Sci Rep. 2024 Dec 28;14(1):31503. doi: 10.1038/s41598-024-82981-9.

ABSTRACT

The study aims to address the critical issue of toxic side effects resulting from drug combinations, which can significantly increase health risks, clinical complications, and lead to drug being withdrawn from the market. A model named TSEDDI (toxic side effects of drug-drug interaction) has been developed to improve the identification of drug pairs that may induce toxicity or adverse reactions. By utilizing drug chemical structures and diverse proteins, we employ a convolutional neural network (CNN) to extract features from molecular images, enzyme proteins, transporter proteins, and target proteins. Furthermore, we introduce a weighted binary cross entropy loss function to tackle class imbalance and integrate the multi-head attention mechanism with residual connections to enhance model performance. Our model outperformed advanced baseline models in predicting drug-drug interaction (DDI) side effects, achieving an accuracy of 0.9059 (± 0.0010) and consistently excelling across various evaluation metrics. The case study confirms the potential mechanisms by which four pairs of drugs cause side effects, thus demonstrating the effectiveness of our model in predicting DDI side effects. The TSEDDI model combines multiple attention mechanisms and residual connections, enhancing its ability to detect toxic and adverse effects related to DDIs. As a result, it becomes a valuable resource for promptly identifying adverse reactions in clinical trials. Future research could investigate drug substructures prone to toxic side effects.

PMID:39733005 | DOI:10.1038/s41598-024-82981-9

Sci Rep. 2024 Dec 28;14(1):31201. doi: 10.1038/s41598-024-82575-5.

ABSTRACT

BACKGROUND: NK-1 receptor antagonists (NK-1RAs) are proven to be successful in preventing chemotherapy-induced nausea and vomiting (CINV). The safety profile of NK-1RAs has not been systematically analyzed in the real world. This pharmacovigilance study investigated the differences in adverse events (AEs) between NK-1RAs.

METHODS: Adverse events (AEs) associated with NK-1RAs were gathered and standardized using data from the FAERS database spanning from the first quarter of 2009 to the fourth quarter of 2023. Various disproportionality techniques were employed for data analysis, such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).

RESULTS: A total of 5434AE reports listing NK-1RAs as the primary suspected drugs were identified. The System Organ Classes (SOC) appeared as significant safety signals were found. Among NK-1RAs, the most frequently reported AEs were related to general disorders and administration site conditions. In terms of PT level, the strong signals were mainly injection site reactions associated with aprepitant and fosaprepitant. Moreover, toxic encephalopathy and encephalopathy of the aprepitant were all positive with four algorithms. A significant finding was the recognition of adverse events linked to endocrine disorders, which were not previously mentioned in the medication instructions.

CONCLUSION: The safety profile of NK-1RAs has been reported to be variable.If intravenous formulations were used in the clinic, injection site reactions should be a concern. In addition, more attention should be paid to the management of encephalopathy toxicity in patients treated with aprepitant in combination with ifosfamide. Besides known AEs, we have identified several new high-risk AEs, such as inappropriate antidiuretic hormone secretion, adrenal insufficiency and hyponatraemia. Overall, clinicians should closely monitor the occurrence of NK-1RA-related AEs in clinical applications.

PMID:39732926 | DOI:10.1038/s41598-024-82575-5

Ter Arkh. 2024 Dec 16;96(11):1049-1055. doi: 10.26442/00403660.2024.11.202992.

ABSTRACT

AIM: To study the adverse reactions that develop as a result of complex antibiotic therapy in patients with non-tuberculous lung mycobacterial (NTML) and to determine methods for their elimination without compromising the effectiveness of NTML treatment.

MATERIALS AND METHODS: Examined 147 patients with confirmed NTML, for which they received treatment in accordance with the results of drug susceptibility of the pathogen. Before and during treatment, a study of clinical, biochemical blood tests, urinalysis, electrocardiogram, external respiration function, ultrasound of the abdominal organs and kidneys was performed.

