Burden Of Adverse Events Research Articles

The paradox of CAC score and plaque vulnerability

Abstract Introduction The effect of coronary artery calcification on plaque vulnerability remains unclear. The coronary artery calcium (CAC) score, quantified using coronary computed tomography, has a strong correlation with total atherosclerotic burden and risk of adverse cardiac events. Nevertheless, different patterns in the distribution of coronary artery calcium have been reported to convey different effects on plaque stability. Some biomechanical models suggest that microcalcifications can intensify stress in the fibrous cap, promoting plaque rupture. On the other hand, large calcium deposits are hypothesized to promote plaque stability, as statin therapy has been shown to promote the calcification of atherosclerotic lesions. The purpose of this study is to investigate the relationship between CAC score and vulnerable plaque using coronary computed tomographic angiography (CCTA) in patients with an acute coronary syndrome (ACS). Methods CCTA was performed in 444 patients; these patients were divided into two groups (those with vulnerable plaque and those without). CAC score of each patient was obtained. We calculated median value of CAC score of both groups and compared them using Two Sample Mann-Whitney U Test. All tests were 2-sided, p values below a threshold of 0.05 were considered to be significant. All statistical analyses were performed using IBM SPSS Statistics 29.0 (SPSS Inc, Chicago, IL). Results Out of 444 patients with an ACS and evaluated with CCTA, vulnerable plaques were found in 57 patients (13%). The median value of CAC score in patients with vulnerable plaques was significantly higher compared with patients without vulnerable plaques (mean CAC score 1065,07 AU (95% Confidence Intervals 526,26-2656,40 AU) vs 444,03 AU (95% CI 120,18-766,88 AU, p < 0.001). Using Mann–Whitney U test, we found a statistically significant difference between CAC score of patients with vulnerable plaques and those that did not have such plaques. Conclusion Although CAC score is a reliable marker of atherosclerosis it is still uncertain whether CAC score is an indicator of plaque vulnerability. In our study, CAC score was higher in patients with vulnerable plaque compared to those without such plaques. A highly statistically significant difference was found between the median value of CAC score between these two groups of patients.Boxplot

A retrospective analysis of patients with very HIGH level of LDL-C and the predictors of mortality (HIGH-LDL-PM Registry)

Abstract Introduction Elevated levels of LDL cholesterol (LDL-C) significantly contribute to the development and progression of cardiovascular diseases (CVDs). In HIGH-LDL-PM Registry, we aimed to investigate the demographics and clinical characteristics of patients with very high level of LDL-C and the predictors of mortality, retrospectively. Methods We retrospectively searched the electronic database of Istanbul University-Cerrahpasa Institute of Cardiology and included patients with very high level of LDL-C (>190 mg/dl) in HIGH-LDL-PM registry. The study group were classified as patients with high probability of familial hypercholesterolemia (FH) and low probability of FH according to Dutch Lipid Clinic Network Score (DLCNS). Results The study group were consisted of 1127 patients and almost two thirds (61.5%) were female. The mean age was 56.5 12.2 years. Hypertension, diabetes, chronic kidney disease (CKD) were seen in 55.8%, 23.5% and 3.7%, respectively. One third of study group (31.1%) had coronary artery disease (CAD) and rest of them were primary prevention patients. the main rhythm was sinus in most of the patients (92,2) and 7.8% patients had atrial fibrillation (AF). Only minority of patients (3.9%) had stigmata for elevated cholesterol levels. While 41.8% of patients had high clinical probability for FH, 58.2% of them had low probability according to DLCNS. While 69% of patients were using lipid lowering treatments (LLTs), 42% of them had drug adherence. High dose (HD) statins (atorvastatin 40-80 and rosuvastatin 20-40 mg) were prescribed in more than half (55.2%) of patients with LLTs. Ezetimibe was the preferred agent as combination therapy in 6.9% and PCSK-9is were prescribed only in 2.5% of patients with LLTs. In 38.8% of study population, ASA was prescribed. 50% decrease in LDL-C levels or decreasing LDL-C below 70 or 100 mg/dl as a treatment goal were achieved in 37.1% and 15% of study population. MACE (MI, stroke, PCI or peripheral revascularization) was recorded in 21% of study population and the mortality rate was 10.4% at 12-years FU (6-145 months). Patients with low probability of FH had better survival than patient with high probability (91.4% vs 88.4%). The age, low dose statin use and higher level of LDL-C at FU were predictors of mortality in Cox-regression analysis. Conclusion Our retrospective analysis of patients with very high levels of LDL-C underscores the multifaceted nature of dyslipidemia management and its impact on cardiovascular outcomes. Despite advancements in pharmacotherapy, suboptimal adherence to lipid-lowering treatments remains a significant challenge, contributing to a notable burden of major adverse cardiovascular events and mortality. Identification of predictors of mortality, such as age, statin dosage, and LDL-C levels, highlights the importance of individualized risk assessment and tailored treatment approaches in this high-risk population.

