Epilepsy Res. 2024 Apr 3;202:107358. doi: 10.1016/j.eplepsyres.2024.107358. Online ahead of print.

ABSTRACT

BACKGROUND: Nonadherence to antiepileptic drugs (AEDs) is a prevalent issue in India, contributing to suboptimal seizure control, higher morbidity and mortality, increased hospitalization rates, and a substantial effect on the overall quality of life for individuals with epilepsy.

OBJECTIVES: This study aimed to measure the prevalence of medication adherence among individuals with epilepsy in India and to identify factors associated with nonadherence.

METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, Embase, and Google Scholar for studies on AED adherence in India. Quality assessment employed Newcastle Ottawa Scale adapted for cross-sectional studies. Pooled prevalence was ascertained using a random-effects model in R software (version 4.2.2), with a 95% confidence interval. Heterogeneity was estimated with the I2 statistic, and publication bias was appraised via a funnel plot. Subgroup analyses, based on study region and adherence measurement tool, were done to investigate heterogeneity.

RESULTS: Nine cross-sectional studies with 1772 participants were analyzed. The pooled prevalence of adherence to AEDs in India stood at 49.9% (95% CI: 39.8%-60.1%). Subgroup analyses showed comparable adherence rates in the South (50.9%) and North (46.5%) regions of India. However, adherence rates varied substantially based on the measurement tool: Morisky Medication Adherence Scale-4 (MMAS-4) reported 71.3%, MMAS-8 indicated 45.9%, and Morisky Green Levine (MGL) adherence scale exhibited 42.0%. Factors contributing to non-adherence to antiepileptic therapies involved poor socioeconomic status, lower education levels, polytherapy, drug-related side effects, and substance abuse.

CONCLUSIONS: Almost half of persons with epilepsy in India were non-adherent to their AEDs. This underscores the importance for healthcare professionals to pay greater attention to improving the adherence rate to AEDs within the healthcare service.

PMID:38603915 | DOI:10.1016/j.eplepsyres.2024.107358

Proc ACM Int Conf Inf Knowl Manag. 2023 Oct;2023:4724-4730. doi: 10.1145/3583780.3615490. Epub 2023 Oct 21.

ABSTRACT

Predicting adverse drug reactions (ADRs) of drugs is one of the most critical steps in drug development. By pre-estimating the adverse reactions, researchers and drug development companies can greatly prevent the potential ADR risks and tragedies. However, the current ADR prediction methods suffer from several limitations. First, the prediction results are based on pure drug-related information, which makes them impossible to be directly applied for the personalized ADR prediction task. The lack of personalization of models also makes rare adverse events hard to be predicted. Therefore, it is of great interest to develop a new personalized ADR prediction method by introducing additional sources, e.g., patient health records. However, few methods have tried to use additional sources. In the meantime, the variety of different source formats and structures makes this task more challenging. To address the above challenges, we propose a novel personalized multi-sourced-based drug adverse reaction prediction model named pADR. pADR first works on every single source to transform them into proper representations. Next, a hierarchical multi-sourced Transformer is designed to automatically model the interactions between different sources and fuse them together for the final adverse event prediction. Experimental results on a new multi-sourced ADR prediction dataset show that PADR outperforms state-of-the-art drug-based baselines. Moreover, the case and ablation studies also illustrate the effectiveness of our proposed fusion strategies and the reasonableness of each module design.

PMID:38601743 | PMC:PMC11005853 | DOI:10.1145/3583780.3615490

Can J Hosp Pharm. 2024 Apr 10;77(2):e3491. doi: 10.4212/cjhp.3491. eCollection 2024.

ABSTRACT

BACKGROUND: Expansion of the scope of pharmacists' activities in hospital is associated with reductions in adverse events and drug-related readmissions. However, the breadth of hospital pharmacists' clinical activities varies widely across Ontario due to provisions in the provincial Public Hospitals Act. Few data exist defining expanded scope in institutions across Ontario.

OBJECTIVES: The primary objective was to describe the scope of practice of hospital pharmacists in Ontario who were undertaking expanded clinical activities based on policies or medical directives. The secondary objectives included determining benefits, limitations, facilitators, and barriers associated with implementing these activities.

