Occurrence Of Adverse Events Research Articles

Real-World Evidence on Adverse Events and Healthcare Resource Utilization in Patients with Chronic Lymphocytic Leukaemia in Spain Using Natural Language Processing: The SRealCLL Study.

Objectives: The SRealCLL study described the occurrence of adverse events (AEs) and healthcare resource utilization in patients with chronic lymphocytic leukaemia (CLL) using artificial intelligence in a real-world scenario in Spain. Methods: We collected real-world data on patients with CLL from seven Spanish hospitals between January 2016 and December 2018, focusing on their AE and healthcare service utilization. Data extraction from electronic health records of 385,904 patients was performed using the EHRead® technology, which is based on natural language processing and machine learning. Results: Among the 534 CLL patients finally included, 270 (50.6%) were categorized as watch and wait (W&W), 230 (43.1%) as first-line treatment (1L), and 58 (10.9%) as relapse/refractory with second-line treatment (2L). The median study follow-up periods were 14.4, 8.4, and 6 months for W&W, 1L, and 2L, respectively. The most common antineoplastic treatments were ibrutinib (64.8%) and bendamustine + rituximab (12.6%) in 1L, and ibrutinib (62.1%) and venetoclax (15.5%) in 2L. Among the most frequent AEs, anaemia and thrombocytopenia presented higher rates in the treated groups (1L and 2L) compared with W&W (2.01 and 2.32 vs. 0.93; p ≤ 0.05 and 1.29 and 1.62 vs. 0.42; p ≤ 0.05). Moreover, several AEs, such as major bleeding, digestive symptoms, general symptoms, or Richter syndrome, were more frequent in 1L than W&W (all p ≤ 0.05). No differences were shown between groups in the rates of outpatient visits. However, rates of outpatient visits due to AE were higher in 1L than in W&W (1.07 vs. 0.65, p ≤ 0.05). The rates of patients being hospitalized were higher in the treated groups compared to W&W (1.68 and 1.9 vs. 0.88; p ≤ 0.05), and those due to AE were higher in 1L than W&W (1.23 vs. 0.60; p ≤ 0.05). Conclusions: Patients with CLL in 1L or 2L treatments often require healthcare resources due to AEs, particularly cytopenias. The methodology used in this study likely enabled us to identify higher rates of AEs that may be underreported using other real-world approaches. Addressing AEs with effective agents that maximize patient safety and optimize healthcare resource use is crucial in this typically older and comorbid population.

Sex differences in patients with atrial fibrillation and acute coronary syndrome or undergoing PCI: a real-world study

Background In patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI), female patients have a worse short-term prognosis than male patients has been consistently concluded in many studies. However, the impact of sex differences on long-term prognosis remains uncertain. Additionally, women are underrepresented in clinical trials exploring optimal antithrombotic strategies in patients with atrial fibrillation (AF) and ACS or PCI. To bridge this gap, this study aimed to investigate sex differences in clinical characteristics, treatment, and long-term clinical outcomes in patients with AF and ACS or PCI. Patients and methods This study included a total of 1237 patients with AF and ACS and 539 patients with AF and stable coronary artery disease (SCAD) who underwent PCI at the Fuwai Hospital of the Chinese Academy of Medical Sciences from January 2017 to December 2019. Patients were followed up until the end of 2021 to observe the occurrence of major adverse cardiovascular events (MACE). The relationship between sex and MACE was evaluated using Cox regression models and Kaplan–Meier’s survival curves. Results In patients with AF and ACS, multivariable COX regression analysis revealed that female patients were independently associated with a higher risk of MACE (HR = 1.45, 95% CI 1.11–1.89, p = .006). However, in AF patients with SCAD who underwent PCI, the analysis showed that female patients were not independently associated with MACE risk (HR = 1.12, 95% CI 0.62–2.03, p = .717). Conclusions In patients with AF and ACS, females have a significantly higher risk of long-term MACE compared to males. However, among patients with AF and SCAD who underwent PCI, there was no significant difference in long-term MACE risk between males and females.

Sex differences of fall-risk-increasing drugs in the middle-aged and elderly: a descriptive, cross-sectional study of FDA adverse event reporting system

