Patient-reported Adverse Events Research Articles

과체중 또는 비만인 소아청소년의 체중 감량을 위한 가미태음조위탕의 임상활용: 다기관, 후향적 차트 리뷰

Objectives The purpose of this study is to evaluate the effects of Gamitaeeumjowi-tang on the weight changes and adverse events in overweight or obese prediatric-adolescents. Methods A multicenter and retrospective chart review was performed on 425 overweight and obese pediatric-adolescents who took Gamitaeeumjowi-tang from May 2022 to November 2023. Outcomes were measured in terms of total weight loss and weight loss percentage, as well as the percentage of patients who lost at least 5% and 10% of their baseline weight. Patient-reported adverse events were collected and analyzed for frequency of occurrence, and whether they were serious enough to require discontinuation. Results A total of 47 patients were included, with a mean (±standard deviation) age of 15.00±1.90 years, weight of 85.59 ±19.24 kg, and body mass index of 30.81±4.98 kg/m2; 74.47% were female. The mean (±standard deviation) weight loss was 8.84±4.93 kg and the mean weight loss rate was 10.23±4.28%. The percentage of patients who lost at least 5% and 10% of their baseline weight was 95.74% and 54.20% respectively. No serious adverse events were reported. Conclusions Gamitaeeumjowi-tang was shown to help pediatric-adolescents who were overweight or obese to lose weight, and no serious adverse events were associated with discontinuation of the medication. Further well-designed clinical studies are recommended.

Apical Suspension Repair for Vaginal Vault Prolapse: A Randomized Clinical Trial.

The optimal surgical repair of vaginal vault prolapse after hysterectomy remains undetermined. To compare the efficacy and safety of 3 surgical approaches for vaginal vault prolapse after hysterectomy. This was a multisite, 3-arm, superiority and noninferiority randomized clinical trial. Outcomes were assessed biannually up to 60 months, until the last participant reached 36 months of follow-up. Settings included 9 clinical sites in the US National Institute of Child Health and Human Development (NICHD) Pelvic Floor Disorders Network. Between February 2016 and April 2019, women with symptomatic vaginal vault prolapse after hysterectomy who desired surgical correction were randomized. Data were analyzed from November 2022 to January 2023. Mesh-augmented (either abdominally [sacrocolpopexy] or through a vaginal incision [transvaginal mesh]) vs transvaginal native tissue repair. The primary outcome was time until composite treatment failure (including retreatment for prolapse, prolapse beyond the hymen, or prolapse symptoms) evaluated with survival models. Secondary outcomes included patient-reported symptom-specific results, objective measures, and adverse events. Of 376 randomized participants (mean [SD] age, 66.1 [8.7] years), 360 (96%) had surgery, and 296 (82%) completed follow-up. Adjusted 36-month failure incidence was 28% (95% CI, 20%-37%) for sacrocolpopexy, 29% (95% CI, 21%-38%) for transvaginal mesh, and 43% (95% CI, 35%-53%) for native tissue repair. Sacrocolpopexy was found to be superior to native tissue repair (adjusted hazard ratio [aHR], 0.57; 99% CI, 0.33-0.98; P = .01). Transvaginal mesh was not statistically superior to native tissue after adjustment for multiple comparisons (aHR, 0.60; 99% CI, 0.34-1.03; P = .02) but was noninferior to sacrocolpopexy (aHR, 1.05; 97% CI, 0-1.65; P = .01). All 3 surgeries resulted in sustained benefits in subjective outcomes. Mesh exposure rates were low (4 of 120 [3%] for sacrocolpopexy and 6 of 115 [5%] for transvaginal mesh) as were the rates of dyspareunia. Among participants undergoing apical repair for vaginal vault prolapse, sacrocolpopexy and transvaginal mesh resulted in similar composite failure rates at study completion; both had lower failure rates than native tissue repair, although only sacrocolpopexy met a statistically significant difference. Low rates of mesh complications and adverse events corroborated the overall safety of each approach. ClinicalTrials.gov Identifier: NCT02676973.

Adverse Event Reporting in Cancer Clinical Trials: Incorporating Patient-Reported Methods. A Systematic Scoping Review.

The history of clinical trials is fraught with unethical practices. Since 1945, robust frameworks have evolved to standardise the collection and reporting of safety data, most notably, the Common Terminology Criteria for Adverse Events (CTCAE) from the National Cancer Institute; used by investigators to report side effects experienced by participants. As medicine moves into the patient-centred model, interest has been growing to collect data on adverse events directly from participants (patient-reported adverse events). The aim of this systematic scoping review was to investigate the inclusion of patient-reported adverse event data within safety/tolerability analyses and explore the collection and reporting of patient-reported adverse event data. A database search was undertaken and the Covidence platform was used to manage the review; results were analysed descriptively. Sixty-eight studies were included in the analysis. An increase in the number of studies that incorporate patient-reported adverse event data was seen by year. Seventy instruments were used for the collection of patient-reported adverse event data with recall period, mode, frequency and site of administration varying across studies; the duration of data collection ranged from 28 days to 6 years. Frequently, information on these details was omitted from publications. The number of instruments used by studies to collect patient-reported adverse event data ranged from one to seven instruments. Despite growing calls for the inclusion of patient-reported adverse events, this has not yet translated into published reports. The collection and reporting of these data were variable and conducted using instruments that were not designed for purpose. To address these inconsistencies, standardisation of data collection and reporting using a purpose-built validated instrument is required.

