Eur Arch Psychiatry Clin Neurosci. 2024 Mar 10. doi: 10.1007/s00406-024-01767-2. Online ahead of print.

ABSTRACT

Epidemiologic data indicate that overweight and obesity are on the rise worldwide. Psychiatric patients are particularly vulnerable in this respect as they have an increased prevalence of overweight and obesity, and often experience rapid, highly undesirable weight gain under psychotropic drug treatment. Current treatment strategies in psychiatry are oriented towards polypharmacy, so that the information on drug-induced weight gain from earlier monotherapy studies is of very limited validity. We have analyzed the longitudinal data of 832 inpatients with ICD-10 diagnoses of either F2 (schizophrenia; n = 282) or F3 (major depression; n = 550) with the goal of ranking treatment regimens in terms of weight gain, side effects, and response to treatment. The patient data were complemented by the data of 3180 students aged 18-22 years, with which we aimed to identify factors that enable the early detection and prevention of obesity and mental health problems. After 3 weeks of treatment, 47.7% of F2 patients and 54.9% of F3 patients showed a weight gain of 2 kg and more. Major predictive factors were "starting weight" (r = 0.115), "concurrent medications" (r = 0.176), and "increased appetite"(r = 0.275). Between 11 and 30% of the observed variance in weight gain could be explained by these factors, complemented by sex and age. The comparison between monotherapy (n = 409) and polypharmacy (n = 399) revealed significant drawbacks for polypharmacy: higher weight gain (p = 0.0005), more severe side effects (p = 0.0011), and lower response rates (F2: p = 0.0008); F3: p = 0.0101). The data of 3180 students made it clear that overweight and obesity often begin early in life among those affected, and are interconnected with personality traits, while increasing the risk of developing psychosomatic disturbances, mental health problems, or somatic illnesses. Although the available data did not readily lead to a comprehensive, clinically applicable model of unwanted weight gain, our results have nevertheless demonstrated that there are ways to successfully counteract such weight gain at early stages of treatment.

PMID:38462586 | DOI:10.1007/s00406-024-01767-2

Drug Saf. 2024 Apr;47(4):355-363. doi: 10.1007/s40264-024-01400-0. Epub 2024 Mar 9.

ABSTRACT

BACKGROUND: Pulmonary toxicity has been associated with drug use. This is often not recognized in clinical practice, and underestimated.

OBJECTIVE: We aimed to establish whether polymorphisms in certain genes corresponding with a metabolic pathway of drug(s) used are associated with pulmonary toxicity in patients with suspected drug-induced interstitial lung disease (DI-ILD).

METHODS: This retrospective observational study explored genetic variations in three clinically relevant cytochrome P450 (CYP) iso-enzymes (i.e., CYP2D6, CYP2C9, and CYP2C19) in a group of patients with a fibroticinterstitial lung disease, either non-specific interstitial pneumonia (n = 211) or idiopathic pulmonary fibrosis (n = 256), with a suspected drug-induced origin.

RESULTS: Of the 467 patients, 79.0% showed one or more polymorphisms in the tested genes accompanied by the use of drug(s) metabolized by a corresponding affected metabolic pathway (60.0% poor metabolizers and/or using two or more drugs [likely DI-ILD], 37.5% using three or more [highly likely DI-ILD]). Most commonly used drugs were statins (63.1%) with a predominance among men (69.4 vs 47.1%, p < 0.0001). Nitrofurantoin, not metabolized by the tested pathways, was prescribed more frequently among women (51.9 vs 4.5%, p < 0.00001).

CONCLUSIONS: In our cohort with suspected DI-ILD, 79% carried one or more genetic variants accompanied by the use of drugs metabolized by a corresponding affected pathway. In 60%, the diagnosis of DI-ILD was likely, whereas in 37.5%, it was highly likely, based on CYP analyses. This study underlines the importance of considering both drug use and genetic make-up as a possible cause, or at least a contributing factor, in the development and/or progression of fibrotic lung diseases.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00267800, registered in 2005.

PMID:38460070 | DOI:10.1007/s40264-024-01400-0

Drug Ther Bull. 2024 Mar 8:dtb-2023-000053. doi: 10.1136/dtb.2023.000053. Online ahead of print.

NO ABSTRACT

PMID:38458656 | DOI:10.1136/dtb.2023.000053

Medicine (Baltimore). 2024 Mar 8;103(10):e37204. doi: 10.1097/MD.0000000000037204.

