Int J Older People Nurs. 2025 Jan;20(1):e70003. doi: 10.1111/opn.70003.

ABSTRACT

BACKGROUND: Age, polypharmacy and comorbidity are examples of known factors that increase the risk of adverse drug reactions in patients. The use of high-risk medication also entails a heightened risk of harm. There is currently no information available on the home care patients' experiences and medication burden experienced due to their high-risk medication use and how they manage their medication. Further investigation with regard to this combination is necessary. The patient's experiences and medication burden related to high-risk medication use can be taken into account when drawing up guidelines and standards of care for healthcare professionals.

OBJECTIVES: To describe home care patients' experiences and medication burden related to high-risk medication use, more specifically how patients manage their high-risk medication use, which professional support they receive and which potential adverse drug reactions they experience.

DESIGN: A cross-sectional study of home care patients in Belgium, aged 65 years and older who took at least one high-risk medication.

RESULTS: In our population of 106 home care patients, a median use of 8 medications per patient is reported, of which 2 can be considered high-risk medication. Metformin, insulin and lormetazepam are the most frequently used high-risk medications. Home care patients believe their medication is important to them, are able to manage the intake and seem to have a high level of therapy adherence. Most patients do not believe their medication intake implies a certain risk. Most patients are supported by a home care nurse for the preparation of their medication. A mean number of 5 symptoms/potential adverse drug reactions is reported out of the 21 potential adverse drug reactions questioned. The potential adverse drug reaction most frequently attributed to medication use was bleeding.

CONCLUSIONS: Practice guidelines with detailed medicine-specific protocols are needed to enhance (high-risk) medication-related care in an overall high-risk medication policy. Understanding the patient's risk experiences and communicating with the patient is important to ensure safe medication care but also to identify patients at risk for nonadherence and adverse reactions. The patient's experiences with their medication intake provide rich information for healthcare providers and should therefore be included in patient observations. Home care nurses should closely follow up on the home care patient's medication therapy with respect for the patient's autonomy.

PMID:39663656 | DOI:10.1111/opn.70003

JAMA Dermatol. 2024 Dec 11. doi: 10.1001/jamadermatol.2024.5059. Online ahead of print.

ABSTRACT

IMPORTANCE: Psoriasis is a chronic, immune-mediated skin disease with an unmet need for biologic treatment options.

OBJECTIVE: To assess the safety, pharmacokinetics, and efficacy of QX004N in healthy individuals and patients with moderate to severe plaque psoriasis in China.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was composed of 2 parts. Part 1 was a first-in-human, single-ascending-dose, phase 1a clinical trial conducted from November 2, 2021, to January 16, 2023. Part 2 was a double-blind, multiple dose-escalation, phase 1b clinical trial conducted from February 15, 2023, to January 5, 2024, at 5 clinical centers in China, involving patients with moderate to severe plaque psoriasis.

INTERVENTIONS: In part 1, healthy participants in each cohort were assigned in a 4:1 ratio to receive a single subcutaneous injection of QX004N (ranging from 10 mg to 600 mg) or placebo. In part 2, patients in each cohort were assigned in a 4:1 ratio to receive QX004N or placebo at doses of 150 mg, 300 mg, and 600 mg once every 2 weeks.

MAIN OUTCOMES AND MEASURES: For part 1, the primary outcome was the safety of a single dose of QX004N in healthy participants, and the secondary outcome was the pharmacokinetic profile. For part 2, the primary efficacy end point was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) by week 12; other efficacy end points were considered secondary.

RESULTS: The phase 1a clinical trial (part 1) enrolled 55 healthy participants (mean [SD] age, 35.9 [6.0] years; 30 [54.5%] female), and the phase 1b clinical trial (part 2) enrolled 30 patients with moderate to severe plaque psoriasis. The mean (SD) age of QX004N-treated participants in part 2 was 41.4 (7.5) years, and 19 of 24 QX004N-treated participants (79.2%) were male. The mean (SD) age of the placebo cohort in part 2 was 35.3 (8.4) years, and 5 of 6 placebo-treated participants (83.3%) were male. QX004N exhibited linear pharmacokinetics and was tolerated well in both healthy participants and patients with psoriasis. Most adverse events were mild to moderate in severity, with no drug-related serious adverse events reported. The proportion of patients receiving QX004N who achieved PASI 75 at week 12 and PASI 90 (90% improvement in PASI) at week 16 in the 150-mg, 300-mg, and 600-mg cohorts was 100%, significantly higher than that in the placebo cohorts (33.3%). The maximum proportion of patients achieving Investigator's Global Assessment score of 0 or 1 was 100% in the 3 QX004N cohorts.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, QX004N was well tolerated and demonstrated superior efficacy compared to placebo in patients with moderate to severe plaque psoriasis.

TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: CTR20212313 and CTR20223457.

PMID:39661362 | DOI:10.1001/jamadermatol.2024.5059

Health Expect. 2024 Dec;27(6):e70122. doi: 10.1111/hex.70122.

ABSTRACT

BACKGROUND: Psychotropic medications are a common treatment modality for people living with severe and persistent mental illness (SPMI). While effective in reducing relapse and hospitalisation, psychotropic medications cause numerous side effects, varying in nature and severity. Identification and management of side effects is crucial in the ongoing management of SPMI.

OBJECTIVE: To characterise the side effects of psychotropic medications, experienced by a sample of consumers living with SPMI, using a validated tool.

SETTING AND PARTICIPANTS: Consumers with SPMI living in the community were recruited from all 25 community pharmacies across four Australian regions, which were allocated to the intervention arm of the Bridging the Gap between Physical and Mental Illness (PharMIbridge) randomised controlled trial (RCT).

MAIN OUTCOME MEASURES: Responses to the My Medicines & Me Questionnaire (M3Q).

RESULTS: Consumers (n = 156) most frequently reported side effects in the categories of sleep-related side effects (80.8%, n = 126), mood-related side effects (75.6%, n = 118) and weight and appetite changes (60.3%, n = 107). Daytime somnolence was the most reported individual side effect (68.6%, n = 107). Mood-related side effects were ranked as the most bothersome, followed by sleep-related side effects and weight and appetite changes. More than one-quarter (29.5%, n = 46) of consumers reported choosing not to take their medications due to side effects. Consumers more frequently told family and friends about the side effects rather than healthcare professionals.

CONCLUSIONS: An overwhelming majority of consumers experienced at least one side effect attributed to their psychotropic medication, with many experiencing multiple. These findings highlight the critical need to regularly engage with consumers to discuss, identify and manage side effects to treatment burden, reduce risk of non-adherence and improve their treatment experience.

PATIENT OR PUBLIC CONTRIBUTION: The PharMIbridge RCT included a training programme and intervention service that was co-designed and co-delivered with people with lived experience of mental illness. The research team, expert advisory panel and mentors who supported the delivery and implementation of the training and intervention included participants who have lived experience of mental illness or caring for someone with mental illness.

TRIAL REGISTRATION: ANZCTR12620000577910.

PMID:39660682 | DOI:10.1111/hex.70122

Gut. 2024 Dec 10:gutjnl-2024-332125. doi: 10.1136/gutjnl-2024-332125. Online ahead of print.

ABSTRACT

Immune checkpoint inhibitors (ICI) have led to breakthrough improvements in the management of malignancy including hepatocellular (HCC) and biliary tract cancer, improving decades-old standards of care and increasing patient survival. In both liver tumour types, which commonly arise in the context of liver inflammation and underlying functional impairment, the lack of validated predictors of response underscores the need to balance predicted gains in survival with risk of treatment-related hepatoxicity and decompensation of underlying chronic liver disease.In addition, the liver is implicated in the toxicity associated with ICI therapy for non-liver cancers, which exhibits a high degree of variability in presentation and severity. An accurate assessment is mandatory for the diagnosis and management of ICI-induced liver injury.In this Recent Advances article, we provide an overview of the mechanisms of efficacy and toxicity of anticancer immunotherapy in liver tumours and liver toxicity in extrahepatic malignancies.We compare and contrast characteristics, management strategies and outcomes from immune-related liver injury in patients with chronic hepatitis/cirrhosis or with an underlying healthy liver and discuss the latest findings on how toxicity and decompensation may impact the outlook of patients with liver tumours and extrahepatic malignancies offering insights into the future directions of clinical research and practice in the field.

PMID:39658265 | DOI:10.1136/gutjnl-2024-332125

Pediatr Hematol Oncol. 2024 Dec 10:1-13. doi: 10.1080/08880018.2024.2437047. Online ahead of print.