Patient-Reported Adverse Events and Early Treatment Discontinuation Among Patients With Multiple Myeloma

There is substantial interest in capturing cancer treatment tolerability from the patient's perspective using patient-reported outcomes (PROs). To examine whether a PRO question, item 5 from the Functional Assessment of Cancer Therapy-General General Physical Wellbeing Scale (GP5), was associated with early treatment discontinuation (ETD) due to adverse events. This prospective survey study was conducted from February to April 2023. Among participants in the ECOG-ACRIN E1A11 trial (a phase 3, parallel design trial conducted between 2013 and 2019), patients with newly diagnosed multiple myeloma were randomized to receive bortezomib (VRd) or carfilzomib (KRd) plus lenalidomide and dexamethasone as induction therapy. The GP5 item was administered at baseline (pretreatment) and at 1 month, 2.8 months, and 5.5 months postbaseline. Eligible participants included patients with newly diagnosed multiple myeloma treated at community oncology practices or academic medical centers in the US. GP5 response options were "very much," "quite a bit," "somewhat," "a little bit," and "not at all." Responses at each assessment while undergoing treatment (1 month, 2.8 months, and 5.5 months) were categorized as high adverse event bother (ie, "very much," and "quite a bit") and low adverse event bother (ie, "somewhat," "a little bit," or "not at all"). In addition, change from baseline to each assessment while undergoing treatment was calculated and categorized as worsening by 1 response category and 2 or more response categories. ETD due to adverse events (yes vs no) was analyzed using logistic regression adjusting for treatment group, performance status, gender, race, and disease stage. Of the 1087 participants in the original trial, 1058 (mean [SD] age 64 [9] years; 531 receiving VrD [50.2%]; 527 receiving KRd [49.8%]) responded to item GP5 and were included in the secondary analysis. A small proportion (142 patients [13.4%]) discontinued treatment early due to AEs. For those with high adverse-effect bother, GP5 while undergoing treatment was associated with ETD at 1 month (adjusted odds ratio [aOR], 2.20; 95% CI, 1.25-3.89), 2.8 months (aOR, 3.41; 95% CI, 2.01-5.80), and 5.5 months (aOR, 4.66; 95% CI, 1.69-12.83). Worsening by 2 or more response categories on the GP5 was associated with ETD at 2.8 months (aOR, 3.02; 95% CI, 1.64-5.54) and 5.5 months (aOR, 5.49; 95% CI, 1.45-20.76). In this survey study of the E1A11 trial, worse GP5 response was associated with ETD. These findings suggest that simple assessment of adverse-effect bother while receiving treatment is an efficient way to indicate treatment tolerability and ETD risk.

Discontinuation of Fumaric Acid Esters is Affected by Depressive Symptomatology: A Retrospective Analysis.

Fumaric acid esters (FAEs) remain a widespread therapy option for moderate-to-severe psoriasis. However, drug survival of FAEs is limited by adverse events (AEs) or inadequate treatment response. Depressive disturbances are highly prevalent in psoriasis patients and are hypothesized to be associated with the reporting of AEs and therapy discontinuation. This study's aim was to analyze whether psoriasis patients with comorbid depressive symptomatology are more likely to discontinue treatment with FAEs due to AEs and/or inadequate treatment response. Data were retrospectively extracted from the records of patients starting therapy with FAEs in the Department of Dermatology, University Hospital Essen, Germany between 2017 and 2022, covering the first 52 weeks of treatment. Psoriasis severity and depressive symptomatology, as well as AEs and therapy discontinuation, were analyzed. Psoriasis patients (N = 95, 47.37% female) with depressive symptomatology (42.11%) were more likely to discontinue therapy due to patient-reported AEs, while the total number of reported AEs was not associated with depression. The results support the hypothesis that among psoriasis patients with depressive symptoms, the associated introspection and somatization may result in increased sensitivity for AEs and thus in quicker therapy discontinuation. In these patients, the occurrence of nocebo effects should be minimized, e.g. by special communication techniques.

A multi-center cross-sectional study of Chinese Herbal Medicine-Drug adverse reactions using active surveillance in Singapore’s Traditional Chinese Medicine clinics

BackgroundThis study aimed to investigate the rates and causality of patient-reported adverse events (AEs) associated with concomitant Chinese Herbal Medicine (CHM) and Western Medicine prescription drug (WMPD) consumption through active surveillance in Singapore’s Traditional Chinese Medicine (TCM) clinics.MethodsA cross-sectional study was conducted at five TCM clinics across Singapore from 8th May till 8th July 2023. Patients were screened to determine rates of CHM and WMPD consumption, and then interviewed if an AE was reported. An expert committee assessed the AE reports to determine causality. Along with descriptive statistics, odds ratios were calculated to determine AE occurrence likelihoods for patients who consumed both CHM and WMPD compared to CHM consumption alone.Results1028 patients were screened and 62.65% of them reported concurrent CHM-WMPD consumption. Patients who consumed CHM and WMPD were 3.65 times more likely to experience an AE as compared to CHM consumption alone. 18 AE reports were adjudicated, with most AEs deemed unlikely due to CHM consumption.ConclusionsA large proportion of patients consumed CHM and WMPD concurrently, thus increasing their risk of experiencing AEs compared to those consuming CHM only. Active surveillance is applicable for detecting AEs, collecting data for causality assessment, and analysis.

