Symptomatic Events Research Articles

Cardiotoxicity in children with cancer treated with anthracyclines: A position statement on dexrazoxane.

Cardiovascular disease is the leading cause of non-malignant morbidity and mortality in childhood cancer survivors (CCSs). Anthracyclines are included in many treatment regimens for paediatric cancer, but unfortunately, these compounds are cardiotoxic. One in 10 CCSs who has received an anthracycline will develop a symptomatic cardiac event over time. Given the crucial need to mitigate anthracycline-related cardiotoxicity (ARC), the authors critically examined published data to identify effective cardioprotective strategies. Based on their expert analysis of contemporary literature data, it was concluded that consideration should be given for routine use of dexrazoxane in children with cancer who are at risk of ARC.

End Point Considerations for Clinical Trials in Enteric Hyperoxaluria.

Enteric hyperoxaluria is a medical condition characterized by elevated urinary oxalate excretion due to increased gastrointestinal oxalate absorption. Causative features include fat malabsorption and/or increased intestinal permeability to oxalate. Enteric hyperoxaluria has long been known to cause nephrolithiasis and nephrocalcinosis, and, more recently, an association with CKD and kidney failure has been shown. Currently, there are no US Food and Drug Administration-approved therapies for enteric hyperoxaluria, and it is unclear what end points should be used to evaluate the efficacy of new drugs and biologics for this condition. This study represents work of a multidisciplinary group convened by the Kidney Health Initiative to review the evidence supporting potential end points for clinical trials in enteric hyperoxaluria. A potential clinical outcome is symptomatic kidney stone events. Potential surrogate end points include ( 1 ) an irreversible loss of kidney function as a surrogate for progression to kidney failure, ( 2 ) asymptomatic kidney stone growth/new stone formation observed on imaging as a surrogate for symptomatic kidney stone events, ( 3 ) urinary oxalate and urinary calcium oxalate supersaturation as surrogates for the development of symptomatic kidney stone events, and ( 4) plasma oxalate as a surrogate for the development of the clinical manifestations of systemic oxalosis. Unfortunately, because of gaps in the data, this Kidney Health Initiative workgroup was unable to provide definitive recommendations. Work is underway to obtain robust information that can be used to inform trial design and medical product development in this space.

Symptomatic adverse events in lung cancer clinical trials included in US drug labels from 2015 to 2021 to inform patient-reported outcomes.

e13642 Background: FDA recommends assessing expected symptomatic adverse events (symAEs) as a core patient-reported outcome (PRO) in cancer clinical trials (CTs). Several core PRO symptom lists exist that measure the same symptoms across trial contexts; however, many were developed in an era when cytotoxic chemotherapy was the main mechanism of action (MOA). To further research relevant PROs in modern cancer CTs, we identified common symAEs from recently approved lung cancer drugs across MOAs. Methods: We identified lung cancer drug approvals from 2015 through 2021 using an FDA database. The drug US Prescribing Information (PI) was used to extract indication, MOA, CT information, and all-grade symAEs reported in ≥20% of patients in the investigational arm. To improve symAE attribution to the drug, we limited analysis to CTs with a monotherapy investigational arm. We determined the most common symAEs based on the number of CTs reporting a specific symAE in ≥20% of patients. Results: Of 54 approvals identified, 31 lung cancer CTs (30 for NSCLC, 1 for SCLC) with monotherapy investigational arms were included, with AE data from 9,829 patients. Drug MOAs were classified broadly as growth pathway inhibitors (GPI) for 21 CTs (68%), immunotherapy (IO) for 9 CTs (29%), and cytotoxic chemotherapy for 1 CT (3%). Most common symAEs are presented in Table 1 (truncated to symAEs in ≥9 CTs, based on All CTs). In comparing MOAs, symAEs reported at ≥20% incidence in ≥5 GPI CTs but in no IO CTs included: diarrhea (76% of GPI CTs), edema (38%), nail toxicity/paronychia (29%), vomiting (29%), stomatitis (29%), and dry skin (24%). Fifteen other symAEs were reported at ≥20% incidence in ≥3 GPI CTs, but in no IO CTs [data not shown]. Conclusions: While there were several common symAEs across lung cancer CTs, our analysis using AE data in PIs of recently approved drugs showed important variability between CTs and broad GPI and IO groups, demonstrating that consideration of MOA and expected toxicity are important for ensuring relevant high frequency symAEs are included as PROs. Final selection of expected symAEs from a PRO item library is context dependent, requiring consideration of all available clinical data and patient input.[Table: see text]

Health-related quality of life (HRQoL) and pain outcomes for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who received abiraterone (abi) and olaparib (ola) versus (vs) abi and placebo (pbo) in the phase III PROpel trial.