RESULTS: Under the conditions of antimicrobial therapy (AMT) for non-tuberculous mycobacteriosis of the lungs, 41 (27.9%) patients developed adverse drug reaction (ADR). The most frequent adverse reactions were: allergic reactions in the form of urticaria, nausea, vomiting, arthralgia, nephro- and ototoxic reactions; 34 (82.9%) patients required treatment adjustment without discontinuation of AMT, and only in 7 (17.1%) cases, AMT was discontinued. A full course of multicomponent AMT was completed in 124 (84.4%) patients with NTML. An algorithm for monitoring therapy in NTML patients from the standpoint of preventing ADR has been developed. The categories of patients with potential risks of developing ADR under AMT were determined. Patients without the development of ADR had a positive radiological dynamics in 27.9% of cases, sputum conversion - in 42%. Patients with ADR had positive clinical dynamics in 39% of cases, radiological - in 31.7% of cases, sputum conversion - in 36.6% of cases.

CONCLUSION: The incidence of ADR development remains high when complex AMT is administered to patients with NTML. The patient's comorbid background is the main risk factor for the development of ADR when prescribing multicomponent AMT. A multivariate analysis of the effectiveness of treatment in NTML patients showed comparable data among patients taking complex AMT and receiving only alternative therapies. The success of NTML treatment depends on a comprehensive personalized approach.

PMID:39731765 | DOI:10.26442/00403660.2024.11.202992

Sci Rep. 2024 Dec 28;14(1):31161. doi: 10.1038/s41598-024-82474-9.

ABSTRACT

Spontaneous adverse drug reactions (ADRs) reporting by health care professionals (HCPs) plays a vital role in pharmacovigilance (PV). However, under-reporting remain a major challenge worldwide, especially in low and middle-income countries, including Lao PDR. This cluster-randomized controlled trial evaluated the effectiveness of the modified TaWai mobile app for ADR reporting compared with the usual practice in hospitals. Two tertiary hospitals in Lao PDR (cluster units) were randomized into two groups: the intervention group (16 HCPs), which used the modified TaWai mobile app along with an educational workshop, and the control group (18 HCPs), which followed usual practice with the same educational workshop. The intervention group reported more ADR cases (28 vs. 3), and produced a higher number of high-quality reports (28 vs. 2) than the control group. The modified TaWai mobile app was highly rated by all participating HCPs. Questionnaire responses indicated that the tool is user-friendly, time-efficient, and well-suited for ADR reporting in hospitals in Lao PDR. In conclusion, these findings highlight the potential of the modified TaWai mobile app to enhance ADR reporting practices in hospitals, and its features make it a promising solution for strengthening PV in Lao PDR and similar settings.

PMID:39730897 | DOI:10.1038/s41598-024-82474-9

Sci Rep. 2024 Dec 28;14(1):30983. doi: 10.1038/s41598-024-82105-3.

ABSTRACT

Immune checkpoint inhibitors (ICIs) have been approved for monotherapy and combined therapy with chemotherapy and/or radiotherapy in China since 2018. The number of patients receiving ICIs has significantly increased in recent years, and the collection and analysis of this data are crucial for a comprehensive understanding of their clinical outcomes and adverse effects. The effects of ICIs may vary among different ethnic groups, and there is a lack of such data in the Chinese population. This study aimed to investigate the occurrence rate of various types of immune-related adverse events (irAEs) of ICIs in cancer survivors with different types of cancer and explore the associated risk factors. Demographic data, cancer type, dosage, Eastern Cooperative Oncology Group Performance Score (ECOG-PS), and details of irAEs were collected from 120 participants who underwent ICI treatment. Descriptive statistics were used to summarise the patient population characteristics, while t-tests and Chi-square tests assessed associations between variables. Multiple logistic regression evaluated the relationships between independent variables and the likelihood of experiencing irAEs. The results indicated that the occurrence of less severe G1 and G2 irAEs was 25%, while more severe G3 to G5 irAEs accounted for 5.8% of the total. Among the irAEs, skin toxicity had the highest incidence rate (14.2%), followed by gastrointestinal toxicity (6.7%), and endocrine toxicity had the lowest incidence rate of 2.5%. The multiple logistic regression model revealed that patients with ECOG-PS ≥ 2 are over five times more likely to experience irAEs compared to those with lower ECOG-PS (OR: 5.03, 95% CI: 1.05-24.17). Additionally, patients with cancer stage IV have 11.47 times the odds of experiencing irAEs (OR: 11.47, 95% CI: 1.05-24.17). In conclusion, a substantial proportion of patients receiving ICIs experienced irAEs. Patients with an ECOG-PS score of ≥ 2 and advanced cancer stage are at increased risk for these events, necessitating close monitoring by healthcare professionals. The identification of skin and gastrointestinal toxicities as the most common irAEs revealed the need for targeted education for the patients and their carers to recognise and manage these issues. Furthermore, our findings, in conjunction with existing literature, may guide future research on predictive modelling for high-risk patients receiving ICIs.