Prostatic Artery Embolisation Versus Transurethral Resection of the Prostate for Benign Prostatic Obstruction: 5-year Outcomes of a Randomised, Open-label, Noninferiority Trial

Background and objectiveProstatic artery embolisation (PAE) and transurethral resection of the prostate (TURP) are two of the surgical options for treatment of lower urinary tract symptoms/benign prostatic obstruction (LUTS/BPO). Our aim was to compare the efficacy and safety of PAE and TURP for LUTS/BPO treatment at long-term follow-up. MethodsWe conducted a randomised, open-label, single-centre trial at a Swiss tertiary care centre. The main outcome was the change in International Prostate Symptom Score (IPSS) after PAE versus TURP. Secondary outcomes included patient-reported outcomes, functional measures, and adverse events assessed at baseline and at 3, 6, 12, 24, and 60 mo. Between-group differences in the change from baseline to 5 yr were tested using two-sided Mann-Whitney and t tests. Key findings and limitationsOf the 103 patients with refractory LUTS/BPO who were randomised between 2014 and 2017, 18/48 who underwent PAE and 38/51 who underwent TURP reached the 60-mo follow-up visit. The mean reduction in IPSS from baseline to 5 yr was −7.78 points after PAE and −11.57 points after TURP (difference 3.79 points, 95% confidence interval [CI] −0.66 to 8.24; p = 0.092). TURP was superior for most patient-reported secondary outcomes except for erectile function. At 5 yr, PAE was less effective than TURP regarding objective parameters, such as the improvement in maximum urinary flow rate (3.59 vs 9.30 ml/s, difference −5.71, 95% CI −10.72 to −0.70; p = 0. 027) and reduction in postvoid residual volume (27.81 vs 219.97 ml; difference 192.15, 95% CI 83.79–300.51; p = 0.001). Conclusions and clinical implicationsThe improvement in LUTS/BPO at 5 yr after PAE was inferior to that achieved with TURP. The limitations of PAE should be considered during patient selection and counselling. Patient summaryIn this study, we show the long-term results of prostate artery embolisation (PAE) in comparison to transurethral resection of the prostate (TURP) for the treatment of benign prostate enlargement causing urinary symptoms. PAE shows good long-term results in properly selected patients, although the improvements are less pronounced than with TURP.This trial is registered on ClinicalTrials.gov as NCT02054013.

Switching to Doravirine in cART-Experienced Patients: An Effective and Highly Tolerated Option With Substantial Cost Savings.

Doravirine is a non-nucleoside reverse transcriptase inhibitor with demonstrated efficacy as a third agent in treatment-naive and treatment-experienced people living with HIV (PLWH) in registration studies. However, limited real-world data are available. By searching electronic health care records, PLWH using doravirine-based regimens were selected with at least 1 year of follow-up after their first prescription. All stable PLWH who were switched to a doravirine-based regimen were included in the analysis. The primary outcome was the durability of a doravirine-based regimen 1 year after prescription. Reasons for stopping were also collected. Secondary outcomes for PLWH continuing a doravirine-based regimen after 1 year were routine laboratory assessment, body mass index, and differences in medication costs compared with their previous cART. A total of 687 patients (92% men) were included from September 2019 to August 2022: 97.7% switched to doravirine/tenofovir/lamivudine (DOR/TDF/3TC). After 1 year, 94/687 (13.6%) PLWH stopped this therapy. The main reason for discontinuation was patient-reported adverse events in 70/687 (10.2%). Medical reasons for discontinuation included increased alanine tranaminase levels in 6/687 (0.9%), decreased estimated glomerular filtration rate in 3/687 (0.4%), and precautions after diagnosis of osteoporosis in 2/687 (0.3%) patients. Virologic failure occurred in 4/687 cases (0.6%), and 1 case demonstrated resistance mutations. The secondary outcomes demonstrated a statistically significant increase in alanine tranaminase levels and decrease in LDL-c levels. The switch to a doravirine-based regimen in the Netherlands reduced medication costs by 27%. This study demonstrated that switching to a doravirine-based regimen, mostly DOR/TDF/3TC, was highly effective and generally well tolerated, with substantial cost savings.

