Prospective Comparative Effectiveness Research Articles

Holmium versus thulium fibre laser for ureteroscopy and lithotripsy: When, why and how?

Background: The holmium: yttrium-aluminum-garnet (Ho:YAG) laser, which has been the gold standard for lithotripsy, has evolved to high frequency systems with pulse modulation. However, there is now an alternative laser for lithotripsy - the thulium fiber laser (TFL). Purpose: While bench testing has shown superior fragmentation performance of the TFL compared to Ho:YAG, initial clinical results for ureteroscopy have not been as dramatic. We therefore analyze laboratory and clinical studies comparing these two laser platforms. Our goal is to offer insights into when and why to choose one laser over the other for ureteroscopy, along with strategies for optimal use. Methods: In this narrative review we describe the characteristics of each laser and provide an overview of the in vitro studies comparing Ho:YAG and TFL for fragmentation, retropulsion and heat generation. We also review evidence from prospective comparative effectiveness clinical trials for ureteroscopy and lithotripsy. We provide our schema for when we use each laser for ureteroscopy, the rationale and our approach with laser settings. Conclusions: Ho:YAG and TFL have distinct wavelengths, pulse duration, peak power, and water absorption parameters that make them suitable for different scenarios. The decision between which laser to choose rests upon individual preferences and confidence levels of use, with the ultimate priority for safe patient use.

Childhood Arthritis and Rheumatology Research Alliance Biologic Disease-Modifying Antirheumatic Drug Consensus Treatment Plans for Refractory Moderately Severe Juvenile Dermatomyositis.

The objective was to develop consensus treatment plans (CTPs) for patients with refractory moderately severe juvenile dermatomyositis (JDM) treated with biologic disease-modifying antirheumatic drugs (bDMARDs). The Biologics Workgroup of the Childhood Arthritis and Rheumatology Research Alliance JDM Research Committee used case-based surveys, consensus framework, and nominal group technique to produce bDMARD CTPs for patients with refractory moderately severe JDM. Four bDMARD CTPs were proposed: tumor necrosis factor α (TNFα) inhibitor (adalimumab or infliximab), abatacept, rituximab, and tocilizumab. Each CTP has different options for dosing and/or route. Among 76 respondents, consensus was achieved for the proposed CTPs (93% [67 of 72]) as well as for patient characteristics, assessments, outcome measures, and follow-up. By weighted average, respondents indicated that they would most likely administer rituximab, followed by abatacept, TNFα inhibitor, and tocilizumab. CTPs for the administration of bDMARDs in refractory moderately severe JDM were developed using consensus methodology. The implementation of the bDMARD CTPs will lay the groundwork for registry-based prospective comparative effectiveness studies.

MRI and Clinical Variables for Prediction of Outcomes After Pediatric Severe Traumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of death and disability in children, and predicting functional outcome after TBI is challenging. Magnetic resonance imaging (MRI) is frequently conducted after severe TBI; however, the predictive value of MRI remains uncertain. To identify early MRI measures that predict long-term outcome after severe TBI in children and to assess the added predictive value of MRI measures over well-validated clinical predictors. This preplanned prognostic study used data from the Approaches and Decisions in Acute Pediatric TBI (ADAPT) prospective observational comparative effectiveness study. The ADAPT study enrolled 1000 consecutive children (aged <18 years) with severe TBI between February 1, 2014, and September 30, 2017. Participants had a Glasgow Coma Scale (GCS) score of 8 or less and received intracranial pressure monitoring. Magnetic resonance imaging scans performed as part of standard clinical care within 30 days of injury were collected at 24 participating sites in the US, UK, and Australia. Summary imaging measures were correlated with the Glasgow Outcome Scale-Extended for Pediatrics (GOSE-Peds), and the predictive value of MRI measures was compared with the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) core clinical predictors. Data collection, image analysis, and data analyses were completed in July 2023. Pediatric severe TBI with an MRI scan performed as part of clinical care. All measures were selected a priori. Magnetic resonance imaging measures included contusion, ischemia, diffuse axonal injury, intracerebral hemorrhage, and brainstem injury. Clinical predictors included the IMPACT core measures (GCS motor score and pupil reactivity). All models adjusted for age and sex. Outcome measures included the GOSE-Peds score obtained at 3, 6, and 12 months after injury. This study included 233 children with severe TBI who were enrolled at participating sites and had an MRI scan and preselected clinical predictors available. Their median age was 6.9 (IQR, 3.0-13.3) years, and more than half of participants (134 [57.5%]) were male. In a multivariable model including MRI measures and IMPACT core clinical variables, contusion volume (odds ratio [OR], 1.13; 95% CI, 1.02-1.26), brain ischemia (OR, 2.11; 95% CI, 1.58-2.81), brainstem lesions (OR, 5.40; 95% CI, 1.90-15.35), and pupil reactivity were each independently associated with GOSE-Peds score. Adding MRI measures to the IMPACT clinical predictors significantly improved model fit and discrimination between favorable and unfavorable outcomes compared with IMPACT predictors alone (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.72-0.85 vs 0.67; 95% CI, 0.61-0.76 for GOSE-Peds score >3 at 6 months after injury). In this prognostic study of children with severe TBI, the addition of MRI measures significantly improved outcome prediction over well-established and validated clinical predictors. Magnetic resonance imaging should be considered in children with severe TBI to inform prognosis and may also promote stratification of patients in future clinical trials.