PMID:39730637 | DOI:10.1038/s41598-024-82105-3

Dent J (Basel). 2024 Dec 10;12(12):403. doi: 10.3390/dj12120403.

ABSTRACT

Background/Objectives: The etiology of diffuse gingival enlargement is multifactorial, and the definitive diagnosis may be challenging. To highlight the nuances of the differential diagnosis, we present two cases of generalized gingival overgrowth and discuss the diagnostic dilemmas. Case description: In the first case, an 82-year-old male with a medical history of hypertension and prostatitis had a chief complaint of symptomatic oral lesions of a 20-day duration, accompanied by fever and loss of appetite. The clinical examination revealed diffusely enlarged, hemorrhagic, and focally ulcerative upper and lower gingiva, ecchymoses on the buccal mucosa, as well as bilateral cervical lymphadenitis. The histopathologic and immunohistochemical findings combined with the hematologic examination led to a final diagnosis of acute myeloid leukemia, and the patient was referred to a specialized hematology/oncology unit for further management. The second case was a 74-year-old female with a medical history of breast cancer (successfully managed in the past), type II diabetes mellitus, and cardiovascular disease, taking various medications. An intraoral examination revealed diffusely enlarged, erythematous, and hemorrhagic upper and lower gingiva. An incisional biopsy showed hyperplastic granulation and fibrous connective tissue with a predominantly chronic inflammatory infiltrate. Considering the patient's medical history and current medications, the clinical and microscopic findings were in support of the diagnosis of drug-induced gingival overgrowth associated with calcium channel blocker (amlodipine), partially controlled diabetes serving as an additional predisposing factor. Gingivectomy and periodontal scaling, along with substitution of the offending medication, were curative, and better diabetic control was recommended. Conclusions: Diffuse gingival overgrowth may be caused by a variety of diverse conditions, ranging from an exuberant response to local factors, potentially exacerbated by hormonal influences (e.g., puberty or pregnancy), to drug side effects to genetic, systemic, or even neoplastic diseases. A careful evaluation of the medical and drug history and clinicopathologic correlation is essential for accurate diagnosis and appropriate management.

PMID:39727460 | DOI:10.3390/dj12120403

Basic Clin Pharmacol Toxicol. 2025 Jan;136(1):e14121. doi: 10.1111/bcpt.14121.

ABSTRACT

BACKGROUND: Drug-induced organ toxicity is a significant health concern, with gentamicin known for its effective antibacterial properties but also severe side effects, particularly cytotoxicity in liver and kidney tissues. This current study observed the preventive role of baicalein and bergenin against hepatic and renal injuries caused by gentamicin in rats.

METHODS: Thirty-two male Sprague Dawley rats were divided into four groups, namely, control, gentamicin (gentamicin 80 mg/kg/day), baicalein (gentamicin 80 mg/kg/day + baicalein 100 mg/kg/day) and bergenin (gentamicin 80 mg/kg/day + bergenin 100 mg/kg/day). Hepatotoxicity and nephrotoxicity were induced by giving gentamicin (80 mg/kg/day). We evaluated the biochemical markers, including alkaline phosphatase (ALP), urea, alanine transaminase (ALT), creatinine and aspartate transaminase (AST) levels, antioxidant enzymes, oxidative stress parameters and histopathological and immunohistochemical changes.

RESULTS: Gentamicin increased oxidative stress parameters and decreased antioxidant activity. The treatment with baicalein and bergenin significantly restored these markers.

CONCLUSIONS: Baicalein and bergenin significantly mitigated gentamicin-induced hepatic and renal toxicity by restoring biochemical markers, reducing oxidative stress and enhancing antioxidant enzyme activity. Histopathological and immunohistochemical analyses confirmed the protective effects of both compounds against organ damage. No statistically significant differences were observed between the two drugs for these parameters. These results suggest their potential as therapeutic agents to prevent gentamicin-induced organ toxicity.