METHODS: A survey was sent to the pharmacy leadership of Groups A and B public hospitals across Ontario. The survey contained quantitative and qualitative questions focused on 3 domains of expanded-scope activities: adaptation, discontinuation, and renewal of medication orders; prescriptive authority; and drug monitoring.

RESULTS: Of 56 hospitals invited, 46 (82%) submitted a survey response, with 1 exclusion (due to no response on some mandatory questions). The most common expanded-scope activity was independent performance of therapeutic drug monitoring (71%, 32/45). Pharmacists had the authority to independently adapt, discontinue, or renew inpatient medication orders in 60% (27/45) of hospitals, and could independently initiate medication orders in 20% (9/45). Barriers to implementing expanded-scope activities included limited time and staffing. Facilitators included proactive leadership, demonstrated clinical value, and strong rapport with other health care providers.

CONCLUSIONS: Many institutions in Ontario have established polices to expand pharmacists' clinical activities, but there is a great deal of variability in scope of practice. Advocacy at the provincial level to unify scope of practice will help to optimize patient outcomes.

PMID:38601132 | PMC:PMC10984262 | DOI:10.4212/cjhp.3491

Glomerular Dis. 2024 Mar 14;4(1):64-73. doi: 10.1159/000538255. eCollection 2024 Jan-Dec.

ABSTRACT

INTRODUCTION: Toxic gain-of-function Apolipoprotein L1 (APOL1) variants contribute to the development of proteinuric nephropathies collectively referred to as APOL1-mediated kidney disease (AMKD). Despite standard-of-care treatments, patients with AMKD experience accelerated progression to end-stage kidney disease. The identification of two APOL1 variants as the genetic cause of AMKD inspired development of inaxaplin, an inhibitor of APOL1 channel activity that reduces proteinuria in patients with AMKD.

METHODS: We conducted two phase 1 studies evaluating the safety, tolerability, and pharmacokinetics of single-ascending doses (SAD) and multiple-ascending doses (MAD) of inaxaplin in healthy participants. In the SAD cohorts, participants were randomized to receive inaxaplin as a single dose (range, 7.5 mg to 165 mg) or placebo. In the MAD cohorts, participants were randomized to receive multiple doses of inaxaplin (range, 15 to 120 mg daily) or placebo for 14 days. We assessed safety and tolerability based on adverse events (AEs), clinical laboratory values, electrocardiograms (ECGs), and vital signs.

RESULTS: A total of 178 participants were randomized in the SAD/MAD cohorts of both studies (mean age: 36.7 years; 94.9% male). The proportion of participants with any AEs was similar in the inaxaplin (24.6%) and placebo (22.7%) groups. All AEs were mild or moderate in severity; there were no serious AEs. Headache was the most common AE: 10.4% and 2.3% in the inaxaplin and placebo groups, respectively. There were no drug-related treatment discontinuations and no clinically relevant trends in laboratory values, ECGs, or vital signs.

DISCUSSION/CONCLUSION: Inaxaplin is safe and well tolerated at single doses up to 165 mg and multiple doses up to 120 mg daily for 14 days. These results are consistent with the favorable safety profile of inaxaplin in a completed phase 2a proof-of-concept study. Together, these findings support continued evaluation of inaxaplin in an ongoing phase 2/3 pivotal trial as a potential precision medicine for patients with AMKD.

PMID:38600955 | PMC:PMC11006409 | DOI:10.1159/000538255

Clin Cancer Res. 2024 Apr 15;30(8):1685-1695. doi: 10.1158/1078-0432.CCR-23-0914.

ABSTRACT

PURPOSE: Combination therapies are a promising approach for improving cancer treatment, but it is challenging to predict their resulting adverse events in a real-world setting.

EXPERIMENTAL DESIGN: We provide here a proof-of-concept study using 15 million patient records from the FDA Adverse Event Reporting System (FAERS). Complex adverse event frequencies of drugs or their combinations were visualized as heat maps onto a two-dimensional grid. Adverse event frequencies were shown as colors to assess the ratio between individual and combined drug effects. To capture these patterns, we trained a convolutional neural network (CNN) autoencoder using 7,300 single-drug heat maps. In addition, statistical synergy analyses were performed on the basis of BLISS independence or χ2 testing.

