iScience. 2024 Oct 5;27(11):111072. doi: 10.1016/j.isci.2024.111072. eCollection 2024 Nov 15.

ABSTRACT

Chemotherapy resistance is still a great challenge for clinical treatment of lung cancer. Here, we found that doxorubicin (DOX) induced an increase of labile Zn2+ in lung cancer cells, and these labile Zn2+ protected tumor cells against DOX cytotoxicity. Nanoparticles encapsulating N,N,N',N'-Tetrakis (2-pyridylmethyl)-ethylenediamine (TPEN) were then constructed to chelate labile Zn2+ for tumor therapy. Application of nanoparticle-encapsulated TPEN at low dose not only avoided severe side effects caused by removing physiological Zn2+ but also effectively chelated drug-induced labile Zn2+, and thereby enhanced DOX cytotoxicity. Mechanistically, nanosized TPEN inhibits ABCB1-mediated drug export potentiated by drug-induced labile Zn2+. Finally, the results unraveled that nanosized TPEN at low dose endowed DOX with the killing ability on resistant tumor cells. Taken together, our results demonstrate that chelating drug-induced labile Zn2+ by nanosized TPEN at low dose enhances lung cancer chemotherapy by inhibiting ABCB1, providing a feasible strategy to overcome chemoresistance in lung cancer.

PMID:39507258 | PMC:PMC11539588 | DOI:10.1016/j.isci.2024.111072

PLoS Negl Trop Dis. 2024 Nov 6;18(11):e0012634. doi: 10.1371/journal.pntd.0012634. eCollection 2024 Nov.

ABSTRACT

BACKGROUND: Benzimidazole derivatives are widely used anthelmintic drugs, particularly in mass campaigns for intestinal parasitosis treatment. Despite their generally good safety profile, serious adverse reactions have been reported. This study aims to identify potential pharmacovigilance signals for benzimidazole derivatives using disproportionality analysis in the WHO database.

METHODOLOGY: A case/non-case study was conducted using data from the WHO VigiBase database (2000-2023). Cases were individual case safety reports (ICSRs) where at least one suspected serious adverse event of interest was reported, while non-cases were ICSRs reporting any adverse events other than the serious adverse events of interest. Reporting Odds Ratios (RORs) and 95% confidence intervals were calculated to assess disproportionate reporting. Analyses were adjusted for potential confounding factors and a sensitivity analysis with imputed missing data was performed.

PRINCIPAL FINDINGS: Among 19,068 serious reports analyzed, significant disproportionality signals were found for benzimidazole derivatives compared to other anthelmintic drugs, notably for bone marrow failure and hypoplastic anemia (adjusted ROR 9.44 [5.01-18.9]), serious leukopenia (3.89 [2.64-5.76]), serious hepatic disorders (3.10 [2.59-3.71]), hepatitis (2.88, 95% CI 2.29-3.63) and serious urticaria (2.02, 95% CI 1.36-2.99). We have also highlighted a new signal not mentioned in the summaries of product characteristics for seizures with benzimidazole derivatives. Secondary analysis revealed these signals were primarily reported with albendazole.

CONCLUSIONS/SIGNIFICANCE: This study identified potential pharmacovigilance signals for serious hematological and hepatic adverse events for benzimidazole derivatives, particularly albendazole. New signal for benzimidazole derivatives has been described for seizures. These findings underscore the need for vigilant monitoring during benzimidazole derivatives use and warrant further pharmacoepidemiologic studies to confirm these signals and investigate underlying mechanisms.

PMID:39504320 | DOI:10.1371/journal.pntd.0012634

Curr Opin Crit Care. 2024 Dec 1;30(6):563-570. doi: 10.1097/MCC.0000000000001210. Epub 2024 Sep 13.

ABSTRACT

PURPOSE OF REVIEW: The aim of this review is to provide a discussion of new perspectives for up-to-date definitions, a contemporary classification system, and the potential role of stress and damage biomarkers in the context of drug related kidney diseases and disorders.

