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EPR25-120: Second Primary Malignancy in Multiple Myeloma Survivors: A Population-Based Retrospective Cohort Study
No full textVerdiperstat in Amyotrophic Lateral Sclerosis: Results From the Randomized HEALEY ALS Platform Trial
No full textIMPORTANCE: Myeloperoxidase is one of the most abundant peroxidase enzymes in activated myeloid cells. Myeloperoxidase inhibitors may have a clinical benefit in amyotrophic lateral sclerosis (ALS) by slowing neurodegeneration via reduced neuroinflammation and oxidative stress.
OBJECTIVE: To determine the safety, tolerability, and efficacy of verdiperstat, a selective myeloperoxidase inhibitor, in ALS.
DESIGN SETTINGS AND PARTICIPANTS: Verdiperstat was tested as a regimen of the HEALEY ALS Platform Trial, a multicenter, double-blind, perpetual platform design, randomized clinical trial, with sharing of trial infrastructure and placebo data across multiple regimens. The study was conducted at 54 ALS referral centers across the US from July 2020 to April 2022. Adult participants with a diagnosis of clinically possible, probable, laboratory-supported probable, or definite ALS defined by the revised El Escorial criteria were randomized to verdiperstat or regimen-specific placebo. An additional group of participants concurrently randomized to placebo from other regimens was included in the analyses.
INTERVENTIONS: Eligible participants were randomized in a 3:1 ratio to receive oral verdiperstat, 600 mg, twice daily or matching placebo for a planned placebo-controlled duration of 24 weeks.
MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was change from baseline through week 24 in disease severity, as measured by a joint model of ALS Functional Rating Scale-Revised and survival, with the treatment effect quantified by the disease rate ratio (DRR), with DRR less than 1 indicating a slowing in disease progression of verdiperstat relative to placebo.
RESULTS: A total of 167 participants (mean [SD] age, 58.5 [11.4] years; 59 [35.3%] female; 108 [64.6%] male) were randomized to either verdiperstat (126 [75.4%]) or to placebo (41 [25.6%]). Among the participants randomized to the verdiperstat regimen, 130 (78%) completed the trial. The estimated DRR was 0.98 (95% credible interval, 0.77-1.24; posterior probability = 0.57 for slowing of disease progression [DRR \u3c 1]). Verdiperstat was estimated to slow progression by 2% vs placebo (95% credible interval, -23% to 24%; posterior probability 0.57). Verdiperstat was overall safe and well tolerated. Common adverse events in the verdiperstat group were nausea, insomnia, and elevated thyrotropin levels.
CONCLUSIONS AND RELEVANCE: Results demonstrate that treatment with verdiperstat was unlikely to alter disease progression in ALS.
TRIAL REGISTRATION: Clinical Trial Identifiers: NCT04297683 and NCT04436510
Protocol for a multisite, parallel-group, randomized clinical trial comparing a brief tele-cognitive behavioral therapy intervention (BRIGHT) with attention control for the reduction of body image-related distress among head and neck cancer survivors
No full textOne in four head and neck cancer (HNC) survivors experience clinically significant body image distress (BID), a devastating psychosocial morbidity that adversely affects quality of life. To date, effective interventions for these patients are lacking. BRIGHT (Building a Renewed ImaGe after Head and neck cancer Treatment), a brief cognitive behavioral treatment (CBT), has shown potential efficacy as a novel treatment paradigm for HNC survivors with BID. The primary objective of this randomized clinical trial (RCT) is to test the hypothesis that BRIGHT improves BID among HNC survivors relative to an Attention Control (AC) intervention. In this multisite RCT, N = 180 HNC survivors with BID will be randomized 1:1 to six weeks of BRIGHT or AC of dose and delivery-matched survivorship education. Outcomes are assessed at baseline and 2, 3, 6, and 9-months post-randomization. The primary endpoint is the IMAGE-HN (Inventory to Measure and Assess imaGe disturbancE-Head and Neck) score, a validated patient-reported outcome of HNC-related BID. Secondary endpoints include the HN Shame and Stigma Scale, the PROMIS SF v1.0-Depression 8a, Anxiety 8a, and Ability to Participate in Social Activities 8a, the Beck Scale for Suicidal Ideation, and the EORTC QLQ-HN35 Trouble with Social Eating and Trouble with Social Contact subscales. The trial will also evaluate whether the effect of BRIGHT on BID is mediated through improvements in automatic thinking and body image coping strategies. Findings from this multisite RCT will provide a rigorous test of the efficacy of BRIGHT as the first evidence-based strategy to manage BID among HNC survivors. TRIAL REGISTRATION ID: NCT05442957
Multi-institutional study on image quality for a novel CBCT solution on O-ring linac
No full textINTRODUCTION: This work presents a multi-institutional study on image quality provided by a novel cone beam computed tomography (CBCT). The main goal is to investigate the consistency of imaging performance across multiple institutions.