Implementation of statistical features of a Bayesian two-armed responsive adaptive randomization trial with post hoc analysis of time trend drift

ABSTRACT Bayesian adaptive designs with response adaptive randomization (RAR) have the potential to benefit more participants in a clinical trial. While there are many papers that describe RAR designs and results, there is a scarcity of works reporting the details of RAR implementation from a statistical point exclusively. In this paper, we introduce the statistical methodology and implementation of the trial Changing the Default (CTD). CTD is a single-center prospective RAR comparative effectiveness trial to compare opt-in to opt-out tobacco treatment approaches for hospitalized patients. The design assumed an uninformative prior, conservative initial allocation ratio, and a higher threshold for stopping for success to protect results from statistical bias. A particular emerging concern of RAR designs is the possibility that time trends will occur during the implementation of a trial. If there is a time trend and the analytic plan does not prespecify an appropriate model, this could lead to a biased trial. Adjustment for time trend was not pre-specified in CTD, but post hoc time-adjusted analysis showed no presence of influential drift. This trial was an example of a successful two-armed confirmatory trial with a Bayesian adaptive design using response adaptive randomization.

Feasibility of Conducting Comparative Effectiveness Research and Validation of a Clinical Disease Activity Score for Chronic Nonbacterial Osteomyelitis.

Prospective comparative effectiveness research (CER) in chronic nonbacterial osteomyelitis (CNO) is lacking. Our objectives were to (1) determine the use and safety of each consensus treatment plan (CTP) regimen for CNO, (2) assess the feasibility of using the Chronic Nonbacterial Osteomyelitis International Registry (CHOIR) data for CER, and (3) develop and validate a CNO clinical disease activity score (CDAS) using CHOIR. Consenting children or young adults with CNO were enrolled into CHOIR. Demographic, clinical, and imaging data were prospectively collected. The CNO CDAS was developed through a Delphi survey and nominal group technique. External validation surveys were administered to CHOIR participants. One hundred forty (78.2%) CHOIR participants enrolled between August 2018 and September 2020 received at least 1 CTP regimen. Baseline characteristics from different CTP groups were well matched. Patient pain, patient global assessment, and clinical CNO lesion count were key variables included in the CNO CDAS. The CDAS showed a strong correlation with patient/parent report of difficulty using a limb, back, or jaw and patient/parent report of disease severity, but a weak correlation with patient/parent report of fatigue, sadness, and worry. The change in CDAS was significant in patients reporting disease worsening or improvement (P < 0.001). The CDAS significantly decreased after initiating second-line treatments from median 12.0 (IQR 8.0-15.5) to 5.0 (IQR 3.0-12.0; P = 0.002). Although second-line treatments were well tolerated, psoriasis was the most common adverse event. The CNO CDAS was developed and validated for disease monitoring and assessment of treatment effectiveness. CHOIR provided a comprehensive framework for future CER.

Pragmatic, Prospective Comparative Effectiveness Trial of Carbon Ion Therapy, Surgery, and Proton Therapy for the Management of Pelvic Sarcomas (Soft Tissue/Bone) Involving the Bone: The PROSPER Study Rationale and Design.

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.

Patient-reported Outcomes After External Beam Radiotherapy With Low Dose Rate Brachytherapy Boost vs Radical Prostatectomy for Localized Prostate Cancer: Five-year Results From a Prospective Comparative Effectiveness Study.