RECENT FINDINGS: Acute kidney disease (AKD) is a term recently introduced in the literature describing an abnormality in kidney structure and function that lasts for less than 3 months. Drugs in the context of AKD is described as a new perspective; referred to as drug induced AKD. A framework that includes drugs into the 2X2 classification schema for acute kidney injury (AKI) is provided. Finally, stress and damage biomarkers are examined to assess risk of drug associated AKI (D-AKI), differentiate which drugs cause AKI, differentiate drugs from other etiologies and assess the prognosis of D-AKI.

SUMMARY: Consistent definitions should be adopted with consideration to drug related diseases and disorders. Drug management can be guided using novel biomarkers to isolate a possible drug cause in the presence of more than one nephrotoxin or a nondrug cause, assisting with the diagnosis of pseudo-AKI, and deciding the likelihood AKI recovery. Furthermore, stress and damage kidney biomarkers provide the opportunity to detect subclinical AKI for early intervention in patients at high-risk for severe AKI.

PMID:39503206 | DOI:10.1097/MCC.0000000000001210

Pediatr Pulmonol. 2024 Nov 6. doi: 10.1002/ppul.27382. Online ahead of print.

ABSTRACT

BACKGROUND: The benefits of Elexecaftor-Tezacaftor-Ivacaftor (ETI) therapy on the health and wellbeing of people with CF (pwCF) are well documented. Since approval, however, a growing number of potential side effects have emerged in reports from clinical practice. With current understanding of ETI tolerability limited to data from clinical trials, the prevalence of side effects and their impact on care decision making remains poorly categorized.

METHODS: A 10-question survey was developed and distributed to patients 18 years or older who were treated at the Massachusetts General Hospital CF centers. Reports of side effects were measured across 12 distinct categories, and dose adjustments and discontinuation due to side effects were collected. If a patient reported no side effects, they did not have to complete the entire survey.

RESULTS: Among 92 respondents initiated on ETI, 51 respondents (55.4%) reported potential side effects and 41 (44.5%) respondents reported no adverse events. The most commonly reported side effects were mental health, changes in appearance, and gastrointestinal complaints, which were reported by 22.8%, 30.4%, and 21.7% of patients, respectively. Eighteen (19.6%) respondents modified their dosing in response to side effects, and six discontinued treatment permanently (6.52%) due to persistent side effects.

CONCLUSIONS: Responses demonstrated marked heterogeneity, with most respondents reporting at least one side effect following initiation. Dose modification was commonly utilized to mitigate adverse effects, however few respondents had to discontinue treatment. These findings demonstrate the importance of monitoring for potential drug-related side effects of ETI in clinical settings.

PMID:39503182 | DOI:10.1002/ppul.27382

Drug Ther Bull. 2024 Nov 5:dtb-2024-000064. doi: 10.1136/dtb.2024.000064. Online ahead of print.

NO ABSTRACT

PMID:39500547 | DOI:10.1136/dtb.2024.000064

Front Pharmacol. 2024 Oct 21;15:1378208. doi: 10.3389/fphar.2024.1378208. eCollection 2024.

ABSTRACT

INTRODUCTION: Systematic collection of diverse adverse events during herbal medicine administration is crucial. The Korea Adverse Event Reporting System (KAERS) compiles spontaneously reported adverse event data for medicinal products including herbal medicines. This study focused on extracting and analyzing adverse event data specifically related to herbal medicine products from the KAERS database.

METHODS: Individual case safety reports (ICSRs) encompassing 84 types of herbal medicine products, identified by item codes from 2012 to 2021, were extracted from the KAERS database. Descriptive statistics were employed to analyze the characteristics of the extracted reports, and adverse event information was systematically categorized and analyzed based on the MedDRA System Organ Class and preferred term classification.

RESULTS: In total, 1,054 ICSRs were extracted, with some documenting multiple adverse events in a single ICSR, resulting in 1,629 extracted adverse events. When categorized by the MedDRA System Organ Class, gastrointestinal disorders were the most prevalent (28.7%), followed by skin and subcutaneous tissue disorders (20.1%). Based on the preferred terms, the most frequently reported adverse events were diarrhea (5.8%), urticaria (5.3%), pruritus (4.7%), rash (4.4%), and abdominal discomfort (4.2%). The most frequently reported herbal medicines were Bangpungtongseong-san (297 cases), Kyeongok-go (144 cases), and Eunkyo-san (108 cases).