P1072 Upadacitinib appears effective in inducing clinical, biochemical, endoscopic and histologic improvements in previously treatment refractory Ulcerative Colitis

Abstract Background Upadacitinib is a novel, oral agent which acts by inhibition of JAK signaling. It has proven efficacy in large-scale, randomised trials for the treatment of UC. We report our real-world experience of upadacitinib as induction therapy in a single centre study of UC patients, including patients who were refractory or intolerant of other advanced therapies. Methods We performed a retrospective analysis of outcomes in patients who were commenced on upadacitinib for UC at a tertiary IBD centre between October 2022 to October 2023. The parameters used to assess disease activity were the Simple Clinical Colitis Activity Index (SCCAI), faecal calprotectin (FCP), Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Nancy Histological Index (NHI). Clinical response was defined as a reduction of SCCAI of ≥3 points, clinical remission as SCCAI of ≤2, biochemical remission as FC<150ug/g. Endoscopic remission was defined as UCEIS 0-1 and histological remission as NHI 0-1. Medical records were reviewed for patient-reported adverse events. Wilcoxon matched-pairs signed rank test was used to compare pre- and post-treatment continuous variables. Results 42 patients were started on 45mg once daily upadacitinib over this period. 20 were female, the mean age was 39. 31 had left sided disease, 8 had pancolitis. 39 (93%) patients had prior experience of advanced therapy and 22 (52%) had ≥2 prior therapies. At baseline, mean SCCAI was 7 (1-15), and mean FCP 1328 (42-6810) μg/g. Baseline endoscopy demonstrated a mean UCEIS of 5 (3-7) and baseline histology a mean NHI of 3 (1-4). At the 6-week follow up, paired data on clinical and biochemical responses were available in 23 and 27 patients respectively, showing an improvement to a mean SCCAI of 3 (p=0.0004) and mean FCP of 491 μg/g (p=0.002). 16 (70%) achieved clinical response, 14 (61%) were in clinical remission. 15 (56%) had a reduction in FCP to <150 μg/g. Endoscopic reevaluation took place after a minimum of 12 weeks on treatment. Paired endoscopic outcomes in 20 patients demonstrated an improvement of UCEIS to a mean of 1 (p<0.0001), with 16 (80%) patients in endoscopic remission. Week 12 histology showed improvement to a mean NHI of 2 (p<0.0001, n=19), with 9 (47%) patients achieving histological remission. 6 (14%) patients were non-responders. 3 required a colectomy, 2 necessitated a switch in medical therapy, 1 remained on extended induction. 3 patients (7%) reported facial acne as an adverse event, no others were reported. Conclusion Upadacitinib appears effective at inducing significant clinical, biochemical, endoscopic and histological improvements within 12 weeks, amongst a real-world cohort of patients with moderate-to-severe UC that has proved refractory to other advanced therapies.

Acute epistaxis management by hemostatic agents a systematic review

Background: When compared to nasal packing, the data shows that hemostatic medications are more successful in controlling acute epistaxis. A comprehensive analysis was conducted to assess the effectiveness of topical hemostats in the treatment of epistaxis. Method: Four databases were searched thoroughly for literature. Only admissible observational studies were included. Information retrieved from eight studies included the following: country, rate of short-term and 30-day hemostatic control, patient-reported outcome measures, adverse events, sample size, intervention, treating method, and length of stay in hospital. Results: Eight papers were included in the review when it reached the second stage and satisfied the qualifying requirements. A total of 268 individuals were involved in three cohort and five case series investigations; 232 of them received absorbable intranasal medications. Two investigations on oxidized cellulose compounds and 5 studies on agents that promote the common coagulation pathway were presented. While oxidized regenerated cellulose was inserted endoscopically on the bleeding site in one trial and sutured to the nasal septum in another study, the earlier medicines were applied intranasally. Successful short-term hemostasis was attained in 80% to 100% of patients in 7 out of 8 trials. Patients treated with oxidized regenerated cellulose had considerably lower pain scores than those treated with nasal packing. There were no negative effects linked to the use of intranasal agents in any of the investigations. Conclusion: When compared to nasal packing, the data shows that hemostatic medications are more successful in controlling acute epistaxis.

Safety of COVID-19 Vaccination in Patients With Breast Cancer: Cross-Sectional Study in China.

The widespread use of vaccines against the novel coronavirus disease (COVID-19) has become one of the most effective means to establish a population immune barrier. Patients with cancer are vulnerable to COVID-19 infection, adverse events, and high mortality, and should be the focus of epidemic prevention and treatment. However, real-world data on the safety of vaccines for patients with breast cancer are still scarce. This study aims to compare the safety of COVID-19 vaccines between patients vaccinated before or after being diagnosed with breast cancer. Patients with breast cancer who sought medical advice from October 2021 to December 2021 were screened. Those who received COVID-19 vaccines were enrolled in this study to analyze the safety of the vaccines. The primary outcome was patient-reported adverse events (AEs). All events after vaccine injection were retrospectively documented from the patients. A total of 15,455 patients with breast cancer from 41 hospitals in 20 provinces in China were screened, and 5766 patients who received COVID-19 vaccines were enrolled. Of those enrolled, 45.1% (n=2599) of patients received vaccines before breast cancer diagnosis, 41.3% (n=2379) were vaccinated after diagnosis, and 13.6% (n=784) did not known the accurate date of vaccination or cancer diagnosis. Among the patients vaccinated after diagnosis, 85.4% (n=2032) were vaccinated 1 year after cancer diagnosis and 95.4% (n=2270) were vaccinated during early-stage cancer. Of all 5766 vaccinated patients, 93.9% (n=5415) received an inactivated vaccine, 3.7% (n=213) received a recombinant subunit vaccine, and 2.4% (n=138) received other vaccines, including adenovirus and mRNA vaccines. In the first injection of vaccines, 24.4% (n=10, 95% CI 11.2-37.5) of patients who received an adenovirus vaccine reported AEs, compared to only 12.5% (n=677, 95% CI 11.6-13.4) of those who received an inactivated vaccine. Patients with metastatic breast cancer reported the highest incidence of AEs (n=18, 16.5%, 95% CI 9.5-23.5). Following the second injection, patients who received an inactivated vaccine (n=464, 8.7%, 95% CI 8.0-9.5) and those who received a recombinant vaccine (n=25, 8.7%, 95% CI 5.5-12.0) reported the same incidence of AEs. No significant differences in patient-reported AEs were found between the healthy population and patients with breast cancer (16.4% vs 16.9%, respectively); the most common AEs were local pain (11.1% vs 9.1%, respectively), fatigue (5.5% vs 6.3%, respectively), and muscle soreness (2.3% vs 3.6%, respectively). The type of vaccine and time window of vaccination had little impact on patient-reported AEs. Compared with patients vaccinated before breast cancer diagnosis, there were no significant differences in patient-reported AEs in the patients vaccinated after diagnosis. Thus, it is safe for patients with breast cancer, especially for those in the early stage, to receive COVID-19 vaccines. Chinese Clinical Trial Registry ChiCTR2200055509; https://tinyurl.com/33zzj882.