ABSTRACT

INTRODUCTION: The use of immune checkpoint inhibitors (ICIs) is gradually increasing; ICIs produce a variety of immune-related adverse events (irAEs), especially ICI-induced hypoadrenocorticism, which can be a lethal complication if treatment is delayed.

PATIENT CONCERNS: A 63-year-old man received chemotherapy with pembrolizumab for nonsmall cell lung cancer. He developed drug-induced interstitial pneumonia 366 days after receiving pembrolizumab and was treated with prednisolone. Five hundred thirty-seven days later, he developed drug-induced eosinophilic enteritis, and pembrolizumab was discontinued and prednisolone was continued. After discontinuation of prednisolone, general malaise and edema of the lower extremities appeared, and adrenal insufficiency was suspected.

DIAGNOSIS: In blood tests on admission adrenocorticotropic hormone (ACTH) was 2.2 pg/mL and cortisol was 15 μg/dL, with no apparent cortisol deficiency. However, the cortisol circadian rhythm disappeared and remained low throughout the day; a corticotropin-releasing hormone stimulation test showed decreased reactive secretion of ACTH. Pituitary magnetic resonance imaging showed pituitary emptying, suggesting Empty Sella syndrome.

INTERVENTIONS AND OUTCOMES: We started hydrocortisone and his symptoms were improved.

CONCLUSIONS: The administration of high-dose steroids after ICI administration may mask the symptoms of hypoadrenocorticism as irAEs. Therefore, we should bear in mind the possibility of hypoadrenocorticism when we stop steroid therapy in patients who are treated with steroids after ICI administration.

PMID:38457550 | DOI:10.1097/MD.0000000000037204

J Med Internet Res. 2024 Mar 8;26:e47685. doi: 10.2196/47685.

ABSTRACT

BACKGROUND: Actively engaging patients with cancer and their families in monitoring and reporting medication safety events during care transitions is indispensable for achieving optimal patient safety outcomes. However, existing patient self-reporting systems often cannot address patients' various experiences and concerns regarding medication safety over time. In addition, these systems are usually not designed for patients' just-in-time reporting. There is a significant knowledge gap in understanding the nature, scope, and causes of medication safety events after patients' transition back home because of a lack of patient engagement in self-monitoring and reporting of safety events. The challenges for patients with cancer in adopting digital technologies and engaging in self-reporting medication safety events during transitions of care have not been fully understood.

OBJECTIVE: We aim to assess oncology patients' perceptions of medication and communication safety during care transitions and their willingness to use digital technologies for self-reporting medication safety events and to identify factors associated with their technology acceptance.

METHODS: A cross-sectional survey study was conducted with adult patients with breast, prostate, lung, or colorectal cancer (N=204) who had experienced care transitions from hospitals or clinics to home in the past 1 year. Surveys were conducted via phone, the internet, or email between December 2021 and August 2022. Participants' perceptions of medication and communication safety and perceived usefulness, ease of use, attitude toward use, and intention to use a technology system to report their medication safety events from home were assessed as outcomes. Potential personal, clinical, and psychosocial factors were analyzed for their associations with participants' technology acceptance through bivariate correlation analyses and multiple logistic regressions.

RESULTS: Participants reported strong perceptions of medication and communication safety, positively correlated with medication self-management ability and patient activation. Although most participants perceived a medication safety self-reporting system as useful (158/204, 77.5%) and easy to use (157/204, 77%), had a positive attitude toward use (162/204, 79.4%), and were willing to use such a system (129/204, 63.2%), their technology acceptance was associated with their activation levels (odds ratio [OR] 1.83, 95% CI 1.12-2.98), their perceptions of communication safety (OR 1.64, 95% CI 1.08-2.47), and whether they could receive feedback after self-reporting (OR 3.27, 95% CI 1.37-7.78).

CONCLUSIONS: In general, oncology patients were willing to use digital technologies to report their medication events after care transitions back home because of their high concerns regarding medication safety. As informed and activated patients are more likely to have the knowledge and capability to initiate and engage in self-reporting, developing a patient-centered reporting system to empower patients and their families and facilitate safety health communications will help oncology patients in addressing their medication safety concerns, meeting their care needs, and holding promise to improve the quality of cancer care.