CONCLUSION: Spontaneously reported adverse events associated with herbal medicine products were systematically documented using the KAERS database. This study, which focused on voluntarily reported adverse reactions, underscores the need for additional research to estimate the incidence rate of adverse events and assess causality.

PMID:39498343 | PMC:PMC11532164 | DOI:10.3389/fphar.2024.1378208

Nursing. 2024 Nov 1;54(11):26-33. doi: 10.1097/NSG.0000000000000083. Epub 2024 Oct 18.

ABSTRACT

Treatment with immune checkpoint inhibitors for cancer is associated with a high prevalence of multiple immune-related toxicities. Immune-related adverse events (irAEs) can occur anytime during treatment and up to 3 months after treatment. This article discusses checkpoint inhibitor therapy and describes the implementation of a patient education program focused on recognizing immunotherapy irAEs and their toxicities.

PMID:39497665 | DOI:10.1097/NSG.0000000000000083

Hum Vaccin Immunother. 2024 Dec 31;20(1):2423479. doi: 10.1080/21645515.2024.2423479. Epub 2024 Nov 4.

ABSTRACT

We aimed to explore the efficacy of rechallenge after first-line immunotherapy in advanced gastric cancer (AGC) and to analyze the factors affecting prognosis based on clinical characteristics. Eighty-five AGC patients who underwent rechallenged after the failure of first-line treatment with immune checkpoint inhibitors (ICIs) were retrospectively collected from July 2019 to December 2022 in Jiangsu Cancer Hospital. Potential factors affecting prognosis were analyzed by univariate and multivariate Cox analysis. Survival analysis was performed by Kaplan-Meier method and Log rank test. Stratified factors included human epidermal growth factor receptor 2 (HER-2) and programmed cell death-ligand 1 combined positive score (PD-L1 CPS). The objective response rate (ORR) was 15.3%, and the disease control rate (DCR) was 74.1%. The median progression-free survival (PFS) was 4.8 months. Results showed that patients in the I + C group had the best response. The ORR was 20.0% VS 8.7% in the I + C group and I + C + AAD group. The DCR was 78.0% VS 65.2%, and the median PFS was 6.7 VS 4.7 months [hazard ratio (HR): 0.55, 95% confidence interval (CI): 0.30-1.00, p = .022]. The ORR was 20.0% VS 8.3% in the I + C group and I + C + ADC group. The DCR was 78.0% VS 75.0%, and the median PFS was 6.7 VS 4.4 months (HR: 0.59, 95%CI: 0.26-1.30, p = .112). The median PFS was 4.7 VS 4.4 months in the I + C + AAD group and I + C + ADC group (HR: 1.21, 95%CI: 0.60-2.47, p = .580). Adverse events (AEs) were found in 34 patients, mainly including leukopenia 9 (10.6%), and neutropenia 8 (9.4%). The incidence of grade 3-4 AEs was 8.2%. There were no drug-related deaths and all AEs were manageable. Rechallenge after first-line immunotherapy showed good survival benefit and acceptable safety in the therapy of AGC. Especially for patients with HER-2-positive and PD-L1 CPS ≥ 1%, rechallenge may be an effective treatment modality.

PMID:39494935 | DOI:10.1080/21645515.2024.2423479

Cureus. 2024 Oct 3;16(10):e70788. doi: 10.7759/cureus.70788. eCollection 2024 Oct.

ABSTRACT

Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia. Its use is often limited due to its well-known association with a variety of side effects. Hepatotoxicity is a less common side effect and has been infrequently reported. Here, we present the case of a patient who developed abdominal discomfort and right upper quadrant pain after clozapine was initiated. Liver transaminases were found to be elevated and continued to rise despite cessation of another psychiatric medication more commonly associated with hepatotoxicity. Discontinuation of clozapine resulted in relief of symptoms and normalization of liver enzymes without any complications.

PMID:39493089 | PMC:PMC11531323 | DOI:10.7759/cureus.70788

Cureus. 2024 Oct 4;16(10):e70852. doi: 10.7759/cureus.70852. eCollection 2024 Oct.

