Clinical Adverse Effects Research Articles

Developing and validating a global trigger tool for assessing frequency, level of harm, and preventability of adverse drug events in pediatric inpatients units.

Medications are a major cause of harm to patients in hospitals, and several studies have found that they cause approximately 20% of injuries that occur in medical institutions. It was found that the rate of adverse drug events (ADEs) in pediatric hospitalizations ranges from 11 to 40 events per 100 hospitalizations and 1% of cases caused death.Objectives: This is a comparative and retrospective study. The overarching objective is to adapt the Pediatric Trigger Tool (PTT) of the 'Child Health Corporation of America' to pediatric wards in Israel, with the intention of using it to assess the rate of adverse events that occur during medication given in pediatric wards. The study characterized ADEs and examined the ability of the PTT to identify ADEs in relation to those that were voluntarily reported by the staff. This study included internal and surgical pediatric wards at an academic pediatric medical center. The PTT was validated on medical record data from 700 hospitalizations between the years 2015 - 2017. The study also determined, among other things: the stage of drug administration at which the events occurred, the percentage of all events that could have been prevented, the degrees of damage the ADE caused and more. The Positive Predictive Value (PPV) of the customized tool stands at 16.91%.The study found 108 ADEs in 78 hospitalizations. The ADE rate per 100 hospitalizations was 15.4, the ADE rate per 1,000 drug doses was 3.9, and the ADE rate per 1,000 hospitalization days was 22.8, of which 18.5% were preventable. The category of drugs that led to the highest number of ADEs was painkillers. Those ADEs led to a large number of adverse clinical effects: constipation, hypokalemia, vomiting, and rash. The most common reason for coming to the hospital was suspicion or treatment of a hematologic disease, followed by hospitalization due to a burn. The customized tool found 10.8 times more ADEs than those reported voluntarily-subjectively by the clinicalstaff. The study found that, properly adapted, the PTT tool can be used to detectADEs in internal and surgical pediatric wards.

Beta-hydroxy-beta-methylbutyrate (HMB) improves daily activity and whole-body protein metabolism in Duchenne muscular dystrophy dogs: a pilot study

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease due to loss of dystrophin, leading to progressive muscle wasting and physical inactivity. In this pilot study, we studied the effect of daily supplementation of the anabolic substrate beta-hydroxy-beta-methylbutyrate (HMB) on whole body protein and amino acid kinetics using novel isotope methods and daily activity in a canine model of DMD. Six DMD dogs were administered 3 g daily of HMB or placebo for 28 days according to a randomized, placebo-controlled, double-blinded crossover design. We measured pre- and post-intervention daily activity, biochemistry markers, and whole-body amino acid kinetics. We tracked daily activity with an activity monitoring device and measured plasma creatine kinase and standard clinical biochemistry panels to monitor muscle and organ function. To calculate whole body and intracellular amino acid production, we administered in the postabsorptive state an IV stable isotope solution containing 20 amino acid tracers. We collected blood before and six times after until two hours post tracer pulse administration and measured amino acid enrichments and concentrations by LC–MS/MS, subsequently followed by (non) compartmental modeling of the decay enrichment curves. Results were expressed as mean with 95% CI. Whole body production, plasma concentrations, and intra-/extracellular compartmental analyses of various amino acids were attenuated in HMB-dosed DMD dogs. Specifically, the plasma concentration of hydroxyproline (marker of collagen breakdown) was significantly higher in the placebo group compared to the HMB group. The intra- and extracellular pool sizes and flux between the two compartments of hydroxyproline was reduced in HMB treated dogs. DMD dogs treated with HMB as compared to placebo had a respective 40% increase in exertional (play) (951 [827, 1075] versus 569 [491, 647]; p < 0.0001) and 10.5% increase in non-exertional (active) activity (15,366 [14742, 15990] versus 13,806 [13148,14466]; p = 0.0016). In addition, a 6% reduction was found in rest time after HMB supplementation compared to placebo (23,857 [23,130, 24,584], versus 25,363 [24500, 26225]; p = 0.0122). Creatine kinase was not statistically different between groups. We did not observe any adverse clinical or biochemical-related effects of HMB dosing. Daily HMB supplementation in DMD dogs can safely and positively influence protein and amino acid metabolism and improve overall daily activity.