It’s well known that sex is a risk factor for the occurrence of adverse events (AEs), most of which have found sex differences. Real-world data studies on the sex differences of fall-risk-increasing drugs (FRIDs) are few and far between, with most small-scale retrospective studies based on FRID classes. To establish a list of FRIDs and describe their sex differences, we used preferred terms from the Medical Dictionary for Regulatory Activities to search for AEs in the FDA Adverse Event Reporting System (FAERS), and then perform disproportionality analyses and female/male ratio analyses. During January 2004 to March 2023, 101,746 fall-related AEs were reported in FAERS from patients aged 50 to 100, with 68,492 (67.3%) females and 32,547 (32.0%) males. We found 261 signals for females while 284 for males. For females, the top 3 signals with the highest reporting odds ratio (ROR) were anethole trithione, clopenthixol, nikethamide (ROR: 388.88, 212.10, 113.94), while the top 3 signals with the highest lower limit of information component (IC025) were nikethamide, anethole trithione, benzbromarone (IC025: 3.91, 3.15, 2.49). For males, the top 3 signals with the highest ROR were fluprednidene acetate, potassium hydroxide, ketazolam (ROR: 216.86, 108.43, 108.43), while the top 3 signals with the highest IC025 were clomethiazole, piribedil, melperone (IC025: 3.31, 3.24, 2.99). Moreover, among the 119 shared signals found between males and females, 33 were positively correlated with falls in females and 38 with falls in males. Signals showing significant sex differences were mainly concentrated on agents of the immune, nervous, musculo-skeletal, and cardiovascular systems. We offered a series of FRIDs and suggested their sex differences in falls through the FAERS. In the future, it is essential to balance the inclusion of women and men, and analyse sex-stratified for FRIDs.

Application of Healthcare Failure Mode and Effect Analysis in the Management of Patients With Intrathecal Morphine Pump Implantation

BackgroundIntrathecal morphine pump helps alleviate pain in the advanced stages of cancer, and thus, ensuring safe intrathecal morphine pump infusion is important. In this study, we investigated the effect of healthcare failure mode and effects analysis (HFMEA) in the management of patients with intrathecal morphine pump implantation. MethodsWe included 112 cancer patients with severe pain who met the inclusion criteria for intrathecal morphine pump implantation treatment in the pain department of our hospital from November 2021 to October 2022. We analyzed the severity, likelihood, and crisis of potential failure modes, causes, and results of intrathecal morphine pumps during this period, compiled the records, and formulated the appropriate improvement measures based on the results of the analysis. From November 2022 to October 2023, the HFMEA model was applied to 125 patients in the department, and the effectiveness of the model was evaluated by assessing the patients’ VAS (visual analog scale) score, SAS (self-rating anxiety scale) score, SDS score, PSQI (Pittsburgh Sleep Quality Index) score and quality of life (QOL) (self-rating depression scale) score. ResultsThe occurrence of adverse events (6 cases vs. 2 cases, p < .05), and the total incidence of adverse events (8.9% vs. 1.6%, X2= 6.600, p = .010) was significantly different before and after HFMEA was applied. For patients who received intrathecal morphine pump implantation, the VAS scores and the related pain indices were significantly lower after HFMEA than before. Additionally, the score of SAS (48.91 ± 6.03 vs. 47.02 ± 6.77), PSQI (37.30 ± 5.78 vs. 39.63 ± 5.64), and QOL (9.93 ± 3.04 vs. 8.98 ± 2.31) of patients improved significantly. ConclusionsWith the application of the HFMEA model, a multidisciplinary team assessed the risks associated with the use of intrathecal morphine pumps and prioritized measures to reduce them. By implementing the improvement measures, potential errors decreased significantly during the intrathecal morphine pump process. It allowed nursing managers to change the safety incidents related to drug administration using an intrathecal morphine pump from negative treatment after the event to active prevention before the event, greatly improved the level of drug use safety management, reflected the continuous improvement of nursing quality, and ensured nursing safety.

Efficacy and Safety of Nemolizumab in Patients With Moderate to Severe Prurigo Nodularis

Prurigo nodularis (PN) is a chronic and debilitating skin condition, characterized by intense itch with multiple nodular lesions. Nemolizumab demonstrated significant improvements in itch and skin nodules in adults with moderate to severe PN in a previous 16-week phase 3 study (OLYMPIA 2). To assess the efficacy and occurrence of adverse events in adults with moderate to severe PN treated with nemolizumab vs those receiving placebo. OLYMPIA 1 was a multicenter, placebo-controlled, phase 3 randomized clinical trial, conducted from August 2020 to March 2023 at 77 centers across 10 countries in adults with moderate to severe PN (at least 20 nodules and an Investigator's Global Assessment [IGA] score ≥3) and Peak Pruritus Numerical Rating Scale (PP-NRS) score of at least 7.0; consisted of screening (up to 4 weeks), 24-week treatment, and 8-week follow-up periods. Patients were randomized (2:1) to nemolizumab monotherapy, 30 mg or 60 mg (depending on baseline weight of less than 90 kg vs 90 kg or greater, respectively), or matching placebo administered every 4 weeks for 24 weeks. The primary end points were the proportion of patients with itch response (≥4-point improvement from baseline in weekly average PP-NRS) and IGA success (score of 0/1 [clear/almost clear] and 2-grade or more improvement from baseline) at week 16. Of 286 patients (mean [SD] age, 57.5 [13.0] years; mean [SD] body weight, 85.0 [20.7] kg; 166 [58.0%] female), 190 were randomized to receive nemolizumab, and 96 were randomized to placebo. A significantly greater proportion of patients assigned to nemolizumab vs placebo achieved itch response (111/190 [58.4%] vs 16/96 [16.7%]; Δ, 40.1% [95% CI, 29.4%-50.8%]; P < .001) and IGA success (50/190 [26.3%] vs 7/96 [7.3%]; Δ, 14.6% [95% CI, 6.7%-22.6%]; P = .003) at week 16. At week 24, the proportion of patients with itch response was 58.3% vs 20.4% (Δ, 38.7% [95% CI, 27.5%-49.9%]) in the ad hoc analysis, and IGA success was 58/190 (30.5%) vs 9/96 (9.4%) (Δ, 19.2% [95% CI, 10.3%-28.1%]) in the nemolizumab-treated vs placebo group. During the treatment period, 134 patients (71.7%) receiving nemolizumab vs 62 patients (65.3%) receiving placebo had at least 1 adverse event; most events were of mild to moderate severity. In this randomized clinical trial, nemolizumab monotherapy led to clinically meaningful and statistically significant improvements in core signs and symptoms of PN. ClinicalTrials.gov Identifier: NCT04501666.