PMID:39726240 | DOI:10.1111/bcpt.14121

Toxicology. 2024 Dec 24:154039. doi: 10.1016/j.tox.2024.154039. Online ahead of print.

ABSTRACT

Mycotoxin occurrence in food worldwide is estimated to increase due to climate change. Moreover, studies on how these food contaminants interfere with medications and especially anticancer therapies are rare. With the rise of anticancer immunotherapies, particularly mycotoxins with immunomodulatory activity, such as alternariol (AOH) or deoxynivalenol (DON), are of great concern. Both mycotoxins interfere with the pro-inflammatory nuclear factor kappa B (NF-κB) pathway in myeloid cells. This pathway not only plays an important role in the anticancer immune response but also inflammatory side effects induced by chemotherapeutic drugs. Consequently, the aim of this study was to investigate possible beneficial or detrimental immunomodulatory interactions between these mycotoxins and anticancer drugs. To assess the combined influence of mycotoxins and anticancer therapies on immune cell stimulation, THP-1 NF-κB reporter cells were utilized as monocytes as well as differentiated and polarized macrophages. Parameters for activation (NF-κB activity and protein expression), differentiation (CD14 and CD71 surface marker expression) and polarization (interleukin 10 (IL10), interleukin 8 (CXCL8), tumor necrosis factor α (TNF), prostaglandin-endoperoxide synthase 2 expression and CXCL8 secretion) were assessed upon combinatory treatment. Both mycotoxins affected the immunostimulatory effects of the pre-selected anticancer drugs oxaliplatin and triapine, although in opposing directions. While AOH generally suppressed a drug-induced activation and increased anti-inflammatory IL10 levels, DON potentiated activation and pro-inflammatory markers, such as CXCL8 and TNF in immune cells. In conclusion, AOH and DON have the potential to alter the immunological effects of anticancer therapies, which should be considered during therapy as well as in their future risk assessment.

PMID:39725263 | DOI:10.1016/j.tox.2024.154039

J Dtsch Dermatol Ges. 2024 Dec 26. doi: 10.1111/ddg.15639. Online ahead of print.

ABSTRACT

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of the heterogeneous group of cutaneous T-cell lymphomas (CTCL). With the expansion of the biologic treatment landscape, new treatment options have become available in recent years, most notably the C-C chemokine receptor 4 (CCR4)-directed monoclonal antibody mogamulizumab. Based on the phase III pivotal trial, mogamulizumab is recommended by the German S2k guidelines for the second-line treatment of stage IB and above SS and MF, after at least one prior systemic therapy. Since then, new insights on safety and efficacy of mogamulizumab were generated by post hoc analyses and real-world evidence. A panel of CTCL-experts discussed available literature and own experiences and developed relevant recommendations on the use of mogamulizumab in clinical practice in Germany. The recommendations cover patient criteria, prior therapies, use of mogamulizumab as monotherapy or combination therapy, management of side effects, duration of therapy, and monitoring schedules. The aim of these clinical recommendations is to support healthcare professionals in their decision-making and use of mogamulizumab in daily practice.

PMID:39723687 | DOI:10.1111/ddg.15639

Immun Inflamm Dis. 2024 Dec;12(12):e70057. doi: 10.1002/iid3.70057.

ABSTRACT

OBJECTIVE: This study aimed to investigate the efficacy and safety of a triple therapy consisting of colchicine, thalidomide and total glucosides of paeony (TGP) in Behcet's disease (BD) patients with mucocutaneous involvement.

METHODS: Totally 355 newly diagnosed BD patients with mucocutaneous involvement were recruited, who received dexamethasone and colchicine for the first 2 weeks, then they were categorized into "sustained triple-therapy (ST)" (n = 231) and "colchicine to triple-therapy (CT)" (n = 124) groups respectively: for ST group, patients received colchicine, thalidomide plus TGP from Month (M)0.5 to M12; for CT group, patients received colchicine from M0.5 to M2, then switched to colchicine, thalidomide plus TGP from M3 to M12.