ABSTRACT

Convenient multiday dosing of antiemetic regimens for the prevention of chemotherapy-induced nausea and vomiting (CINV) are needed in pediatric patients, who are more likely than adults to be treated with emetogenic chemotherapy over multiple consecutive days. Intravenous (IV) fosaprepitant is approved for the prevention of CINV in children aged 6 months and older. This open-label, single-arm study assessed the safety and tolerability of a 3-day fosaprepitant regimen (consecutive daily IV administration on days 1-3) plus a serotonin receptor antagonist with or without dexamethasone in pediatric patients (6 months to 17 years) receiving emetogenic chemotherapy. Study treatment was initiated at the start of a chemotherapy cycle (cycle 1); patients completing cycle 1 could participate in optional cycles 2 and 3. Primary endpoints included adverse events (AEs) and AE-related discontinuation during cycle 1.98/100. Patients completed cycle 1; 69 participated in optional cycles 2 and 3. The AE profile during cycle 1 was typical of cancer patients receiving emetogenic chemotherapy; 80/100 (80.0%) patients experienced ≥1 AE. AE rates were generally similar between patients aged 6 months to <2 years (11/15 patients [73.3%]), 2 to <6 years (22/30 [73.3%]), 6 to <12 years (24/25 [96.0%]), and 12-17 years (23/30 [76.7%]). Rates of drug-related AEs (4/100 [4.0%]) and AE-related discontinuations (2/100 [2.0%]) were low. Similar trends in safety outcomes were observed during cycles 2 and 3. No deaths were reported. The 3-day IV fosaprepitant regimen for the prevention of CINV was generally well tolerated in pediatric patients receiving emetogenic chemotherapy.

PMID:39655741 | DOI:10.1080/08880018.2024.2437047

J Immunotoxicol. 2024 Oct;21(sup1):S1-S4. doi: 10.1080/1547691X.2024.2354213. Epub 2024 Dec 10.

ABSTRACT

Innovative therapeutics like biologicals that modulate the immune system are on the rise. However, their immune-modulating characteristics can also lead sometimes to the induction of adverse effects, by triggering unintended immune reactions. Due to the complexity and target-specificity of such therapeutics, these drug-induced adverse events could remain undetected during non-clinical development, if the test systems are, for example, animal-based, and only emerge in clinical development when tested in humans and subsequently lead to discontinuance of otherwise promising drug candidates. To identify adverse effects on the human immune system at an early stage, new approaches, assays, and technologies are needed. The Innovative Medicine Initiative (IMI) cooperation Immune Safety Avatar (imSAVAR) project aims to develop a tool for integrated non-clinical safety assessment for immune-modulatory new therapeutic drugs and clinical trial applications. To achieve this goal, imSAVAR has relied on the Adverse Outcome Pathway (AOP) framework to gather knowledge in a structured approach and to design, select or develop, when needed, appropriate test systems for prediction of the immune-related adverse outcomes. So far, the imSAVAR consortium has identified the "mode of action" for certain classes of drugs that needed improved risk assessment, including chimeric antigen receptor T cells (CAR T cells), immune checkpoint inhibitors (ICIs), and recombinant proteins (e.g. interleukin [IL]-2), has linked those to their immune-related adverse outcomes and has formulated literature-based immune-related AOPs (irAOPs). Models to measure those immune-specific perturbations were selected, adjusted, or newly developed. The imSAVAR work described in this special issue of The Journal of Immunotoxicology supports our understanding of immune-mediated adverse effects and their early discovery during development to improve the safety of innovative biomedicals.

PMID:39655496 | DOI:10.1080/1547691X.2024.2354213

Cureus. 2024 Nov 7;16(11):e73220. doi: 10.7759/cureus.73220. eCollection 2024 Nov.

ABSTRACT

Introduction Effective strategies to minimize postoperative pain following total knee arthroplasty (TKA) are essential to improve functional outcomes. This study aimed to evaluate the effectiveness and safety of tapentadol nasal spray as a form of patient-controlled analgesia (PCA) for postoperative pain management after TKA. The intranasal route was chosen for the study as intranasal tapentadol has been shown to have superior pain reduction as compared to intravenous tapentadol. Intranasal instillation of tapentadol is rapid and more effective than the parenteral or oral route. Additional advantages of the intranasal route include enhanced comfort, convenience, and safety. Methods The present study was a single-center prospective observational study including 120 patients undergoing unilateral TKA who were administered tapentadol nasal spray post-surgery (22.5 mg of tapentadol per spray). Pain was objectively assessed using the visual analog scale (VAS) on postoperative days (POD) 1, 2, and 3, before and after spray administration. The pain severity was graded into mild (VAS 1-3), moderate (VAS 4-6), and severe (VAS 7-10) based on the VAS score. The time duration required for the pain severity to become mild from the pre-spray level post-administration of the nasal spray was recorded on all three PODs. The time required in hours for the pain severity to worsen from mild (VAS 1-3) to moderate (VAS 4-6) or severe (VAS 7-10) was also recorded on all three PODs. The statistical analysis plan for this study involved the analysis of VAS scores collected on PODs 1, 2, and 3. Categorical variables were expressed as percentages, while numerical variables were presented as means and standard deviations. The significance of differences between pre and post-treatment VAS scores was analyzed using Student's t-test. Differences between proportions were analyzed using the Chi-square or Fisher's exact test. The Kolmogorov-Smirnov test was used to test the normality of the quantitative data. The Analysis of Variance (ANOVA) test was applied to compare the means across the three PODs. A two-tailed significance level of 0.05 was set for all tests to determine statistical significance. Results The mean pre-spray VAS scores recorded on POD 1, 2, and 3 were 8.07, 7.64, and 7.40 respectively. The mean post-spray VAS scores recorded on POD 1, 2, and 3 were 4.63, 4.71, and 3.95 respectively. There was a statistically significant reduction in the VAS scores on each of the three days when measured before and after spray administration (p<0.001). The average time needed for the pain severity to become mild from the pre-spray level in minutes on POD 1, 2, and 3 was 14.07, 13.36, and 12.34 respectively. Thus, this metric significantly declined (p<0.001) from POD 1 to POD 3. The time taken in hours for the pain severity to worsen from mild to moderate or severe on POD 1, 2, and 3 was 6.57, 6.70, and 6.98 respectively indicating that there was a significant increase in the time till the pain severity worsened from POD 1 to POD 3 (p<0.001). There were no major drug-induced adverse reactions following the administration of intranasal tapentadol. Conclusion Intranasal tapentadol spray (22.5 mg per spray) is an acceptable modality of postoperative pain management in patients undergoing TKA. It has a long-lasting effect, rapid onset, minimal side effects, and can be self-administered by the patient.