PMID:38457204 | DOI:10.2196/47685

Cureus. 2024 Feb 5;16(2):e53669. doi: 10.7759/cureus.53669. eCollection 2024 Feb.

ABSTRACT

Cancer drug-induced thrombotic microangiopathy (DITMA) is an important and serious cause of kidney disease in cancer patients. In addition to classical chemotherapy, the increasing use of targeted therapy and immunotherapy has led to more oncotherapy-associated thrombotic microangiopathy (TMA). It is important for clinicians to recognize this potentially life-threatening adverse effect and gain knowledge of the patient's clinical course and treatment response. In this paper, we report a patient with lung cancer, who was treated with three different classes of anti-neoplastic agents, gemcitabine, ramucirumab, and pembrolizumab. This patient subsequently developed renal-limited thrombotic microangiopathy(rTMA) requiring hemodialysis. The varying features of TMA caused by these therapies were discussed. We also described the clinical course, diagnostic challenges, and management of this patient.

PMID:38455838 | PMC:PMC10918209 | DOI:10.7759/cureus.53669

Chin J Cancer Res. 2024 Feb 29;36(1):46-54. doi: 10.21147/j.issn.1000-9604.2024.01.05.

ABSTRACT

OBJECTIVE: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics, tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.

METHODS: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles. Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.

RESULTS: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea (85.7%), vomiting (28.6%), nausea (25.0%) and decreased appetite (17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response (CR), and three achieved partial response (PR). The objective response rate (ORR) and disease control rate (DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival (PFS) was 3.98 months.

CONCLUSIONS: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase III trial (No. NCT05122494).

PMID:38455366 | PMC:PMC10915640 | DOI:10.21147/j.issn.1000-9604.2024.01.05

Zhongguo Fei Ai Za Zhi. 2024 Feb 20;27(2):138-146. doi: 10.3779/j.issn.1009-3419.2024.102.06.

ABSTRACT

In recent years, there has been a consensus regarding the enhancement of prognosis in patients with advanced non-small cell lung cancer (NSCLC) through the utilization of immune checkpoint inhibitors (ICIs). Numerous clinical studies have also demonstrated the substantial value of immunotherapy for resectable NSCLC patients. Nevertheless, there remain controversies surrounding the exploration of immune combination strategies, treatment-related side effects, prognostic biomarkers, as well as other issues in the neoadjuvant therapy setting. Consequently, this article presents a comprehensive overview of the recent advancements in neoadjuvant immunotherapy for resectable NSCLC, stimulating fresh perspectives and delving into its merits and challenges in clinical application. .

PMID:38453446 | PMC:PMC10918244 | DOI:10.3779/j.issn.1009-3419.2024.102.06

Behav Pharmacol. 2024 Apr 1;35(2-3):122-131. doi: 10.1097/FBP.0000000000000761. Epub 2023 Nov 15.

ABSTRACT

Prescription opioids are the gold standard for treating moderate to severe pain despite their well-documented adverse effects. Of all prescription medications, opioids are abused most widely, and fatal overdoses have reached epidemic levels. One strategy for improving the margin of safety of opioids is combining them with non-opioid drugs to decrease the opioid dose needed for pain relief, thereby reducing adverse effects that occur with larger doses. The N-methyl-D-aspartate receptor antagonist ketamine has been used safely as an analgesic but only under a very limited range of conditions. The current studies characterized the antinociceptive, behavioral suppressant, and gastrointestinal effects of morphine and ketamine alone and in mixtures to determine their interaction in 24 adult male Sprague-Dawley rats (n = 8 per assay). Given alone, both morphine and ketamine produced antinociception, decreased responding for food, and reduced gastrointestinal transit (i.e. produced constipation). The effects of morphine:ketamine mixtures generally were additive, except for the antinociceptive effects of 1:1 mixtures for which the difference in slope (i.e. non-parallel shift) between the observed and predicted effects suggested synergy at smaller doses and additivity at larger doses. The potency of morphine to produce constipation was not enhanced by administration of morphine:ketamine mixtures with antinociceptive effects. The nature of the interaction between morphine and ketamine for adverse effects such as dependence, withdrawal, abuse, or respiratory depression remains unknown but also might be related to the ratio of each drug in mixtures. It will be important to identify conditions that produce the largest potential therapeutic window in humans.