RESULTS: The trained CNN model was able to decode patterns, showing that adverse events occur in global rather than isolated and unique patterns. Patterns were not likely to be attributed to disease symptoms given their relatively limited contribution to drug-associated adverse events. Pattern recognition was validated using trial data from ClinicalTrials.gov and drug combination data. We examined the adverse event interactions of 140 drug combinations known to be avoided in the clinic and found that near all of them showed additive rather than synergistic interactions, also when assessed statistically.

CONCLUSIONS: Our study provides a framework for analyzing adverse events and suggests that adverse drug interactions commonly result in additive effects with a high level of overlap of adverse event patterns. These real-world insights may advance the implementation of new combination therapies in clinical practice.

PMID:38597991 | PMC:PMC11016889 | DOI:10.1158/1078-0432.CCR-23-0914

JAMA Netw Open. 2024 Apr 1;7(4):e245960. doi: 10.1001/jamanetworkopen.2024.5960.

ABSTRACT

IMPORTANCE: Psilocybin has been studied in the treatment of depression and anxiety disorders. Clinical studies have mainly focused on efficacy, with systematic reviews showing favorable efficacy; however, none have primarily focused on psilocybin safety.

OBJECTIVE: To evaluate the acute adverse effects of psilocybin at therapeutic doses in the treatment of depression and anxiety.

DATA SOURCES: MEDLINE via PubMed, Web of Science, and ClinicalTrials.gov were searched for publications available between 1966 and November 30, 2023.

STUDY SELECTION: Randomized, double-blind clinical trials that reported adverse effects of psilocybin in patients treated for depression and anxiety were screened.

DATA EXTRACTION AND SYNTHESIS: Data were independently extracted by 2 authors and verified by 2 additional authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The inverse variance method with the Hartung-Knapp adjustment for the random-effects model was used, with a continuity correction of 0.5 for studies with 0 cell frequencies. Sensitivity analysis was conducted by sequentially removing 1 study at a time to assess the robustness of the results.

MAIN OUTCOMES AND MEASURES: The primary outcome was considered as the adverse effects of psilocybin at high and moderate (ie, therapeutic) dose regimens and compared with placebo, low-dose psilocybin, or other comparator in the treatment of depression and/or anxiety.

RESULTS: Six studies met the inclusion criteria with a total sample of 528 participants (approximately 51% female; median age 39.8 years; IQR, 39.8-41.2). Seven adverse effects were reported in multiple studies and included in the analysis. Among these, headache (relative risk [RR], 1.99; 95% CI 1.06-3.74), nausea (RR, 8.85; 95% CI, 5.68-13.79), anxiety (RR, 2.27; 95% CI, 1.11-4.64), dizziness (RR, 5.81; 95% CI, 1.02-33.03), and elevated blood pressure (RR, 2.29; 95% CI, 1.15- 4.53) were statistically significant. Psilocybin use was not associated with risk of paranoia and transient thought disorder.

CONCLUSIONS AND RELEVANCE: In this meta-analysis, the acute adverse effect profile of therapeutic single-dose psilocybin appeared to be tolerable and resolved within 48 hours. However, future studies need to more actively evaluate the appropriate management of adverse effects.

PMID:38598236 | DOI:10.1001/jamanetworkopen.2024.5960

Eur J Cancer. 2024 Mar 30;203:114039. doi: 10.1016/j.ejca.2024.114039. Online ahead of print.

ABSTRACT

BACKGROUND: cemiplimab is an immunoglobulin G4 monoclonal antibody targeting the programmed cell death-1 receptor. A nominal use program is available in Italy in advanced cervical cancer (CC) patients treated with platinum based chemotherapy based on the results of EMPOWER-Cervical 1/GOG-3016/ENGOTcx9 trial. This real-world, retrospective cohort, multicenter study aimed at describing clinical outcomes of patients with advanced CC treated with cemiplimab in Italy.

METHODS: The primary objective of the study was to assess the feasibility and the replicability of the initial results in a real world setting of cemiplimab nominal use. The primary endpoint of our analysis was progression free survival (PFS). Secondary endpoints included overall response rate (ORR), overall survival (OS) and safety data.