Graph neural network-based subgraph analysis for predicting adverse drug events

PurposeAdverse drug events (ADEs) are a significant global public health concern, and they have resulted in high rates of hospital admissions, morbidity, and mortality. Prior to the use of machine learning and deep learning methods, ADEs may not become well recognized until long after a drug has been approved and is widely used, which poses a significant challenge for ensuring patient safety. Consequently, there is a need to develop computational approaches for earlier identification of ADEs not detected during pre-registration clinical trials. MethodsThis paper presents a state-of-the-art network-based approach that models patients as subgraphs composed of nodes of International Classification of Diseases (ICD) codes and directed edges illustrating disease progression. Four Graph Neural Network (GNN) variants were employed to make sub-graph level predictions that answer three Research Questions (RQ): 1) whether ADE(s) would occur given a patient's prior diagnoses history, 2) when an ADE would occur, and 3) which ADE would occur. The first and second RQs were addressed using a binary classification approach. The third RQ was addressed using a multi-label classification model. ResultsThe proposed network-based approach demonstrated superior performance in predicting ADEs, with the GraphSage model exhibiting the highest accuracy for both RQ 1 (0.8863) and RQ 3 (0.9367), while the Graph Attention Networks (GAT) model was found to perform best for RQ 2 (0.8769). Furthermore, an analysis segmented by ADE classification revealed that while RQs 1 and 3 exhibited minimal variance across different ADE categories, a distinct advantage was observed for categories B, C, and E in the context of RQ 2 when applying this sub-graph method. ConclusionThe network-based approach demonstrates the potential of GNNs in supporting the early detection and prevention of ADEs. Accurately predicting ADEs could enable healthcare professionals to make informed clinical decisions, take preventive measures and adjust medication regimens before serious adverse events occur. The proposed prediction method could also lead to optimized usage of healthcare resources by preventing hospital admissions and reducing the overall burden of adverse drug events on the healthcare systems.

High Burden of Ileus and Pneumonia in Clozapine-Treated Individuals With Schizophrenia: A Finnish 25-Year Follow-Up Register Study.

The authors used longitudinal biobank data with up to 25 years of follow-up on over 2,600 clozapine users to derive reliable estimates of the real-world burden of clozapine adverse drug events (ADEs). A total of 2,659 participants in the FinnGen biobank project had a schizophrenia diagnosis and clozapine purchases with longitudinal electronic health record follow-up for up to 25 years after clozapine initiation. Diseases and health-related events enriched during clozapine use were identified, adjusting for disease severity. The incidence and recurrence of ADEs over years of clozapine use, their effect on clozapine discontinuation and deaths, and their pharmacogenetics were studied. Median follow-up time after clozapine initiation was 12.7 years. Across 2,157 diseases and health-related events, 27 were enriched during clozapine use, falling into five disease categories: gastrointestinal hypomotility, seizures, pneumonia, other acute respiratory tract infections, and tachycardia, along with a heterogeneous group including neutropenia and type 2 diabetes, among others. Cumulative incidence estimates for ileus (severe gastrointestinal hypomotility) and pneumonia were 5.3% and 29.5%, respectively, 20 years after clozapine initiation. Both events were significantly associated with increased mortality among clozapine users (ileus: odds ratio=4.5; pneumonia: odds ratio=2.8). Decreased genotype-predicted CYP2C19 and CYP1A2 activities were associated with higher pneumonia risk. Clozapine-induced ileus and pneumonia were notably more frequent than has previously been reported and were associated with increased mortality. Two CYP genes influenced pneumonia risk. Pneumonia and ileus call for improved utilization of available preventive measures.

The burden of paediatric adverse medical events

The burden of paediatric adverse medical events

Improving Type 2 Diabetes Care with Extended-Release Metformin: Real-Life Insights from a Physician Educational Program.

Compared to Immediate-Release (IR) metformin, Extended-Release (ER) metformin reduces side effects and pill burden while improving adherence; however, there is little real-life data on patient satisfaction with this innovative formulation to guide physicians toward a more holistic approach. Our goal is to train general practitioners on holistic patient management, with the aim of increasing patient satisfaction and treatment adherence, reducing side effects, and improving quality of life in patients with poor tolerance to metformin-IR. We designed an educational program for physicians called SlowDiab, aimed at establishing a holistic patient approach. In this context, adult patients with T2DM who experienced gastrointestinal discomfort with metformin-IR were enrolled and switched to metformin- ER. Data on glycemic control were collected at baseline and 2 months after switching. A survey was carried out on patients to assess their level of satisfaction. In 69 enrolled patients (mean (min-max) age, 68.2 (41-90)), side effects decreased after switching from 61.8% to 16.2% (p < 0.01), and the mean perceived burden of adverse events on a scale of 1 to 10 also decreased (6.17 vs. 3.82; p < 0.05). Among patients previously intolerant to metformin-IR, 74.3% reported no longer experiencing any side effects after the switch. The mean number of tablets taken daily (2.28 vs. 1.66; p < 0.01) and mean plasma glycated hemoglobin (HbA1c) values (7.0% vs. 6.7%; p < 0.05) decreased, while 93.8% of patients were satisfied with the treatment change. Moreover, 84.2% reported an improvement in glycemic control after the switch. In a real-life setting, an educational program for general practitioners confirmed that metformin ER reduces side effects and improves pill burden, therapeutic adherence, and patient satisfaction compared to metformin IR.