Self-assembled natural triterpenoids for the delivery of cyclin-dependent kinase 4/6 inhibitors to enhance cancer chemoimmunotherapy.

Immunogenic cell death (ICD) has recently emerged as a promising strategy in reinforcing anti-PD-L1 blockade immunotherapy of triple-negative breast cancer (TNBC). The CDK4/6 inhibitor palbociclib (PAL), as a clinical star medicine targeting the cell cycle machinery, is an ideal candidate for fabricating a highly efficient ICD inducer for TNBC chemoimmunotherapy. However, the frequently observed chemoresistance and clinical adverse effects, as well as significant antagonistic effects when co-administered with certain chemotherapeutics, have seriously restricted the efficiency of PAL and the feasibility of combination strategies. Herein, we screened and identified six self-assembled natural pentacyclic triterpenoid (PT) molecules that can serve as competent co-administration nanoplatforms for the synergistic or combined delivery of PAL. Analysis of two representative PT-PAL nano-assemblies validated that PT-mediated co-assembly enhances the cytotoxicity and synergy of PAL by inhibiting the PI3K/AKT/mTOR signaling pathway, rather than directly targeting CDK4/6 proteins. Importantly, the PAL nanoassemblies exhibited multiple favorable therapeutic features and stronger accumulative ICD induction, ensuring highly efficient synergistic anti-PD-L1 chemoimmunotherapy by simultaneously facilitating T-cell immune response and reversing the immunosuppressive tumor microenvironment. This study offers possibilities for improving the anticancer efficacy of CDK4/6 inhibitors and potential avenues for clinical applications of chemoimmunotherapy in treating TNBC.

Disruption of serotonin homeostasis in intestinal organoids provides insights into drug-induced gastrointestinal toxicity

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.

Longitudinal observational digital analysis of occlusion in Hall Technique.

To evaluate volumetric changes over time in teeth treated with the Hall Technique (HT) and their opposing teeth. Secondary aims included assessing occluso-vertical dimension (OVD), temporomandibular joint (TMJ) function, and children's treatment perceptions. Twenty-eight children (5-9 years-old) requiring HT treatment for one first primary molar were recruited. Dental impressions were taken. Mean volume differences were digitally calculated from scanned models (Rapidform2006) between HT-treated and opposing teeth over time. Canine overlap (to measure OVD) was assessed with digital calipers. TMJ function was evaluated using Helkimo Clinical Dysfunction Index and AAPD Temporomandibular Disorders guidance. Data were collected pre-treatment (T0), immediately post-treatment (T1), at one-month (T2), and three-months (T3) after. Children's perceptions were assessed at T3. The mean volume differences (mm³)±Standard error of the mean(SEM),(min-max) for HT teeth were:T0-T1:71.0 ± 3.2, (43.18 to 113.3mm³); T1-T2:10.1 ± 1.2 (0.02 to 23.52mm³); T2-T3:4.3 ± 1.0 (-4.11 to 15.43mm³) and for opposing teeth: T1-T2:6.8 ± 1.1 (-4.30 to 21.51mm³); T2-T3:0.5 ± 0.9 (-11.12 to 15.24mm³). Crowns and canine overlap measurements resolved within one month (p < 000.1), reflecting occlusion re-establishment. TMJ assessments showed mild-dysfunction in two children (8 %), resolved by T3, Children's perceptions: 26 children (93 %) "strongly agreed" or "agreed" they were happy with their crowned-tooth; one child preferred not to show it, and 26 (93 %) reported no discomfort or pain. The volumetric changes in HT-treated and opposing teeth, along with canine overlap, indicate gradual occlusion re-establishment, primarily within one month. OVD changes resolved, there was minimal TMJ dysfunction and high patient satisfaction. This study demonstrates that occlusal adjustments in Hall Technique-treated teeth mainly occur within one month of crown placement, with minimal effects on TMJ function and occlusion. Results support the Hall-Technique as a child-friendly option for managing carious primary molars with high acceptance and limited clinical adverse effects.