PMID:38451024 | DOI:10.1097/FBP.0000000000000761

Brain Behav. 2024 Mar;14(3):e3442. doi: 10.1002/brb3.3442.

ABSTRACT

BACKGROUND: The association of systolic blood pressure (SBP) and ischemic stroke outcome has recently been proved to be varied at different time points within 72 h after acute ischemic stroke onset; however, the specific status of how SBP affects prognosis at different time points within 72 h after endovascular treatment (EVT) among patients with large vessel occlusion (LVO) remains unclear.

METHODS: Consecutive LVO patients treated with EVT were enrolled in our study. BP data were collected at eight time points (1, 2, 4, 8, 16, 24, 48, and 72 h post-EVT). Outcome measure of interest was functional dependence, which was defined as mRS >2 at 90 days.

RESULTS: A total of 406 LVO patients treated with EVT from 2016 to 2022 were included. At 16 h after EVT, the relationship between SBP and functional dependence showed a nonlinear association. At other time points after EVT, SBP had linear relationships with functional dependence. Furthermore, higher SBP, as either a linear or quadratic term, had an adverse effect on functional outcome. In addition, three SBP trajectories were observed, and the high-to-low group was independently associated with functional dependence.

CONCLUSION: Taken together, higher SBP within the first 72 h after EVT has a time-dependent association with adverse clinical outcomes. Optimal blood pressure management during the first 72 h after EVT may be important to improve clinical outcome.

PMID:38450968 | DOI:10.1002/brb3.3442

Sci Rep. 2024 Mar 7;14(1):5592. doi: 10.1038/s41598-024-56335-4.

ABSTRACT

To provide evidence for optimization of multi-kinase inhibitors (MKIs) use in the clinic, we use the public database to describe and evaluate electrolyte disorders (EDs) related to various MKIs treated for renal cell carcinoma. We analyzed spontaneous reports submitted to the Food and Drug Administration Adverse Events Reporting System (FAERS) in an observational and retrospective manner. Selecting electrolyte disorders' adverse events to multikinase inhibitors (axitinib, cabozantinib, lenvatinib, pazopanib, sunitinib, and sorafenib). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms to analyze suspected adverse reactions of electrolyte disorders induced by MKIs (which were treated for renal cell carcinoma) between January 2004 and December 2022. As of December 2022, 2772 MKIs (which were treated for renal cell carcinoma) ICSRs were related to electrolyte disorders AEs. In general, there were more AEs cases in males, except lenvatinib and 71.8% of the cases were submitted from North America. ICSRs in this study, the age group most frequently affected by electrolyte disorders AEs was individuals aged 45-64 years for axitinib, cabozantinib, pazopanib, and sunitinib, whereas electrolyte disorders AEs were more common in older patients (65-74 years) for sorafenib and lenvatinib. For all EDs documented in ICSRs (excluding missing data), the most common adverse outcome was hospitalization(1429/2674, 53.4%), and the most serious outcome was death/life-threat(281/2674, 10.5%). The prevalence of mortality was highest for sunitinib-related EDs (145/616, 23.5%), excluding missing data (n = 68), followed by cabozantinib-related EDs (20/237, 8.4%), excluding missing data (n = 1). The distribution of time-to-onset of Each drug-related ICSRs was not all the same, and the difference was statistically significant (P = 0.001). With the criteria of ROR, the six MKIs were all significantly associated with electrolyte disorders AEs, the strongest association was the association between cabozantinib and hypermagnesaemia. MKIs have been reported to have significant electrolyte disorders AEs. Patients and physicians need to recognize and monitor these potentially fatal adverse events.

PMID:38454105 | DOI:10.1038/s41598-024-56335-4

Front Cardiovasc Med. 2024 Feb 21;11:1342832. doi: 10.3389/fcvm.2024.1342832. eCollection 2024.

ABSTRACT

INTRODUCTION: Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease.

METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175 mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment.

RESULTS: Forty patients aged 65.6 ± 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (-16% and -28%, respectively), not observed in placebo. Regarding plaque progression analysis, variation in plaque parameter values was wide, and no difference between groups was observed.

CONCLUSION: In patients with multivessel chronic coronary artery disease and optimized medical therapy, LDE-paclitaxel was safe and showed clues of potential benefits in reducing inflammatory biomarkers.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04148833, identifier (NCT04148833).