PMID:39651001 | PMC:PMC11624896 | DOI:10.7759/cureus.73220

Front Pharmacol. 2024 Nov 22;15:1480994. doi: 10.3389/fphar.2024.1480994. eCollection 2024.

ABSTRACT

BACKGROUND: To evaluate and identify reports of adverse events related to hearing impairment with drugs approved in the past 20 years, to identify new adverse reaction signals related to hearing impairment that have not yet been reported, and to improve the safety of drug treatments.

METHODS: The adverse event report data from the FAERS database from the first quarter of 2004 to the fourth quarter of 2023 were retrieved. "Hearing disorders" was used as the keyword to screen for drugs related to the adverse event. After standardizing the drug name and the adverse drug event name, the adverse event reports with hearing disorders as the main suspect were collected, and the proportional imbalance algorithm was used to detect the potential adverse event signals to drug-related hearing impairment.

RESULTS: The top five drugs with the highest number of reported adverse events to hearing impairment were sacubitril/valsartan (2,674), adalimumab (2,479), etanercept (1,834), tofacitinib (1,812), and apixaban (1,600). Except for adalimumab, the risk of hearing impairment is not mentioned in the instructions. The top five drugs for new signal strength are pancuronium (n = 13, ROR 67.57, PRR 53.61, IC5.74, EBGM 53.06), paromomycin (n = 6, ROR 46.3, PRR 39.33, IC5.30, EBGM 39.33), tafamidis (n = 300, ROR 14.90, PRR 14.13, IC3.82, EBGM 14.07), vildagliptin/metformin (n = 83, ROR 11.47, PRR 11.02, IC3.46, EBGM 11.01), and atorvastatin calcium/ezetimibe (n = 6, ROR 10.76, PRR 10.36, IC3.37, EBGM 10.36).

CONCLUSION: Our study covered 20 years of real-world data on reports of adverse events related to hearing impairment in the FAERS database, validating previous reports and studies, as well as identifying drugs that signal new adverse events of hearing impairment, especially some drugs commonly used for the treatment of chronic diseases (a combination of hypoglycemic drugs, antihypertensive drugs, and lipid modulators) and some new drugs in the 5-year post-market period.

PMID:39650160 | PMC:PMC11620887 | DOI:10.3389/fphar.2024.1480994

Liver Int. 2024 Dec 8. doi: 10.1111/liv.16174. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The safety and tolerability of bulevirtide (BLV), a novel entry inhibitor of hepatitis delta virus, were evaluated in an integrated analysis of clinical trial results from patients with chronic hepatitis delta (CHD).

METHODS: Week 48 on-treatment clinical and laboratory results from two Phase 2 trials (MYR203 [NCT02888106] and MYR204 [NCT03852433]) and one Phase 3 trial (MYR301 [NCT03852719]) were pooled (N = 269). Patients were grouped as follows: BLV 2 mg (n = 64), BLV 10 mg (n = 115), pegylated interferon-alfa (n = 39) and control (n = 51). The control group consisted of patients assigned to the delayed treatment group in Study MYR301.

RESULTS: Adverse events (AEs) that occurred more frequently with BLV 2 mg and BLV 10 mg versus control included increased total bile acid levels (20% and 17% vs. 0%), injection-site reactions (16% and 20% vs. 0%), headache (16% and 17% vs. 0%), pruritus (11% and 10% vs. 0%) and eosinophilia (9% and 4% vs. 0%). Increases in total bile acid levels were observed with BLV without clear correlation with AEs, such as pruritus, eosinophilia or vitamin D deficiency. Grade 3 or 4 study drug-related AEs occurred in a higher proportion of patients receiving pegylated interferon-alfa (51%) than with BLV 2 or 10 mg (3% and 4%, respectively). There were no serious AEs related to BLV, and no patients discontinued BLV due to an AE. Neither hepatic decompensation nor death occurred.