5012 Background: PROpel (NCT03732820) met its primary endpoint and showed significantly prolonged investigator-assessed rPFS with abi + ola vs abi + pbo at primary analysis (data cut-off [DCO]: 7/30/21; median 24.8 vs 16.6 months (m); hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54–0.81; P<0.001). HRQoL (based on The Functional Assessment of Cancer Therapy-Prostate [FACT-P] total score) was not different when ola was combined with standard-of-care abi. We present data at the final prespecified overall survival (OS) DCO (10/12/22). Methods: PROpel is a randomised, double-blind trial in 1L mCRPC. Time to pain progression (TTPP) was based on the Brief Pain Inventory-Short Form (BPI-SF) Item 3 ‘worst pain in 24 hours’ and opiate analgesic use (analgesic quantification algorithm) score. Time to first symptomatic skeletal related event (SSRE) was time to use of therapy to prevent/relieve skeletal symptoms, new bone fractures, spinal compression or surgery on bone metastases. HRQoL was assessed by change from baseline (BL) in FACT-P total and subscale scores, BPI-SF pain severity, pain interference and worst pain score between arms using a mixed model for repeated measures. Results: At median follow-up of 33.6 m with abi + ola and 32.1 m with abi + pbo, 17.0% pts (68/399) in the abi + ola arm and 15.1% pts (60/397) in the abi + pbo arm had pain progression (PP) events. The % of pts who had not experienced PP with abi + ola vs abi + pbo was 76.9% vs 77.2% at 24 m and 70.7% vs 71.0% at 36 m. No meaningful difference in TTPP was observed (16% maturity, HR 1.06, 95% CI 0.75–1.50, P=0.75 [nominal], median not reached [NR] either arm). The % of pts who had not had a SSRE with abi + ola vs abi + pbo was 86.1% vs 82.2% at 24 m and 80.8 vs 78.5% at 36 m. No meaningful difference in time to SSRE was observed (12% maturity, HR 0.82, 95% CI 0.55–1.22, P=0.32 [nominal], median NR vs NR). Least-squares mean changes from BL between arms in BPI-SF pain severity (difference, −0.06; 95% CI −0.23–0.12), pain interference (difference, −0.12; 95% CI −0.31–0.06), worst pain score (difference, −0.12; 95% CI −0.35–0.11) and FACT-P total score (difference, −0.54; 95% CI –3.00–1.92) suggest no clinically meaningful difference in HRQoL with abi + ola vs abi + pbo. Least-squares mean change from BL values for FACT-P subscale scores were consistent with FACT-P total score result. Conclusions: PROpel demonstrated a significant delay in rPFS for pts receiving abi + ola vs abi + pbo. Most pts in the trial did not experience a PP event. Abi + ola showed no difference in HRQoL (assessed by FACT-P total and subscale scores, BPI-SF domain and worst pain scores) vs abi + pbo, suggesting pts can derive clinical benefit from abi + ola while maintaining a similar HRQoL compared with a current standard-of-care treatment. Clinical trial information: NCT03732820 .

Completion rates and trends of the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) across 14 oncology clinical trials.

1579 Background: With growing emphasis on patient-centered regulatory decision making, there is a greater need to incorporate the patient’s voice in oncology clinical trials. Regulatory guidelines outline core patient-reported outcomes (PROs) to include which can inform risk/benefit evaluation. Self-reported symptomatic adverse events (AE) form part of these core PROs, with the new 2023 draft FDA guidance acknowledging the benefits of including them to enhance the assessment of tolerability in early phase dose optimization trials. Given the clinical symptoms and disease burden in oncology, patient burden needs to be thoughtfully considered when incorporating PROs into trials. We assessed trends and feasibility of electronic data collection for symptomatic AEs by analyzing completion compliance and time to complete the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) across 14 oncology trials. Methods: All PRO-CTCAE were collected electronically on Clario Tablets. Operational data for completion status (completed or missed) and duration of time to complete the PRO-CTCAE in seconds was extracted. Completion rates over time were examined overall and for every 3-month interval (quarters Q1 to Q9+). The median was selected for analyses of time to complete to account for skewness. Results: The sample included 14 studies across Phase I-III trials across a range of cancers including multiple myeloma, mesothelioma and cancers of the lung, prostate, head/neck, gastric, breast, and ovary. Study durations were 24 weeks and up. The PRO-CTCAE form was completed 13,122 times and missed in 1,182 instances, giving an overall completion rate of 91.7%. On average, 25 questions (range 5-47) covered an average of 13 symptoms (range: 4-25). Completion rate was not associated with the number of questions asked or time since enrollment. The overall median time to complete the PRO-CTCAE was 82s (study-specific median range: 24s to 276s). Examining time to completion as a function of the number of questions revealed a significant positive association, such that each additional question added 5.2 seconds to the time it took to complete the assessment. Conclusions: Completion compliance was high for PRO-CTCAE and remained high regardless of study length and the number of questions included in the PRO-CTCAE form. This suggests that electronic PRO-CTCAE is a feasible solution for collecting self-reported symptomatic AEs. Although time to complete the form increased with the number of questions, results suggest that including a higher number of PRO-CTCAE questions does not negatively impact compliance rate. Our data showing high completion rates may also reflect the benefits of electronic PROs in reducing patient burden and enhancing data quality, as acknowledged by regulatory agencies.