RESULTS: The percentages of oral ulceration (at M1, M2) and genital ulceration (at M1) were lower in ST group compared to CT group, whereas there was no difference of other clinical manifestations (including uveitis, erythema nodosum, thrombosis, arterial involvement or nervous system involvement) at each time point between the two groups. For biochemical indexes, ESR was higher at M1 but rapidly reduced at M2 in ST group compared to CT group, while CRP level was similar at all time points between the two groups. For side effects, occurrences of drug-related cytopenia and diarrhea were increased, in ST group compared to CT group.

CONCLUSIONS: A triple therapy consisting of colchicine, thalidomide and TGP is more effective and equally tolerated compared to colchicine alone in treating BD patients with mucocutaneous involvement.

PMID:39722576 | DOI:10.1002/iid3.70057

Pharmacol Res Perspect. 2025 Feb;13(1):e70046. doi: 10.1002/prp2.70046.

ABSTRACT

Data addressing safety concerns related to potential drug interactions between cannabis-derived products and pharmaceutical medications in the pediatric population are lacking. In this study, we retrieved case reports through a published literature search using PubMed and spontaneous reporting data using the Food and Drug Administration's Adverse Event Reporting System (FAERS) to identify potential cannabis- and cannabinoid-drug interactions in individuals younger than 18 years old. To evaluate the published case reports, we used the Drug Interaction Probability Scale (DIPS), a 10-item questionnaire designed to discern the causal relationship between a potential drug interaction and adverse drug reactions (ADRs). FAERS reports were deduplicated and analyzed to gather information regarding patient demographics, associated drugs, nature of the ADRs, outcomes, professions of the reporters, and reporting timelines. Seven published case reports and 9142 FAERS ADRs reports were included in the final analysis. Based on the findings, caution is warranted when cannabis or cannabinoids are used in combination with prescribed medications, including methadone, everolimus, fluoxetine, and paroxetine. Cannabinoids may inhibit drug-metabolizing enzymes, including several cytochrome P450s, leading to increased drug exposure and potentially, an increased risk for ADRs.

PMID:39719830 | DOI:10.1002/prp2.70046

Diagn Microbiol Infect Dis. 2024 Dec 19;111(3):116659. doi: 10.1016/j.diagmicrobio.2024.116659. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the rationality of the clinical use of ceftazidime-avibactam (CAZ-AVI) for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in a real-world setting.

METHODS: We established the rational evaluation criteria based on drug instructions and relevant guidelines to retrospectively evaluate the use of CAZ-AVI to treat CRKP infections from June 2020 to June 2023 in a tertiary hospital in China. Patients were divided into the rational use group and irrational use group. The differences in clinical efficacy, 14- and 28-day mortality, microbiological response and side effects between these two groups were analyzed.

RESULTS: Seventy-five adult patients were enrolled. The clinical application of CAZ-AVI was rational in 32 (42.7 %) patients. Irrational dosage and irrational treatment regimens were observed in 19 (25.3 %) and 31 (41.3 %) patients, respectively. The clinical treatment success rate of the rational use group was higher than that of the irrational use group, whereas the 28-day mortality rate was slightly lower. However, the microbial clearance rate was significantly higher in the irrational use group, probably due to the high percentage of microbial replacement. The rational use group had a lower incidence of acute kidney injury and acute drug-induced liver injury. Multivariate logistic regression analysis showed that continuous renal replacement therapy (CRRT) negatively impacted rational CAZ-AVI use (OR 0.13, 95 % CI 0.03-0.72, P = 0.019).

CONCLUSIONS: To optimize clinical outcomes and reduce side effects of CAZ-AVI, unnecessary combination therapy should be avoided, and dose adjustments should be made according to the drug instructions.

PMID:39719811 | DOI:10.1016/j.diagmicrobio.2024.116659

Eur Heart J Cardiovasc Pharmacother. 2024 Dec 24:pvae095. doi: 10.1093/ehjcvp/pvae095. Online ahead of print.

ABSTRACT

OBJECTIVES: This review aims to examine the evidence on the benefits and risks of lipid lowering drugs in patients with liver disease. Elevated liver enzyme levels often lead to cautious discontinuation of these drugs, potentially withholding from patients their benefit in reducing cardiovascular disease morbidity and mortality.