Adverse events from topical corticosteroid use in chronic hand eczema — Findings from the Danish Skin Cohort

BackgroundTopical corticosteroids (TCS) are used to treat most patients with chronic hand eczema (CHE), but knowledge about TCS-related adverse events in CHE is limited. ObjectivesTo investigate patient-reported adverse events to TCS in CHE patients. MethodsData on adverse events related to TCS use in CHE patients were analyzed from the Danish Skin Cohort; a prospective survey of a hospital cohort. We assessed patients’ knowledge about TCS use and adverse event risks, and preference of TCS vs. a non-steroidal topical alternative. ResultsOf 724 adults with CHE (64.0% women; mean age 57.5 [standard deviation 12.8] years), 64.1% reported skin atrophy, 41.4% cracks/fissures, 23.9% bleeding, 45.9% pain/stinging sensation, 40.0% reduced hand dexterity, and 40.2% worsening of CHE signs or symptoms from using TCS. We observed CHE-severity-dependent associations (all groups; p<0.0001). Most patients (76.4%) would prefer a non-steroidal option, 10.9% were neutral/indifferent, and 12.7% would prefer TCS for CHE. The median numerical rating scale-score (ranging from 0-10) was 10 (interquartile range 6-10) for preferring a non-steroidal topical treatment. LimitationsDifferences across TCS formulations were unexplored. ConclusionTCS-related cutaneous adverse events were common. There is a desire from patients for novel steroid-free topical alternatives for CHE treatment.

Abstract C067: Patient-reported baseline symptomatic adverse events in early-phase trials of combination treatments with immune checkpoint blockade, and their association with concurrent global health status, health utilities and clinical factors

Abstract Background: We examined patient-reported symptomatic adverse events (AEs) prior to trial start, and their association with concurrent global health status, health utilities and clinical factors in patients enrolled in early-phase trials combining immune checkpoint blockade with other anticancer therapy. Methods: Within 2 weeks prior to trial start, patients consented to begin an early phase trial of a combination treatment including at least 1 immune checkpoint inhibitor completed validated items of the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measuring severity and/or frequency of selected symptomatic adverse events (score range: 0-4, higher scores=worse severity/increased frequency) in the last 7 days. Patients also completed the validated EuroQoL-5 dimensions questionnaire measuring global health status (score range: 0-100, higher scores=better health status) and health utilities (e.g., problems with self-care, mobility). Clinical data were extracted from the EMR. Statistical tests included χ2 and Spearman’s correlations. Results: 206 patients (median age=59y; 54% male; 84% White) from 54 early-phase trials participated. Prevalent moderate-to-severe symptomatic AEs at baseline prior to trial start included fatigue (43% of patients), decreased sexual interest (24%), appetite loss (21%), dry mouth (17%) and shortness of breath (16%). Frequent-to-almost constant general pain, abdominal pain and nausea were reported by 27%, 13% and 5% of patients, respectively. Worse fatigue, and more frequent general pain and abdominal pain were associated with diminished global health status (P&amp;lt;0.001 for each). Worse fatigue was also linked to problems with mobility, self-care, anxiety, and usual activities (P&amp;lt;0.001 for each), and to lower concurrent lymphocyte counts (P=0.002), hemoglobin (P=0.002) and serum albumin (P=0.029). Loss of appetite was related to lower lymphocytes (P=0.005), platelets (P=0.011), and serum albumin (P=0.021) and higher neutrophils (P=023). Dyspnea was linked to lower albumin (P=0.014). Loss of sexual interest was associated with worse pain (P&amp;lt;0.001), anxiety (P=0.011), and problems with usual activities (P&amp;lt;0.001), lower serum albumin (0.005), lymphocytes (P=0.010), hemoglobin (0.019), and creatinine (P=0.03) and higher neutrophils (P=0.009) and white blood cells (0.023). Conclusions: Patients in early-phase trials of combination treatments with an immune checkpoint inhibitor may report considerable moderate-to-severe symptomatic AEs, even at baseline. Patient-reported symptomatic AEs impact global health status, health utilities, and a constellation of clinical factors. Thus, it is critical in early-phase trials to baseline symptomatic AEs including from the patient’s perspective in order to more completely assess the impact of combination treatments that include a checkpoint inhibitor. Citation Format: Goldy C. George, Sarina A Piha-Paul, Siqing Fu, Ecaterina Dumbrava, Vivek Subbiah, Apostolia Tsimberidou, George Blumenschein, Shubham Pant, Grace Appleton, Laila Noor, Jordi Rodon Ahnert, Timothy Yap, Funda Meric-Bernstam, Charles Cleeland, Tito Mendoza, David S Hong. Patient-reported baseline symptomatic adverse events in early-phase trials of combination treatments with immune checkpoint blockade, and their association with concurrent global health status, health utilities and clinical factors [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C067.