METHODS: Phantoms for measuring relative electron density (RED) and image quality were sent to six institutions for imaging on Ethos and Halcyon units equipped with HyperSight CBCT. The imaging protocols included tube potential from 100 to 140 kVp and exposure from 80 to 800 mAs. Imaging performance was evaluated with regard to RED versus Hounsfield units (HU), uniformity, contrast-to-noise ratio (CNR), slice thickness, circular symmetry, modulation transfer function (MTF), and spatial resolution.
RESULTS: Among all institutions, some variability was observed among institutions in the RED-to-HU relationship, especially for RED values greater than 1, although no outliers were found (|z-score| \u3c 2 in all cases). In this range, RED/HU slopes were 475 ± 25 10(-6) RED/HU at 100kVp, 505 ± 20 10(-6) RED/HU at 125kVp, and 550 ± 20 10(-6) RED/HU at 140kVp. Radial uniformity ranged from 1 to 7 HU, depending on protocol. Circular symmetry for two points 50 mm apart showed consistency within one-pixel dimension. Integral nonuniformity was between 1 and 10, with no difference observed between vertical and horizontal dimensions. Contrast rods with 1% gave CNR = 0.5, 1 and 2 for 100(88), 125(176), and 140(528) in kVp(mAs), and contrast rods with 0.5% had CNR = 0.2, 0.4 and 0.8 for 100(88), 125(176), and 140(528) in kVp(mAs). Spatial resolution given by MTF at 10% and 50% yielded values of 0.55 ± 0.01 mm(-1) and 0.35 ± 0.02 mm(-1), respectively.
CONCLUSIONS: This multi-institutional analysis of CBCT imaging performance showed consistency in radial uniformity, circular symmetry, integral nonuniformity, contrast, and spatial resolution. Some variability was seen in the RED-to-HU relationship for RED \u3e 1 depending on exposure. More data from different institutions would be necessary to establish more robust statistical metrics, which ensure quality parameters
Gastrointestinal Bleeds Are a Rare Event After Total Hip and Knee Arthroplasty
No full textBACKGROUND: The presence of a gastrointestinal (GI) bleed after elective total hip arthroplasty and total knee arthroplasty (THA and TKA, respectively) is concerning and a potential cause for hospital readmission. This condition can also be life-threatening if not identified and treated appropriately. Many surgeons use multimodal analgesia protocols to limit opioid use and also use venous thromboembolism prophylaxis. Aspirin and nonsteroidal anti-inflammatories, often a component of these protocols, reduce prostaglandin production necessary for gastric mucosal protection. The authors hypothesized that the incidence of a GI bleed after TKA and THA would be rare.
METHODS: This was a retrospective review of 8,207 patients 18 years or older who had THA or TKA at a single institution between 2015 and 2022. Patients who were evaluated for GI bleed within 90 days postoperatively were identified. Perioperative risks were analyzed based on demographics, procedures, and other risk factors.
RESULTS: The incidence of GI bleeding was 0.33%, in which 27 patients sustained a GI bleed in 8,206 THA and TKA cases. The average days from the time of surgery for GI bleed were 18.6 days. There was a difference in the occurrence of GI bleeds by age, with increasing age being positively associated with an increase in the odds of GI bleeds, odds ratio = 1.15 (95% CI [confidence interval]: 1.09 to 1.21), P \u3c 0.01. No statistical difference was found based on other demographic data, procedure type, or site.
CONCLUSIONS: This institution\u27s perioperative protocol, including the use of nonsteroidal anti-inflammatories and aspirin for TKA and THA, had a low incidence of GI bleeds in the perioperative setting at our community hospital over the course of 2015 to 2022
Durability of Active Surveillance for Localized Renal Masses: 3-year Outcomes in the Michigan Urological Surgery Improvement Collaborative
No full textBACKGROUND AND OBJECTIVE: In Michigan, around 50% of patients with localized renal masses of ≤7 cm (cT1RMs) are managed without immediate intervention, contradicting previous reports indicating active surveillance (AS) rates of \u3c 10-20%. Questions remain regarding the durability of AS when applied so broadly. We evaluated the oncologic outcomes of patients at 1, 2, and 3 yr after the initiation of AS, including survival and delayed intervention rates, hypothesizing that these will be comparable to prior reports.
METHODS: Between May 2017 and September 2023, data regarding 2161 (52% of 4178) patients with cT1RMs who initiated AS at Michigan Urological Surgery Improvement Collaborative (MUSIC) practices were reviewed. Factors associated with staying on AS were analyzed. Overall survival and the cumulative incidence of treatment were assessed using the Kaplan-Meier method.
KEY FINDINGS AND LIMITATIONS: In total, 2161 patients from 21 practices initiated AS, including 51% with tumors of ≤ 2 cm, 26% with tumors of 2.1-3.0 cm, and 24% with tumors of 3.1-7.0 cm. At 36 mo, overall survival was 90%, with metastasis and death from kidney cancer in only one patient who refused intervention. The cumulative incidence rates of treatment were 6%, 11%, and 13% at 1, 2, and 3 yr, respectively, with 9.6% for ≤ 2 cm, 16% for 2.1-3.0 cm, and 18% for \u3e3 cm tumors at 3 yr. Limitations include the study\u27s retrospective review of prospectively enrolled data limiting conclusions beyond 3 yr of follow-up.