Trends of diagnostic adverse events in hospital deaths: longitudinal analyses of four retrospective record review studies.

To investigate longitudinal trends in the incidence, preventability, and causes of DAEs (diagnostic adverse events) between 2008 and 2019 and compare DAEs to other AE (adverse event) types. This study investigated longitudinal trends of DAEs using combined data from four large Dutch AE record review studies. The original four AE studies included 100-150 randomly selected records of deceased patients from around 20 hospitals in each study, resulting in a total of 10,943 patient records. Nurse reviewers indicated cases with potential AEs using a list of triggers. Subsequently, experienced physician reviewers systematically judged the occurrence of AEs, the clinical process in which these AEs occurred, and the preventability and causes. The incidences of DAEs, potentially preventable DAEs and potentially preventable DAE-related deaths initially declined between 2008 and 2012 (2.3 vs. 1.2; OR=0.52, 95 % CI: 0.32 to 0.83), after which they stabilized up to 2019. These trends were largely the same for other AE types, although compared to DAEs, the incidence of other AE types increased between 2016 (DAE: 1.0, other AE types: 8.5) and 2019 (DAE: 0.8, other AE types: 13.0; rate ratio=1.88, 95 % CI: 1.12 to 2.13). Furthermore, DAEs were more preventable (p<0.001) and were associated with more potentially preventable deaths (p=0.016) than other AE types. In addition, DAEs had more and different underlying causes than other AE types (p<0.001). The DAE causes remained stable over time, except for patient-related factors, which increased between 2016 and 2019 (29.5 and 58.6 % respectively, OR=3.40, 95 % CI: 1.20 to 9.66). After initial improvements of DAE incidences in 2012, no further improvement was observed in Dutch hospitals in the last decade. Similar trends were observed for other AEs. The high rate of preventability of DAEs suggest a high potential for improvement, that should be further investigated.

Therapeutic Monoclonal Antibody─Antidrug Antibody Affinity Constant Determination Using Capillary Electrophoresis-Tandem Mass Spectrometry.

Monoclonal antibody (mAbs) therapeutics cannot evade the occurrence of adverse effects. Thus, mAbs are commonly triggering immune responses corresponding to the expression of antidrug antibodies. Antidrug antibodies can neutralize mAbs, leading to their inhibition and hasten clearance, which dramatically hampers their therapeutic effects. Therefore, studies concerning the affinity between a mAbs and the corresponding antidrug antibody are demonstrating a growing interest to further understand the outcome of biotherapeutics after administration. We describe a novel analytical approach for the determination of the dissociation constant (Kd) between a mAb and an antidrug antibody using capillary electrophoresis coupled to mass spectrometry (CE-MS/MS). The CE-MS/MS method employs a competitive assay, followed by the quantification of the residual amount of the active mAbs. The methodology allowed for the measurement of Kd using serum samples without the implementation of immobilization to achieve protein-protein interaction. This characteristic enabled us to generate the interaction in conditions reflecting the physiological environment. A mathematical treatment was developed to calculate Kd from MS/MS data, taking into account the stoichiometry of the mAbs/antidrug antibody complex and the bivalent properties of the two immunoglobulins. Prior to CE-MS/MS analysis, the interaction of the two proteins was studied by using mass photometry (MP) to determine equilibrium conditions and complexation stoichiometry. CE-MS/MS was used to investigate the interaction between infliximab and a neutralizing anti-infliximab antibody. Results allowed to measure a Kd of 14.4 ± 2.9 nM. MS instrumentation sensitivity and specificity showed to be relevant to achieve accurate and robust Kd measurements for strong interactions in the nanomolar range.