AHOD2131: A Randomized Phase 3 Response-Adapted Trial Comparing Standard Therapy with Immuno-Oncology Therapy for Children and Adults with Newly Diagnosed Stage I and II Classic Hodgkin Lymphoma

Background: Chemotherapy in combination with radiotherapy (RT) is the standard for early-stage (ES) Hodgkin lymphoma (cHL). Despite high cure rates (12-year overall survival (OS) &amp;gt;93%), there is room to improve short and long-term outcomes for children and adults with ES cHL. Incorporation of immunotherapy (IO) into front line treatment of ES cHL is an opportunity to both improve progression-free survival (PFS) and maintain OS, while minimizing long-term morbidity and mortality by reducing exposure to RT and high-dose chemotherapy. Study Design and Methods: HL leaders of the NCTN groups, expert HL researchers and physicians, and representatives from the Cancer Therapy Evaluation Program (CTEP) formed a working group in April 2020 with the goals of harmonizing treatment approaches for ES cHL across pediatric and adult patients and reaching consensus regarding the optimal study design for incorporating IO therapy into frontline treatment. Study champions identified from each of the North American cooperative groups [Children's Oncology Group (COG), SWOG, ECOG-ACRIN, Alliance, NRG] and experts in imaging, radiation oncology, lymphoma biology and patient-reported outcomes (PROs) were included. The resulting COG-led clinical trial, AHOD2131, represents the largest ES cHL trial in the history of North American cooperative groups and the first to enroll patients across the age continuum. AHOD2131 (NCT05675410; Figure) is a randomized, phase 3 trial enrolling patients ages 5 to 60 years with newly diagnosed, previously untreated stage I and II cHL and will investigate the addition of the CD30-antibody drug conjugate brentuximab vedotin (Bv) with PD-1 blockade (nivolumab) compared to standard chemotherapy +/- RT. Since the April 2023 activation, 97 North American sites have activated the trial, and 21 participants have enrolled. Target enrollment is 1875 patients over 5 years of accrual, for an estimated 1782 eligible and evaluable patients. The primary objective is to compare the 3-year PFS of patients with ES cHL treated through a response-adapted, superiority design with either standard therapy or with an IO approach (BV + nivolumab). All patients will be stratified as favorable or unfavorable based on disease risk features at enrollment. Based on initial response assessment by PET/CT (via central review) after 2 cycles of ABVD, patients were classified to PET2 positive (SER, defined as 5 Point Score 4 or 5, ~15% of patients) and PET negative (RER). Those who are PET positive will receive involved site RT (ISRT). The SER and RER patients will be randomized to standard chemotherapy vs. IO therapy respectively. In addition to the primary outcome of PFS, there are 11 secondary and 10 exploratory aims. The secondary aims focus on OS, PFS of subgroups, and event-free survival at 12 years, physician-reported treatment-related adverse event (AE) rates, patient-reported AE using pediatric and adult versions of Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and the capture of representation by self-report and the use of electronic PRO data collections. The exploratory aims include the assessment of imaging central review as compared to local institutional review and the use of convolutional neural networks through artificial-intelligence machine learning. The study will examine the effect of therapy on acute and long-term adverse effects including health-related quality of life (HRQoL) and OS for up to 12 years. The study will compare patient self-report and provider AE reports and evaluate the associations of self-reported race/ethnicity and social determinants of health (SDOH)and post-progression/post-relapse OS. AHOD2131 strengthens the effort between the North American cooperative groups to conduct collaborative clinical trials and aims to harmonize an improved standard of care for ES cHL across the age continuum.