ABSTRACT

Statins, commonly used for hyperlipidemia and more importantly having proven efficacy in lowering cardiovascular risk, are a very popular class of medications. Side effects are usually mild, and the class as a whole is generally well-tolerated by patients. However, one rare and more serious side effect is statin-induced autoimmune necrotizing myopathy. A 65-year-old woman with a past medical history of hyperlipidemia on atorvastatin for four years, type 2 diabetes, sciatica, and a prior history of endometrial cancer, presented to the emergency department due to proximal muscle weakness worsening over 2-3 months. On labs, her aspartate transaminase (AST) and alanine transaminase (ALT) were both elevated at 344 and 244, respectively. Additionally, creatine kinase (CK) was 13,000, C-reactive protein (CRP) was 42, and aldolase was 80.4. She was antinuclear antibody (ANA) negative but found to be anti-3-hydroxy-3- methylglutaryl-coenzyme A reductase (HMGCR ab) positive. Her magnetic resonance imaging (MRI) showed significant edema in bilateral thighs. During her hospital course, she was started on prednisone, fluids, and intravenous immunoglobulin (IVIG). Once completing two days of IVIG, the patient was discharged to rehab with rheumatology follow-up. The purpose of this case is to elucidate a rare side effect of a medication despite being on it for several years and to increase awareness and attention to an adverse effect that may one day lead to stratifying patients' risk on the medication.

PMID:39493067 | PMC:PMC11531928 | DOI:10.7759/cureus.70852

Clin Microbiol Infect. 2024 Nov 2:S1198-743X(24)00507-X. doi: 10.1016/j.cmi.2024.10.025. Online ahead of print.

ABSTRACT

OBJECTIVE: To demonstrate the noninferiority of intravenous (IV) sulopenem to IV ertapenem, each followed by an oral regimen, in adults with complicated intraabdominal infections (cIAI).

METHODS: Hospitalized adults with cIAI were randomized to 5 days of IV sulopenem followed by oral sulopenem etzadroxil/probenecid twice daily or 5 days of IV ertapenem followed by oral ciprofloxacin/metronidazole or amoxicillin-clavulanate depending on baseline pathogen susceptibility. The target treatment duration was 7-10 days. The primary (FDA-specified) endpoint was clinical response at Day 28 [Test-of-Cure (TOC)] in the micro-Modified Intent to Treat (micro-MITT) population.

RESULTS: 674 patients were randomized. The two treatment arms were well-balanced. E. coli (395 patients) and B. fragilis (111 patients) were the most frequently isolated pathogens. Clinical success rates in the micro-MITT population were 81.9% (204/249) for sulopenem-treated patients and 87.9% (233/265) for ertapenem-treated patients. The lower bound of the confidence interval (CI) for the treatment difference of the primary endpoint was below the prespecified non-inferiority margin of -10.0 [treatment difference -6.0%, 95% CI [-12.2, 0.2]. In all other analysis populations, the lower limit of the 95% CI was above -10.0. Treatment emergent adverse events (all, 26.0% [87/335] vs 23.4% [78/333]; related, 6.0% [20/335] vs 5.1% [17/333]) were similar for sulopenem and ertapenem, respectively. Most events were mild to moderate in severity. There were more serious adverse events in the sulopenem arm (7.5% [25/335] vs 3.6% [12/333]), only two of which were considered possibly drug-related.

CONCLUSIONS: Sulopenem IV followed by oral sulopenem etzadroxil/probenecid was not noninferior to ertapenem followed by oral step-down in treating cIAI in the micro-MITT population. This finding should be interpreted in the context of country regulations, as endpoint timing, primary analysis population and noninferiority margin may vary regionally. Both IV and oral sulopenem were well-tolerated; the oral formulation allowed patients with resistant pathogens to step down from IV therapy.

CLINICAL TRIAL REGISTRATION: NCT03358576.

PMID:39491784 | DOI:10.1016/j.cmi.2024.10.025

Sci Rep. 2024 Nov 3;14(1):26543. doi: 10.1038/s41598-024-77935-0.