The Efficacy and Safety of Roxadustat for Anemia in Hemodialysis Patients with Chronic Kidney Disease: A Meta-Analysis of Randomized Controlled Trials

Background: Patients undergoing hemodialysis (HD) for chronic kidney disease (CKD) often encounter anemia. Roxadustat has not only undergone phase II-III clinical trials in patients suffering from CKD and undergoing HD; a number of post-marketing clinical studies have been conducted using the drug. This article was to assess the effectiveness and safety of roxadustat in managing anemia among patients with CKD undergoing HD. Methods: A thorough search was performed across eight databases, including PubMed, Web of Science, Cochrane Library, Embase, Wan Fang, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQ VIP), and SinoMed to identify randomized clinical trials (RCTs) examining the effectiveness and safety of roxadustat in managing anemia among individuals suffering from CKD and undergoing HD. This search included studies from the inception of these databases to April 2023. Results: Two phase II, one phase III, and 16 post-marketing studies with 1688 participants were included. Serum iron (SI), transferrin, and total iron-binding capacity (TIBC) levels changed from baseline (∆SI, ∆transferrin, and ∆TIBC) and were significantly more increased for roxadustat than for erythropoiesis-stimulating agents (ESAs): MD 2.55, (95% CI 1.51 to 3.60), p &lt; 0.00001; MD 0.55, (95% CI 0.41 to 0.69), p &lt; 0.00001; and MD 6.54, (95% CI 4.50 to 8.59), p &lt; 0.00001, respectively. Roxadustat was not inferior to ESAs with regard to increasing Hb (∆Hb) levels [MD 1.17 (95% CI 0.71 to 1.63), p &lt; 0.00001] (g/dL). No statistically significant distinctions of the ∆ferritin, ∆hepcidin, and transferrin saturation (TSAT) from baseline (∆TSAT) level were identified between roxadustat and ESAs. C-reactive protein (CRP) levels changed from baseline (∆CRP) and were significantly more reduced for roxadustat than for ESAs. As for safety, the analysis indicated no notable difference in the occurrence of adverse events (AEs) and serious adverse events (SAEs) between roxadustat and ESAs. Conclusion: This meta-analysis demonstrated that roxadustat outperformed ESAs in enhancing SI, transferrin, and TIBC levels while also decreasing CRP levels. Roxadustat was not inferior to ESAs in terms of improving Hb levels and safety. These findings suggest that roxadustat was well tolerated and a potent alternative to ESAs in managing anemia among patients suffering from CKD and undergoing HD.

Physical, but not laboratory, treatment-related adverse events are associated with favorable outcomes of enfortumab vedotin for advanced urothelial carcinoma: A landmark analysis.

While the occurrence of immune-related adverse events has been recognized as a prognostic marker in patients receiving immune checkpoint inhibitors, the prognostic significance of treatment-related adverse events (trAEs) in patients undergoing antibody-drug conjugates such as enfortumab vedotin (EV) is controversial. We reviewed 106 patients with advanced urothelial carcinoma who were treated with EV therapy at 10 institutions between 2021 and 2023. Associations of clinical parameters with overall survival and progression-free survival were assessed using the Cox proportional hazards model. For the assessment of trAEs, landmark analysis was conducted to minimize immortal time bias. Of 106 patients, 55 (51.9%) experienced disease progression and 44 (41.5%) died during the follow-up period. Any grade and grade ≥3 trAEs occurred in 94 (88.7%) and 44 (41.5%) patients, respectively. Common trAEs included skin disorders (74.5%), gastrointestinal disorders (62.3%), fatigue (50.0%), peripheral neuropathy (36.8%), and hematological disorders (37.7%). One patient died of interstitial pneumonia (grade 5). According to landmark analysis using 88 patients who survived for 2 months or more, trAEs were significantly associated with longer survival. Furthermore, when trAEs were classified into "physical trAEs" such as skin disorders and "laboratory trAEs" such as hematological disorders, the former were associated with longer survival while the latter were associated with shorter survival. Physical, but not laboratory, trAEs are associated with favorable outcomes of EV therapy for advanced urothelial carcinoma. Both managing trAEs and utilizing them as prognostic markers are key points in the use of antibody-drug conjugates such as EV.

Managerial tools used for the prevention of adverse events in Intensive Care Units

Patient safety in Intensive Care Units (ICUs) is a critical priority due to the complexity of care and the high risk of adverse events (AEs). Objective: This study aimed to identify the managerial tools used for the prevention of AEs in ICUs through an integrative literature review. Method: Searches were conducted in the Scielo, Virtual Health Library (VHL), and PubMed databases using descriptors such as "Patient Safety," "Intensive Care Unit," "Near Miss," "Adverse Events," "Reporting," "Nursing," and "Safety Culture." Inclusion criteria considered full-text articles available in English and Portuguese, while duplicate articles and those that did not directly address the prevention of AEs and patient safety in ICUs were excluded. Data analysis was performed using narrative synthesis, assisted by the Rayyan software. Managerial tools identified included the Hospital Survey on Patient Safety Culture (HSOPSC), the Global Trigger Tool (GTT), the Neonatal Trigger Tool, the U.S. Paediatric Trigger Tool, the Nursing Activities Score (NAS), and the Brazilian Nursing Work Index-Revised (B-NWI-R), all adapted for use in Brazil. These tools aim to prevent AEs and promote patient safety in ICUs. Results:The results highlight the need to strengthen the safety culture and invest in the continuous training of healthcare professionals. Conclusion:The implementation of a broad and continuous safety culture with investments in permanent education can reduce the occurrence of AEs and improve the quality of care in ICUs.