RESULTS: From March 2022 to December 2023, 135 patients were treated in 12 Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) Centers. Forty-two percent of patients had one or more comorbidities, hypertension being the most common (23.4%). Median PFS was 4.0 months (range 3.0-6.0) and median OS was 12.0 months (12.0- NR) with no differences according to PD-L1 status. Complete response (CR) or no evidence of disease (NED) were observed in 8.6%; partial response (PR) in 21.1%, stable disease (SD) in 14.8% and progression was recorded in 44.5% of patients. Most common drug related adverse events (AEs) were anemia (39.1%) and fatigue (27.8%). Immune related AEs occurred in 18.0%.

CONCLUSIONS: This study confirms the feasibility and the replicability of the cemiplimab nominal use in advanced CC, in a real-world practice in Italy.

PMID:38598922 | DOI:10.1016/j.ejca.2024.114039

Trials. 2024 Apr 10;25(1):250. doi: 10.1186/s13063-024-08093-x.

ABSTRACT

BACKGROUND: Acute type A aortic dissection (aTAAD) is a critical and life-threatening condition. Previous research has demonstrated that the use of ketorolac not only reduces the progression, incidence, and severity of aortic aneurysms in animal models, but also decreases postoperative mortality and complications in patients undergoing open abdominal aortic aneurysm replacement. However, there is a lack of studies investigating the efficacy of ketorolac in treating aTAAD in humans. Therefore, we conducted a study to evaluate the safety and efficacy of ketorolac in patients with aTAAD. Our hypothesis was that ketorolac treatment for aTAAD patients would meet safety indicators and effectively improve patient prognosis.

METHODS/DESIGN: This study is a single-center, randomized, double-blinded, and placebo-controlled study. A total of 120 patients with aTAAD will be recruited and will be randomized into the ketorolac group and placebo group with a ratio of 1:1. Ketorolac tromethamine 60 mg per 2 ml will be intramuscularly injected within 2 h before surgery, followed by intramuscular injections of 30 mg per 1 ml BID. on the first and second postoperative days in the Ketorolac group, while 0.9% saline will be administered at the same dose, dosage form, and time in the placebo group. This study aims to evaluate the safety and efficacy of ketorolac in improving the prognosis of aTAAD. The primary endpoint is the composite endpoint event concerning drug-related adverse events. Secondary endpoints include drug-related adverse events, laboratory examination of blood, diagnostic imaging tests, clinical biomarkers, etc. DISCUSSION: This study has been approved by the Medical Ethics Committee of Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical College (approval number: 2023-197-02). This study is designed to evaluate the safety and efficacy of ketorolac in patients with aTAAD. All participating patients will sign an informed consent form, and the trial results will be published in international peer-reviewed journals.

TRIAL REGISTRATION: The Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) ChiCTR2300074394. Registered on 4 October 2023.

PMID:38600561 | DOI:10.1186/s13063-024-08093-x

Int J Surg. 2024 Apr 10. doi: 10.1097/JS9.0000000000001397. Online ahead of print.

ABSTRACT

BACKGROUND: Thermal ablation is routinely used for solitary colorectal liver metastases (SCLM), but the added value of adjuvant systemic therapy in SCLM remains unclear. This study aimed to compare the long-term outcomes for SCLM treated by ablation alone (AB) versus ablation plus systemic therapy (AS).

METHODS: This multicenter retrospective study using nationwide data from fourteen institutions between October 2010 and May 2023, 369 patients with initial SCLM smaller than 5 cm, no extrahepatic metastases, and colorectal cancer R0 resection treated by thermal ablation were included. The crude analysis was used to analyze eligible cases between the two groups. The propensity score matching (PSM) to control for potential confounders in each matched group. Subgroup analyses were performed to identify specific survival benefits.

RESULTS: 61.2% (226/369) of eligible patients were treated with AS and 38.8% (143/369) with AB. During the median follow-up period of 8.8 years, 1-/3-/5-year DFS/OS rates did not differ between the two groups, when analyzed via PSM (P=0.52/0.08). Subgroup analysis revealed that AS was significantly associated with better OS than AB in patients with plasma CEA >5 ug/L (P=0.036), T (III-IV) category of primary cancer (P=0.034), or clinical risk score (1-2) (P=0.041). In each matched group, we did find a significant difference in drug-related adverse events (P<0.001) between AS group (24.1%, 28/116) and AB group (0.0%, 0/116).