PMID:38450375 | PMC:PMC10915057 | DOI:10.3389/fcvm.2024.1342832

Cureus. 2024 Feb 5;16(2):e53642. doi: 10.7759/cureus.53642. eCollection 2024 Feb.

ABSTRACT

In a rare case, a 70-year-old female with polycythemia vera developed late-onset melanonychia, a seldom-documented side effect of hydroxyurea. Typically, melanonychia emerges within months of treatment, but this case is unique as it occurred four years into therapy. Notably, the patient, with darker skin, also had hyperpigmentation of her hands and tongue. Her history of hydroxyurea-associated ulcers and symptoms worsening with dose adjustment suggested drug involvement. While mucocutaneous hyperpigmentation from hydroxyurea is known, melanonychia and tongue hyperpigmentation are rarely reported, mostly in early treatment. This case highlights the importance of recognizing these side effects, especially in diverse populations and darker skin tones. The diverse skin tones seen in Sub-Saharan Africa add complexity to diagnosing such dermatological conditions, highlighting the need for awareness. Melanonychia can mimic severe conditions such as subungual melanoma, emphasizing the significance of accurate recognition and management without invasive tests. Educating clinicians and patients about these benign drug-related phenomena is essential for precise identification and management. This case contributes to understanding late-onset hydroxyurea-induced melanonychia and tongue hyperpigmentation, enhancing clinical knowledge in diverse populations.

PMID:38449930 | PMC:PMC10917399 | DOI:10.7759/cureus.53642

PLoS One. 2024 Mar 6;19(3):e0298984. doi: 10.1371/journal.pone.0298984. eCollection 2024.

ABSTRACT

The Western diet has undergone a massive switch since the second half of the 20th century, with the massive increase of the consumption of refined carbohydrate associated with many adverse health effects. The physiological mechanisms linked to this consumption, such as hyperglycaemia and hyperinsulinemia, may impact non medical traits such as facial attractiveness. To explore this issue, the relationship between facial attractiveness and immediate and chronic refined carbohydrate consumption estimated by glycemic load was studied for 104 French subjects. Facial attractiveness was assessed by opposite sex raters using pictures taken two hours after a controlled breakfast. Chronic consumption was assessed considering three high glycemic risk meals: breakfast, afternoon snacking and between-meal snacking. Immediate consumption of a high glycemic breakfast decreased facial attractiveness for men and women while controlling for several control variables, including energy intake. Chronic refined carbohydrate consumption had different effects on attractiveness depending on the meal and/or the sex. Chronic refined carbohydrate consumption, estimated by the glycemic load, during the three studied meals reduced attractiveness, while a high energy intake increased it. Nevertheless, the effect was reversed for men concerning the afternoon snack, for which a high energy intake reduced attractiveness and a high glycemic load increased it. These effects were maintained when potential confounders for facial attractiveness were controlled such as age, age departure from actual age, masculinity/femininity (perceived and measured), BMI, physical activity, parental home ownership, smoking, couple status, hormonal contraceptive use (for women), and facial hairiness (for men). Results were possibly mediated by an increase in age appearance for women and a decrease in perceived masculinity for men. The physiological differences between the three meals studied and the interpretation of the results from an adaptive/maladaptive point of view in relation to our new dietary environment are discussed.

PMID:38446775 | PMC:PMC10917283 | DOI:10.1371/journal.pone.0298984

IEEE J Biomed Health Inform. 2024 Mar;28(3):1773-1784. doi: 10.1109/JBHI.2024.3349570.

ABSTRACT

Drug-drug interaction (DDI) has attracted widespread attention because when incompatible drugs are taken together, DDI will lead to adverse effects on the body, such as drug poisoning or reduced drug efficacy. The adverse effects of DDI are closely determined by the molecular structures of the drugs involved. To represent drug data effectively, researchers usually treat the molecular structure of drugs as a molecule graph. Then, previous studies can use the handcrafted graph neural network (GNN) model to learn the molecular graph representations of drugs for DDI prediction. However, in the field of bioinformatics, manually designing GNN architectures for specific molecular structure datasets is time-consuming and depends on expert experience. To address this problem, we propose an automatic drug-drug interaction prediction method named AutoDDI that can efficiently and automatically design the GNN architecture for drug-drug interaction prediction without manual intervention. To this end, we first design an effective search space for drug-drug interaction prediction by revisiting various handcrafted GNN architectures. Then, to efficiently and automatically design the optimal GNN architecture for each drug dataset from the search space, a reinforcement learning search algorithm is adopted. The experiment results show that AutoDDI can achieve the best performance on two real-world datasets. Moreover, the visual interpretation results of the case study show that AutoDDI can effectively capture drug substructure for drug-drug interaction prediction.