Comparing the Efficacy of Combined Intralesional Triamcinolone Acetonide With Topical Calcipotriol Versus Intralesional Triamcinolone Acetonide Monotherapy in Scalp and Beard Alopecia Areata: Results From a Randomized Single-Blinded Clinical Trial.

Intralesional (IL) steroids are the first-line treatment option for localized alopecia areata (AA). The present study aimed to compare the efficacy of topical calcipotriol with IL triamcinolone acetonide versus IL triamcinolone acetonide alone in AA. This randomized single-blinded clinical trial was conducted in a dermatology outpatient department. Both groups A and B received IL triamcinolone acetonide injections every 4 weeks for 12 weeks. Group A also received twice-daily topical calcipotriol. Follow-up was done every 4 weeks till 12 weeks. The primary outcome parameter was hair density assessment using a hair regrowth scale (RGS). Other parameters were the presence or absence of poor clinical response (less than 50% hair density), regrowth patterns, dermoscopy features, and adverse effects. Seventy-three (179 patches) patients completed the study. RGS and patches with more than 50% terminal hair regrowth significantly improved in both the groups beginning in the fourth week and going forward (P-value: .001, .001). The two treatment groups exhibited no statistically significant difference in terminal hair density (P values: .930, .616, .178). However, subgroup analysis showed a statistically significant difference in scalp patches of group A compared to group B in the 12th week of the study (P = .018) but not in beard patches (P-value: .527). Group A exhibited more irritation with a reduced incidence of atrophy. The addition of topical calcipotriol to IL steroid showed increased efficacy in scalp patches of AA but not in beard patches. Also, the incidence of atrophy was lower in the combination group.

Real-World Efficacy and Safety of Escalation to Weekly Adalimumab for Chronic Non-Infectious Uveitis: A Multicenter Study Involving Pediatric and Adult Patients

ABSTRACT Purpose To evaluate the efficacy and safety of weekly adalimumab (ADA) treatment in non-infectious uveitis (NIU) patients, including both pediatric and adult populations, and identify factors influencing treatment efficacy. Methods A retrospective cohort study at two hospitals in Türkiye included 51 NIU patients (29 children, 22 adults) who escalated from bi-weekly to weekly ADA due to inadequate disease control. Data on six clinical parameters (anterior chamber reaction, vitreous haze, visual acuity, central macular thickness [CMT], prednisone use, uveitis flare-up frequency), adverse effects, and treatment-related factors were collected. Statistical analyses involved non-parametric tests and regression models. Results Weekly ADA led to clinical improvement in 88.2% of patients, with uveitis control achieved in 76.4% by the 6th month. Escalation to weekly dosing significantly improved all clinical parameters compared to the 6-month period before ADA initiation (p < 0.001). Patients on combined weekly ADA and DMARD therapy experienced fewer uveitis attacks (B = - 2.272, 95% CI = [−4.289, −0.254], p = 0.028). Starting ADA as first-line treatment reduced uveitis attacks (p = 0.002) and increased the likelihood of inactive uveitis (OR = 10.349, 95% CI = [1.379, 77.687], p = 0.023). Patients resistant to multiple biologics had worse preADA visual acuity (p = 0.011). Conclusion Weekly ADA is effective and safe for controlling NIU when bi-weekly dosing is insufficient. Combining ADA with DMARDs enhances outcomes and reduce uveitis attacks. Poor preADA visual acuity may suggest resistance to biologics. Prospective studies should validate these findings, explore anti-ADA antibody development, and assess how DMARD addition affects immunological parameters and treatment efficacy.

Clinical Benefits and Adverse Effects of Vonoprazan in Long-Term Maintenance Therapy

Clinical Benefits and Adverse Effects of Vonoprazan in Long-Term Maintenance Therapy

Influence of Ozonated Water on Solid Ehrlich Tumor Induced in MICE: Clinical and Anatomopathological Study