ABSTRACT

This study aimed to measure relative telomere length (RTL) in blood leukocytes of advanced-stage NSCLC patients either with or without Osimertinib-induced ADRs and determine whether RTL could serve as a biomarker of Osimertinib-induced ADRs. Blood leukocytes RTL were measured in 63 advanced-stage NSCLC patients and 62 age-matched healthy controls using real-time polymerase chain reaction. In patients with advanced-stage NSCLC, RTL was significantly shorter than that in healthy controls (P < 0.001). Compared to patients without ADRs and those with mild/moderate ADRs, patients with severe ADRs exhibited significantly decreased RTL (P < 0.001, P < 0.001, respectively). ROC curve analysis uncovered a diagnostic value of RTL as a biomarker of Osimertinib-induced ADRs (AUC = 1.000, P < 0.001). Kaplan-Meier analysis revealed a significant association between shorter RTL and increased cumulative incidence of Osimertinib-induced ADRs in patients with advanced-stage NSCLC (P < 0.001). Shorter RTL in blood leukocytes would reflect the occurrence of Osimertinib-induced ADRs and might emerge as a promising biomarker for identifying advanced-stage NSCLC patients who are at risk of experiencing Osimertinib-induced ADRs, particularly those with severe ADRs.

PMID:39489788 | DOI:10.1038/s41598-024-77935-0

J Immunother Cancer. 2024 Nov 3;12(11):e009902. doi: 10.1136/jitc-2024-009902.

ABSTRACT

BACKGROUND: To date, evidence on late-onset immune-related adverse events (irAEs) with immune checkpoint inhibitors (ICIs) is limited to a small number of clinical cases. This study aimed to identify drug- and patient-related characteristics potentially associated with the reporting of late-onset irAEs with ICIs in VigiBase, the WHO global database of individual case safety reports (ICSRs).

METHODS: Observational study comparing deduplicated ICSRs with ICIs reporting late-onset irAEs (occurred >90 days after ICI discontinuation) versus ICSRs with ICIs not reporting late-onset irAEs, collected in VigiBase from 2011 to December 31, 2022. Logistic regression was used to model the relationship between drug-related and patient-related characteristics of ICSRs and the reporting of late-onset irAEs. Significance was determined for variables with the lower bound of the 95% CI of the reporting OR (ROR) higher than 1 and a p value <0.05.

RESULTS: The study population consisted of 6006 ICSRs with ICI-related irAEs (4574, 76.2%, originated from Europe; 3900, 64.9%, involved males; median patient age was 67 years, IQR 59-74 years). Of these, 344 (5.7%) ICSRs reported a total of 388 late-onset irAEs, among which the most frequent were thyroiditis (n=45), pneumonitis (n=37), interstitial lung disease (n=25), hepatitis (n=23) and vitiligo (n=19). Median time to onset since ICI discontinuation was 167 days (IQR 115-294 days), with negligible proportion (3.2%) of co-reported antineoplastic agents during the discontinuation period. Logistic regression models showed disproportionate reporting of late-onset irAEs with ICI combination therapy (ROR 2.33, 95% CI 1.19 to 4.57), reporting of multiple irAEs (ROR 3.96, 95% CI 2.85 to 5.52), reporting of cutaneous irAEs (ROR 1.83, 95% CI 1.24 to 2.71), and melanoma (ROR 1.47, 95% CI 1.04 to 2.06).

CONCLUSIONS: This global pharmacovigilance study provides the largest case series of late-onset irAEs with ICIs to date and identifies characteristics of ICSRs associated with disproportionate reporting. Dedicated prospective observational studies focused on long-term sequelae, quality of life and survival of patients developing late-onset irAEs with ICIs should be planned to confirm whether these reporting characteristics are predictors of actual occurrence. Furthermore, translational research should be encouraged to clarify the molecular mechanisms underlying late-onset irAE development.

PMID:39489542 | DOI:10.1136/jitc-2024-009902

Neurologia (Engl Ed). 2024 Oct 31:S2173-5808(24)00082-8. doi: 10.1016/j.nrleng.2024.10.001. Online ahead of print.

ABSTRACT

BACKGROUND: We describe the epidemiological and clinical characteristics of thrombosis with thrombocytopenia syndrome (TTS) cases reported in Spain.