CONCLUSIONS: For patients with plasma CEA >5 ug/L, T (III-IV) category of primary cancer, or clinical risk score (1-2), thermal ablation plus systemic therapy appeared to be associated with improved overall survival. Thermal ablation was equally effective in disease-free survival for treating solitary colorectal liver metastasis, whether with or without adjuvant systemic therapy.

PMID:38597399 | DOI:10.1097/JS9.0000000000001397

J Investig Med. 2024 Apr 10:10815589241247796. doi: 10.1177/10815589241247796. Online ahead of print.

ABSTRACT

Cisplatin use is often limited by its ototoxic side effects, which can lead to irreversible hearing loss. Preventing cisplatin-induced ototoxicity is crucial to improve patient outcomes. Fluoxetine and fluvoxamine, both SSRI antidepressants, inhibit the NLRP3 inflammasome, a potential therapeutic target for preventing ototoxicity. However, human studies have not evaluated if these antidepressants may protect against cisplatin-induced ototoxicity. The object of this study is to assess the association between fluoxetine or fluvoxamine use and the incidence of hearing loss or tinnitus in a large cohort of patients receiving cisplatin chemotherapy. We use a retrospective cohort study within the U.S. Department of Veterans Affairs (VA) healthcare system. Adult patients with cancer who received cisplatin chemotherapy between 2000 and 2023 are included. Incidence of ototoxicity, defined by ICD-9-CM or ICD-10-CM diagnoses of hearing loss or tinnitus is compared between concurrent use of fluoxetine or fluvoxamine and cisplatin alone. A total of 20,552 patients were included. Of those, 489 received cisplatin and fluoxetine or fluvoxamine. After propensity score adjustment, the hazard of ototoxicity was lower in the group receiving fluoxetine or fluvoxamine compared to the group receiving cisplatin alone (HR=0.62, 95% CI=(0.41-0.94)). Fluoxetine or fluvoxamine use may be associated with a reduced risk of cisplatin-induced ototoxicity. Randomized clinical trials are needed to confirm these findings and establish the efficacy of the medications in ototoxicity prevention. Further research is also warranted to investigate the potential mechanisms underlying this protective effect.

PMID:38597272 | DOI:10.1177/10815589241247796

J Pediatr Pharmacol Ther. 2024 Apr;29(2):119-129. doi: 10.5863/1551-6776-29.2.119. Epub 2024 Apr 8.

ABSTRACT

OBJECTIVE: Care coordination for children and youth with special health care needs and medical complexity (CYSHCN-CMC), especially medication management, is difficult for providers, parents/caregivers, and -patients. This report describes the creation of a clinical pharmacotherapy practice in a pediatric long-term care facility (pLTCF), application of standard operating procedures to guide comprehensive medication management (CMM), and establishment of a collaborative practice agreement (CPA) to guide drug therapy.

METHODS: In a prospective case series, 102 patients characterized as CYSHCN-CMC were included in this pLTCF quality improvement project during a 9-month period.

RESULTS: Pharmacists identified, prevented, or resolved 1355 drug therapy problems (DTP) with an average of 13 interventions per patient. The patients averaged 9.5 complex chronic medical conditions with a -median length of stay of 2815 days (7.7 years). The most common medications discontinued due to pharmacist assessment and recommendation included diphenhydramine, albuterol, sodium phosphate enema, ipratropium, and metoclopramide. The average number of medications per patient was reduced from 23 to 20. A pharmacoeconomic analysis of 244 of the interventions revealed a monthly direct cost savings of $44,304 ($434 per patient per month) and monthly cost avoidance of $48,835 ($479 per patient per month). Twenty-eight ED visits/admissions and 61 clinic and urgent care visits were avoided. Hospital -readmissions were reduced by 44%. Pharmacist recommendations had a 98% acceptance rate.

CONCLUSIONS: Use of a CPA to conduct CMM in CYSHCN-CMC decreased medication burden, resolved, and prevented adverse events, reduced health care-related costs, reduced hospital readmissions and was well-accepted and implemented collaboratively with pLTCF providers.