The design, implementation, and impact of an automated patient-reported outcome data collection and adverse event surveillance tool: a randomized trial

BackgroundIncorporating patient-reported outcome measures into routine clinical care can improve the patient experience, increase engagement, and establish a structured method for gathering adverse event (AE) data. Systematically collecting this information on a large scale can also inform new solutions for removing treatment barriers like medication nonadherence. This study evaluated whether implementing a patient-reported outcome data collection and adverse event surveillance tool would result in greater treatment continuation for patients receiving care on a telehealth platform.MethodsWe used iterative plan-study-do-act cycles to evaluate how this data collection and surveillance tool—a short prompt for patients to provide information on treatment satisfaction and side effects—impacted treatment continuation, the outcome of interest. We tested two cycles in n = 2,000 patients receiving care for erectile dysfunction on a telehealth platform as a randomized controlled trial, and accounted for incidents where true randomization was not possible during implementation. The first cycle tested the tool alone, while the second cycle tested the tool in conjunction with a messaging template system that provided standardized side effect counseling.ResultsCompared to patients in the control group, patients in the intervention group were more likely to refill their prescription over the duration of the study period (75% vs. 71%, Kaplan Meier log-rank test, p = 0.04). Receiving standardized counseling as part of the AE response system was positively associated with treatment continuation (p = 0.0005).ConclusionsPrompting patients to report side effects and outcomes outside of routine clinical visits has the potential to improve quality of care in virtual treatment.Trial registrationThis trial has been retrospectively registered as a clinical trial (ClinicalTrials.gov Identifier: NCT05895539, registered June 8, 2023).

Use of patient-reported outcomes (PRO) data to complement exposure–response analysis in early clinical cancer drug development

BackgroundThis proof-of-concept retrospective case study investigated whether patient-reported outcomes (PRO) instruments, designed to capture symptomatic adverse event data, could identity a known exposure–response (ER) relationship for safety characterized in an original FDA analysis of an approved anti-cancer agent. PRO instruments have been designed to uniquely quantify the tolerability aspects of exposure-associated symptomatic adverse events. We explored whether standard ER analyses of clinician-reported safety data for symptomatic adverse events could be complemented by ER analysis using PRO data that capture and quantify the tolerability aspects of these same symptomatic adverse events.MethodsExposure-associated adverse event data for diarrhea were analyzed in parallel in 120 patients enrolled in a clinical trial using physician reported Common Terminology Criteria for Adverse Events (CTCAE) and patient-reported symptomatic adverse event data captured by the National Cancer Institute’s (NCI) PRO Common Terminology Criteria for Adverse Events (PRO-CTCAE) instrument. Comparative ER analyses of diarrhea were conducted using the same dataset. Results from the CTCAE and PRO-CTCAE ER analyses were assessed for consistency with the ER relationship for diarrhea established in the original NDA using a 750-patient dataset. The analysis was limited to the 120-patient subset with parallel CTCAE and PRO-CTCAE assessments.ResultsWithin the same 120-patient dataset, ER analysis using dense, longitudinal PRO-CTCAE-derived data was sensitive to identify the known ER relationship for diarrhea, whereas the standard CTCAE based ER analysis was not.ConclusionsER analysis using PRO assessed symptomatic adverse event data may be a sensitive tool to complement traditional ER analysis. Improved identification of relationships for safety, by including quantification of the tolerability aspect of symptomatic adverse events using PRO instruments, may be useful to improve the sensitivity of exposure response analysis to support early clinical trial dosage optimization strategies, where decision making occurs within limited small patient datasets.

Image-free handheld robotic-assisted technology improved the accuracy of implant positioning compared to conventional instrumentation in patients undergoing simultaneous bilateral total knee arthroplasty, without additional benefits in improvement of clinical outcomes

PurposeThe purpose of this study was to compare the clinical and radiological outcomes in patients who underwent simultaneous bilateral total knee arthroplasty (SB-TKA) using either robotic-assisted TKA (RA-TKA) or conventional TKA (C-TKA).MethodsIncluded were the patients who underwent SB-TKA between January 2018 and January 2020 and had a minimum follow-up of 2 years. Of 151 patients included, 117 patients were operated using an image-free handheld robotic sculpting system (RA-TKA group) and 34 patients operated using conventional instrumentation (C-TKA group). The key outcomes noted were multiple patient-reported outcomes (PROs), adverse events, and radiological outcomes. Two investigators independently measured the radiological outcomes on pre- and post-operative radiographs in coronal plane (medial proximal tibial angle [MPTA] and anatomic lateral distal femoral angle [aLDFA]) and sagittal plane (posterior tibial slope [PTS] and posterior condylar offset [PCO]). The chi-square test was used to examine categorical variables. Student’s t test was used to analyze the continuous variables.ResultsPatients in both groups were similar in baseline characteristics (gender, body mass index, incidence of comorbidities, and length of hospital stay) except that RA-TKA group patients younger (66.7 ± 8.9 vs 70.4 ± 10.5, P = 0.037) than C-TKA group. The operative time was longer in RA-TKA group as compared to C-TKA (189.3 ± 37.1 vs 175.0 ± 28.2, P = 0.040). The final PROs at each were similar between the two groups (P > 0.05). The values of PROs at final follow-up in RA-TKA compared to C-TKA were VAS pain (0.4 ± 0.9 vs 0.4 ± 0.5), KOOS-JR (89.3 ± 5.8 vs 87.1 ± 5.3), and physical (55.9 ± 2.8 vs 55.4 ± 3.2), mental (61.1 ± 4.4 vs 60.2 ± 4.7) component of VR-12 scores, and KSS satisfaction (37.5 ± 1.1 vs 37.1 ± 2.2) (all P > 0.50 or non-significant [n.s.]). While one patient in RA-TKA required revision of femoral component for peri-prosthetic fracture, none of the patient in conventional group were revised (0.85% vs 0%, P = n.s.). The proportion of patients with outliers in RA-TKA group was lower for aLDFA (2.6% vs 22.1%, P < 0.01) and PTS (0% vs 35%, P < 0.01).ConclusionThis comparative study in patients undergoing SB-TKA found reduction of outliers in femoral and tibial implant positioning with RA-TKA as compared to C-TKA. There were no differences in both groups for pain, function, and satisfaction at a minimum of 2 years of follow-up.Level of evidenceIII Therapeutic Study.