PMID:38446657 | DOI:10.1109/JBHI.2024.3349570

J Psychosoc Nurs Ment Health Serv. 2024 Mar;62(3):7-10. doi: 10.3928/02793695-20240207-01. Epub 2024 Mar 1.

ABSTRACT

VigiBase, the World Health Organization's collaborative global pharmaco-vigilance database, provides storage for millions of adverse drug reaction (ADR) reports. Pharmacovigilance scientists use the database to detect signals, assess, and understand trends in ADRs so that potential harms can be communicated. A search for pharmacovigilance studies on psychotropic-related ADR reports published over the past 5 years in VigiBase identified the majority to be antipsychotic-related ADRs, and within the antipsychotic class, clozapine-related. The nine antidepressant-related ADR reports were reviewed in more detail and provide an example of how the science of pharmacovigilance identifies and communicates medication risks. [Journal of Psychosocial Nursing and Mental Health Services, 62(3), 7-10.].

PMID:38446626 | DOI:10.3928/02793695-20240207-01

JAMA Netw Open. 2024 Mar 4;7(3):e241342. doi: 10.1001/jamanetworkopen.2024.1342.

ABSTRACT

IMPORTANCE: Guidelines recommend deprescribing opioids in older adults due to risk of adverse effects, yet little is known about patient-clinician opioid deprescribing conversations.

OBJECTIVE: To understand the experiences of older adults and primary care practitioners (PCPs) with using opioids for chronic pain and discussing opioid deprescribing.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study conducted semistructured individual qualitative interviews with 18 PCPs and 29 adults 65 years or older prescribed opioids between September 15, 2022, and April 26, 2023, at a Boston-based academic medical center. The PCPs were asked about their experiences prescribing and deprescribing opioids to older adults. Patients were asked about their experiences using and discussing opioid medications with PCPs.

MAIN OUTCOME AND MEASURES: Shared and conflicting themes between patients and PCPs regarding perceptions of opioid prescribing and barriers to deprescribing.

RESULTS: In total, 18 PCPs (12 [67%] younger that 50 years; 10 [56%] female; and 14 [78%] based at an academic practice) and 29 patients (mean [SD] age, 72 [5] years; 19 [66%] female) participated. Participants conveyed that conversations between PCPs and patients on opioid use for chronic pain were typically challenging and that conversations regarding opioid risks and deprescribing were uncommon. Three common themes related to experiences with opioids for chronic pain emerged in both patient and PCP interviews: opioids were used as a last resort, opioids were used to improve function and quality of life, and trust was vital in a clinician-patient relationship. Patients and PCPs expressed conflicting views on risks of opioids, with patients focusing on addiction and PCPs focusing on adverse drug events. Both groups felt deprescribing conversations were often unsuccessful but had conflicting views on barriers to successful conversations. Patients felt deprescribing was often unnecessary unless an adverse event occurred, and many patients had prior negative experiences tapering. The PCPs described gaps in knowledge on how to taper, a lack of clinical access to monitor patients during tapering, and concerns about patient resistance.

CONCLUSIONS AND RELEVANCE: In this qualitative study, PCPs and older adults receiving long-term opioid therapy viewed the use of opioids as a beneficial last resort for treating chronic pain but expressed dissonant views on the risks associated with opioids, which made deprescribing conversations challenging. Interventions, such as conversation aids, are needed to support collaborative discussion about deprescribing opioids.

PMID:38446478 | DOI:10.1001/jamanetworkopen.2024.1342

Eur J Hosp Pharm. 2024 Mar 6:ejhpharm-2024-004089. doi: 10.1136/ejhpharm-2024-004089. Online ahead of print.

ABSTRACT

Brentuximab vedotin (BV) is an antibody-drug conjugate, consisting of a CD30-directed antibody, conjugated by a protease-cleavable linker to a microtubule disrupting agent auristatin E (MMAE). Although the safety datasheet of BV does not warn of severe toxic effects of extravasation, we report a third case of a patient with anaplastic large cell lymphoma who developed severe epidermal necrosis after extravasation. The reason for what happened could be attributed to the fact that MMAE belongs to the group of vinca alkaloids so it should be handled like other tissue-necrotising chemotherapeutics. Reporting of all cases of extravasation involving new conjugated chemotherapeutic drugs is of the utmost importance to be able to develop updated guidelines. Hospital pharmacists can provide information on how to manage extravasation, assess the potential risk, and have a crucial role in drafting hospital protocols.