PMID:38596413 | PMC:PMC11001202 | DOI:10.5863/1551-6776-29.2.119

Cureus. 2024 Mar 9;16(3):e55865. doi: 10.7759/cureus.55865. eCollection 2024 Mar.

ABSTRACT

Clozapine has become a widely popular and effective medication in the treatment of refractory schizophrenia and refractory bipolar disorder. Although the use of clozapine proves to be an effective resort, it has to be closely monitored due to its narrow therapeutic range and multiple dangerous adverse effects. In rare cases, clozapine has been known to cause an antagonistic myoclonic jerk that leads to knee buckling. Here, we present the case of a 29-year-old female who is being treated for schizoaffective disorder, bipolar, manic type, who reported two instances of knee buckling associated with falls while taking clozapine.

PMID:38595866 | PMC:PMC11002468 | DOI:10.7759/cureus.55865

J Oncol Pharm Pract. 2024 Apr 9:10781552241229662. doi: 10.1177/10781552241229662. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer patients are at a significantly increased risk of drug-related problems due to multiple drugs. An inclusive review of drug-related problems would offer an approach for healthcare providers to decrease the frequency of drug-related problems in cancer patients. The purpose of this study was to assess all characteristic components of drug-related problems in cancer patients, and explore actions taken to resolve the detected drug-related problems the results could be used as a baseline for epidemiology and potential related risk factors for drug-related problems in cancer patients.

METHODS: The present systematic review was done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search consisted of studies listed from January 2015 and up to May 2023. A systematic review was carried out using an electronic database with a combination of Medical subject Headings of key words Medical Subject Heading terms.

RESULTS: This evaluation included 17 studies from 11 different nations having 11 prospective and 6 retrospective studies. Pharmaceutical Care Network Europe classification system is the most commonly used to classify the drug-related problems. The prevalence of drug-related problems varied from 9.6% to 92.8%. The key predictors of the drug-related problems were age, polypharmacy, multiple comorbidities, and the stage of the disease.

CONCLUSION: Drug-related problems are significantly more common among cancer patients. The age, polypharmacy, multiple comorbidities, and the stage of the malignancy all enhance the risk of acquiring drug-related problems. This review raises awareness of drug-related problems, encourages their early detection, and emphasizes the necessity for framing effective drug-related problem management strategies which will enhance patient care.

PMID:38594941 | DOI:10.1177/10781552241229662

Front Immunol. 2024 Mar 15;15:1348189. doi: 10.3389/fimmu.2024.1348189. eCollection 2024.

ABSTRACT

Older patients with cancer, particularly those over 75 years of age, often experience poorer clinical outcomes compared to younger patients. This can be attributed to age-related comorbidities, weakened immune function, and reduced tolerance to treatment-related adverse effects. In the immune checkpoint inhibitors (ICI) era, age has emerged as an influential factor impacting the discovery of predictive biomarkers for ICI treatment. These age-linked changes in the immune system can influence the composition and functionality of tumor-infiltrating immune cells (TIICs) that play a crucial role in the cancer response. Older patients may have lower levels of TIICs infiltration due to age-related immune senescence particularly T cell function, which can limit the effectivity of cancer immunotherapies. Furthermore, age-related immune dysregulation increases the exhaustion of immune cells, characterized by the dysregulation of ICI-related biomarkers and a dampened response to ICI. Our review aims to provide a comprehensive understanding of the mechanisms that contribute to the impact of age on ICI-related biomarkers and ICI response. Understanding these mechanisms will facilitate the development of treatment approaches tailored to elderly individuals with cancer.

PMID:38590525 | PMC:PMC11000233 | DOI:10.3389/fimmu.2024.1348189

Drug Ther Bull. 2024 Apr 9:dtb-2024-000021. doi: 10.1136/dtb.2024.000021. Online ahead of print.

NO ABSTRACT

PMID:38594060 | DOI:10.1136/dtb.2024.000021

Transl Androl Urol. 2024 Mar 31;13(3):433-441. doi: 10.21037/tau-24-96. Epub 2024 Mar 25.