Development and implementation of a digital health intervention (DHI) electronic patient-reported outcome measure (ePROM) platform to monitor patients with cancer.

163 Background: Cancer is heterogeneous diseases associated with a significant burden of symptoms and treatment-related adverse events. Digital Health Interventions (DHIs) emerge as promising tools for active/continuous monitoring of patients (pts). Evidence suggests that DHIs may enhance healthcare delivery and improve clinical outcomes by facilitating symptom detection and enabling more effective real-time informed decisions. We aim to develop and implement an electronic Patient-reported Outcome Measure (ePROM) platform to monitor pts undergoing cancer treatment. Methods: We developed ThummiOnco, a DHI ePROM platform designed for monitoring of pts during cancer treatment. It allows pts to report their symptoms (reported and graded according to the CTCAE), quality-of-life (QoL) (EORTC EQ-5D questionnaire), emotional state, treatment adherence (Morisky-Green questionnaire), Emergency Room (ER) visits and hospitalizations through a mobile application. Upon registration, pts consent to share their data with their medical team and provide essential demographic information such as age, sex, cancer type, and treatment regimen. A medical algorithm analyzes the collected data to generate instant personalized recommendations and guidance, including indicating the need of seeking emergency care in the case of serious high-grade or worrisome complaints. Patients also have the option to engage in real-time conversations with the medical team through an online chat feature. Treating physicians and the medical team can continuously access pts data real-time, through an online dashboard, enabling them to visualize information and statistics, address symptom alerts, and make informed management decisions. ThummiOnco is available at no cost to pts at htt ps://thummi.global . Results: Between August 2021 and March 2024, ThummiOnco monitored 925 pts across 7 institutions in Brazil, encompassing both private and public health systems. The majority of pts (72%) were female, with 28% being male. The most frequently monitored cancer types were Breast Cancer (39%), Lung Cancer (7%) and Colon Cancer (6%). During this period, a total of 71.373 interactions were recorded, including 36.175 (51%) chat messages, 21.644 (30%) symptom reports, 10.597 (15%) emotional state reflections, 2.819 (4%) QoL assessments, and 138 (0.2%) ER registries. A total of 23 different symptoms were reported, with the most frequent being: fatigue (16%), joint pain (8%), and nausea (7%). 13.187 (61%) grade 1, 6.545 (30%) grade 2, and 1.912 (9%) grade 3 symptoms were registered. In total, the medical algorithm generated 1.921 recommendations for seeking emergency care. Conclusions: ThummiOnco's capacity to detect a wide range of symptoms and enable real-time informed decisions underscores its potential to enhance patient outcomes and healthcare service delivery.

The influence of adverse events on inpatient outcomes in a tertiary hospital using a diagnosis-related group database

Adverse events (AEs) are a significant concern for healthcare systems. However, it is difficult to evaluate their influence because of the complexity of various medical services. This study aimed to assess the influence of AEs on the outcomes of hospitalized patients using a diagnosis-related group (DRG) database. We conducted a case–control study of hospitalized patients at a multi-district tertiary hospital with 2200 beds in China, using data from a DRG database. An AE refers to an unintended physical injury caused or contributed to by medical care that requires additional hospitalization, monitoring, treatment, or even death. Relative weight (RW), a specific indicator of DRG, was used to measure the difficulty of diagnosis and treatment, disease severity, and medical resources utilized. The primary outcomes were hospital length of stay (LOS) and hospitalization costs. The secondary outcome was discharge to home. This study applied DRG-based matching, Hodges–Lehmann estimate, regression analysis, and subgroup analysis to evaluate the influence of AEs on outcomes. Two sensitivity analyses by excluding short LOS and changing adjustment factors were performed to assess the robustness of the results. We identified 2690 hospitalized patients who had been divided into 329 DRGs, including 1345 patients who experienced AEs (case group) and 1345 DRG-matched normal controls. The Hodges–Lehmann estimate and generalized linear regression analysis showed AEs led to prolonged LOS (unadjusted difference, 7 days, 95% confidence interval [CI] 6–8 days; adjusted difference, 8.31 days, 95% CI 7.16–9.52 days) and excess hospitalization costs (unadjusted difference, $2186.40, 95% CI: $1836.87-$2559.16; adjusted difference, $2822.67, 95% CI: $2351.25-$3334.88). Logistic regression analysis showed AEs were associated with lower odds of discharge to home (unadjusted odds ratio [OR] 0.66, 95% CI 0.54–0.82; adjusted OR 0.75, 95% CI 0.61–0.93). The subgroup analyses showed that the results for each subgroup were largely consistent. LOS and hospitalization costs increased significantly after AEs in complex diseases (RW ≥ 2) and in relation to high degrees of harm subgroups (moderate harm and above groups). Similar results were obtained in sensitivity analyses. The burden of AEs, especially those related to complex diseases and severe harm, is significant in China. The DRG database serves as a valuable source of information that can be utilized for the evaluation and management of AEs.