You have accessJournal of UrologyErratum1 Feb 2023Patient-reported Outcomes After External Beam Radiotherapy With Low Dose Rate Brachytherapy Boost vs Radical Prostatectomy for Localized Prostate Cancer: Five-year Results From a Prospective Comparative Effectiveness Studyis correction ofPatient-reported Outcomes After External Beam Radiotherapy With Low Dose Rate Brachytherapy Boost vs Radical Prostatectomy for Localized Prostate Cancer: Five-year Results From a Prospective Comparative Effectiveness Study View All Author Informationhttps://doi.org/10.1097/JU.0000000000003082AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Volume 208, Issue 6, Page 1226: “*Co-first author.” was added to the footnotes on page 1227. The online and PDF versions of the article have been revised. © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology25 Aug 2022Patient-reported Outcomes After External Beam Radiotherapy With Low Dose Rate Brachytherapy Boost vs Radical Prostatectomy for Localized Prostate Cancer: Five-year Results From a Prospective Comparative Effectiveness Study Volume 209Issue 2February 2023Page: 450-450 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Expand All Advertisement Advertisement PDF downloadLoading ...

The Determining Effective Testing in Emergency Departments and Care Coordination on Treatment Outcomes (DETECT) for Hepatitis C (Hep C) Linkage-to-Care Trial: rationale and design of an emergency department-based randomized clinical trial of linkage-to-care strategies for hepatitis C

BackgroundHepatitis C (HCV) poses a major public health problem in the USA. While early identification is a critical priority, subsequent linkage to a treatment specialist is a crucial step that bridges diagnosed patients to treatment, cure, and prevention of ongoing transmission. Emergency departments (EDs) serve as an important clinical setting for HCV screening, although optimal methods of linkage-to-care for HCV-diagnosed individuals remain unknown. In this article, we describe the rationale and design of The Determining Effective Testing in Emergency Departments and Care Coordination on Treatment Outcomes (DETECT) for Hepatitis C (Hep C) Linkage-to-Care Trial.MethodsThe DETECT Hep C Linkage-to-Care Trial will be a single-center prospective comparative effectiveness randomized two-arm parallel-group superiority trial to test the effectiveness of linkage navigation and clinician referral among ED patients identified with untreated HCV with a primary hypothesis that linkage navigation plus clinician referral is superior to clinician referral alone when using treatment initiation as the primary outcome. Participants will be enrolled in the ED at Denver Health Medical Center (Denver, CO), an urban, safety-net hospital with approximately 75,000 annual adult ED visits. This trial was designed to enroll a maximum of 280 HCV RNA-positive participants with one planned interim analysis based on methods by O’Brien and Fleming. This trial will further inform the evaluation of cost effectiveness, disparities, and social determinants of health in linkage-to-care, treatment, and disease progression.DiscussionWhen complete, the DETECT Hep C Linkage-to-Care Trial will significantly inform how best to perform linkage-to-care among ED patients identified with HCV.Trial registrationClinicalTrials.govID: NCT04026867Original date: July 1, 2019URL: https://clinicaltrials.gov/ct2/show/NCT04026867

A qualitative exploration of experiences accessing community and social services among pregnant low-income people of color during the COVID-19 pandemic.

The COVID-19 pandemic has been associated with increased social and economic stressors among pregnant individuals. While community and social services have been available to mitigate stressors in pregnancy (e.g. food insecurity and financial hardship) and reduce the risk of adverse maternal outcomes, it is unclear how the pandemic impacted access to these resources, particularly in communities of color with lower incomes. To examine the experiences accessing community and social service resources during the COVID-19 pandemic among pregnant people of color with low incomes. Participants for this COVID-related qualitative study were recruited from two sources-a prospective comparative effectiveness study of two models of enhanced prenatal care and the California Black Infant Health Program between August and November of 2020. We conducted 62 interviews with Medicaid-eligible participants in California's Central Valley. During their interviews, study participants were asked to share their pregnancy-related experiences, including how they felt the pandemic had affected those experiences. We identified two broad themes: challenges with accessing community and social service resources during the pandemic and opportunities for improving access to these resources. Sub-themes related to challenges experienced included difficulty with remote access, convoluted enrollment processes for community and social services, and problems specific to accessing COVID-19 resources (e.g. testing). Sub-themes related to opportunities to improve access included leveraging instrumental support from perinatal staff and informational (e.g. practical) support from other community programs and pregnant peers. Participant recommendations included leveraging opportunities to improve client experiences through increased transparency and better patient-provider communication. This study highlights some important trends that emerged with the rollout of remote service delivery for social services among a vulnerable population. Many participants were able to leverage support through other programs and perinatal staff. These individuals identified additional opportunities to improve client experiences that can inform the future implementation of support services for pregnant people.