METHODS AND RESULTS: Using a literature search of PubMed, we examine the efficacy and safety profiles of various lipid lowering agents, including statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, fibrates, and icosapent ethyl, focusing particularly on their potential side effects related to liver health. A major challenge in the assessment of drug-induced hepatotoxicity is the fact that it relies heavily on case reports rather than real world evidence. There is currently a lack of robust evidence on lipid-lowering therapy in people with pre-existing liver disease. Nevertheless, we have attempted to summarize the available data for all the drugs mentioned in order to provide guidance for the treatment of patients with liver dysfunction.

CONCLUSION: This review highlights the need for further research to optimize treatment strategies for patients with coexisting liver and cardiovascular disease.

PMID:39719399 | DOI:10.1093/ehjcvp/pvae095

Front Immunol. 2024 Dec 9;15:1495540. doi: 10.3389/fimmu.2024.1495540. eCollection 2024.

ABSTRACT

BACKGROUND: Alarmins mediate type 2 T helper cell (Th2) inflammation and serve as upstream signaling elements in allergic inflammation and autoimmune responses. The alarmin interleukin (IL)-25 binds to a multi-domain receptor consisting of IL-17RA and IL-17RB subunits, resulting in the release of Th2 cytokines IL-4, IL-5, IL-9 and IL-13 to drive an inflammatory response. Therefore, the blockage of IL-17RB via SM17, a novel humanized monoclonal antibody, offers an attractive therapeutic target for Th2-mediated diseases, such as asthma.

METHODS: Wild-type mice were stimulated with house dust mite (HDM) extracts for evaluation of SM17's pre-clinical efficacy in allergic asthma. The safety, pharmacokinectics (PK), pharmacodynamics (PD), and immunogenicity of intravenous (IV) doses of SM17 were assessed in a 2-part clinical study in healthy adult subjects. In Part A, 53 healthy participants were enrolled to receive a single IV dose of SM17 (2, 20, 70, 200, 400, 600, 1200 mg) or placebo. In Part B, 24 healthy subjects were enrolled to receive a single IV dose of SM17 every two weeks (Q2W; 200, 400, 600 mg) or placebo for a total of 3 doses.

RESULTS: Animal studies demonstrated that SM17 significantly suppressed Th2 inflammation in the bronchoalveolar lavage fluid and infiltration of immune cells into the lungs. In the Phase I clinical study, no drug-related serious adverse events were observed. Total SM17 exposure increased by approximately 60- to 188-fold with a 60-fold increase in dose from 20 to 1200 mg SM17. Upon administration of the third dose, mean accumulation ratios over 200-600 mg was 1.5 to 2.1, which confirms moderate accumulation of SM17. After Q2W dosing of SM17 over 4 weeks, total exposure increased in a dose-proportional manner from 200 mg to 600 mg SM17.

CONCLUSION: In the pre-clinical studies, we demonstrated that SM17 is a potential therapeutic agent to treat allergic asthma. In the Phase 1 clinical trial, a single IV dose of SM17 up to 1200 mg and three Q2W doses up to 600 mg were well tolerated in healthy participants and demonstrated a favorable safety profile. The pre-clinical efficacy and clinical PK and immunogenicity results of SM17 support further clinical development.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, identifier NCT05332834.

PMID:39717777 | PMC:PMC11663749 | DOI:10.3389/fimmu.2024.1495540

Khirurgiia (Mosk). 2024;(12):74-80. doi: 10.17116/hirurgia202412174.

ABSTRACT

OBJECTIVE: To compare the results of postoperative opiate and non-opiate analgesia.

MATERIAL AND METHODS: The study was carried out as a part of the OPERAS global trial. Analysis was conducted in accordance with the STROBE reporting guidelines for observational studies. A prospective cohort study included data of patients after emergency and elective abdominal surgery. Primary outcomes were duration of severe pain and patient satisfaction with pain relief during the first week after surgery. Data were collected through review of case reports and interviews with patients one week after surgery.

RESULTS: The study involved 173 postoperative patients. Opioid analgesia after surgery was prescribed in 52 patients (30.1 %); 10% of patients reported severe pain within the first week after surgery and rated satisfaction with analgesia as 90 out of 100 points. After adjusting for confounders, opiate analgesia was independently associated with higher pain (hazard ratio 1.52, 95% CI 1.31 to 1.76; p<0.001) and need for medical care for drug-related side effects (OR 2.38, 95% CI 1.36 to 4.17; p=0.004). Opiate analgesia was not associated with satisfaction with analgesia (β coefficient 0.92, 95% CI -1.52 to 3.36; p=0.468) compared to non-opiate analgesia.