CONCLUSIONS AND CLINICAL IMPLICATIONS: MUSIC practices initiate AS for \u3e50% of patients with 13% incidence of delayed intervention and \u3c 1% incidence of metastasis within 3 yr, indicating that AS is a safe and durable option for many patients with cT1RMs. Further investigations into imaging protocols and longer-term outcomes of AS are warranted.
PATIENT SUMMARY: In Michigan, most patients diagnosed with localized renal masses of \u3c 4 cm and some with tumors up to 7 cm in size elect active surveillance (AS), with a 13% cumulative incidence of undergoing intervention within 3 yr of detection. At 3 yr after initiating AS, the cohort had 90% overall survival and \u3e99% cancer-specific survival, indicating that AS is a safe and durable strategy
Single bladder instillation of gemcitabine versus mitomycin C after minimally invasive radical nephroureterectomy: A propensity-score match analysis from the ROBUUST 2.0 collaborative group
No full textOBJECTIVE: Radical nephroureterectomy (RNU) is considered the standard of care for patients with high-risk upper tract urothelial carcinoma. Current literature reveals a deficit in direct comparative studies evaluating the efficacy of different chemotherapeutic agents administered in single postoperative instillation following RNU. The primary aim of this study was to compare the bladder recurrence (BR) rates between patients receiving a single instillation of mitomycin C (MMC) versus gemcitabine (Gem) after RNU.
METHODS: The ROBUUST (ROBotic surgery for Upper tract Urothelial cancer STudy) 2.0 is an international, multicenter registry that aggregates data on patients who have undergone curative surgery for upper tract urothelial carcinoma across participating centers from January 2015 to December 2022. Data including primary baseline variables of the patients, characteristics of the tumors, surgical management, and definitive histopathological characterizations were collected and stratified based on the type of postoperative bladder instillation: MMC (the MMC group) and Gem (the Gem group). We selected variables correlated with our primary outcome to conduct a propensity-score match analysis.
RESULTS: One hundred patients in the MMC group were matched 1:1 with 100 patients in the Gem group. At 36 months of follow-up, 30 patients in the MMC group and 39 patients in the Gem group experienced BR, representing recurrence rates of 30% and 39%, respectively (p=0.2). The Cox proportional hazards model comparing BR between the groups revealed a hazard ratio of 1.58 (95 % confidence interval: 0.98–2.55) with a non-statistically significant increased risk of BR in the Gem group compared with the MMC group (p=0.059).
CONCLUSION: A single perioperative instillation of Gem or MMC seems to offer similar efficacy in reducing the risk of BR in patients undergoing RNU. Further research, ideally within the framework of prospective studies, is warranted to elucidate the optimal chemotherapeutic approach in this setting
Exercise Training in Patients with Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
No full textOf the 5 randomized controlled trials (RCTs) included, chronic thromboembolic pulmonary hypertension (CTEPH) patients constituted 20% of the overall pulmonary hypertension (PH) patient population. We did not find any RCTs that evaluated the role of exercise training in patients with CTEPH. The results of this study indicate that exercise training may be effective at improving exercise capacity, as measured by 6-min walk distance, in patients with PH. Another notable finding from this analysis is the lack of adverse events associated with exercise training, suggesting that contrary to widespread perception, exercise training is safe in CTEPH and PAH patients
Conduction system pacing versus biventricular pacing for atrial fibrillation in patients undergoing atrioventricular junction ablation: a meta-analysis
No full textHealth-related social needs screening, reporting, and assistance in a large health system
No full textBACKGROUND: National mandates require screening for and addressing health-related social needs (HRSNs) in healthcare settings. However, differences in HRSN screening process (i.e., completed screenings, screening results, documented offer of assistance, documented assistance request) have been reported by population subgroup. Knowledge of the most effective HRSN screening and intervention methods is limited. We sought to describe differences in completed HRSN screenings, screening results, and assistance request rates across patient and healthcare visit characteristics.
METHODS: We examined data from all patients aged ≥18 years and residing in the US receiving services at a large, Midwestern healthcare system with a goal to screen all patients for HRSN at least once annually between July 2021-June 2023 (n = 1,190,488). We examined the proportion of patients with any HRSN screening, with any reported HRSN, asked whether they wanted assistance, or who requested assistance for a reported HRSN stratified by patient demographics and healthcare visit characteristics (i.e., payer, screening location, who completed the screening).
RESULTS: Less than half of eligible patients (47.0 %) were screened for HRSNs. About one-sixth (16.9 %) reported any HRSN. Although most patients reporting HRSNs were asked whether they wanted assistance, only about one-quarter (26.8 %) responded affirmatively. Proportions included in each step of the HRSN screening process significantly differed by patient and healthcare visit characteristics.
DISCUSSION: This study is one of the first to investigate various steps of a population-wide HRSN screening program. Our findings suggest that examining differences in HRSN screening process by population subgroup is key to addressing HRSNs through a health equity lens