Patient-reported Outcomes After External Beam Radiotherapy With Low Dose Rate Brachytherapy Boost vs Radical Prostatectomy for Localized Prostate Cancer: Five-year Results From a Prospective Comparative Effectiveness Study.

Data comparing radical prostatectomy and external beam radiation therapy with low dose rate brachytherapy boost are lacking. To better guide shared decision making regarding treatment, we compared patient reported outcomes through 5 years following radical prostatectomy or external beam radiation therapy with low dose rate brachytherapy boost for localized prostate cancer. From 2011-2012, men aged <80 years with localized prostate adenocarcinoma were enrolled and followed longitudinally. Patient reported outcomes included the Expanded Prostate Index Composite. Regression models adjusted for baseline scores and covariates were constructed. The study population included 112 men treated with external beam radiation therapy with low dose rate brachytherapy boost and 1,553 treated with radical prostatectomy. Compared to radical prostatectomy, external beam radiation therapy with low dose rate brachytherapy boost was associated with clinically meaningful worse urinary irritative/obstructive (adjusted mean score difference [95% confidence interval]: 5.0 [-8.7, -1.3]; P = .008 at 5 years) and better urinary incontinence function (13.3 [7.7, 18.9]; P < .001 at 5 years) through 5 years. Urinary function bother was similar between groups (P > .4 at all timepoints). Treatment with external beam radiation therapy with low dose rate brachytherapy boost was associated with worse bowel function (-4.0 [-6.9, -1.1]; P = .006 at 5 years) through 5 years compared to radical prostatectomy. Treatment with external beam radiation therapy with low dose rate brachytherapy boost was associated with better sexual function at 1 year (12.0 [6.5, 17.5]; P < .001 at 1 year) compared to radical prostatectomy, but there was insufficient evidence to reject the supposition that no difference was seen at 3 or 5 years. Compared to radical prostatectomy, external beam radiation therapy with low dose rate brachytherapy boost was associated with clinically meaningful worse urinary irritative/obstructive and bowel functions but better urinary incontinence function through 5 years after treatment. These patient-reported functional outcomes may clarify treatment expectations and help inform treatment choices for localized prostate cancer.

Prospective Comparative Effectiveness Trial of Multidisciplinary Lung Cancer Care Within a Community-Based Health Care System.

Multidisciplinary lung cancer care is assumed to improve care delivery by increasing transparency, objectivity, and shared decision making; however, there is a lack of high-level evidence demonstrating its benefits, especially in community-based health care systems. We used implementation and team science principles to establish a colocated multidisciplinary lung cancer clinic in a large community-based health care system and evaluated patient experience and outcomes within and outside this clinic. We conducted a prospective frequency-matched comparative effectiveness study (ClinicalTrials.gov identifier: NCT02123797) evaluating the thoroughness of lung cancer staging, receipt of stage-appropriate treatment, and survival between patients receiving care in the multidisciplinary clinic and those receiving usual serial care. Target enrollment was 150 patients on the multidisciplinary arm and 300 on the serial care arm. We frequency-matched patients by clinical stage, performance status, insurance type, race, and age. A total of 526 patients were enrolled: 178 on the multidisciplinary arm and 348 on the serial care arm. After adjusting for other factors, multidisciplinary patients had significantly higher odds (odds ratio [OR]: 2.3 [95% CI, 1.5 to 3.4]) of trimodality staging compared with serial care. Patients on the multidisciplinary arm also had higher odds of receiving invasive stage confirmation (OR: 2.0 [95% CI, 1.4 to 3.1]) and mediastinal stage confirmation (OR: 1.9 [95% CI, 1.3 to 2.8]). Additionally, patients receiving multidisciplinary care were significantly more likely to receive stage-appropriate treatment (OR: 1.8 [95% CI, 1.1 to 3.0]). We found no significant difference in overall or progression-free survival between study arms. The multidisciplinary clinic delivered significant improvements in evidence-based quality care on multiple levels. Even in the absence of a demonstrable survival benefit, these findings provide a strong rationale for recommending this model of care.

Poractant alfa versus bovine lipid extract surfactant: prospective comparative effectiveness study.