CONCLUSIONS: BLV monotherapy was safe and well tolerated through 48 weeks of treatment in patients with CHD.

TRIAL REGISTRATION: NCT02888106, NCT03852433 and NCT03852719.

PMID:39648559 | DOI:10.1111/liv.16174

Best Pract Res Clin Gastroenterol. 2024 Sep;72:101945. doi: 10.1016/j.bpg.2024.101945. Epub 2024 Aug 21.

ABSTRACT

Immune checkpoint inhibitors have revolutionised management for a variety of different types of malignancies. However, gastrointestinal adverse effects, in particular colitis and hepatitis, are relatively common with up to 30 % of patients being affected. The gut microbiome has emerged as a potential contributor to both the effectiveness of immune checkpoint inhibitors and their side effects. This review will attempt to examine the impact the microbiome has on adverse effects as a result of immune checkpoint inhibitors as well as the potential for manipulation of the microbiome as a form of management for immune mediated colitis.

PMID:39645281 | DOI:10.1016/j.bpg.2024.101945

Toxicology. 2024 Dec 4:154028. doi: 10.1016/j.tox.2024.154028. Online ahead of print.

ABSTRACT

Drug-induced gastrointestinal toxicity is a frequent clinical adverse event that needs to be carefully monitored and managed to ensure patient compliance. While preclinical assessment of drug-induced gastrointestinal toxicity mostly relies on animal experimentation, intestinal organoids have gained increasing attention to identify gastrointestinal toxicants in vitro. Nonetheless, current in vitro protocols primarily assess structural alterations induced by drugs, whereas gastrointestinal adverse events can often stem from functional disturbances. Disruption of serotonin signaling in the gastrointestinal tract is associated with impaired motility, as well as nausea and vomiting. We aimed to investigate alterations of serotonin homeostasis in organoids derived from the canine small intestine as a driver of drug-induced gastrointestinal toxicity. Treatment of the organoids with a compound (NVS-1) inducing acute gastrointestinal toxicity in dogs as well as with three tyrosine kinase inhibitors with known preclinical and clinical gastrointestinal adverse effects (afatinib, crizotinib and vandetanib) led to increased supernatant serotonin levels. Mechanistic assays showed that, while NVS-1 and afatinib stimulate serotonin release, crizotinib and vandetanib inhibit serotonin re-uptake via direct inhibition of the serotonin re-uptake transporter. Using a data mining approach, we further suggest that inhibition of serotonin re-uptake could contribute to gastrointestinal toxicity observed with multiple marketed drugs. In conclusion, we present the implementation of a novel in vitro gastrointestinal toxicity endpoint that could complement current methods and serve as a mechanistic and predictive/screening tool for drug-induced gastrointestinal toxicity.

PMID:39643203 | DOI:10.1016/j.tox.2024.154028

Sci Rep. 2024 Dec 6;14(1):30412. doi: 10.1038/s41598-024-82324-8.

ABSTRACT

Drug Information Centres (DICs) are providing clinicians with evidence-based support for rational drug treatment. However, knowledge gaps in the literature may hinder DICs from offering optimal guidance. This study examined the extent and nature of these knowledge gaps and their impact on clinical pharmacological advice, using real-world query data from a Swedish regional DIC. Data from 2022 at the Sahlgrenska University Hospital were analysed, focusing on queries outside off-label prescriptions and pharmaceutical aspects. A qualitative text content analysis identified phrases indicating a lack of evidence. Responses were categorized by the presence of these signalling phrases and the presence or absence of knowledge gaps. Among 209 responses, the majority were patient-specific (79%), posed by physicians (95%), and often related to adverse effects (37%). The analysis revealed that 23% of the responses had scientific knowledge gaps, and in 18% of the responses, no clinical pharmacological advice could be provided. Knowledge gaps were particularly associated with queries on adverse effects, long-term medication safety, specific patient cases and comorbidities, drug comparisons, or patient populations with limited literature coverage. This analysis highlights the potential of DICs to identify unmet clinical needs in drug treatment and to promote research for evidence-based, patient-centred drug treatment.

PMID:39638886 | DOI:10.1038/s41598-024-82324-8

BMJ Open Diabetes Res Care. 2024 Dec 5;12(6):e004343. doi: 10.1136/bmjdrc-2024-004343.