ABSTRACT This study was based on clinical and anatomopathological evaluations of the solid Ehrlich tumor (SET) experimentally induced in mice, treated with different ozonized water protocols. A total of 198 animals were used, divided into four groups: two treated with ozonized water at concentrations of 5 ppm-5 mg/L (G1/N = 60) and 8 ppm-8 mg/L (G2/N = 60); a vehicle control group with physiological sodium chloride solution (G3/n = 60); and a negative control group (NCG/N = 18). Groups were further subdivided by administration route (intratumoral and peritumoral), number of ozonized water applications (one or two), and observation periods after applications (24 hours, five days, and 30 days). No differences were observed between groups in terms of behavioral changes, tumor volume, or survival rates. However, an increase in necrotic area was noted in all groups treated with ozonized water at 24 hours and in some groups at 30 days. Mitosis counts were lower in groups treated with a higher ozone concentration at both 24 hours and 30 days. It is concluded that treatment with ozonized water did not induce adverse clinical effects, promoting increased necrosis and reduced mitosis counts, suggesting a direct antineoplastic effect of medical ozone applied to this tumor type.

P0709 Patient Satisfaction with Subcutaneous versus Intravenous Vedolizumab: A Prospective Observational Study

Abstract Background Vedolizumab (VDZ) is a selective biologic agent that is available in both intravenous (IV) and subcutaneous (SC) forms for maintenance treatment. The SC route offers advantages such as the convenience of self-administration, although some patients may prefer the IV route. The aim of our study was to determine patients’ preferences and satisfaction with their treatment when switching to VDZ SC or continuing with an IV administration. Methods A prospective, observational study was conducted in patients with inflammatory bowel disease (IBD) receiving VDZ IV who were in clinical remission. Patients had the option to continue with VDZ IV or switch to SC and were grouped according to their preference. A baseline visit (before the switch) and another at 24 weeks were conducted. During both visits, patients completed the treatment satisfaction questionnaire (SATMED-Q) and quality of life questionnaire (IBDQ9). Clinical activity, treatment adherence, adverse effects, general bloodwork, and fecal calprotectin were also analyzed. Results Forty-one IBD patients were included, 43% of which were women, and 63% had ulcerative colitis. Almost half (41%) continued with VDZ IV while 59% switched to SC. There were no differences in gender, type, or characteristics of IBD between the groups. However, the age of patients in the SC group was significantly younger than that of the IV group (median 46 [32-63] vs. 66 [59-77] p=0.03). Fewer patients in the SC group had previously received IV biologics (SC 31% vs. IV 69%, p=0.012). The median SATMED-Q before the switch was lower in the SC group (SC 53 [40-61] vs. IV 61 [46-64], p=0.032), as was the IBDQ9 (SC 65.5 [59.4-68.5] vs. IV 70.8 [68.5-77.1], p=0.037). At 24 weeks, there were no differences in SATMED-Q or IBDQ9 scores or disease clinical activity. Drug persistence and frequency of adverse events were similar in both groups. Vedolizumab levels increased significantly in the SC group at 24 weeks (p=0.041). Conclusion Switching to VDZ SC showed similar treatment satisfaction to VDZ IV at 24 weeks in IBD patients, with comparable clinical outcomes and safety profiles. There was a clear preference for subcutaneous administration among younger patients and those without previous IV treatment. This suggests that patient demographics and prior treatment experiences can influence the choice of administration route. The lack of significant differences in clinical outcomes, quality of life scores, and treatment satisfaction between the SC and IV groups at 24 weeks highlights the clinical equivalence of these two administration routes for maintenance therapy in IBD.

Translated article] Prospective observational follow-up study of psychoactive drug treatment initiated in the intensive care unit.

The treatment and prevention of delirium in the intensive care unit (ICU) have gained significant importance in patient care in recent years. Some studies have linked delirium with increased risks of mortality, prolonged hospital stay, and more days of mechanical ventilation. This study aims to analyse the use of psychotropic drugs initiated in the ICU and their continuation upon hospital discharge, as well as to evaluate their contribution to polypharmacy and associated adverse clinical effects. A multicentre prospective observational case study was designed, focusing on patients over 18 years old admitted to the ICU and treated with psychotropic drugs. Data on demographics, variables related to admission and psychotropic drug treatment, as well as clinical outcomes and adverse effects, will be collected. Among other variables, the frequency of psychotropic treatments initiated in the ICU and continued upon discharge from the ICU and the hospital will be measured. Data collection will be performed through review of electronic medical records and prescription programmes, and IBM SPSS 20.0 statistical package will be used for analysis. Delirium is common in ICU patients and is associated with long-term negative consequences. Although antipsychotics are used to treat delirium, their prolonged use can have adverse effects, and their continuation after ICU discharge contributes to polypharmacy. This study aims to provide information on the use of psychotropic drugs initiated in the ICU and their continuation upon discharge, with the goal of identifying opportunities for intervention and reducing unnecessary use of these medications.