METHODS: We included all venous or arterial thrombosis with thrombocytopenia following adenovirus vector-based vaccines (AstraZeneca or Janssen) to prevent COVID-19 disease between February 1st and September 26th, 2021. We describe the crude rate and the standardized morbidity ratio. We assessed the predictors of mortality.

RESULTS: Sixty-one cases were reported and 45 fulfilled eligibility criteria, 82% women. The crude TTS rate was 4/1,000,000 doses and 14-15/1,000,000 doses between 30-49 years. The number of observed cases of cerebral venous thrombosis was 6-18 higher than the expected in patients younger than 49 years. Symptoms started 10 (interquartile range (IQR): 7-14) days after vaccination. Eighty percent (95% confidence interval (CI): 65-90%) had thrombocytopenia at the time of the emergency department visit, and 65% (95% CI: 49-78%) had D-dimer >2000 ng/mL. Patients had multiple location thrombosis in 36% and fatal outcome in 24% cases. A platelet nadir <50,000/μL (odds ratio (OR): 7.4; CI 95%: 1.2-47.5) and intracranial hemorrhage (OR: 7.9; IC95%: 1.3-47.0) were associated with fatal outcome.

CONCLUSION: TTS must be suspected in patients with symptoms 10 days after vaccination and thrombocytopenia and/or D-dimer increase.

PMID:39488251 | DOI:10.1016/j.nrleng.2024.10.001

Cancer Immunol Immunother. 2024 Nov 2;74(1):1. doi: 10.1007/s00262-024-03854-8.

ABSTRACT

BACKGROUND: Immune-related adverse events (irAEs) pose substantial challenges in the realm of cancer immunotherapy, frequently affecting treatment efficacy and patient safety. To address the urgent need for identifying risk factors associated with irAEs, we conducted a comprehensive phenotype-wide Mendelian randomization analysis (MR-PheWAS).

METHODS: Utilizing publicly accessible genome-wide association study (GWAS) data, this investigation evaluated the impact of over 5000 exposure variables on susceptibility to irAEs using univariate Mendelian randomization (MR). We categorized these correlations and further explored potential mechanisms by which associated traits might influence irAEs through multivariate MR.

RESULTS: MR-PheWAS identified numerous risk factors for irAEs, encompassing both previously documented and novel associations. Specifically, we identified 105 traits with probable causal relationships to all-grade irAEs and 119 traits with suggestive associations. For high-grade irAEs, we categorized 122 traits as probably associated and 141 as suggestively associated. Notably, multivariate MR analyses uncovered intricate interactions, particularly highlighting how diabetes impacts all-grade irAEs through mediators such as body mass index and sex hormone-binding globulin.

CONCLUSIONS: This study has not only identified new risk factors for irAEs but also confirmed several well-established ones. Further investigation is crucial to validate and assess these identified risk factors within clinical trials. A mechanistic understanding of these causal factors is essential for improving the management and prevention of irAEs.

PMID:39487892 | DOI:10.1007/s00262-024-03854-8

Pharmacol Res Perspect. 2024 Dec;12(6):e70024. doi: 10.1002/prp2.70024.

ABSTRACT

Cytokine release syndrome (CRS) can occur following cancer immunotherapies, but is most often mild and of limited duration. International Classification of Diseases (ICD)-10 codes allowing identification of CRS were introduced in 2020 but may be underutilized. We evaluated the performance of a published claims-based algorithm to detect CRS (any grade) and high-grade CRS (HG, grades 2-5), as well as identified indicators of HG CRS in retrospective data. Adults with low-grade and HG CRS during an encounter coinciding with administrations of blinatumomab or chimeric antigen receptor-T therapy were identified in three types of retrospective databases (hospital chargemaster data, electronic health records, and administrative claims). The algorithm's sensitivity in detecting any CRS and HG CRS was reported. A least absolute shrinkage and selection operator (LASSO) regression model was developed to identify indicators of HG CRS. Performance of the model was evaluated using area under the curve (AUC). The sensitivity of the algorithm to detect any grade CRS ranged between 77%-100% and between 8%-80% for HG CRS, depending on the type of database. The LASSO model identified hypotension, positive pressure (including mechanical ventilation), tocilizumab, and vasopressors as indicators of HG CRS. AUC varied between 60% and 75%. The algorithm accurately detected any grade CRS for over three-quarters of instances, but was not as reliable for HG CRS. Results varied based on database attributes. Hypotension, vasopressors, positive pressure, and tocilizumab were associated with HG CRS and may be methodologically helpful signals of CRS severity in retrospective data.