ABSTRACT

INTRODUCTION: Diabetes mellitus (DM) is increasingly recognized as a possible consequence of statin therapy. Secondary analysis of randomized clinical trials and limited observational cohort analyses have suggested that women may be more likely than men to experience statin-associated DM. No analyses of real-world drug safety data addressing this question have been published.

RESEARCH DESIGN AND METHODS: This was a retrospective pharmacovigilance analysis of spontaneously reported adverse drug events (ADEs) submitted to the Food and Drug Administration Adverse Event Reporting System between January 1997 through December 2023. We analyzed cases that mentioned atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin in aggregate as well as cases reporting atorvastatin, pravastatin, rosuvastatin, simvastatin individually. DM events were identified using the Medical Dictionary for Regulatory Activities. We used the proportional reporting ratio to identify increased rates of statin-associated DM events in women and men compared with all other medications, and the reporting OR to compare reporting rates in women versus men.

RESULTS: A total of 18,294,814 ADEs were reported during the study period. Among statin-associated ADEs, 14,874/519,209 (2.9%) reports mentioned DM in women compared with 7,411/489,453 (1.5%) in men, which were both significantly higher than background (0.6%). Statins were the primary-suspected or secondary-suspected cause of the ADE significantly more often in women than men (60 vs 30%), and reporting rates were disproportionately higher in women than in men for all statins. (reporting OR 1.9 (95% CI 1.9 to 2.0)). The largest difference in reporting of statin-associated DM between women and women was observed with atorvastatin.

CONCLUSIONS: Analysis of post-marketing spontaneous ADE reports demonstrated a higher reporting rate of DM-associated with statin use compared with other medications with a significantly higher reporting rate in women compared with men. Future studies should consider mechanisms of statin-associated DM moderated by sex.

PMID:39638563 | DOI:10.1136/bmjdrc-2024-004343

Epilepsy Res. 2024 Dec 4;209:107482. doi: 10.1016/j.eplepsyres.2024.107482. Online ahead of print.

ABSTRACT

OBJECTIVE: Efficacy, tolerability, and behavioral/executive functioning during long-term adjunctive brivaracetam treatment were assessed in pediatric patients with focal-onset seizures (FOS) with/without cognitive/learning comorbidities (CLC).

METHODS: Post hoc analysis of a phase 3 open-label follow-up trial (N01266/NCT01364597). Patients with FOS (<16 years at core trial entry; direct enrollers ≥4-<17 years) received ≤5 mg/kg/day brivaracetam (≤200 mg/day). Subgroup analyses were performed for patients with and without ongoing CLC at baseline.

RESULTS: Patients with CLC (84/185 [45.4 %]) had longer epilepsy duration and higher number of prior antiseizure medications. Kaplan-Meier-estimated brivaracetam retention at 1, 3, and 5 years was 75.0 %/78.2 %, 61.9 %/61.9 %, and 52.2 %/53.3 % in patients with/without CLC. Efficacy assessments (patients >2 years of age) showed numerically lower median percent reduction in FOS frequency/28 days (43.8 %/74.1 % [n = 63/60]), 50 % responder rates for FOS (46.0 %/61.7 % [n = 63/60]), and ≥12-month continuous freedom from all seizures (31.7 %/55.9 % [n = 60/68 patients with ≥12 months treatment]) in patients with/without CLC. Treatment-emergent adverse events were reported in 94.0 %/95.0 % of patients with/without CLC (serious: 33.3 %/27.7 %; drug-related: 31.0 %/33.7 %). From baseline to last evaluation, most patients with/without CLC had no shift in T-score category for each Achenbach Child Behavior Checklist (CBCL) 1.5-5 syndrome (≥50.0 %/≥72.2 %), CBCL 6-18 syndrome (≥66.0 %/≥69.1 %), and Behavior Rating Inventory of Executive Function scale (≥66.7 %/≥69.0 %).

CONCLUSIONS: These data indicate that brivaracetam could be an efficacious and well-tolerated treatment option for pediatric patients with FOS with and without CLC. Behavior and executive functioning were generally stable or slightly improved in patients with and without CLC.

PMID:39637726 | DOI:10.1016/j.eplepsyres.2024.107482

Cell Oncol (Dordr). 2024 Dec 5. doi: 10.1007/s13402-024-01021-w. Online ahead of print.

ABSTRACT

PURPOSE: Neoadjuvant immunochemotherapy is emerging as a promising regimen for patients with locally advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma. However, it remains unclear whether immunochemotherapy will bring more adverse events (AEs) leading to a delay or even cancellation of surgeries. We aimed to provide a comprehensive analysis of the toxicity profiles for immune checkpoint inhibitors (ICIs) combined with chemotherapy among patients with G/GEJ adenocarcinoma.