Mepolizumab efficacy and safety in patients with eosinophilic granulomatosis with polyangiitis in real practice: Data from a Spanish retrospective multicentric register from Rheumatology departments.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of ANCA-associated vasculitis mostly mediated by eosinophils. Mepolizumab (MPZ) reduces the absolute number of eosinophils in the peripheral blood and tissues and has proven efficacy in the maintenance of EGPA, as shown in a randomized controlled trial. The aim of this study is to describe the use of MPZ in EGPA in real clinical practice. This is a descriptive, retrospective and comparative analysis of the clinical features, course, response rates, outcomes and adverse effects of patients receiving MPZ for EGPA in thirteen Spanish Rheumatology departments. A total of 30 EGPA patients treated with MPZ were included in the analysis. Up to 19 patients needed at least one concomitant immunosuppressant. The mean follow-up was 16 months. The use of MPZ reduced the median Birmingham Vasculitis Activity Score (BVAS), as well as the mean C-reactive protein and the levels of eosinophils. In addition, the median dose of glucocorticoids (GC) required was reduced in 79.3% of the patients and was completely suspended in 57.1%. Interestingly, the median Vasculitis Damage Index (VDI) was also calculated in 27 patients (90%), and remained stable (3 [0-12] pre-MPZ and 3 [0-12] post-MPZ). None of the patients suffered severe adverse effect, local reactions or serious infections during the treatment. Our data on the real practice use of MPZ in EGPA suggests that this drug has good efficacy, is safe and reduces the dependence on glucocorticoids or even their complete withdrawal. Furthermore, it appears to prevent the organic damage progression associated with this disease.

Characterising immune-related adverse events in different types of cancer among Chinese patients receiving immune checkpoint inhibitors

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.

First use of cord blood platelet-rich plasma in the treatment of vulvar lichen sclerosus: a preliminary study towards a randomized controlled trial.

Although topical corticosteroids (TCS) represent first-line treatment for vulvar lichen sclerosus (VLS) and as such should be prescribed to all women at time of diagnosis, approximately 30% of patients do not experience complete symptom resolution following such treatment. TCS may not effectively improve vulvar trophism and elasticity, both of which are crucial for sexual function. Owing to its regenerative and healing properties, cord blood platelet-rich plasma (CB-PRP) may represent an efficacious supplementary therapy, to be administered following first line treatment with TCS. The primary aim of this study was to assess safety and tolerability of CB-PRP in women with VLS. This is a pilot study which precedes a randomized controlled trial of CB-PRP vs placebo in women with VLS. Ten consecutive patients with VLS, who had previously undergone standard TCS-treatment, received three vulvar CB-PRP injections monthly. Follow-up was conducted three months after the last injection using vulvoscopy and validated questionnaires to evaluate safety and tolerability, as well as patient satisfaction, symptom improvement, sexual function, psychological well-being, quality of life, frequency of TCS application as a maintenance treatment, vulvar trophism and architectural modifications. No adverse clinical effects were observed. Five patients (50%) were either satisfied or very satisfied with the procedure, four (40%) were uncertain about their satisfaction with the treatment. One patient (10%) dropped out for personal reasons and was classified as unsatisfied according to an intention-to-treat analysis. At follow-up median numeric rating scale scores were significantly reduced for vulvar burning compared to baseline (p<0.05) there was a trend toward improvement in itching, dyspareunia, and dysuria. A significant improvement in sexual arousal and satisfaction was observed in all treated women (p<0.05). CB-PRP may be a promising treatment for VLS. It appears to be safe and improve symptoms and sexual function.

Chimeric Antigen Receptor (CAR) T-cell Therapy in the Treatment of Diffuse Large B-cell Lymphoma (DLBCL): A Systematic Review.