Serum Alpha-fetoprotein Associated with Treatment Efficacy of Immune Checkpoint Inhibitors in Patients with Hepatocellular Carcinoma: A Meta-Analysis and a Retrospective Cohort Study

Context: Serum alpha-fetoprotein (AFP) has been shown to be valuable in tumor staging and predicting survival outcomes. In this investigation, we conducted a retrospective cohort analysis and a meta-analysis to assess the predictive significance of initial AFP levels in patients with hepatocellular carcinoma (HCC) who underwent treatment with immune checkpoint inhibitors (ICIs). Methods: We searched databases from inception until 14 July 2024 to identify cohort studies involving ICI treatments in HCC patients with baseline AFP data. We also retrospectively analyzed patients with HCC treated with ICIs to assess the therapeutic effect in the high AFP (AFP ≥ 400 ng/mL) group and the low AFP (AFP &lt; 400 ng/mL) group in terms of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: In the meta-analysis, a total of 34 studies, comprising 8,799 patients, were included, while the retrospective cohort study encompassed 55 patients. In the meta-analysis, the summarized hazard ratios (HRs) of AFP ≥ 400 ng/mL versus AFP &lt; 400 ng/mL for ICI therapy indicated that the high AFP group had a poorer outcome compared to the low AFP group, with a pooled HR for OS of 1.69 (95% CI: 1.57 - 1.82, P &lt; 0.001) and a pooled HR for PFS of 1.47 (95% CI: 1.33 - 1.63, P &lt; 0.001). In the retrospective cohort study, higher AFP levels were associated with a lower DCR for ICIs, with a DCR of 42.9% in the high AFP group and 77.8% in the low AFP group (P = 0.008). Cox model analysis showed that higher serum AFP was an independent predictor for shorter OS (HR 3.584, 95% CI: 1.466 - 8.762, P = 0.005). The toxicity analysis also displayed a strong association between high AFP and the occurrence of immune-related adverse events (irAEs) (P = 0.008). Conclusions: Higher serum AFP is associated with poorer efficacy of ICI treatment in HCC patients.

Outcome of video laryngoscopy versus direct laryngoscopy for emergency tracheal intubation in emergency department: a propensity score matching analysis

BackgroundThe high incidence of airway management failure in the emergency department (ED) necessitates a comparative analysis of laryngoscopy methods. This study aims to compare the success and complications associated with video-assisted laryngoscopy (VL) and direct laryngoscopy (DL) in emergency tracheal intubation in ED.MethodsThis retrospective cohort study was conducted at the ED of Thammasat University Hospital. It involved adult patients undergoing emergency tracheal intubation using either VL (GlideScope®) or DL (Macintosh®). The outcomes assessed were success rates of intubation and occurrence of peri-intubation adverse events. Propensity score matching and multivariable risk regression analysis were employed for statistical evaluation.ResultsThe study included 3,424 patients, with 342 in the VL group and 3,082 in the DL group. The initial analysis revealed no significant differences in the intubation success rates between the two methods. However, the VL group experienced fewer peri-intubation adverse events (33% compared to 40%). After propensity score matching, a higher first-attempt success rate was observed in the DL group (88.9% vs. 81.3%, risk difference: 7.6, 95% CI: 1.9 to 13.2, p=0.009), but there was no statistically significant difference in peri-intubation adverse events. VL had a lower first-attempt success rate among low-experience intubators. Subgroup analyses of intubators with moderate and high experience, as well as patients who received both induction agents and neuromuscular blocking agents, show results consistent with the analysis of the entire cohort.ConclusionBoth VL and DL have comparable first-attempt success rates and peri-intubation adverse events. VL is particularly beneficial when used by moderately or highly experienced intubator. The choice of intubation method, combined with clinical experience and technique plays a critical role in the success and safety of emergency intubations.

Health-related quality of life in patients treated with en bloc resection for primary tumors of the spine.

Retrospective analysis. The aim of this study is to evaluate the functional outcomes and the health-related quality of life (HRQOL) in patients undergoing en bloc resection of spinal tumor. En bloc resection in the spine is a surgical procedure designed to completely remove a tumor in one piece, with wide margins preserved, in order to reduce the risk of local recurrences. This demanding procedure has been shown to improve local control and survival rate, besides a relatively high morbidity. Between 2016 and 2021, 70 patients underwent en bloc resection surgery for a primary spine tumor and 38 came out to be eligible for this analysis. Eligibility criteria include at least one follow-up visit within a two-year period from surgery and Patient Reported Outcomes evaluation collected prospectively at baseline and at least one follow- up in the range 4-24 months. The outcome variables (EQ5D Numeric Scale and Index, SF36 scores and NRS score) were analyzed with multilevel linear mixed-effects regression. Baseline- (age, gender, localization, histotype, number of levels of resection, previous surgery) and time-dependent covariates (adverse events, spinal cord damage) were included. Beside a slight improvement of all the scores, no significant differences were found between baseline and follow up times for EQ-5D-3L Numeric Scale and Index and for SF-36 Standardized Physical component. SF-36 Standardized Mental component appeared to be significantly better at 12-month FU compared to baseline. Ultimately, age over 50 years old and the occurrence of adverse events emerged to be as the two main factor determining worsening in several HRQOL scores. Pain came out to be significantly reduce at 24-month compared to baseline. The aim of en bloc resection in the treatment of primary spinal tumors is to improve survival rates and reduce local recurrences. Despite its radicality, our preliminary results suggest that patients experience a slight to moderate improvement postoperatively compared to their preoperative perceived health status.