ABSTRACT

BACKGROUND: ARASENS has demonstrated the efficacy and safety for darolutamide (DARO) with androgen deprivation therapy (ADT) plus docetaxel in metastasis hormone-sensitive prostate cancer (mHSPC). There is a lack of reports for DARO with ADT in mHSPC though the regimen is used in clinical from time to time. Moreover, recent studies have supported the importance of early and rapid prostate-specific antigen (PSA) reduction, which correlates with reduced disease progression and improved survival in patients with mHSPC. This study aims to evaluate PSA reduction as a primary endpoint for DARO with ADT in the treatment of mHSPC and to evaluate the real-world short-term PSA control of DARO with ADT from two leading medical centers in China.

METHODS: We retrospectively reviewed the clinical records of patients with mHSPC receiving ADT and DARO (600 mg, b.i.d.). The collection of data spanned from March 1, 2022, to July 31, 2023. The main observation indicators were PSA level and drug-related adverse events (AE) after medication. PSA levels were closely monitored prior to treatment initiation and at 2-week intervals, as well as at 1, 3, and 6 months after the initiation of treatment. We also conducted an analysis to determine the proportion of patients achieving a PSA reduction of 50% or more (PSA50) and 90% or more (PSA90) as well as the percentage of patients with a notable decrease in PSA level to 0.2 ng/mL and PSA nadir of ≤0.02 ng/mL.

RESULTS: Fifty-one patients were included in the study, with a median age of 73 years. At diagnosis of HSPC, the majority of patients had a Gleason score ≥8 (n=40, 78.40%) and a median baseline PSA level of 88 ng/mL. Approximately 45.1% (n=23) of patients had a Charlson Comorbidity Index over 1 and were receiving one or more nontumor-related treatments. The median follow-up time was 9.3 months (range, 1.16-15.8 months). The median reductions in PSA levels compared to baseline were 84.37%, 91.48%, 94.67% and 99.81% at 2 weeks, 1 month, 3 months and 6 months after administration of DARO with ADT, respectively. The median time to PSA50, PSA90, significant PSA reduction (PSA <0.2 ng/mL), and PSA nadir (PSA <0.02 ng/mL) was 0.97, 1.27, 1.98, and 2.08 months, respectively. AE mainly included fatigue (two patients) and arm pain (one patient), all of which were grade I or II AE. No grade III or AE were observed.

CONCLUSIONS: For treating prostate cancer, DARO with ADT has good early efficacy, demonstrating prompt and substantial control of PSA levels, with a favorable safety profile.

PMID:38590967 | PMC:PMC10999023 | DOI:10.21037/tau-24-96

Cureus. 2024 Mar 8;16(3):e55819. doi: 10.7759/cureus.55819. eCollection 2024 Mar.

ABSTRACT

Amiodarone is a commonly used antiarrhythmic used to treat atrial fibrillation and ventricular tachycardias. While this agent can present with pulmonary, thyroid, and hepatic side effects, it can also, less commonly cause neurologic toxicity, particularly optic neuropathy. Optic neuropathy can manifest as acute vision loss. The management of amiodarone-associated optic neuropathy (AAON) includes early recognition of symptom manifestation so that the medication can be discontinued promptly. Here, we describe a case of a 64-year-old male who developed acute onset complete left-sided vision loss after initiation of amiodarone.

PMID:38590471 | PMC:PMC10999886 | DOI:10.7759/cureus.55819

Cureus. 2024 Mar 6;16(3):e55666. doi: 10.7759/cureus.55666. eCollection 2024 Mar.

ABSTRACT

Immune-related adverse events (IrAEs) involving the bladder are seldom reported and tend to be overlooked by oncologists. Cystitis caused by immune checkpoint inhibitors (ICIs) is rarely reported, with only four documented instances in the literature, of which just one case is attributed to pembrolizumab. We present a rare occurrence of pembrolizumab-induced hemorrhagic cystitis in a 71-year-old male with stage II-b lung adenocarcinoma with an chronic indwelling Foley catheter. He presented with persistent hematuria despite the completion of a course of antibiotics for a urinary infection; a cystoscopic examination was also normal. Drug-induced cystitis was suspected and the patient was treated with prednisone as well as temporary discontinuation of pembrolizumab, which was followed by an improvement of symptoms.