Chimeric antigen receptor (CAR) T-cell therapy has shown very promising results in the treatment of refractory or relapsed diffuse large B-cell lymphoma (DLBCL). This systematic review evaluates the effectiveness and side effects of CAR T-cell therapies, focusing on factors affecting both clinical outcomes and adverse effects. This review included data from 14 studies involving 1392 patients with DLBCL who underwent CAR T-cell therapy. These studies include both randomized clinical trials and observational studies, which would help to analyze the effectiveness and safety profiles. The review highlights that CAR T-cell therapies, mainly tisagenlecleucel (Tisa-cel) and axicabtagene ciloleucel (Axi-cel), have shown superior effectiveness in comparison to standard chemotherapy in patients with relapsed or refractory DLBCL. Lisocabtagene maraleucel (Liso-cel) showed significant improvement outcomes in event-free and progression-free survival. However, CAR T-cell therapies are associated with many side effects. The most common side effects include hematologic toxicity, prolonged neutropenia, and infections, while clinical outcomes are highly impacted by many factors, which include a pro-inflammatory state, PPM1D gene mutation, infusion timing, and circulating monocytes.

Nurses' adverse event reporting attitudes and related factors: a cross-sectional study in maternal and child specialized hospitals in China.

To investigate the current situation of nurses' attitude toward adverse event reporting and identify its related factors in maternal and child specialized hospitals. A questionnaire survey was conducted among 943 nurses in 18 second-level and above maternal and child specialized hospitals in Sichuan province in China. The questionnaire included general information and the Chinese version of Reporting of Clinical Adverse Effects Scale (C-RoCAES). The total score of adverse events reported by nurses was 63.98 ± 8.77. The scores of the dimensions from high to low were reporting standard (3.13 ± 0.46), reporting impact (2.80 ± 0.54), reporting purpose (1.98 ± 0.66), and reporting environment (1.98 ± 0.42). Educational background (β = -1.87, p < 0.001), professional title (β = -3.51, p < 0.001), and adverse event experience (β = -7.05, p < 0.001) were the positively associated with higher levels of nurses' attitude toward adverse event reporting in maternal and child specialized hospitals (p < 0.05). The attitude of nurses in maternal and child specialized hospitals to report adverse events is at the middle level. Hospital managers should improve the reporting standards for adverse events, improve the hospital safety culture, strengthen the relevant training for nurses with low education and low professional titles, so as to improve nurses' awareness of adverse event reporting and reporting rate.

Evaluation of Treatments with Radiotherapy Alone and Radiotherapy Plus Chemo-immunotherapy in Patients with Primary Liver Cancer based on Blood Biomarkers.

It is critical to assess primary liver cancer patients likely to benefit from radiotherapy (RT) or RT plus chemo-immunotherapy. Many potential peripheral biomarkers from blood samples have been proposed for clinical application. Therefore, the aim of this study was to evaluate treatments with radiotherapy alone and radiotherapy plus chemo-immunotherapy in patients with unresectable primary liver cancer based on blood biomarkers. From January, 2017, to February, 2022, 63 unresectable primary liver cancer patients receiving radiotherapy alone (RT, n = 21) or radiotherapy plus chemo-immunotherapy (RT plus C/IT, n = 42) were included in this study. We compared the clinical outcomes and adverse effects of these two groups. Also, distant metastasis-free survival (DMFS), overall survival (OS), and progress- free survival (PFS) were retrospectively analyzed. Finally, univariable and multivariable Cox analyses were used to explore the prognostic role of blood biochemical biomarkers. In this study, 1, 2, and 3 years of OS after RT treatment were 63.9%, 27.0%, and 13.5%, and after RT plus C/IT were 68.2%, 37.0%, and 24.7%, respectively (p = 0.617). Compared with baseline, white blood cells (WBC) and lymphocytes were significantly decreased after RT (p = 0.002 and p = 0.001, respectively) or RT plus C/IT therapy (p = 0.135 and p<0.001, respectively). In multivariable Cox regression analyses, higher lymphocyte counts before RT (pre-Lymphocyte) were associated with better OS and PFS (HR=0.439, p = 0.023; HR=0.539, p = 0.053; respectively), and higher lymphocyte counts before RT (pre- Platelets) were a poor prognostic factor associated with DMFS (HR=1.013, p = 0.040). Importantly, OS and PFS were significantly better for patients (pre-Lymphocyte ≥1.10 x 109/L) (p = 0.006; p = 0.066, respectively). The DMFS was significantly better for patients (pre-platelets < 233.5 ×109/L) (p<0.001). Our evaluation of blood biomarkers before and after radiotherapy or plus chem-immunotherapy for primary liver cancer revealed a potential marker for clinics to decide on precise treatment strategies.