PMID:38448203 | DOI:10.1136/ejhpharm-2024-004089

Radiother Oncol. 2024 Mar 4:110194. doi: 10.1016/j.radonc.2024.110194. Online ahead of print.

ABSTRACT

High precision, image-guided radiotherapy (RT) has increased the therapeutic ratio, enabling higher tumor and lower normal tissue doses, leading to improved patient outcomes. Nevertheless, some patients remain at risk of developing serious side effects.In many clinical situations, the radiation tolerance of normal tissues close to the target volume limits the dose that can safely be delivered and thus the potential for tumor control and cure. This is particularly so in patients being re-treated for tumor progression or a second primary tumor within a previous irradiated volume, scenarios that are becoming more frequent in clinical practice.Various normal tissue 'radioprotective' drugs with the potential to reduce side effects have been studied previously. Unfortunately, most have failed to impact clinical practice because of lack of therapeutic efficacy, concern about concurrent tumor protection or excessive drug-related toxicity. This review highlights the evidence indicating that targeting the CXCL12/CXCR4 pathway can mitigate acute and late RT-induced injury and reduce treatment side effects in a manner that overcomes these previous translational challenges. Pre-clinical studies involving a broad range of normal tissues commonly affected in clinical practice, including skin, lung, the gastrointestinal tract and brain, have shown that CXCL12 signalling is upregulated by RT and attracts CXCR4-expressing inflammatory cells that exacerbate acute tissue injury and late fibrosis. These studies also provide convincing evidence that inhibition of CXCL12/CXCR4 signalling during or after RT can reduce or prevent RT side effects, warranting further evaluation in clinical studies. Greater dialogue with the pharmaceutical industry is needed to prioritize the development and availability of CXCL12/CXCR4 inhibitors for future RT studies.

PMID:38447871 | DOI:10.1016/j.radonc.2024.110194

Gynecol Oncol. 2024 Mar 5;185:186-193. doi: 10.1016/j.ygyno.2024.01.045. Online ahead of print.

ABSTRACT

OBJECTIVE: Evaluate the antitumor activity and safety profile of the triplet combination of mirvetuximab soravtansine (MIRV), carboplatin, and bevacizumab in recurrent, platinum-sensitive ovarian cancer.

METHODS: Participants with recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer (1-2 prior lines of therapy) received MIRV (6 mg/kg adjusted ideal body weight), carboplatin (AUC5), and bevacizumab (15 mg/kg) once every 3 weeks. Carboplatin could be discontinued after 6 cycles per investigator discretion; continuation of MIRV+bevacizumab as maintenance therapy was permitted. Eligibility included folate receptor alpha (FRα) expression by immunohistochemistry (≥50% of cells with ≥2+ intensity; PS2+ scoring); prior bevacizumab was allowed. Tumor response, duration of response (DOR), progression-free survival (PFS), and adverse events (AEs) were assessed.

RESULTS: Forty-one participants received triplet therapy, with a median of 6, 12, and 13 cycles of carboplatin, MIRV, and bevacizumab, respectively. The confirmed objective response rate was 83% (9 complete and 25 partial responses). The median DOR was 10.9 months; median PFS was 13.5 months. AEs (any grade) occurred as expected, based on each agent's safety profile; most common were diarrhea (83%), nausea (76%), fatigue (73%), thrombocytopenia (71%), and blurred vision (68%). Most cases were mild to moderate (grade ≤2), except for thrombocytopenia, for which most drug-related discontinuations occurred, and neutropenia.

CONCLUSIONS: This triplet regimen (MIRV+carboplatin+bevacizumab) was highly active, with a tolerable AE profile in participants with recurrent, platinum-sensitive, FRα-expressing ovarian cancer. Thrombocytopenia was the primary cause of dose modifications. These outcomes compare favorably to historical data reported for platinum-based chemotherapy plus bevacizumab regimens in similar patient populations.

PMID:38447347 | DOI:10.1016/j.ygyno.2024.01.045