PMID:38586668 | PMC:PMC10997305 | DOI:10.7759/cureus.55666

EClinicalMedicine. 2024 Jan 8;68:102364. doi: 10.1016/j.eclinm.2023.102364. eCollection 2024 Feb.

ABSTRACT

BACKGROUND: RBT-1 is a combination drug of stannic protoporfin (SnPP) and iron sucrose (FeS) that elicits a preconditioning response through activation of antioxidant, anti-inflammatory, and iron-scavenging pathways, as measured by heme oxygenase-1 (HO-1), interleukin-10 (IL-10), and ferritin, respectively. Our primary aim was to determine whether RBT-1 administered before surgery would safely and effectively elicit a preconditioning response in patients undergoing cardiac surgery.

METHODS: This phase 2, double-blind, randomised, placebo-controlled, parallel-group, adaptive trial, conducted in 19 centres across the USA, Canada, and Australia, enrolled patients scheduled to undergo non-emergent coronary artery bypass graft (CABG) and/or heart valve surgery with cardiopulmonary bypass. Patients were randomised (1:1:1) to receive either a single intravenous infusion of high-dose RBT-1 (90 mg SnPP/240 mg FeS), low-dose RBT-1 (45 mg SnPP/240 mg FeS), or placebo within 24-48 h before surgery. The primary outcome was a preoperative preconditioning response, measured by a composite of plasma HO-1, IL-10, and ferritin. Safety was assessed by adverse events and laboratory parameters. Prespecified adaptive criteria permitted early stopping and enrichment. This trial is registered with ClinicalTrials.gov, NCT04564833.

FINDINGS: Between Aug 4, 2021, and Nov 9, 2022, of 135 patients who were enrolled and randomly allocated to a study group (46 high-dose, 45 low-dose, 44 placebo), 132 (98%) were included in the primary analysis (46 high-dose, 42 low-dose, 44 placebo). At interim, the trial proceeded to full enrollment without enrichment. RBT-1 led to a greater preconditioning response than did placebo at high-dose (geometric least squares mean [GLSM] ratio, 3.58; 95% CI, 2.91-4.41; p < 0.0001) and low-dose (GLSM ratio, 2.62; 95% CI, 2.11-3.24; p < 0.0001). RBT-1 was generally well tolerated by patients. The primary drug-related adverse event was dose-dependent photosensitivity, observed in 12 (26%) of 46 patients treated with high-dose RBT-1 and in six (13%) of 45 patients treated with low-dose RBT-1 (safety population).

INTERPRETATION: RBT-1 demonstrated a statistically significant cytoprotective preconditioning response and a manageable safety profile. Further research is needed. A phase 3 trial is planned.

FUNDING: Renibus Therapeutics, Inc.

PMID:38586479 | PMC:PMC10994969 | DOI:10.1016/j.eclinm.2023.102364

Korean J Fam Med. 2024 Apr 5. doi: 10.4082/kjfm.23.0220. Online ahead of print.

ABSTRACT

Medication review is an intervention with the potential to reduce drug-related problems (DRPs) in the elderly. This study aimed to determine the effect of pharmacists' medication reviews on geriatric patients. This study accessed two online databases, MEDLINE Complete and Scopus, and examined all studies published in English between 2019 and 2023, except for reviews. The studies included (1) participants over 65 years of age and (2) medication reviews conducted by pharmacists. The titles, abstracts, and full texts were reviewed for data extraction to determine whether the studies satisfied the inclusion and exclusion criteria. Forty-four of the initial 709 articles were included in this study. The articles included discussions on the incidence rates of DRPs and potentially inappropriate medications (PIMs) (n=21), hospitalization (n=14), medication adherence (n=9), quality of life (QoL) (n=8), and falls (n=7). Pharmacist medication reviews were associated with a reduced incidence of DRPs and PIMs, and improved adherence to medications. Patients' overall QoL is also increasing. However, pharmacist medication reviews were not strongly associated with decreased hospitalization or falls. A pharmacist's medication review may be a feasible intervention for reducing the incidence rates of DRPs and PIMs, regardless of whether it is performed as a sole intervention or supplemented with other interventions. The intervention was also effective in increasing medication adherence and QoL.

PMID:38583876 | DOI:10.4082/kjfm.23.0220