Baseline symptom, health status, and health utilities in patients in early-phase clinical trials combining immune checkpoint blockade with other anticancer therapies.

12117 Background: The overall goal of our prospective and longitudinal study (NCI R01CA242565) is to examine the use of patient report to evaluate symptomatic adverse events associated with combination treatment including at least one immune checkpoint inhibitor in early-stage clinical trials. We present here the baseline symptom, health status and utilities in patients prior to trial start, and their association with clinical factors. Methods: Patients scheduled to start an early-phase trial of combination treatment with at least one immune checkpoint inhibitor and who had not received clinical trial-related treatment completed the validated MD Anderson Symptom Inventory - Immunotherapy (0-10, higher scores = worse severity) and the validated EuroQoL-5 dimensions questionnaire including a visual analog scale (EQ5D VAS) (0-100, higher scores = better health status) and health utility items (e.g., self-care, mobility). Clinical data were extracted from the EMR. Statistical tests included Spearman’s correlation coefficients. Results: At baseline prior to start of trial-related treatment, 38% of patients (N = 164; median age = 60 y; 52% male; 85% White; 17% ECOG PS 0, 89% ECOG PS 1, 3% ECOG PS 2) experienced at least 1 severe symptom (≥7 on 0-10 scale). The most frequent severe baseline symptoms were pain (21% of patients), fatigue (17%), disturbed sleep (15%), drowsiness (12%), lack of appetite (10%), distress (10%), and pain in the abdomen (10%). Less than 2% of pts experienced severe immunotherapy-specific symptoms of rash, fever/chills and swelling of the hands and feet at baseline. Moderate-severe symptom-related interference (≥4 on 0-10 scale) was worst for activity (40% of patients), work (38%), and enjoyment of life (30%). For the EQ5D health utility dimensions, patients reported the most problems with pain or discomfort (75%) and fewest problems with self-care (10%). Worse composite symptom severity (P = 0.013) and worse problems with activity (P = 0.001) and pain (P = 0.012) were associated with worse and higher ECOG PS. Worse symptom severity (-0.54, P < 0.001), symptom interference with activity- (-0.57, P < 0.001) and mood- (-0.42, P < 0.001) related functioning were associated inversely with superior health status. Worse symptom interference with activity-related functioning was linked with lower concurrent lymphocyte counts (P = 0.01), hemoglobin (P = 0.01) and serum albumin (P = 0.004) levels and higher platelet (P = 0.02) counts. Conclusions: Patients in early-phase trials that combine immunotherapy with other anti-cancer therapies may experience severe symptom burden and symptom interference with functioning, even at baseline prior to treatment start. Thus, it is important to baseline symptoms to fully understand the impact of combination treatments including checkpoint inhibitors in early-stage clinical trials.

Aspirin as a thromboprophylaxis agent after revision knee arthroplasty: A retrospective analysis

IntroductionTotal knee arthroplasty is a common and effective procedure. Although complication rates are low, certain complications such as venous thromboembolism are potentially serious. The optimal prophylactic agent and dosage after revision knee arthroplasty remains unclear. The main objective of this work was to study the efficacy and safety of aspirin as a thromboprophylaxis agent following revision knee arthroplasties. Patients and methodsA retrospective review of patients undergoing revision knee arthroplasty between 2013 and 2020at a University Teaching Hospital was undertaken. The primary outcome was the development of a symptomatic thromboembolic event requiring treatment within 90 days post-surgery. The secondary outcomes were adverse events associated with aspirin therapy: surgical site infection rate; incidence of major bleeding; readmission rate and mortality within 90 days post-surgery. Results490 patients were included. 374 (76.3%) received prophylactic aspirin (150 mg once daily for 28 days) and 75 (15.3%) patients received dalteparin for 28 days due to contraindication to aspirin use. Those already receiving other thromboprophylaxis agents for pre-existing comorbidities continued these after relevant medical consultation. The overall rates of venous thromboembolism and symptomatic DVT after aspirin prophylaxis were 0.6% (3/490) and 0.8% (3/374), respectively. VTE incidence did not significantly differ between those administered aspirin and other agents. No patient experienced major bleeding within 90 postoperative days. Only 2 of 490 (0.4%) patients had wound infection requiring readmission; neither received prophylactic aspirin. ConclusionExtended out-of-hospital thromboembolic prophylaxis with aspirin may be at least as effective as other agents in patients undergoing revision knee arthroplasty. Aspirin is safe, effective, and cheap compared with other agents.