Clinical outcomes of HeartMate 3 left ventricular assist device support with a Bridge to Transplant vs a Destination Therapy strategy: a single-centre retrospective cohort.

Real-world outcomes with the HeartMate3 left ventricular assist device (LVAD) depending on whether it's a bridge to transplantation (BTT) or destination therapy (DT) are poorly studied. We aimed to compare the profile and clinical outcomes of patients supported with HeartMate3 according to a BTT or a DT pre-implantation strategy. All patients consecutively implanted with HeartMate3 at our centre (University Hospital of Lausanne, Switzerland) in 2015-2022 were analysed in a retrospective observational study. Indications for HeartMate3 implantation were advanced heart failure despite optimal medical treatment. Patients were treated with a vitamin K antagonist anticoagulant combined with antiplatelet therapy after HeartMate 3 implantation and were followed up monthly at our institution. Among 71 patients implanted with HeartMate3 between 2015 and 2022, 51 (71.8%) were implanted as a BTT and 20 (28.2%) as DT. Their median age was 58 (IQR: 52-69) years and 84% of patients were classified as INTERMACS profiles 2-4. The median follow-up duration was 18.3 (IQR: 7.5-33.9) months. Patients in the DT group were older than those in the BTT group (p <0.001) and had more chronic renal failure (p <0.001). They also had a lower 5-year survival rate (mean ± standard error: 87.3 ± 5.6% vs 49.4 ± 15.1%)and more adverse events such as renal dysfunction requiring temporary perioperative dialysis (p = 0.08) or bleeding (p = 0.06). Although patients supported with HeartMate3 have favourable survival, those with LVAD-DT have poorer outcomes. There is a need to better select patients eligible for LVAD-DT in order to limit the burden of adverse events and improve their prognosis.

Safety and tolerability of esketamine nasal spray versus quetiapine extended release in patients with treatment resistant depression

In ESCAPE-TRD (NCT04338321), esketamine nasal spray (NS) significantly increased the probability of remission at Week 8, and of being relapse-free through Week 32 after remission at Week 8, versus quetiapine extended release (XR) in patients with treatment resistant depression (TRD). Here, we explore the time course, burden and consequences of treatment emergent adverse events (TEAEs) in the phase IIIb ESCAPE‑TRD trial. Patients with TRD were randomised 1:1 to esketamine NS or quetiapine XR, dosed per label alongside an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. In this secondary publication, safety analyses (comprising patients who received ≥1 dose of study treatment) included incidence, severity and durations (Kaplan‑Meier method) of TEAEs, and subsequent dispositional changes. P values were not adjusted for multiple testing. 336 patients were randomised to esketamine NS and 340 to quetiapine XR; 334 and 336 received ≥1 dose of study treatment, respectively. TEAEs were significantly more common with esketamine NS than quetiapine XR (91.9 % versus 78.0 %; p < 0.001), but were typically mild/moderate and transient in nature: a greater proportion resolved on the same-day (92.0 % versus 12.1 %) and lead to treatment discontinuation in significantly fewer patients (4.2 % versus 11.0 %, respectively; p < 0.001). The proportion of days spent with TEAEs was significantly lower with esketamine NS than quetiapine XR (median: 11.9 % versus 21.3 %; p < 0.001). Although more frequent with esketamine NS, TEAEs were typically transient and mild, with discontinuation less likely versus quetiapine XR. Data were consistent with established safety profiles, with no new safety signals identified. Alongside greater efficacy, the demonstrably more favourable tolerability profile of esketamine NS versus quetiapine XR further supports its use for TRD.

High comorbidity burden and low incidence of adverse events in primary shoulder arthroplasty in tertiary care at a university hospital

BackgroundReducing perioperative risk is in the focus of primary arthroplasty caregivers. Primary shoulder arthroplasty patients are considered among those with the lowest perioperative risk. Nonetheless, in tertiary care centres and university settings patients with significant comorbidities are being treated. It remains unclear whether the overall comorbidity burden is truly higher and if this results in an increased frequency of adverse events (AE). As a result, we conducted a study to assess the comorbidity burden and the frequency of major perioperative adverse events and predictive factors following primary shoulder arthroplasty in the university setting. MethodsA retrospective cohort analysis was conducted on patients undergoing primary shoulder arthroplasty for a non-trauma, non-tumour indication from January 1st, 2014 through December 31st, 2018. Administrative data were recorded to assess comorbidity burden and revision surgery within the first postoperative year. Major adverse events were routinely recorded on a weekly basis by the treating physicians. Descriptive and comparative statistical analyses were performed. The cohort was compared against a large North American sample. ResultsOf 386 patients who underwent 400 primary shoulder arthroplasties 14 (3.5 %) experienced adverse events. While AE were distributed equally among anatomical and reverse shoulder arthroplasties, no adverse event was recorded in the 34 hemiarthroplasty patients. The cohort showed an increased comorbidity burden in international comparison. Peptic ulcer disease was significantly associated with AE, while mild liver disease experienced a trend towards AE. ConclusionWe found an increased comorbidity burden and a low rate of AE for primary shoulder arthroplasty in a tertiary care and university setting. The distinct role of peptic ulcer disease in this cohort and the trend in mild liver disease merit further investigation in larger samples. The findings underscore the importance of perioperative risk assessment and management. Level of evidenceIII, retrospective cohort study.