CONCLUSION: Postoperative opiate analgesia is associated with higher risk of drug-related side effects and aggravation of pain, but not with changes in satisfaction with pain relief. Non-opiate analgesia should be used regularly after surgery.

PMID:39716429 | DOI:10.17116/hirurgia202412174

BMC Cancer. 2024 Dec 23;24(1):1568. doi: 10.1186/s12885-024-13312-4.

ABSTRACT

BACKGROUND: Cancer-treatment toxicity is common and symptoms must be identified quickly and accurately. Since symptom reporting during consultations is hampered by time constraints and patient/oncologist biases, patient-reported outcome-measure (PROM) questionnaires are useful. A strong shift to at-home cancer treatment has led to growing interest in remote symptom monitoring via electronic-PROMs (ePROMs). However, because PROMs are generally designed for medical-staff use, ePROMs must be adapted to patient comprehension/abilities. Here, to meet the oncological-healthcare needs of our region, we developed QuestOnco, a mobile-phone ePROM application. It is based on the symptom descriptions and severity grades of the PRO-CTCAE PROM and is designed for real-time on-demand reporting of 34 common or life-threatening cancer-treatment symptoms. This study describes the development of QuestOnco and its content validation relative to two comparators: PRO-CTCAE and the medical records.

METHODS: The cohort study was conducted in a tertiary-care hospital in 2021 and consisted of two stages. Stage I assessed the comprehensibility of QuestOnco for patients: 24 cancer-therapy patients were asked to try the application for 30 min and then underwent semi-structured cognitive interviews. Stage II tested QuestOnco-content validity against the comparators: patients starting a ~ 6-week cancer-therapy cycle were asked to use QuestOnco in an on-demand fashion and to complete weekly paper PRO-CTCAEs. Total QuestOnco, PRO-CTCAE, and medical-record symptom reports were compared in terms of symptom and symptom-severity frequencies. Severity concordance of each reported symptom was assessed by Kendall's tau-b rank-correlation coefficients.

RESULTS: In the second round of 12 Stage-I patients (total Stage-I enrollment rate = 100%), 0% reported comprehension difficulties. 110 patients were recruited for Stage II (enrollment rate = 23%). QuestOnco, PRO-CTCAE, and the medical records detected 85%, 100%, and 62% of the target symptoms at least once, respectively, and reported grade-1, -2, -3, and -4 toxicities with similar frequencies (56-67%, 23-32%, 6-10%, and 2-3%, respectively). Overall symptom-severity concordance was moderate with PRO-CTCAE (tau-b = + 0.21, range = -0.03 to + 0.38) and strong with the medical records (tau-b = + 0.33, range = -0.01 to + 0.61). Few remarkable discrepancies were observed.

CONCLUSIONS: The QuestOnco application was well-understood by patients and demonstrated good content validity compared to its parent PROM and the medical records.

TRIAL REGISTRATION: ClinicalTrials.gov No. NCT04915274.

PMID:39716103 | DOI:10.1186/s12885-024-13312-4

JCO Clin Cancer Inform. 2024 Dec;8:e2400010. doi: 10.1200/CCI.24.00010. Epub 2024 Dec 23.

ABSTRACT

PURPOSE: Toxicity to systemic cancer treatment represents a major anxiety for patients and a challenge to treatment plans. We aimed to develop machine learning algorithms for the upfront prediction of an individual's risk of experiencing treatment-relevant toxicity during the course of treatment.

METHODS: Clinical records were retrieved from a single-center, consecutive cohort of patients who underwent neoadjuvant treatment for early breast cancer. We developed and validated machine learning algorithms to predict grade 3 or 4 toxicity (anemia, neutropenia, deviation of liver enzymes, nephrotoxicity, thrombopenia, electrolyte disturbance, or neuropathy). We used 10-fold cross-validation to develop two algorithms (logistic regression with elastic net penalty [GLM] and support vector machines [SVMs]). Algorithm predictions were compared with documented toxicity events and diagnostic performance was evaluated via area under the curve (AUROC).