METHODS: Published trials up to January 2024 were identified on Web of Science, Cochrane Library, Embase, and PubMed. Single-group and controlled clinical trials with ICIs in combination with chemotherapy in patients with G/GEJ adenocarcinoma were included. Two reviewers independently extracted data including incidence rate of AEs. The primary outcomes included the proportion of patients with adverse events leading to treatment discontinuation, grade 3 or higher adverse events, and serious adverse events. This study is registered with PROSPERO (CRD42023492676).

RESULTS: Twenty studies were included for a total of 6692 patients. In patients receiving immunochemotherapy, 17% (95% confidence interval (CI), 11-23%) had adverse events leading to treatment discontinuation, 23% (95% CI, 19-27%) had serious adverse events, and 64% (95% CI, 58-70%) had grade 3 or higher adverse events. Compared with patients receiving chemotherapy alone, patients with immunochemotherapy were associated with higher rates of adverse events leading to discontinuation (RR, 1.45; 95% CI, 1.32-1.60), serious adverse events (RR, 1.27; 95% CI, 1.04-1.57), and grade 3 or higher adverse events (RR, 1.15; 95% CI, 1.07-1.23).

CONCLUSIONS: In conclusion, the incidence of adverse events leading to discontinuation, serious adverse events, and grade 3 or higher adverse events were higher in patients receiving immunochemotherapy compared to those with chemotherapy.

PMID:39636470 | DOI:10.1007/s13402-024-01021-w

J Cardiovasc Pharmacol. 2024 Dec 5. doi: 10.1097/FJC.0000000000001660. Online ahead of print.

ABSTRACT

Given the high prevalence of cardiovascular disease in the United States, there is a critical need for new medications to improve outcomes of these diseases. The U.S. Food and Drug Administration (FDA) has approved numerous medications that are able to effectively do so. While these drugs have significantly beneficial effects, just like any other medication, they can come with a multitude of unwanted side effects. It has been noted that cardiovascular drugs have been associated with a considerable number of dermatologic reactions. This review examines current literature on the various cutaneous manifestations of these adverse reactions. It focuses on these newly FDA-approved cardiovascular medications from 2013 to 2023, detailing both common and rare effects in the past decade. As more medications continue to enter the market, the necessity for awareness of more systemic side effects will continue to grow. This comprehensive review aims to guide clinicians in identifying drug-induced reactions in patients on these therapies.

PMID:39636124 | DOI:10.1097/FJC.0000000000001660

J Oncol Pharm Pract. 2024 Dec 5:10781552241304755. doi: 10.1177/10781552241304755. Online ahead of print.

ABSTRACT

INTRODUCTION: The multikinase inhibitor midostaurin is the first targeted drug for the treatment of AML FLT3. It reduces mortality by 23% more than standard chemotherapy group. Although it has many gastrointestinal side effects, there is no data in the literature regarding its association with acute pancreatitis. We wanted to present an acute pancreatitis case that developed after midostaurin treatment in our clinic.

CASE REPORT: A patient with AML FLT3 who developed abdominal pain, elevated amylase-lipase enzymes and increased volume around the pancreas on abdominal imaging after the addition of midostaurin to chemotherapy was hospitalized with a prediagnosis of acute pancreatitis.

MANAGEMENT & OUTCOME: Oral feeding was stopped, intravenous hydration was provided and anti-symptomatic treatment was given. The patient was discharged on the 4th day of hospitalization after the acute pancreatitis clinic resolved.

DISCUSSION: Drug induced acute pancreatitis is a rare clinical condition which is difficult to diagnose. It has a good prognosis and low mortality rate. The mechanisms of drug-induced pancreatitis include immunological reactions, direct toxic effect, accumulation of toxic metabolites, overstimulation of pancreatic acinar cells, ischemia, intravascular thrombosis and increased viscosity of pancreatic secretion. Although there are many gastrointestinal side effects of midostaurin, there are no clear data in the literature regarding the relationship with acute pancreatitis.

PMID:39635990 | DOI:10.1177/10781552241304755

Front Public Health. 2024 Nov 20;12:1480744. doi: 10.3389/fpubh.2024.1480744. eCollection 2024.

ABSTRACT

BACKGROUND: A national Oral Cholera Vaccine (OCV) Euvichol-Plus® campaign was launched in Lebanon, in response to the first outbreak in three decades, recorded in October 2022. The OCV vaccination campaign was carried out between November 2022 and February 2023. This study aims to cover adverse events reports, received at the Lebanese National Pharmacovigilance Program's (LNPVP) passive surveillance system.

METHODS: Case reports were extracted from the LNPVP's database. SPSS software was used to perform statistical analysis, with categorical variables compared using Pearson's χ 2 test. A descriptive analysis was performed based on age, gender, vaccine administered, and adverse event(s) associated with the administered vaccine.