Disease burden, clinical management and unmet treatment need of patients with moderate to severe atopic dermatitis; consensus statements, insights and practices from CERTADE (Central/Eastern EU, Russia, Turkiye AD Experts) Delphi panel.

There is limited insight into the current disease burden and everyday clinical management of moderate-to- severe AD in Poland, Czechia, Russia, and Turkiye. Therefore, this study aimed to get information-driven insights regarding the current disease burden and clinical management of patients with moderate-to-severe AD with common and differentiating aspects of the patient journey and establish a consensus. In this modified 2-round Delphi panel, 133 questions were asked in total to 27 dermatologists. A consensus was achieved when 70% of the panel members strongly agreed or agreed (or strongly disagreed or disagreed) with an item. Statements with <40% agreement dropped from the Delphi rounds and were not repeated. The results state that AD has a significant impact on the quality of life for both patients and their families with social and economic consequences in these countries. While there were significant dissimilarities regarding the current treatment approach by preference order and treatment duration among participants, there was also a high percentage of consensus on literature and guideline-based statements. Current topical therapies and the immune response modifiers were not found to be sufficient by panelists to cover the therapeutic needs of patients with moderate-to-severe AD. Moreover, panelists highlighted the significant burden of adverse events with the off-label use of currently available immunosuppressants. These results underlined that there is a significant disease burden with an unmet treatment need for patients with moderate-to-severe AD in Poland, Czechia, Russia, and Turkiye.

A backward cycling programme for people with Parkinson's disease: a feasibility and preliminary results study.

To assess the feasibility of backward cycling for people with Parkinson's disease. Secondary objectives were to assess changes in gait and balance following a 6-week program. A single-group prospective pre-test, post-test study with 1-month follow-up. Twenty-six people with Parkinson's disease (mean age: 69 (7.74) years, gender: 83% males, time since diagnosis: 6 (4.44) years). Participants pedaled backward on a stationary bicycle for 30 minutes at moderate intensity twice a week for 6 weeks. Feasibility was assessed by acceptability, suitability, and burden. Data collected at pre- and post-intervention with 1-month follow-up included backward stepping response variables, forward/backward gait variables, Mini-Balance Evaluation Systems Test (MBT), and 6 Minute Walk Test. There was a high retention rate (95.8%) and adherence rate (100%) with one adverse event and minimal burden. Significant improvements were seen in step count and excursion distance during backward stepping responses, forward and backward gait velocity, forward step length, and the Mini-BESTest. Backward cycling was a feasible intervention for people with Parkinson's disease, demonstrating low burden with high retention and adherence rates, and it is a safe exercise with the potential for benefits in gait and balance variables.

Adverse events in real-world patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) who received FOLFIRINOX (FFX) or gemcitabine with nab-paclitaxel (GnP) in the first line (1L).