Proximal ROw carpectOmy versus four-corner Fusion (PROOF-trial) for osteoarthritis of the wrist: study protocol for multi-institutional double-blinded randomized controlled trial

BackgroundScapholunate advanced collapse (SLAC) and scaphoid non-union advanced collapse (SNAC) are common types of wrist osteoarthritis (OA). Non-operative treatment consists of pain medication, splinting, and avoiding activities that induce pain. However, in case a course of conservative treatment is unsuccessful, operative treatment is needed. The two most conventional operative approaches for SLAC/SNAC OA are four-corner arthrodesis (FCA) and proximal row carpectomy (PRC). Although FCA is the gold-standard operative technique and may lead to superior grip strength, the evident benefit of PRC is that it obviates any need for hardware removal and controlling for bony union. To date, no high-quality randomized controlled trial comparing FCA and PRC exists. As clinical outcomes seem comparable, a trial that assesses patient-reported outcomes, adverse events, and secondary operations may guide clinical decision making between these two procedures. Thus, the aim of this multi-institutional double-blind randomized controlled trial is to study whether PRC is non-inferior to FCA in treating SLAC/SNAC OA. We hypothesize that PRC is non-inferior to FCA with lower economic expanses.MethodsThe trial is designed as a randomized, controlled, patient- and outcome-assessor blinded multicenter, two-armed 1:1 non-inferiority trial. Patients with SLAC/SNAC-induced wrist pain meeting trial inclusion criteria will undergo wrist arthroscopy to further assess eligibility. Each patient eligible for the trial will be randomly assigned to undergo either FCA or PRC. The primary endpoint of this study is the Patient Rated Wrist Evaluation (PRWE) at 1-year after FCA versus PRC. Secondary outcomes include Quick-Disabilities of the Arm, Shoulder and Hand, EQ-5D-5L, pain, grip strength, wrist active range of motion, radiographic evaluation, and adverse events. Trial design, methods, and statistical analysis plan will be presented here.DiscussionWe present an RCT design comparing FCA vs PRC for SLAC/SNAC-induced OA. The results of this trial will assist in decision making when planning surgery for SLAC/SNAC.Trial registrationClinicalTrials.gov NCT04260165. Registered February 7, 2020.

Cancer Patients’ Experience of a Patient-Safe Pathway Is Associated with Health Literacy and Support from Relatives: A Cross-Sectional Survey

Introduction. The aim was to assess the impact of cancer patients’ health literacy (HL) on their experience of patient safety. Furthermore, we investigated whether support from relatives affected cancer patients’ experiences of patient safety. Methods. A cross-sectional study was conducted using questionnaire data from the Danish National Cancer Patient Survey 2017 among Danish cancer patients (n = 5,389) and sociodemographic characteristic data from national registries. Results. A low level of HL is associated with increased patient safety errors among cancer patients regarding patient-reported adverse events and an experience of inadequate information. Results also showed increased odds of patient safety risks among patients with no support from relatives. Conclusion. Having a low level of HL or no support from relatives has a negative impact on patient safety. Focusing on improvements related to cancer patients’ HL and supportive network may increase patients experiencing a high quality and safe health care system and reduce inequalities and inequity in the cancer pathway.

Durability of Functional Outcomes After MRI-Guided Transurethral Ultrasound Ablation of the Prostate

Long-term data on functional outcomes after MRI-guided transurethral ultrasound ablation (TULSA) are limited. We assess the 5-year post-TULSA durability of outcomes for patient-reported genitourinary function, bowel function, and adverse events in 30 patients with primary, localized prostate cancer treated with TULSA across 3 centers. Patients received a conservative treatment plan in a phase 1 study designed to assess safety and feasibility. Follow-up visits took place at 1, 3, 6, 12 months, and biannually up to 5 years. Median (interquartile range) age at baseline was 69 (67-71) years. Erectile dysfunction (International Index of Erectile Function [IIEF] ≤17) was prevalent at baseline, with a mean (95% confidence interval [CI]) score of 16 (12-19), decreasing to 9 (4-14) at 5 years. At the 5-year visit, 71% of men who attempted intercourse in the recall period reported preservation of IIEF Q2 ≥2 erections sufficient for penetration. The mean (95% CI) International Prostate Symptom Score (IPSS) decreased from 9.0 (7.0-11) to 7.1 (5.0-9.1) from baseline to 5 years; IPSS-quality of life, maximum urinary flow rate, and post-void residual urine were stable or improved. Maintenance of bowel function and urinary continence was 100%. There was no new attributable serious or severe adverse event from 1 to 5 years. With a durably favorable safety profile, TULSA has the potential to treat cancer conservatively while simultaneously alleviating lower urinary tract symptoms. Data from larger studies are pending.