Anticoagulation for post-discharge thromboprophylaxis after hospitalisation for Covid-19

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. Objective Evaluate the incidence of post-discharge thromboembolic and bleeding events and the role of thromboprophylaxis among COVID-19 patients. Methods We systematically searched PubMed, Embase and Cochrane databases, in March 2022, for interventional and observational studies. Results A total of 3 studies were included, providing a total 1569 patients, 325 in post-discharge anticoagulation and 1271 no discharge anticoagulation. In terms of outcomes assessed, both groups had similar symptomatic venous thrombotic events (pooled OR 0.43 [0.05, 3.79], P=0.14, I2=50%) and combined symptomatic and asymptomatic events pooled OR 0.63 [0.14, 2.79], P=0.54, I2=34%). Regarding bleeding events, no statistically significant difference was observed in all bleeding (major and non-major) events (pooled OR 2.85 [0.71, 11.43], P=0.14, I2=50%). Conclusion According to our meta-analysis, in patients hospitalized with COVID-19, extended thromboprophylaxis does not provide additional clinical benefit.

Transarterial chemoembolization followed by moderately hypofractionated radiotherapy in hepatocellular carcinoma: Long-term results of RTF3 regimen

PurposeIn early-stage hepatocellular carcinoma (HCC) patients merely fit for surgery, transarterial chemoembolization (TACE) achieve low long-term disease control. We evaluated the efficacy and safety of its combination with moderately hypofractionated radiotherapy (hRT) using RTF3 regimen. Material and methodsBetween 2006 and 2016, 61 consecutive patients treated in our single expert center for a Barcelona Clinic Liver Cancer (BCLC) A HCC by TACE followed by hRT 3Gy/fraction were retrospectively included. ResultsSixty of the 61 included presented Child-Pugh A cirrhosis (A5, n=41, 67.2%; A6: n=19, 31.1%). Fourteen patients (22.9%) were already treated for a HCC, mainly by radiofrequency (n=12). All patient received a TACE followed by 3Gy per fraction hRT. Mean radiation dose was 54Gy (range: 48–60). After a median follow-up of 118 months, median time-to-progression, progression-free survival (PFS) and overall survival (OS) was 21.3, 18.1, and 31.5 months, respectively. In univariate analysis, PFS was related to dose > 54Gy (HR: 2, P=0.036), and OS was correlated to Child-Pugh A6 or B7 (HR: 1.93, P=0.03) and overall hRT time (HR: 1.06, P=0.015). At progression, orthotopic liver transplantation was performed in 8 patients (13.1%). Severe symptomatic adverse events occurred in 12 patients (19.7%), mainly ascites (n=7). ConclusionIn BCLC-A Child-Pugh A HCC patients ineligible to surgery or thermoablation, TACE-hRT is a safe and effective treatment. Prospective studies are needed to compare this association with radioembolization, TACE-stereotactic radiotherapy, and systemic treatments combinations.

PO-02-004 INCIDENCE OF POST-ABLATION CEREBRAL LESIONS: A COMPARISON OF PULMONARY VEIN ISOLATION USING PULSED FIELD ABLATION VS. RADIOFREQUENCY ENERGY

Pulmonary vein isolation (PVI) utilizing pulsed electric fields is a novel, nonthermal ablative modality in which subsecond electric fields can ablate myocardial tissue with minimal effects on surrounding tissue for atrial fibrillation. Any ablation technique has a potential risk for periprocedural cerebral complications, but limited data are available on the incidence of symptomatic and silent cerebral events after pulsed field ablation (PFA). The purpose of this prospective observational study was to clarify the incidence of magnetic resonance imaging (MRI)-detected acute brain lesions after PFA or radiofrequency catheter ablation (RFCA) and possible differences in target value of activated clotting time (ACT). All paroxysmal atrial fibrillation (PAF) patients (n=28, mean age 62±11 years) underwent PVI. Direct oral anticoagulation was stopped 1 days before intervention and continued by the night after operation. Cerebral 3.0T MRI scanning using diffusion-weighted imaging and fluid–attenuated inversion recovery sequences was performed within 48 hours after ablation. There was no difference in baseline characteristics and ablation procedure between two arms except history of diabetes and coronary artery disease (Figure 1A). The MRI depicted acute cerebral infarctions in 5 patients (35.7%, 1.8 lesions per case), either symptomatic (n=3, 60%) or asymptomatic (n=2, 40%) in the PFA group, statistically significant difference between the group treated by RFCA (0%, p=0.004). No patients developed cerebral hemorrhage. The lower intraprocedural ACT target than the guidelines recommendation may not increase the acute brain events. However, we may achieve higher ACTs than RFCA during PFA procedure.