e16321 Background: FFX and GnP are the most common 1L treatments for mPDAC. Each regimen is associated with a different profile of toxic effects that impact quality of life. However, the regimens have not been directly compared for safety or efficacy in a randomized controlled trial. RW studies of the frequency of adverse events (AEs) under each regimen have reported inconsistent results. Supportive care such as granulocyte colony-stimulating factor (G-CSF) also affects the rate of hematologic AEs. We assessed AEs and G-CSF use in a RW cohort of mPDAC pts treated with FFX or GnP in the 1L. Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between November 2018 and November 2022 who initiated treatment with 1L FFX or GnP within 90 days of their diagnosis for metastatic disease were included in the study. Diarrhea, fatigue, nausea and vomiting, and neuropathy were available in the data as ungraded AEs abstracted from clinician notes. Assessment of hematologic and hepatic AEs were based on observed lab values and were graded according to the Common Terminology Criteria for AEs version 5. Results: 2,918 pts met study inclusion criteria: 1,703 received 1L GnP and 1,215 received 1L FFX. For the GnP vs. FFX cohorts, the median age at 1L initiation was 71yr (IQR: 64–76) vs. 65yr (IQR: 58–71), 52% vs. 57% were male, 65% vs. 68% were white, 9% vs. 15% had an ECOG score of 0, and 40% vs. 39% had an ECOG score of 1. GnP pts had a statistically significantly greater rate of grade 1/2 and 3/4 neutropenia (26% vs. 15%, p = .001; 25% vs. 17%, p = .014), grade 1/2 thrombocytopenia (25% vs. 20%, p &lt; .001), grade 1/2 and 3/4 anemia (87% vs. 68%, p &lt; .001; 19% vs. 6%, p = .001), grade 1/2 elevated ALT (62% vs. 44%, p &lt; .001), grade 1/2 elevated AST (68% vs. 50%, p &lt; .001), and grade 1/2 elevated ALP (68% vs. 58%, p &lt; .001). For GnP vs. FFX, there was no statistically significant difference in grade 3/4 thrombocytopenia (9% vs. 5%, p &lt; .001), grade 3/4 elevated ALT (6% vs. 5%, p = .367), grade 3/4 elevated AST (9% vs. 5%, p = .170), grade 3/4 elevated ALP (11% vs. 11%, p = .417), and grade 1/2 and 3/4 hypokalemia (32% vs. 34%, p = .241; 7% vs. 13%, p = .060). There were not statistically significant differences for GnP vs. FFX for AEs reported in clinician notes including diarrhea (12% vs. 18%, p = .074), fatigue (15% vs. 12%, p = .187), nausea and vomiting (10% vs. 11%, p = .399), and neuropathy (15% vs. 12%, p = .219). G-CSF was used by 19% vs. 57% of GnP vs. FFX patients (p &lt; .001), with median time to first use of G-CSF 14 days (IQR: 7–35) vs. 0 days (IQR: 0–14). Conclusions: In a RW cohort of mPDAC pts treated with 1L GnP or FFX, pts experienced a variety of serious AEs. The burden of AEs was higher among the RW GnP cohort than the RW FFX cohort. G-CSF was more prevalent and began earlier in the FFX cohort, indicating prophylactic use.

The burden of cardiovascular disease and risk for subsequent major adverse cardiovascular events in survivors of childhood cancer: a prospective, longitudinal analysis from the St Jude Lifetime Cohort Study

The effect of the increasing lifetime burden of non-major cardiovascular conditions on risk for a subsequent major adverse cardiovascular event among survivors of childhood cancer has not been assessed. We aimed to characterise the prevalence of major adverse cardiovascular events and their association with the cumulative burden of non-major adverse cardiovascular events in childhood cancer survivors. This is a longitudinal cohort study with participant data obtained from an ongoing cohort study at St Jude Children's Research Hospital: the St Jude Lifetime Cohort Study (SJLIFE). Prospective clinical follow-up was of 5-year survivors of childhood cancer who were diagnosed when aged younger than 25 years from 1962 to 2012. Age-frequency, sex-frequency, and race-frequency matched community-control participants completed a similar one-time clinical assessment. 22 cardiovascular events were graded using a St Jude Children's Research Hospital-modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Cumulative incidence and burden of the primary outcome of major adverse cardiovascular events (cardiomyopathy, myocardial infarction, stroke, and other cardiovascular-related mortality) were estimated. Rate ratios (RR) of the association of major adverse cardiovascular events with 22 non-major adverse cardiovascular events were estimated using multivariable piecewise-exponential regression adjusting for attained age, age at diagnosis, sex, race and ethnicity, treatment era, diagnosis of diabetes, and exposure to cardiotoxic cancer therapies. The St Jude Lifetime Cohort study is registered with ClinicalTrials.gov, NCT00760656, and is ongoing. 9602 5-year survivors of childhood cancer, and 737 community controls were included in the longitudinal follow-up (from Sept 13, 2007, to Dec 17, 2021). The median follow-up was 20·3 years (IQR 12·0-31·4) from the date of primary cancer diagnosis (4311 [44.9%] were females). By the age of 50 years (analysis stopped at age 50 years due to the low number of participants older than that age), the cumulative incidence of major adverse cardiovascular events among survivors was 17·7% (95% CI 15·9-19·5) compared with 0·9% (0·0-2·1) in the community controls. The cumulative burden of major adverse cardiovascular events in survivors was 0·26 (95% CI 0·23-0·29) events per survivor compared with 0·009 (0·000-0·021) events per community control participant. Increasing cumulative burden of grade 1-4 non-major adverse cardiovascular events was associated with an increased future risk of major adverse cardiovascular events (one condition: RR 4·3, 95% CI 3·1-6·0; p<0·0001; two conditions: 6·6, 4·6-9·5; p<0·0001; and three conditions: 7·7, 5·1-11·4; p<0·0001). Increased risk for major adverse cardiovascular events was observed with specific subclinical conditions (eg, grade 1 arrhythmias [RR 1·5, 95% CI 1·2-2·0; p=0·0017]), grade 2 left ventricular systolic dysfunction (2·2, 1·6-3·1; p<0·0001), grade 2 valvular disorders (2·2, 1·2-4·0; p=0·013), but not grade 1 hypercholesterolaemia, grade 1-2 hypertriglyceridaemia, or grade 1-2 vascular stenosis. Among an ageing cohort of survivors of childhood cancer, the accumulation of non-major adverse cardiovascular events, including subclinical conditions, increased the risk of major adverse cardiovascular events and should be the focus of interventions for early detection and prevention of major adverse cardiovascular events. The US National Cancer Institute and the American Lebanese Syrian Associated Charities.

