel.2022.941031. eCollection 2022.

ABSTRACT

The biomedical community is rapidly developing COVID-19 drugs to bring much-need therapies to market, with over 900 drugs and drug combinations currently in clinical trials. While this pace of drug development is necessary, the risk of producing therapies with significant side-effects is also increased. One likely side-effect of some COVID-19 drugs is hearing loss, yet hearing is not assessed during preclinical development or clinical trials. We used the zebrafish lateral line, an established model for drug-induced sensory hair cell damage, to assess the ototoxic potential of seven drugs in clinical trials for treatment of COVID-19. We found that ivermectin, lopinavir, imatinib, and ritonavir were significantly toxic to lateral line hair cells. By contrast, the approved COVID-19 therapies dexamethasone and remdesivir did not cause damage. We also did not observe damage from the antibiotic azithromycin. Neither lopinavir nor ritonavir altered the number of pre-synaptic ribbons per surviving hair cell, while there was an increase in ribbons following imatinib or ivermectin exposure. Damage from lopinavir, imatinib, and ivermectin was specific to hair cells, with no overall cytotoxicity noted following TUNEL labeling. Ritonavir may be generally cytotoxic, as determined by an increase in the number of TUNEL-positive non-hair cells following ritonavir exposure. Pharmacological inhibition of the mechanotransduction (MET) channel attenuated damage caused by lopinavir and ritonavir but did not alter imatinib or ivermectin toxicity. These results suggest that lopinavir and ritonavir may enter hair cells through the MET channel, similar to known ototoxins such as aminoglycoside antibiotics. Finally, we asked if ivermectin was ototoxic to rats in vivo. While ivermectin is not recommended by the FDA for treating COVID-19, many people have chosen to take ivermectin without a doctor's guidance, often with serious side-effects. Rats received daily subcutaneous injections for 10 days with a clinically relevant ivermectin dose (0.2 mg/kg). In contrast to our zebrafish assays, ivermectin did not cause ototoxicity in rats. Our research suggests that some drugs in clinical trials for COVID-19 may be ototoxic. This work can help identify drugs with the fewest side-effects and determine which therapies warrant audiometric monitoring.

PMID:36090793 | PMC:PMC9448854 | DOI:10.3389/fncel.2022.941031

J Allergy Clin Immunol Pract. 2022 Sep;10(9):2395-2396. doi: 10.1016/j.jaip.2022.06.015.

NO ABSTRACT

PMID:36087945 | DOI:10.1016/j.jaip.2022.06.015

Med (N Y). 2022 Sep 9;3(9):600-602. doi: 10.1016/j.medj.2022.08.004.

ABSTRACT

A major goal of cancer therapy is developing chemotherapy strategies that are accurate and efficient without being highly toxic. Recently, Bradley et al.1 and Liu et al.2 developed radioresponsive prodrugs, enabling site-directed, radiotherapy-triggered, and precise chemotherapy, which displays synergistic efficacy and avoids the serious side effects of conventional treatment approaches.

PMID:36087574 | DOI:10.1016/j.medj.2022.08.004

Medicine (Baltimore). 2022 Sep 9;101(36):e30478. doi: 10.1097/MD.0000000000030478.

ABSTRACT

BACKGROUND: Astragalus (Hedysarum Multijugum Maxim., Huangqi) is a Chinese herbal medicine, and according to the theory of traditional Chinese medicine (TCM), Chinese medicinal preparations containing astragalus can be used clinically to treat radiation-induced lung injury (RILI). To systematically review the efficacy and safety of Chinese medicinal preparations containing astragalus in the prevention and treatment of RILI by means of meta-analysis.

METHODS: A systematic literature on randomized controlled trials (RCTs) of prescriptions containing astragalus in the treatment of RILI by Pubmed, Embase, Web of Science, Cochrane Library, China Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, WANFANG Database. The retrieval time is from the establishment of the database to January 18, 2022. Meta-analysis, heterogeneity test and sensitivity analysis were performed on eligible RCTs using Revman 5.4 software and STATA 17.0 software, and a "funnel plot" was used to analyze potential publication bias.

RESULTS: A total of 25 RCTs were included, including 1762 patients, and the most widely used drugs were heat-clearing and detoxifying, yin-nourishing and qi-nourishing. The prescriptions containing astragalus can significantly reduce the total incidence of RILI (P < .01), improve the total effective rate and cure rate of RILI (P < .01), improve the quality of life of patients, alleviate breathing difficulties and reduce the expression of inflammatory factors (P < .01), and no adverse reactions related to TCM treatment were reported.

CONCLUSION: The traditional Chinese medicinal preparation containing astragalus can effectively alleviate the clinical symptoms of RILI, reduce the toxic side effects, and is safe to use in clinic.

PMID:36086738 | DOI:10.1097/MD.0000000000030478

Annu Int Conf IEEE Eng Med Biol Soc. 2022 Jul;2022:1346-1349. doi: 10.1109/EMBC48229.2022.9871431.