PMID:39487576 | DOI:10.1002/prp2.70024

Curr Drug Saf. 2024 Oct 31. doi: 10.2174/0115748863357040241025051122. Online ahead of print.

ABSTRACT

BACKGROUND: Tumor necrosis factor alpha (TNF-α) inhibitors, such as adalimumab, have significantly advanced the treatment of inflammatory diseases. However, these therapies are associated with various cutaneous adverse reactions.

CASE PRESENTATION: We describe two rare instances of isolated facial hyperpigmentation induced by adalimumab. Both patients presented with asymptomatic, isolated brown macules on the cheeks following adalimumab treatment for ankylosing spondylitis. The hyperpigmentation appeared shortly after starting the medication in both cases. In one case, the hyperpigmentation persisted despite stopping the medication, while in the second case, it completely resolved within one month after discontinuation. However, in the second patient, the hyperpigmentation recurred after switching to certolizumab, another TNF-α inhibitor. No skin biopsies were performed, and both patients were otherwise healthy, with normal laboratory evaluations.

CONCLUSION: Hyperpigmentation is an uncommon adverse reaction of this class of drugs, with only a few reported cases in the literature. The recurrence of hyperpigmentation after switching to another TNF-α agent, certolizumab, further suggests that this reaction may be a class effect, adding new insights into the spectrum of cutaneous side effects associated with TNF-α inhibitors. Clinicians should consider this potential side effect in patients presenting with hyperpigmentation, and sun protection should be recommended as a preventive measure.

PMID:39484757 | DOI:10.2174/0115748863357040241025051122

Front Oral Health. 2024 Oct 17;5:1495012. doi: 10.3389/froh.2024.1495012. eCollection 2024.

ABSTRACT

INTRODUCTION: In the last decades, dermal fillers have gained widespread acceptance for cosmetic purposes since their approval for different health conditions, including lip augmentation and aesthetic intervention of the face. Unfortunately, while filler lip procedures are performed using biomaterials with improved physical characteristics, they are not devoid of adverse drug reactions (ADRs), including those with late-onset.

METHODS: This systematic aims to investigate the ADRs associated with lip augmentation procedures using dermal fillers. A systematic review search was conducted in Medline/PubMed, Scopus, Web of Science to answer the PEO question: What are the ADRs in patients undergoing lip augmentation procedures with dermal fillers, and how frequent are they?

RESULTS: The risk of bias was assessed, and a systematic review was conducted. Nineteen studies were included. In total, 30 patients affected by filler lip ADRs were analyzed, of which 29 were females and only 1 was male with a mean age of 50.9 ± 12.8 years. Hyaluronic acid was the most commonly dermal filler used and granulomatous foreign body reaction was the most common filler lip reaction reported. The mean time between filler lip injection and granulomatous foreign body reaction onset was 57.9 ± 54 months (median 24 months).

DISCUSSION: No study reported ADRs to regulatory authorities. Our results indicate that adverse reactions can occur even long-term after the aesthetic procedure. Therefore, ongoing short-term and long-term follow-up visits are essential, as biocompatible materials are not free from ADRs. Additionally, a lack of reporting ADRs to regulatory authorities has emerged, which is crucial for patient safety.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=534656, identifier: CRD42024534656.

PMID:39483115 | PMC:PMC11525007 | DOI:10.3389/froh.2024.1495012

Health Expect. 2024 Dec;27(6):e70019. doi: 10.1111/hex.70019.

ABSTRACT

BACKGROUND: Schizophrenia treatment with antipsychotics often results in side effects that impact adherence and quality of life. Managing these effects remains challenging, as it requires balancing efficacy and tolerability. The Schizophrenia Technological Evaluation of Patient Side Effects (STEP-SE) app aims to aid side effects monitoring and management through shared decision-making (SDM).