244P Eribulin in Chinese advanced breast cancer patients intolerant to first-/second-line taxane-based therapy: The patient-reported outcomes

Taxane-based therapy is commonly applied in patients with advanced breast cancer (BC). It is often accompanied with serious symptomatic adverse events (AEs) which can deteriorate patients’ quality of life (QoL). Eribulin is a non-taxane microtubule inhibitor with respect to less symptomatic AEs and prolonged overall survival. Here, we report the analysis of QoL based on PRO before and after initiating Eribulin in patients with advanced BC intolerant to taxane-based therapy. Patients with advanced BC intolerant to taxane-based first/second-line therapy were screened from multi-centers in China. The PRO was measured by the well-validated taxane-based EORTC QLQ-C30 questionnaire at baseline and at 2 cycles after initialing Eribulin treatment. The questionnaire includes scales for four symptomatic AEs of microtubule therapy (peripheral neurotoxicity, nausea/vomiting, pain, insomnia) and a global health status for QoL (GHS/QoL). Of the 333 enrolled patients, 152 with triple-negative BC, 122 with HR+/HER2- BC, and 59 with HER2+ BC. Significant improvement in all symptomatic AEs and the GHS/QoL (P<0.001) was observed among all patients and the subgroups of the pathological type. Respectively, there were 116 and 73 patients received only combined chemotherapy and mono-chemotherapy both before (taxane-based) and 2 cycles after (Eribulin-based) the treatment. Subgroup analysis showed all symptoms and the GHS/QoL were significantly improved in both treatment settings (P<0.001). The measurements for PRO indicated great improvement on QoL after switching to Eribulin in patients with advanced BC who previously received taxane-based therapy, irrespective of the pathological type and the combination of other chemotherapy regimens. Eribulin is reasonable to be applied in patients with advanced BC intolerant to taxane-based therapy.Table: 244PDimensionsBaselinePost-treatmentPPeripheral neurotoxicity57.9±20.334.3±15.6<0.001Nausea/vomiting58.0±20.734.5±16.3<0.001Insomnia58.2±20.235.1±19.1<0.001Pain56.1±20.035.9±15.5<0.001Global health status33.7±22.558.3±29.4<0.001 Open table in a new tab

Comparing a novel Catfish flow restoration device and the Solitaire stent retriever for thrombectomy revascularisation in emergent largevessel occlusion stroke: a prospective randomised controlled study

BackgroundThe Catfish stent retriever is a newly developed mechanical thrombectomy device for rapid recanalisation in emergent large vessel occlusion (ELVO) stroke. The current trial aimed to assess whether the Catfish...

Thromboembolic Events During Weightbearing vs Nonweightbearing Accelerated Rehabilitation Protocols for Complete Achilles Tendon Ruptures.

Achilles tendon rupture can be treated nonoperatively with functional rehabilitation. However, prolonged immobilization has associated risk of venous thromboembolism (VTE). Early weightbearing may reduce VTE risk, and this was introduced to our rehabilitation protocol. We investigated the prevalence of symptomatic VTE events before and after the introduction of the early weightbearing protocol. Adults with ultrasonography-confirmed complete tendo-Achilles ruptures between January 2017 and June 2020 were included. Preprotocol, patients were instructed to not weightbear for 4 weeks. In 2018, immediate weightbearing was introduced to the treatment protocol. All patients in both cohorts were given low-molecular-weight heparin for 4 weeks. Patients with symptomatic VTE events were investigated with duplex ultrasonographic scan or chest computed tomography. Two independent anonymized examiners collected data from electronic records. Rates of symptomatic VTEs were compared. A total of 296 patients were included. Sixty-nine patients were managed with the nonweightbearing protocol, and 227 patients were managed with the early-weightbearing protocol. Two patients in each group developed deep vein thrombosis and 1 developed pulmonary embolism in the early-weightbearing group. Rates of VTEs were lower in the early-weightbearing group (1.3% vs 2.9%) but did not reach statistical significance (P = .33). In this cohort we found that symptomatic VTE after nonoperatively treated Achilles tendon rupture was uncommon. We did not demonstrate a reduction in symptomatic VTE between our early weightbearing and nonweightbearing rehabilitation protocols. We believe a larger study may help clarify whether early weightbearing is beneficial in VTE reduction. Level III, retrospective cohort study.