Predictive value of triglyceride-glucose index for the evaluation of coronary artery disease severity and occurrence of major adverse cardiovascular events.

The triglyceride-glucose (TyG) index has been proposed as an independent predictor of coronary artery disease (CAD). In this retrospective study we further examine this association and its utility as a predictor for major adverse cardiovascular events (MACE). A total of 870 patients who underwent coronary angiography between May 2008 and June 2009 were included in this retrospective study. The TyG index was calculated using the formula Ln (fasting TG [mg/dL] × FBG [mg/dL]/2). The association of TyG index with the presence and severity of CAD, cardiovascular risk factors, and inflammatory markers was evaluated at baseline. In the longitudinal study, the multivariate adjusted Cox hazard model was used to investigate the associations of the TyG index with the occurrence of MACE during a 5-year follow-up, which was defined as endpoint. The TyG index was significantly associated with the presence and severity of CAD. Multiple linear regression analysis showed that a high TyG index, together with inflammatory markers and dyslipidemia, were independently associated with greater stenotic occlusion of coronary arteries (adjusted R2 = 0.031, p<0.001). Kaplan-Meier survival curve (free of MACE) by tertiles of the TyG index showed a higher incidence of MACE in the upper tertile (log-rank test, p = 0.02). Multivariate Cox analysis demonstrated that the risk of incident MACE during the follow-up was associated with higher levels of TyG index, even after adjusting for inflammatory parameters and cardiovascular risk factors: hazard ratio (HR), 1.54 (95% confidence interval 1.18-2.13; p<0.01). We conclude that elevated TyG index is independently associated with a higher risk of CAD and a poor prognosis for MACE.

Adverse events associated with the delivery of telerehabilitation across rehabilitation populations: A scoping review.

This scoping review aimed to map existing research on adverse events encountered during telerehabilitation delivery, across rehabilitation populations. This includes identifying characteristics of adverse events (frequency/physical/non-physical, relatedness, severity) and examining adverse events by different modes of telerehabilitation delivery and disease states. Telerehabilitation, a subset of telemedicine, has gained traction during the COVID-19 pandemic for remote service delivery. However, no prior scoping review, systematic review, or meta-analysis has identified and summarized the current primary research on adverse events in telerehabilitation. Understanding adverse events, such as falls during physiotherapy or aspiration pneumonia during speech therapy, is crucial for identifying limitations and optimizing delivery through risk mitigation and quality indicators. This understanding could also help to improve the uptake of telerehabilitation among clinicians and patients. This review addresses this gap by summarizing published literature on adverse events during telerehabilitation. The review followed the Joanna Briggs Institute framework and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. The review protocol was registered and published on Open Science Framework. A comprehensive search across multiple databases (MEDLINE ALL/EMBASE/APA PsycINFO/CENTRAL/CINAHL) was conducted. Screening, extraction, and synthesis were performed in duplicate and independently. Data extraction followed the Template for Intervention Description and Replication framework and also involved extraction on authors, publication year (pre- or post-COVID), population, sample size, and modes of telerehabilitation delivery (asynchronous, synchronous, hybrid). For synthesis, data were summarized quantitatively using numerical counts and qualitatively via content analysis. The data were grouped by intervention type and by type of adverse event. This scoping review included qualitative and quantitative studies published between 2013-2023, written in English, and conducted in any geographic area. All modes of telerehabilitation delivery were included. Systematic reviews, meta-analyses, commentaries, protocols, opinion pieces, conference abstracts, and case series with fewer than five participants were excluded. The search identified 11,863 references, and 81 studies were included in this review with a total of 3,057 participants (mean age:59.3 years; females:44.6%). Modes of telerehabilitation delivery (whether asynchronous, synchronous or hybrid) used in the studies included videoconferencing (52), phone calls (25), text messaging (4), email (6), mobile apps (10), and internet-based virtual reality systems (3). A total of 295 adverse events occurred during 84,534 sessions (0.3%), with the majority being physical (e.g., falls or musculoskeletal pain), non-serious/non-severe/mild, and unrelated to (i.e., not caused by) to the telerehabilitation provided. From the 81 included studies, telerehabilitation was delivered with related adverse events being rare, and mostly characterized as mild/non-severe. A comparable occurrence of adverse events (~30%) was found between asynchronous and synchronous telerehabilitation studies. When categorized by disease type, cardiac telerehabilitation studies had the most frequent adverse events. Detailed reporting of telerehabilitation interventions and adverse event characteristics is recommended for future studies (i.e., use of TIDieR reporting guidelines). Telerehabilitation has the potential to make rehabilitation services more accessible to patients; however, more evidence on the safety of telerehabilitation is needed.