AIM: This study aimed to evaluate the usability of the STEP-SE app for patients and clinicians in managing antipsychotic side effects.

METHODS: Sixteen stable outpatients and 14 psychiatrists participated in semi-structured interviews after using the STEP-SE app. Questions explored ease of use, information clarity, user needs fulfilment, patient-clinician collaboration, treatment adherence improvement, patient empowerment and clinical utility. Data were analysed thematically.

RESULTS: Overall satisfaction with STEP-SE was high. Both groups found that the tool improved patient involvement, provided reliable information to enhance therapeutic alliance, posed low risks of misunderstanding and had an intuitive interface. Patients felt more motivated and empowered. Clinicians appreciated guideline consistency. Preferences differed regarding data visualization formats.

DISCUSSION: STEP-SE shows potential for aiding SDM on antipsychotic side effects. Patients gained motivation, and clinicians felt reassured. Refinements around mobile access, graphics and features could augment utility. Generalizability is limited given the stable patient sample.

CONCLUSION: Preliminary findings suggest that STEP-SE effectively engages patients, empowers them and supports clinicians in collaborative side effect management. Further testing with diverse user groups is warranted.

PATIENT OR PUBLIC CONTRIBUTION: The current study was designed to gather patient and public feedback for the development of our decision aid tool, STEP-SE. Participants interacted with the tool's prototype in interactive sessions, providing insights and identifying technical issues. Their feedback was crucial for enhancing the tool, with each suggestion and bug report carefully considered for future iterations. The participants' contributions were key in optimizing STEP-SE's features and ensuring its relevance and reliability. We thank all who shared their time and perspectives, significantly shaping the tool's user-centred design.

PMID:39482944 | DOI:10.1111/hex.70019

Rev Recent Clin Trials. 2024 Oct 30. doi: 10.2174/0115748871306001241017050020. Online ahead of print.

ABSTRACT

BACKGROUND: Helicobacter pylori [H. pylori] infection is the main cause of most PUD; therefore, the eradication of H. pylori is extremely important in the treatment of PUD. There are several recommended treatment regimens suggested to eradicate this organism.

AIM: This study compared the efficacy of three anti-Helicobacter pylori regimens in patients with dyspepsia or peptic ulcer disease [PUD].

OBJECTIVE: The objective of this study was to assess the efficacy of three anti-H Pylori treatments in patients based on C14 urease breath test [C-UBT] results, drug compliance, and adverse effects.

METHODS: This randomized, open-label clinical trial included 136 H. Pylori-infected patients without prior treatment. Patients were randomly divided into three groups. The OAC group received 20 mg Omeprazole capsules twice a day, two 500 mg Amoxicillin capsules twice a day, and 500 mg Clarithromycin capsules twice a day for 14 days. The OAL group received 20 mg Omeprazole capsules twice a day, two 500 mg Amoxicillin capsules twice a day, and Levofloxacin 500 mg capsules twice a day for 14 days. The OAMB group received 20 mg Omeprazole capsules twice a day, two 500 mg Amoxicillin capsules twice a day, Metronidazole 500mg three times a day, and Bismuth 240 mg twice a day for 14 days. Evaluation for compliance and drug-related adverse effects were assessed at the end of two weeks. H. Pylori eradication was evaluated eight weeks after treatment using the C-UBT.

RESULTS: A total of 136 patients participated in this study, and their groups were matched based on age and sex. The results of the C-UBT test showed that the eradication rate of H. Pylori was 82.2%, 91.3%, and 97.3% for the three-drug OAC, OAMB, and OAL treatment regimens, respectively. Moreover, all the regimens showed high compliance among the patients. Only OAC and OAL showed a significant difference in the H. Pylori eradication rate, and no superiority was found between OAMB and OAL or OAC therapies.

CONCLUSION: The regime of OAL achieved a satisfactory rate of H. pylori infection eradication with good tolerance in patients with PUD, without any acute side effects.

CLINICAL TRIAL REGISTRATION NUMBER: IRCT201605189014N100.

PMID:39482907 | DOI:10.2174/0115748871306001241017050020