MP10-07 24-HOUR URINE CORRELATES TO INCREASING STONE BURDEN IN CYSTINURIC PATIENTS

You have accessJournal of UrologyCME1 Apr 2023MP10-07 24-HOUR URINE CORRELATES TO INCREASING STONE BURDEN IN CYSTINURIC PATIENTS Ukrit Rompsaithong, Heiko Yang, Wilson Sui, Rei Unno, David Bayne, Justin Ahn, Marshall Stoller, and Thomas Chi Ukrit RompsaithongUkrit Rompsaithong More articles by this author , Heiko YangHeiko Yang More articles by this author , Wilson SuiWilson Sui More articles by this author , Rei UnnoRei Unno More articles by this author , David BayneDavid Bayne More articles by this author , Justin AhnJustin Ahn More articles by this author , Marshall StollerMarshall Stoller More articles by this author , and Thomas ChiThomas Chi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003225.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Stone growth and recurrence in cystinuric patients is a challenging issue to manage. Controlling 24-hour urine parameters may be the key to preventing kidney stone formation in this population. This study aimed to determine the association between 24-hour urine and stone burden in cystinuric patients. METHODS: We conducted a retrospective study on consecutive patients diagnosed with cystinuria from the Registry for Stones of the Kidney and Ureter (ReSKU) between 2017 and 2022. Patients were classified as having either stable or increased stone burden during clinic visits. An increasing stone burden was defined as an increasing stone number or growth ≥ 3 mm from prior imaging. 24-hour urine specimens were collected every 4-6 months. Clinical characteristics, stone-related symptoms and surgeries, and the average of the 24-hour urine parameters from all visits were compared between the two groups. We performed a longitudinal analysis using the generalized estimating equation to determine the marginal model for the 24-hour urine and increasing stone burden at each visit. The chi-square goodness-of-fit test was applied to evaluate the model. RESULTS: There were 20 patients in the increased stone burden and 24 in the stable group. The median initial stone burden in the increased and stable groups was 13 and 4.5 mm, respectively. Fifty symptomatic stone events were observed in the increased burden group and 16 for the stable group (p=0.014). There were 28 surgical events in the increased burden group and 5 in the stable group (p=0.007). We did not detect a significant difference in the average 24-hour cystine capacity between the two groups (p=0.053). However, in longitudinal analysis, the marginal model demonstrated that urine citrate ≤ 500 mg/d (OR 5.57, 95% CI 2.47–12.53) and a negative value of cystine capacity (OR 4.70, 95% CI 1.48–14.91) were significantly correlated with increasing stone burden at each visit (Table 1). CONCLUSIONS: In cystinuric patients, the 24-hour urine citrate and cystine capacity were highly associated with an increasing stone burden. In addition to general stone prevention advice, maintaining the values of these parameters within the normal range may be important to prevent the formation of kidney stones in this population. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e116 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ukrit Rompsaithong More articles by this author Heiko Yang More articles by this author Wilson Sui More articles by this author Rei Unno More articles by this author David Bayne More articles by this author Justin Ahn More articles by this author Marshall Stoller More articles by this author Thomas Chi More articles by this author Expand All Advertisement PDF downloadLoading ...

MP10-09 THE REAL-WORLD EFFECTIVENESS OF PREVENTIVE PHARMACOLOGICAL THERAPY

You have accessJournal of UrologyCME1 Apr 2023MP10-09 THE REAL-WORLD EFFECTIVENESS OF PREVENTIVE PHARMACOLOGICAL THERAPY John Hollingsworth, Mary Oerline, Ryan Hsi, Joseph Crivelli, Noah Krampe, John Asplin, and Vahakn Shahinian John HollingsworthJohn Hollingsworth More articles by this author , Mary OerlineMary Oerline More articles by this author , Ryan HsiRyan Hsi More articles by this author , Joseph CrivelliJoseph Crivelli More articles by this author , Noah KrampeNoah Krampe More articles by this author , John AsplinJohn Asplin More articles by this author , and Vahakn ShahinianVahakn Shahinian More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003225.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Most efficacy results supporting preventive pharmacological therapy (PPT) used to reduce kidney stone recurrence are based on composite outcomes largely driven by imaging findings. Because these findings are surrogates for things about which patients and their clinicians care, we conducted an observational study to determine whether PPT use led to fewer symptomatic kidney stone events, requiring emergency department (ED) visit, hospitalization, or surgery. METHODS: We identified a cohort of Medicare enrollees who had a 24-hour urine collection processed by a large central laboratory (2011-2016). We linked their clinical data with their pharmacy and medical claims. Among the subset with at least one biochemistry abnormality, we distinguished those who were prescribed guideline-concordant PPT (i.e., thiazides for hypercalciuria, alkali citrate therapy for hypocitraturia or low urine pH, uric acid lowering agents for hyperuricosuria) from those who were not. We differentiated between adherent and nonadherent PPT users based on the proportion of days covered method. We fit multivariate Cox models to estimate the hazard of a symptomatic stone event as a function of PPT use. RESULTS: In total, 7,230 patients met criteria, 55% of whom had hypocitraturia. Sixty-nine percent were untreated, and 31% were prescribed concordant PPT (alkali citrate therapy was used in 66%). Compared to untreated patients, those prescribed concordant therapy and adhered to their medication had a 38% lower hazard of ED visit (P<0.01) and a 46% lower hazard of hospitalization (P=0.04). Put differently, compared to untreated patients, concordant/adherent patients had lower 2-year predicted probabilities of ED visit (4.6% vs. 7.3%) and hospitalization (1.1% vs. 2.0%) (P<0.05 for each comparison). A similar pattern was noted for stone directed surgery but was not significant (Figure 1). CONCLUSIONS: Our findings help strengthen the evidence base for PPT use, providing real-world data on its clinical effectiveness. Source of Funding: National Institute of Diabetes and Digestive and Kidney Diseases R01DK121709 (to J.H.) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e117 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Hollingsworth More articles by this author Mary Oerline More articles by this author Ryan Hsi More articles by this author Joseph Crivelli More articles by this author Noah Krampe More articles by this author John Asplin More articles by this author Vahakn Shahinian More articles by this author Expand All Advertisement PDF downloadLoading ...