Chloroquine-primaquine therapeutic response and safety in patients with uncomplicated Plasmodium vivax malaria in the Colombian Amazon region

BackgroundIn Colombia, published studies on the treatment of uncomplicated Plasmodium vivax malaria with chloroquine-primaquine are scarce. The aim of this study was to evaluate the therapeutic response to two treatment regimens at the 28-day follow-up and the occurrence of adverse events in patients with P. vivax malaria.MethodsA quasi-experimental clinical trial was conducted at 3 sites in the Department of Amazonas. Patients received supervised or unsupervised anti-malarial treatment (chloroquine plus primaquine), and the primary effectiveness endpoint was the clinical and parasitological response. Safety was assessed through adverse event surveillance.ResultsA total of 103 patients were included: 53 in the 7-day primaquine group (Group I) and 50 in the group receiving primaquine for 14 days (Group II). Among the patients in group I, an adequate treatment response of 100% and 89.5% was found in patients who received supervised and unsupervised treatment, respectively. In Group II, adequate responses of 100% and 95% were reported for patients who received supervised and unsupervised treatment, respectively. No adverse events were detected.ConclusionsThe response to combined treatment with chloroquine plus primaquine continues to be adequate for treating P. vivax malaria in the Colombian Amazon region; however, a response to unsupervised treatment in the region is recommended.

Comparative analysis of efficacy and safety between D-TACE + HAIC + lenvatinib and D-TACE + lenvatinib in the treatment of unresectable massive hepatocellular carcinoma

ObjectiveThe aim of this study was to investigate the efficacy and safety of the combined treatment regimen of D-TACE, HAIC, and Lenvatinib in patients with massive hepatocellular carcinoma, with the goal of providing a safer and more effective therapeutic strategy for individuals suffering from massive hepatocellular carcinoma.Materials and methodsA retrospective analysis was conducted using clinical data from 118 patients with unresectable massive hepatocellular carcinoma who underwent treatment at the Interventional Department of Wuhan Union Hospital between June 2018 and December 2021. Based on the treatment approach, the patients were divided into two groups: the D-TACE + HAIC + Lenvatinib group (N = 54) and the D-TACE + Lenvatinib group (N = 64). The primary study endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) of the two groups. Additionally, the occurrence of treatment-related adverse events in both groups was considered as a secondary study endpoint.ResultsFollowing the treatment, the D-TACE + HAIC + Lenvatinib group exhibited significantly higher ORR and DCR compared to the D-TACE + Lenvatinib group (68.5% vs. 43.8%, 90.7% vs. 73.4%, P < 0.05). Moreover, the D-TACE + HAIC + Lenvatinib group demonstrated longer mPFS and mOS in comparison to the D-TACE + Lenvatinib group (8.6 months vs. 6.6 months, P = 0.005; 19.5 months vs. 14.1 months, P < 0.001). There was no statistically significant difference in the occurrence rate of common treatment-related adverse events between the TACE + HAIC + Lenvatinib group and the D-TACE + Lenvatinib group (P > 0.05).ConclusionThe combined treatment regimen of D-TACE, HAIC, and Lenvatinib demonstrated superior therapeutic efficacy and safety in managing unresectable massive hepatocellular carcinoma. This combination therapy may serve as a viable option for improving the prognosis of patients with unresectable massive hepatocellular carcinoma.

Real-world application of disitamab vedotin (RC48-ADC) in patients withbreast cancer with different HER2 expression levels: efficacy and safety analysis.

Disitamab vedotin (RC48-ADC), an antibody-drug conjugate (ADC), combines specific antibody disitamab with cytotoxicity monomethyl auristatin E to effectively target the human epidermal growth factor receptor 2 (HER2) protein on tumor cells for precise elimination. Recent studies have demonstrated that RC48-ADC offers therapeutic benefits for patients with HER2-positive and HER2-low-expression breast cancer (BC). However, a thorough exploration of its efficacy and safety in real-world settings for patients with metastatic breast cancer (mBC) is currently lacking. This retrospective, multicenter, real-world study included patients with mBC who received RC48-ADC from September 2021 to March 2024. These patients include HER2-positive BC and HER2-low-expression BC. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), restricted mean survival time, objective response rate (ORR), and disease control rate (DCR). Factors affecting efficacy and the occurrence of treatment-related adverse events (TRAE) were evaluated. The study included a cohort of 89 patients with mBC, with 48 of those being identified as HER2-positive. As of March 2024, 22 deaths were recorded, with an immature median OS. Total PFS varied from 1.0 to 31.2 months, with a median of 5.5 months (95% CI, 4.368-6.632). HER2-positive patients exhibited prolonged PFS compared with HER2-low-expression patients (6.6 months vs 4.1 months, P = .023). The overall ORR stood at 25.8% (95% CI, 0.178-0.358), with higher rates observed in HER2-positive patients compared with HER2-low-expression patients (31.3% vs 19.5%). Similarly, the overall DCR was 78.7% (95% CI, 0.691-0.859), with HER2-positive patients demonstrating superior DCR compared with HER2-low-expression patients (83.3% vs 73.2%). Notably, HER2 expression emerged as the primary determinant of RC48-ADC efficacy. The most prevalent TRAE among all patients included leukopenia (21.3%) and alopecia (20.2%). RC48-ADC showcases promising efficacy and manageable safety in patients with both HER2-positive and HER2-low-expression mBC.