The role of ventricular assist device in the management of advanced heart failure: a literature review

The ventricular assist device has become a reliable and enduring therapy for patients with end-stage heart failure, with over 22,000 implantations to date. Initially designed as a bridge-to-transplant option but now it has become permanent cure for patients with acute heart failure. VAD has significant advancements in medical management and technology, particularly with the introduction of newer-generation devices, have greatly enhanced patient outcomes. This progress has led to an increasing use of ventricular assist devices as a destination therapy. Nonetheless, the substantial burden of adverse events remains a critical challenge in the current state of ventricular assist device therapy, despite this, its viable alternative of heart transplantation as it has solved the complications of donor heart and proved significant success among patient with acute heart failure.

One-Year Outcomes of Preserflo Microshunt for Primary Open Angle Glaucoma: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis concludes that the PreserFlo Microshunt glaucoma drainage device significantly reduces intraocular pressure in primary open angle glaucoma patients at 12 months postinsertion. A systematic review and meta-analysis on the effect of the PRESERFLO MicroShunt (PF-MS) on intraocular pressure (IOP) at 12 months has been conducted. The PubMed/MEDLINE, Embase, CENTRAL, Google Scholar, Scopus, and Web of Science databases were searched. Inclusion criteria required a diagnosis of open angle glaucoma, PF-MS insertion, and examination of IOP over time. Meta-analyses were conducted on the primary outcome of IOP and the secondary outcome of glaucoma medication regime. Adverse events were also noted. Fourteen studies were identified for inclusion in the meta-analyses, of which none had a high risk of bias. The meta-analyses found a significant mean reduction in IOP of 9.07mmHg (95% CI: 7.88-10.25; P <0.0001) and a significant mean reduction in mean glaucoma medication requirement of 2.37 medications (95% CI: 2.15-2.60; P <0.0001). Hypotony and hyphaema are common early complications. The PF-MS device significantly reduced both IOP and glaucoma medication requirement at 12 months postinsertion in individuals with open angle glaucoma without a significant adverse event burden. Further research is required to determine the economic and environmental effects of widely implementing the PF-MS device into clinical practice.

Surgical management of proximal femoral unicameral bone cyst in children.

The aim of this study is to evaluate the surgical treatment with the best healing rate for patients with proximal femoral unicameral bone cysts (UBCs) after initial surgery, and to determine which procedure has the lowest adverse event burden during follow-up. This multicentre retrospective study was conducted in 20 tertiary paediatric hospitals in France, Belgium, and Switzerland, and included patients aged < 16 years admitted for UBC treatment in the proximal femur from January 1995 to December 2017. UBCs were divided into seven groups based on the index treatment, which included elastic stable intramedullary nail (ESIN) insertion with or without percutaneous injection or grafting, percutaneous injection alone, curettage and grafting alone, and insertion of other orthopaedic hardware with or without curettage. A total of 201 patients were included in the study. The mean age at diagnosis was 8.7 years (SD 3.9); 77% (n = 156) were male. The mean follow-up was 9.4 years (SD 3.9). ESIN insertion without complementary procedure had a 67% UBC healing rate after the first operation (vs 30% with percutaneous injection alone (p = 0.027), 43% with curettage and grafting (p = 0.064), and 21% with insertion of other hardware combined with curettage (p < 0.001) or 36% alone (p = 0.014)). ESIN insertion with percutaneous injection presented a 79% healing rate, higher than percutaneous injection alone (p = 0.017), curettage and grafting (p = 0.028), and insertion of other hardware combined with curettage (p < 0.001) or alone (p = 0.014). Patients who underwent ESIN insertion with curettage had a 53% healing rate, higher than insertion of other hardware combined with curettage (p = 0.009). The overall rate of postoperative complications was 25% and did not differ between groups (p = 0.228). A total of 32 limb length discrepancies were identified. ESIN insertion, either alone or combined with percutaneous injection or curettage and grafting, may offer higher healing rates than other operative procedures. Limb length discrepancy remains a major concern, and might be partly explained by the cyst's location and the consequence of surgery. Therefore, providing information about this risk is crucial.

Patient experiences and perceptions of kidney stone surgery: what lessons can be learned from TikTok?