PD34-06 MACHINE LEARNING PREDICTION OF SYMPTOMATIC KIDNEY STONE RECURRENCE USING 24-HOUR URINE DATA AND ELECTRONIC HEALTH RECORD DERIVED FEATURES

You have accessJournal of UrologyCME1 Apr 2023PD34-06 MACHINE LEARNING PREDICTION OF SYMPTOMATIC KIDNEY STONE RECURRENCE USING 24-HOUR URINE DATA AND ELECTRONIC HEALTH RECORD DERIVED FEATURES Patrick Doyle, Wu Gong, Ryan Hsi, and Nicholas Kavoussi Patrick DoylePatrick Doyle More articles by this author , Wu GongWu Gong More articles by this author , Ryan HsiRyan Hsi More articles by this author , and Nicholas KavoussiNicholas Kavoussi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003327.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While 24-hour (24H) urine studies offer insight into the metabolic profile of recurrent stone formers, their use towards predicting stone recurrence events is limited. We sought to assess the prediction of symptomatic kidney stone recurrence episodes using machine learning models. METHODS: We trained three separate machine learning (ML) models (least absolute shrinkage and selection operator regression [LASSO], random forest [RF], and gradient boosted decision tree [XGBoost] to predict symptomatic kidney stone recurrences from electronic health-record (EHR) derived features and 24H urine data. ML models were compared to logistic regression [LR]. We evaluated all patients with an index stone treatment at our institution and a 24H urine test performed (N=1231). A manual, retrospective review was performed to evaluate for a symptomatic stone event, defined as pain, acute kidney injury or recurrent infections attributed to a kidney stone identified in the clinic or the emergency department, or for any stone requiring surgical treatment. We evaluated performance using area under the receiver operating curve (AUC-ROC) and identified predictors for each model. RESULTS: The 2- and 5- year symptomatic stone recurrence rates were 25% and 31%, respectively. The LASSO model (Figure 1) performed best for symptomatic stone recurrence prediction (2-yr AUC: 0.62, 5-yr AUC: 0.63). The other models demonstrated modest overall performance at 2- and 5-years: LR (0.585, 0.618), RF (0.570, 0.608), and XGBoost (0.580, 0.621). Top prioritized features among all models included age, diabetic status, stone composition and urine pH. Additionally, the LASSO model prioritized BMI and history of gout for prediction. CONCLUSIONS: Throughout our cohorts, ML models demonstrated comparable results to that of LR, with the LASSO model outperforming all other models. Further model optimization should incorporate 24H urine testing and EHR-derived features. Source of Funding: Vanderbilt CTSA Grant UL1TR002243 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e922 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Patrick Doyle More articles by this author Wu Gong More articles by this author Ryan Hsi More articles by this author Nicholas Kavoussi More articles by this author Expand All Advertisement PDF downloadLoading ...

Exploring differences in symptomatic adverse events assessment between nurses and physicians in the clinical trial setting

A cross-sectional study was performed at Hebei Medical University Fourth Affiliated Hospital from April to July 2020 to explore the difference and consistency between nurses and physicians in terms of symptomatic adverse event (AE) assessment. The Common Terminology Criteria for Adverse Events (CTCAE) was utilized by nurses and physicians to assess patients’ symptomatic AEs. Patients self-reported their AEs utilizing the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Four nurses and three physicians were enrolled to assess patients’ symptomatic AEs. Given the same AEs, nurses tended to detect more AEs than physicians, and the differences were statistically significant (P < 0.001). The toxicity grade reported by nurses and physicians showed no difference for all AEs, except for fatigue (χ2 = 5.083, P = 0.024). The agreement between nurses and patients was highest compared to the agreement between nurses versus physicians and physicians versus patients. The differences in symptomatic AE assessment can lead to different symptom management. Thus, it is important to establish a collaborative approach between nurses and physicians to ensure continuity in care delivery.