ABSTRACT

In this work, an attempt has been made to discriminate drug with blood brain barrier (BBB) permeability using clinical phenotypes and extreme gradient boosting (XGBoost) methods. For this, the drug name and their clinical phenotypes namely side effects and indications are obtained from public available database. Prominent clinical phenotypes are selected using genetic algorithm (GA) and binary particle swarm optimization (BPSO). Four machine algorithms namely k-Nearest Neighbours, support vector machines, rotation forest and XGBoost are used for classification of BBB drugs. The result show that the proposed clinical phenotypes based features are able to distinguish drugs with BBB permeability. The maximum number of clinical phenotypes (69%) is reduced by BPSO and GA for classification. The XGBoost method is found to be most accurate [Formula: see text] is discriminating drugs with BBB permeability. The proposed approach are found to be capable of handling multi-parametric characteristics of the drugs. Particularly, the combination of XGBoost with combination of side effects and indications could be used for precision medicine applications. Clinical relevance- This establishes XGBoost approach for improved BBB permeability based drug classification with F1 =98.7% using exclusively clinical phenotypes.

PMID:36085687 | DOI:10.1109/EMBC48229.2022.9871431

J Cyst Fibros. 2022 Sep 7:S1569-1993(22)00657-9. doi: 10.1016/j.jcf.2022.09.002. Online ahead of print.

ABSTRACT

Elexacaftor/tezacaftor/ivacaftor (ELX-TEZ-IVA) is a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator shown to improve lung function and reduce sweat chloride in people with Cystic Fibrosis (CF). The only commonly reported dermatologic adverse effect with CFTR modulators including ELX-TEZ-IVA is rash. In this case series, we describe 19 patients who reported new onset or worsening of acne after initiation of this drug to their CF pharmacist or another member of their CF care team. The mechanism and frequency of this adverse effect is unknown.

PMID:36088208 | DOI:10.1016/j.jcf.2022.09.002

BMC Nephrol. 2022 Sep 9;23(1):309. doi: 10.1186/s12882-022-02934-0.

ABSTRACT

BACKGROUND: Lithium carbonate is commonly used in the treatment of bipolar disorder. A spectrum of side effects is associated with lithium, including nephrogenic diabetes insipidus, renal tubular acidosis, chronic tubulointerstitial nephropathy, and minimal change disease. Although the former three adverse effects are well-known, minimal change disease is relatively rare.

CASE PRESENTATION: We herein report a case of lithium therapy-induced minimal change disease with concurrent chronic tubulointerstitial nephropathy. A 66-year old man with bipolar disorder treated by lithium for 20 years, presented to the hospital with anasarca and decreased urine output for 4 weeks. The medical history also included hyperlipidemia, hypertension, and benign prostatic hyperplasia. Further laboratory investigation revealed elevated serum lithium (2.17 mmol/L), potassium (6.0 mmol/L), and creatinine levels (2.92 mg/dL), nephrotic range proteinuria, and hypoalbuminemia. Lithium was discontinued and the patient was treated with intravenous fluids. He underwent a kidney biopsy, which showed findings consistent with minimal change disease with concurrent acute tubular injury and chronic tubulointerstitial nephropathy. The patient was subsequently treated with steroids in an outpatient setting. He did not respond to the treatment, and hemodialysis was started.

CONCLUSION: Based on the previously reported cases and review of literature, occurrence of lithium-associated minimal change nephropathy is rare. Patients with lithium-associated minimal change disease and acute tubular injury usually respond to discontinuation of lithium therapy and/or steroid treatment. In this case, minimal change nephropathy was steroid-resistant and kidney function of the patient reported here did not recover after 6-month follow-up. We postulated the underlying cause to be minimal change disease with chronic tubulointerstitial nephropathy due to long-term lithium use. This case provides an example of a rare side effect of lithium-induced minimal change nephropathy with chronic tubulointerstitial nephropathy in addition to its well-known complication of interstitial nephritis or diabetes insipidus. In our opinion, these patients likely have much worse clinical outcome.

PMID:36085030 | PMC:PMC9463762 | DOI:10.1186/s12882-022-02934-0

J Assoc Physicians India. 2022 Sep;70(9):11-12.

NO ABSTRACT

PMID:36082900

Int J Mol Sci. 2022 Sep 2;23(17):10056. doi: 10.3390/ijms231710056.

ABSTRACT

Potential drug toxicities and drug interactions of redundant compounds of plant complexes may cause unexpected clinical responses or even severe adverse events. On the other hand, super-additivity of drug interactions between natural products and synthetic drugs may be utilized to gain better performance in disease management. Although without enough datasets for prediction model training, based on the SwissSimilarity and PubChem platforms, for the first time, a feasible workflow of prediction of both toxicity and drug interaction of plant complexes was built in this study. The optimal similarity score threshold for toxicity prediction of this system is 0.6171, based on an analysis of 20 different herbal medicines. From the PubChem database, 31 different sections of toxicity information such as "Acute Effects", "NIOSH Toxicity Data", "Interactions", "Hepatotoxicity", "Carcinogenicity", "Symptoms", and "Human Toxicity Values" sections have been retrieved, with dozens of active compounds predicted to exert potential toxicities. In Spatholobus suberectus Dunn (SSD), there are 9 out of 24 active compounds predicted to play synergistic effects on cancer management with various drugs or factors. The synergism between SSD, luteolin and docetaxel in the management of triple-negative breast cancer was proved by the combination index assay, synergy score detection assay, and xenograft model.

PMID:36077464 | PMC:PMC9456415 | DOI:10.3390/ijms231710056