The aim of this study was to perform an evaluation of patient experiences and perceptions regarding kidney stone surgery on the social media platform TikTok. An increasing number of the public use social media (SoMe) as a platform to share their views regarding their experiences related to surgical treatment. Using the hashtag #kidneystonesurgery, the 100 most recent video posts as of 01.01.2024 on TikTok were included. As well as demographic data such as gender and location, thematic content was also collected. To achieve this, a previously published framework was used and adapted for application in the setting of kidney stone surgery. This was piloted on 20 sample videos to assess its feasibility before revision and establishment of the final framework. This included the following key areas: Pain, Complications, Anxiety, Recovery, Return to work, Finances, Treatment delays, Diet and Prevention and stent complaints. The majority of posts (95%) were from North America, 80% by females and the mean number of video views was 92,826 (range: 261-2,000,000). 76% of the videos discussed ureteroscopy (URS). 49% were filmed at the hospital, which was named in 9% of the videos. Top three topics discussed were: Recovery (65%), pain (62%) and stents (55%). This was followed by anxiety (39%) and complications (24%). 12% of these videos uploaded by lay people included basic medical information that was wholly incorrect. More than half of the posts (51%) were negative in tone. Treatment delays (5%) and a lack of sufficient preoperative information (4%) were also raised, that appeared to contribute to the negative reports. However, the main cause for negative tone owed to the 80% of the patients (n = 44) who discussed stents that focused their video on the pain suffered from the post operative stent. There is a high level of usership and engagement on TikTok on the subject of kidney stone surgery. The proportion of negative videos is high and much of this is related to the bothersome stent symptoms and complications. This could easily lead to misperceptions among potential patients about the true burden of such adverse events.

Comparative effectiveness of azathioprine and mycophenolate mofetil for myasthenia gravis (PROMISE-MG): a prospective cohort study

Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. Treatment typically includes symptomatic oral cholinesterase inhibitors, immunosuppression, and immunomodulation. In addition to corticosteroids, azathioprine and mycophenolate mofetil are the most frequently used immunosuppressants in North America. We aimed to evaluate the comparative effectiveness of these two drugs, and to assess the effect of the dose and duration of treatment. We did a prospective cohort study at 19 academic centres in Canada and the USA. We included patients (aged ≥18 years) with autoimmune myasthenia gravis, who were never treated with immunosuppressants. Treating clinicians determined the choice of medication, dose, follow-up intervals, and drug monitoring. Outcome measures and adverse events were recorded at each visit. We assessed two co-primary outcomes. The first was the patient-reported Myasthenia Gravis-Quality of Life 15-revised (MGQOL-15r) score, measured as the mean change from treatment initiation to the follow-up visit with the lowest score. A clinically meaningful reduction (CMR) in MGQOL-15r was defined as a 5-point decrease. The second was a composite clinical outcome of disease improvement (Myasthenia Gravis Foundation of America Post-Intervention Status Minimal Manifestations or better) and low adverse event burden (defined as grade ≤1 Common Terminology Criteria for Adverse Events). We also compared these outcomes in patients receiving an adequate dose and duration of azathioprine (≥2 mg/kg per day for at least 12 months) or mycophenolate mofetil (≥2 g per day for at least 8 months) and a lower dose or shorter duration of these agents. We used propensity score weighting with generalised linear regression models. This study is registered with ClinicalTrials.gov (NCT03490539). Between May 1, 2018, and Aug 31, 2020, 167 patients were enrolled; 85 did not receive azathioprine or mycophenolate mofetil and were excluded. Four were excluded from outcome analyses because they had scores of 0 on an outcome measure at treatment initiation. Of the 78 patients included in analyses, 47 received mycophenolate mofetil (median follow-up 25 months [IQR 13·5-31·5]) and 31 received azathioprine (median follow-up 20 months [IQR 13-30]). The mean change in MG-QOL15r was -10·4 (95% CI -18·9 to -1·3) with mycophenolate mofetil and -6·8 (-17·2 to 3·6) with azathioprine (mean difference -3·3, 95% CI -7·7 to 1·2; p=0·15). 38 (81%) of 47 patients receiving mycophenolate mofetil and 18 (57%) of 31 receiving azathioprine had a CMR in MG-QOL15r (risk difference 24·0%; 95% CI -0·2 to 48·0; p=0·052). The clinical composite outcome was achieved in 22 (47·7%) of 47 patients who received mycophenolate mofetil and nine (28·1%) of 31 who received azathioprine (risk difference 19·6%, 95% CI -4·9 to 44·2; p=0·12). Descriptive analysis did not find a difference in the proportion of patients reaching a CMR in MG-QOL15r between the adequate dose and duration group and the lower dose or shorter duration group. Adverse events occurred in 11 (32%) of 34 patients who received azathioprine and nine (19%) of 48 who received mycophenolate mofetil. The most frequent adverse events were hepatotoxicity with azathioprine (five [15%] of 34) and gastrointestinal disturbances (seven [15%] of 48) with mycophenolate mofetil. There were no study-related deaths. More than half of patients treated with azathioprine and mycophenolate mofetil felt their quality of life improved; no difference in clinical outcomes was noted between the two drugs. Adverse events associated with azathioprine were potentially more serious than those with mycophenolate mofetil, although mycophenolate mofetil is teratogenic. Lower than recommended doses of azathioprine might be effective, with reduced dose-dependent adverse events. More comparative effectiveness studies are required to inform treatment choices in myasthenia gravis. Patient-Centered Outcomes Research Institute, Myasthenia Gravis Foundation of America.