RESULTS: A total of 115 Adverse Events Following Immunization (AEFIs) were reported, which corresponded to 46 case reports. The top three reported AEFIs were fever (39.13%), diarrhea (30.43%), and vomiting (30.43%). Reported cases were non-serious (82.6%). The highest proportion of Individual Case Safety Reports (ICSRs) received is attributed to females (56.5%), and the age category of 2 and 11 years old (41.3%). Reporters' age range was 1-74 years old.

CONCLUSION: Monitoring AEFIs through the cholera outbreak's emergency campaign favors the safety profile of OCV.

PMID:39635205 | PMC:PMC11614796 | DOI:10.3389/fpubh.2024.1480744

Cureus. 2024 Nov 3;16(11):e72952. doi: 10.7759/cureus.72952. eCollection 2024 Nov.

ABSTRACT

Nilotinib, a tyrosine kinase inhibitor (TKI) used in patients of chronic myeloid leukemia (CML), has been known to cause atherosclerosis and arterial stenosis as a rare complication of long-term or high-dose therapy. Patients in this group are more likely to have coronary or peripheral artery disease; intracranial involvement is comparatively uncommon. Furthermore, studies on nilotinib-induced ischemia in Indian populations are scarce. Here, we present a case of ischemic stroke in a patient on long-term nilotinib treatment who, prior to treatment, had no risk factors for stroke. He presented with subacute symptoms of ataxia, motor and sensory deficit, and a raised low-density lipoprotein. MRI revealed multifocal arterial stenosis, as well as areas of infarction and hypoperfusion in the left cerebral hemisphere. Nilotinib therapy was immediately stopped; the patient was treated with dual antiplatelets, statins, and physiotherapy, and he had no major focal deficits on discharge. However, this case serves as a good reminder that even for patients considered to be largely safe from cardiovascular adverse events, regular monitoring of cardiovascular parameters is important so that timely preventive action can be initiated if necessary.

PMID:39634983 | PMC:PMC11615558 | DOI:10.7759/cureus.72952

PLoS One. 2024 Dec 4;19(12):e0314957. doi: 10.1371/journal.pone.0314957. eCollection 2024.

ABSTRACT

OBJECTIVE: Cilostazol is indicated for alleviating intermittent claudication (IC) in stable-phase peripheral arterial disease (PAD) patients. Conducting data mining on adverse events (AEs) of cilostazol in the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to explore its potential medication risks and advance more rational and secure clinical medication practices.

METHODS: This study utilized the Open Vigil 2.1-MedDRA tool to retrieve and extract AE reporting data related to cilostazol from the FAERS database spanning the first quarter of 2004 to the first quarter of 2024. The primary methodology employed was the application of the reporting odds ratio (ROR) method to detect risk signals associated with AEs of cilostazol.

RESULTS: A total of 2,130 AE reports involving cilostazol were identified as the primary suspect drug, with a total of 7,134 AEs reported. These reports were predominantly concentrated among patients aged 60 and above, with a higher occurrence in males compared to females. Japan ranked first among the reporting countries, and the majority of reports were submitted by healthcare professionals. Through the screening of cilostazol, a total of 323 positive risk signals for AEs were identified, encompassing 23 system organ classes (SOCs). A comparison with the existing cilostazol product label revealed 8 AEs that were not included based on the number of AE reports, and 19 AEs that were not included based on the strength of the risk signals. Cilostazol exhibited positive risk signals for AEs primarily affecting 8 organ systems based on the SOC classification. Among these, cardiac disorders ranked highest, with a total of 53 positive risk signals for cardiovascular-related AEs identified. In terms of the number of reports, cardiac failure ranked first, aligning with the black box warning issued by the FDA regarding cilostazol. The occurrence of adverse reactions related to cilostazol is primarily concentrated within the first month of treatment. However, a certain proportion of adverse reactions have been reported to occur after long-term use (exceeding 360 days) of cilostazol therapy.

CONCLUSION: Our results have further enriched the observations from existing clinical and real-world studies, uncovering new AE signals for cilostazol, including fall, cerebral infarction, pneumonia, loss of consciousness, acute kidney injury, renal impairment, renal failure, cardiac vein perforation, basal ganglia haematoma, cerebral hyperperfusion syndrome, et al. This study also highlights the significant impact of cilostazol on the cardiovascular system, necessitating close attention to potential cardiovascular toxicities. In addition to focusing on the short-term adverse reactions following cilostazol administration, thorough research into its long-term safety profile is also imperative. This study provides recommendations and guidance for the rational and safe clinical use of cilostazol. In the future, prospective studies are needed to explore the occurrence of related AEs further.

PMID:39630707 | DOI:10.1371/journal.pone.0314957