Therapeutic Potential of Cannabinoids in Glaucoma – Hit or Myth? - A Review

Introduction: Glaucoma is a leading cause of irreversible blindness, characterized by elevated intraocular pressure (IOP) that damages the optic nerve. Current treatments mainly focus on reducing IOP, but some patients do not respond adequately to conventional therapies. Cannabinoids, particularly Δ9-tetrahydrocannabinol (Δ9-THC), have been investigated as potential adjunctive treatments for glaucoma. Studies have shown varying effects of cannabinoids on IOP regulation, though their precise mechanisms remain unclear. Aim of Study: This study aims to evaluate the therapeutic potential of cannabinoids in the treatment of glaucoma by examining their effects on IOP, their mechanisms of action, and the risks and benefits associated with their use. Material and methods: A comprehensive literature review of studies on the therapeutic potential of cannabinoids in glaucoma was conducted using the PubMed database. Results and Conclusions: Cannabinoids, especially Δ9-THC, have demonstrated the ability to reduce IOP in both healthy individuals and glaucoma patients. However, the effect is typically short-lived, lasting only 3-4 hours. The efficacy of cannabinoids in reducing IOP is influenced by the method of administration (oral, intravenous, inhalation) and the delivery system used for topical application. Despite some promising results, the use of cannabinoids as a mainstream glaucoma treatment is limited by factors such as the short duration of action, the potential for addiction, and the occurrence of adverse effects like tachycardia, hypotension, and cognitive impairment. Although cannabinoids offer a unique approach to glaucoma management, further research is necessary to address these limitations and determine their long-term therapeutic viability.

Different regimens for eradication of Helicobacter pylori infection in children: a randomized controlled trial

Eradication of Helicobacter pylori (H. pylori) infection in children is challenging due to increased antibiotic resistance and decreased effectiveness of the current therapeutic choices, especially in developing countries. The purpose of this study is to compare the efficacy and safety of triple therapy (TT), sequential therapy (ST), hybrid therapy (HT), concomitant therapy (CT), and ciprofloxacin-based triple therapy (CTT) as an empirical therapy for H. pylori eradication in children. In this randomized controlled trial, 200 children (aged between 3 and 16 years) with both positive rapid urease test and histopathology for H. pylori infection were included. Patients were randomly assigned to receive either TT, ST, HT, CT, or CTT. The eradication status was evaluated using a stool antigen test (SAT) 4 weeks after stoppage of antibiotic therapy and 2 weeks after stoppage of proton pump inhibitors. SAT was performed using an ELISA monoclonal antibody-based kit. The most common presenting symptom was epigastric pain (79%). The most common endoscopic findings were gastric antral erythema (98%) and antral nodularity (54.5%). All gastric biopsies showed superficial lamina propria infiltration with plasma cells and lymphocytes. Active gastritis with neutrophils infiltration was seen in 75% of the cases. Gastric atrophy and intestinal metaplasia were uncommon histopathological findings (8.5% and 1%, respectively). The eradication rates for TT, ST, HT, CT, and CTT were 70%, 77.5%, 80%, 85%, and 90%, respectively, with the latter achieving a statistically significant difference when compared with TT (p = 0.025). The rate of occurrence of adverse effects among different regimens was not statistically different. Conclusion: As an empirical treatment for children with H. pylori infection, CTT is safe and provides the highest eradication rate. HT, ST, and CT might not be superior to TT.Trial registration: This study was registered at the Pan African Clinical Trials Registry, Cochrane South Africa, under the identifier PACTR202201686010590. Date of registration: 04 January 2022.What is Known:• Triple therapy has been the standard eradication regimen for pediatric H. pylori infection. The efficacy of triple therapy has decreased in many countries due to increased antibiotic resistance.What is New:• This randomized controlled trial is the first to compare triple therapy, sequential therapy, hybrid therapy, concomitant therapy, and ciprofloxacin-based triple therapy for the eradication of pediatric H. pylori infection. Triple therapy exhibited the lowest eradication rate among the studied regimens, suggesting it may not be an adequate therapeutic option for infected children. Ciprofloxacin-based triple therapy appears to be a safe and effective therapeutic choice for pediatric H. pylori infection. Additionally, this study provides the first reported eradication rate of hybrid therapy in pediatric H. pylori infection.