RESULTS: A total of 590 patients were identified, 432 in the development set and 158 in the validation set. The median age was 51 years, and 55.8% (329 of 590) experienced grade 3 or 4 toxicity. The performance improved significantly when adding referenced treatment information (referenced regimen, referenced summation dose intensity product) in addition to patient and tumor variables: GLM AUROC 0.59 versus 0.75, P = .02; SVM AUROC 0.64 versus 0.75, P = .01.

CONCLUSION: The individual risk of treatment-relevant toxicity can be predicted using machine learning algorithms. We demonstrate a promising way to improve efficacy and facilitate proactive toxicity management of systemic cancer treatment.

PMID:39715466 | DOI:10.1200/CCI.24.00010

Cureus. 2024 Nov 19;16(11):e74053. doi: 10.7759/cureus.74053. eCollection 2024 Nov.

ABSTRACT

Sulfamethoxazole/trimethoprim (SMX/TMP) is a commonly used antimicrobial agent for treating common bacterial infections such as urinary tract infection (UTI), combined with doxycycline for community-acquired methicillin-resistant Staphylococcus aureus (MRSA), and invaluable in Pneumocystis jirovecii pneumonia (PJP), previously classified as Pneumocystis carinii. Of its known adverse reactions, hepatotoxicity rarely comes to mind, but indeed, it is a recognized but very rare adverse reaction that may lead to liver failure in adults and even rarer in children. We present a case of hepatotoxicity in a 43-year-old male patient on no prior medication who developed jaundice and highly elevated liver enzymes one week after the administration of Bactrim for the treatment of UTI in association with prostatism, symptoms of decreased urinary force due to obstruction of flow through the prostate gland. He made a good recovery over several weeks with discontinuation of the medication and supportive care.

PMID:39712800 | PMC:PMC11659648 | DOI:10.7759/cureus.74053

J Am Acad Dermatol. 2024 Dec 20:S0190-9622(24)03394-2. doi: 10.1016/j.jaad.2024.11.070. Online ahead of print.

NO ABSTRACT

PMID:39710116 | DOI:10.1016/j.jaad.2024.11.070

Arthritis Res Ther. 2024 Dec 21;26(1):225. doi: 10.1186/s13075-024-03456-w.

ABSTRACT

OBJECTIVES: To assess immunogenicity and safety in patients with active rheumatoid arthritis (RA) transitioning from rituximab [US-licensed rituximab: Reference Product (RP); EU-approved rituximab: Reference Medicinal Product (RMP)] to DRL_RI (proposed rituximab biosimilar), in comparison to those continuing on RP/RMP.

METHODS: This double-blind, randomized, Phase 3 study included 140 RA patients having prior exposure to RP/RMP; transitioned to DRL_RI (n = 70) or continued with RP/RMP (n = 70) for two 1000 mg infusions on Days 1 and 15. Assessments included Time-matched Rituximab Concentration (TMRC), anti-drug antibodies (ADAs), neutralizing antibodies (NAbs) and ADA titre over 12 weeks, and safety follow-up till 26 weeks.

RESULTS: The mean age of subjects was 59.8 years (range: 24, 86) and the mean BMI was 27.76 kg/m2 (range: 17.5, 52.0). Incidence of ADA after dosing was low in both groups: 1.4% in DRL_RI group on Day 15, Week 8, and Week 12; and 2.9% in RP/RMP group at Week 12. Only 1 patient in DRL_RI group was positive for NAbs at Week 8. ADA titre values did not significantly differ between the two groups. The time-matched rituximab concentration was comparable between groups, indicating no interference for immunogenicity assessment. Treatment-emergent adverse events (TEAEs) were reported by 34.3% and 38.6% patients, respectively, in DRL_RI and RP/RMP groups. Incidences of TEAEs that were drug-related, leading to treatment discontinuation, grade ≥ 3, or serious, were also comparable.

CONCLUSION: Immunogenicity was low and comparable in RA patients transitioning to DRL_RI or continuing on RP/RMP. The overall safety profile in patients transitioning to DRL_RI did not appear to differ in frequency, severity, or quality from patients continuing on RP/RMP and was in line with the known safety profile of rituximab.

TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT0426877 EudraCT:2019-002810-37 US IND 112766.

PMID:39709462 | DOI:10.1186/s13075-024-03456-w