Reliability and validity of PRO-CTCAE® daily reporting with a 24-hour recall period

PurposeThe standard recall period for the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE®) is the past 7 days, but there are contexts where a 24-hour recall may be desirable. The purpose of this analysis was to investigate the reliability and validity of a subset of PRO-CTCAE items captured using a 24-hour recall.Methods27 PRO-CTCAE items representing 14 symptomatic adverse events (AEs) were collected using both a 24-hour recall (24 h) and the standard 7 day recall (7d) in a sample of patients receiving active cancer treatment (n = 113). Using data captured with a PRO-CTCAE-24h on days 6 and 7, and 20 and 21, we computed intra-class correlation coefficients (ICC); an ICC ≥ 0.70 was interpreted as demonstrating high test–retest reliability. Correlations between PRO-CTCAE-24h items on day 7 and conceptually relevant EORTC QLQ-C30 domains were examined. In responsiveness analysis, patients were deemed changed if they had a one-point or greater change in the corresponding PRO-CTCAE-7d item (from week 0 to week 1).ResultsPRO-CTCAE-24h captured on two consecutive days demonstrated that 21 of 27 items (78%) had ICCs ≥ 0.70 (day 6/7 median ICC 0.76), (day 20/21 median ICC 0.84). Median correlation between attributes within a common AE was 0.75, and the median correlation between conceptually relevant EORTC QLQ-C30 domains and PRO-CTCAE-24 h items captured on day 7 was 0.44. In the analysis of responsiveness to change, the median standardized response mean (SRM) for patients with improvement was − 0.52 and that for patients with worsening was 0.71.ConclusionA 24-hour recall period for PRO-CTCAE items has acceptable measurement properties and can inform day-to-day variations in symptomatic AEs when daily PRO-CTCAE administration is implemented in a clinical trial.

Prescribing patterns of thromboprophylaxis post-bariatric surgeries: no additional benefits of extended prophylaxis

BackgroundVenous thromboembolism is one of the critical complications of bariatric surgeries resulting in life-threatening outcomes. The benefits and duration of appropriate thromboprophylaxis in the morbidly obese patients stay unclear. The study aims to compare the benefits of in-hospital thromboprophylaxis versus extended thromboprophylaxis post-bariatric surgery among a cohort with a high prevalence of morbid obesity.ResultsA retrospective observational cohort study was conducted on 229 morbidly obese patients who had undergone bariatric surgery in a tertiary care teaching hospital in Saudi Arabia. Upon discharge, the patients were split either to receive no thromboprophylaxis or enoxaparin 40 mg once or twice daily for 14–21 days post-discharge. Primary outcomes were the clinical difference between the study groups in the percentage of patients who developed a symptomatic venous thromboembolic event during postoperative hospitalization or after discharge. Among patients who received no thromboprophylaxis (n = 119), no one developed a venous thromboembolic event, while, in the extended prophylaxis group (n = 110), 1.82% developed a non-fatal one (P = 0.23). Additionally, no significant difference in percentages of bleeding events occurred in both groups (p = 0.054).ConclusionsThe incidence of venous thromboembolism and bleeding events that occurred with extended thromboprophylaxis were deemed comparable and non-significant to the conventional in-hospital thromboprophylaxis. However, portal thrombosis stays an enigmatic complication despite its documented sparsity in literature.

CAPItello-280: A phase III study of capivasertib and docetaxel versus placebo and docetaxel in metastatic castration-resistant prostate cancer.

TPS287 Background: Docetaxel is the standard first-line chemotherapy for patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease progressed on an androgen receptor-targeted agent (ARTA; typically, abiraterone, enzalutamide, apalutamide, or darolutamide). However, most patients develop chemotherapy resistance, and median overall survival (OS) remains under 3 years. Preclinical studies have associated phosphoinositide 3-kinase (PI3K)/protein kinase (AKT)/phosphatase and tensin homolog (PTEN) pathway signaling with the development of mCRPC and with resistance to taxane chemotherapy. The ProCAID Phase II trial (NCT02121639) examined whether adding capivasertib, a potent, selective inhibitor of all three AKT isoforms (AKT1/2/3), to docetaxel chemotherapy improved clinical outcomes. Although no difference in the primary endpoint (composite progression-free survival [PFS]) was detected, OS, a secondary endpoint, was extended in the capivasertib plus docetaxel treatment group. A subsequent follow-up analysis at advanced maturity suggested that the OS benefit in ProCAID was restricted to patients who had received prior treatment with an ARTA. Methods: CAPItello-280 is a Phase III study to confirm the efficacy and safety of capivasertib in combination with docetaxel compared with placebo and docetaxel in patients with mCRPC who have not previously received chemotherapy for mCRPC, but whose disease has progressed despite treatment with an ARTA in any setting. Approximately 790 patients will be randomized 1:1 to receive either capivasertib or matching placebo (320 mg orally, twice daily [BD], 4 days on, 3 days off) plus docetaxel (75 mg/m2 on day 1 of each 21-day cycle for 6–10 cycles, with prednisone or prednisolone 5 mg BD or 10 mg once daily) with a background of continued androgen deprivation therapy until disease progression, unacceptable toxicity, death, or withdrawal of consent. The primary endpoint is OS; secondary endpoints include radiographic PFS, time to pain progression, symptomatic skeletal events, safety, and tolerability. Recruitment began in March 2022 and is planned at 207 study sites in 20 countries, including the USA, Canada, Europe, South America, and Asia-Pacific. Clinical trial information: NCT05348577 .