Intravenous versus intramuscular route of administration of natural adrenocorticotropic hormone in infantile epileptic spasm syndrome.

Infantile epileptic spasm syndrome (ISS) is an age-dependent epileptic condition typically emerging within the first year of life, and adrenocorticotropic hormone (ACTH) has been established as a first-line therapeutic drug for the ISS since 1958. However, there is a notable variation in ACTH dosage practices worldwide, with intramuscular injection being common in some countries and intravenous drip preferred in others, including China. This study aimed to identify a preferable administration modality for ACTH-based utilization in treating ISS. A retrospective analysis was conducted on 221 ISS patients treated with ACTH via the two administration routes from January 2021 to December 2022. Clinical efficacy and adverse effects were assessed. Health economics were evaluated using a cost-effectiveness ratio, incorporating direct costs and a comprehensive effectiveness indicator. Intramuscular injection demonstrated a higher effective rate (97.20%) compared to intravenous infusion (80.50%). Adverse effects such as upper respiratory tract infections and diarrhea were significantly less in the intramuscular group. The unit effectiveness cost was significantly lower for intramuscular injection (¥19.53) than for intravenous infusion (¥32.86). Although both routes of administration were successful in controlling spasms in patients, intramuscular injection of ACTH was deemed economically preferable due to its superior clinical efficacy, less adverse effects, and higher safety profile.

Successful treatment of epidermal growth factor receptor exon 19 deletion non-small cell lung cancer with almonertinib after osimertinib-induced interstitial lung disease: A case report.

Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), has revolutionized one of the standard most efficient treatments for EGFR mutation-positive non-small cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently one of most efficient treatments in clinical practice. However, it has a potentially fatal side effect: interstitial lung disease (ILD). When severe ILD occurs, a drug substitution is often required, and there is a rising concern about which drug to choose to inhibit the progression of NSCLC and avoid aggravating while alleviating ILD. Herein, we report an NSCLC case with osimertinib-induced ILD successfully rechallenged by almonertinib. In addition, we conducted a literature review on the clinical efficacy and adverse effects of almonertinib, hoping to provide insight into NSCLC treatment.

Impact of Missense Mutations on AFB1 Metabolism in Bovine Cytochrome P4503A Isoforms: A Computational Mutagenesis and Molecular Docking Analysis.

Cytochrome P450 3A (CYP3A) enzymes catalyze the metabolism of a wide range of endogenous and exogenous compounds. Genetic variations in the 3 CYP3A isoforms (CYP3A28, CYP3A74, and CYP3A76) may influence their expression and activity, leading to inter-individual differences in xenobiotic metabolism. In domestic cattle, understanding how genetic variations modulate CYP3A activity is crucial for both its therapeutic implications (clinical efficacy and adverse drug effects) and food safety (residues in foodstuff). Here, we updated the variant calling of CYP3As in 300 previously sequenced Piedmontese beef cattle, using the most recent reference genome, which contains an updated, longer sequence for CYP3A28. All but one previously identified missense variants were confirmed and a new variant, R105W in CYP3A28, was discovered. Through computational mutagenesis and molecular docking, we computationally predicted the impact of all identified CYP3A variant enzymes on protein stability and their affinity for aflatoxin B1 (AFB1), a potent carcinogen and food contaminant. For CYP3A28, we also computationally predicted its affinity for the probe substrate nifedipine (NIF). We found that CYP3A28 with R105W variant cannot accommodate NIF nor AFB1 in the binding pocket, thus affecting their metabolism. Our work provides computational foundation and prioritized ranking of CYP3A variants for future experimental validations.