To compare short term respiratory outcomes in preterm infants treated with bovine lipid extract surfactant or poractant alfa. Prospective comparative effectiveness cohort study of infants <32 weeks' gestational age requiring surfactant in thirteen centers. Each center provided bovine lipid extract surfactant for a set period of time in the year 2019 and then changed to poractant alfa for the remainder of the year. The primary outcome was total duration of respiratory support. 968 infants were included. 494 received bovine lipid extract surfactant and 474 received poractant alfa. No difference was observed in the total duration of respiratory support (mechanical ventilation or non-invasive) (median 38 vs 40.5 days), need to re-dose surfactant, bronchopulmonary dysplasia, survival to discharge, or length of admission. In this pragmatic study, we did not identify any difference in short term outcomes between the groups based on the type of surfactant received.

50 Poractant alfa versus bovine lipid extract surfactant for respiratory distress syndrome in preterm infants: A prospective comparative effectiveness cohort study

Abstract Primary Subject area Neonatal-Perinatal Medicine Background There is a paucity of comparative effectiveness data for bovine lipid extract surfactant (BLES) and poractant alfa (Curosurf). Objectives To compare duration of respiratory support and short-term outcomes in very preterm infants treated with bovine lipid extract surfactant and poractant alfa. Design/Methods We performed a prospective, multicentre, comparative effectiveness study. Thirteen Canadian level III neonatal intensive care units (NICUs) provided bovine lipid extract surfactant to infants born &amp;lt;32 weeks’ gestational age (GA) for a set period of time in the year 2019 (3 to 9 months), then changed to poractant alfa for the remainder of the year. The primary outcome was total duration of respiratory support (invasive and non-invasive). We utilized the Canadian Neonatal Network database for all study data. Results A total of 968 eligible infants (530 infants &amp;lt; 28 weeks’ GA and 438 infants 280-316weeks’ GA) were included, of which 494 received bovine lipid extract surfactant and 474 received poractant alfa. In unadjusted analysis, no difference was observed in total duration of any respiratory support (median 38 vs. 40.5 days). After adjusting for baseline characteristics and accounting for cluster effects, infants treated with poractant alfa spent a median of 4.16 fewer days on respiratory support (95% CI 0.05, 8.28 days). This reduction was observed in the subgroup of infants 280-316 weeks’ GA, but not in those &amp;lt; 28 weeks’ GA, and was explained by their shorter time on non-invasive respiratory support. No differences were observed in the need to re-dose surfactant, hospital mortality, bronchopulmonary dysplasia, or length of stay in NICU. Conclusion Administration of poractant alfa was associated with shorter median duration of respiratory support compared to bovine lipid extract surfactant in preterm neonates &amp;lt; 32 weeks’ GA.

Five-Year Outcomes From a Prospective Comparative Effectiveness Study Evaluating External Beam Radiotherapy With Low Dose-Rate Brachytherapy Boost and Prostatectomy for Localized Prostate Cancer

High-quality data comparing radical prostatectomy (RP) and external beam radiotherapy plus low dose-rate brachytherapy boost (EBRT-LDR) are lacking. To better inform treatment selection, we compared patient reported functional outcomes (PROs) through 5 years following RP or EBRT-LDR for localized prostate cancer.Men were enrolled from 2011-2012 on this multicenter prospective study. Enrollment criteria were: 1) age < 80 years, 2) prostate-specific antigen < 50 ng/dL, and 3) a pathologically-confirmed diagnosis of localized prostate adenocarcinoma within 6 months of enrollment. PROs collected at baseline, 0.5, 1, 3, and 5 years included the Expanded Prostate Index Composite (EPIC), Short Form Health Survey (SF-36), and the Clark treatment-related regret scale. Regression models adjusted for patient characteristics and baseline function. Minimum clinically important point differences for EPIC domains were defined: 4-6 bowel function, 5-7 urinary irritation, 6-9 urinary incontinence, and 10-12 sexual function.Among the entire cohort, 112 received EBRT-LDR and 1553 RP. EBRT-LDR patients were older (median [quartiles]: 66 [60-71] vs. 62 [57-66); P < 0.001) and more commonly had high-risk disease (24% vs. 17%; P = 0.039). Compared to treatment with RP, treatment with EBRT-LDR was associated with clinically meaningful worse bowel (adjusted mean difference, [95% confidence interval]: -9.1 [-11.9, -6.4] P < 0.001 at 1 year; -4.0 [-6.9, -1.1], P = 0.006 at 5 years), worse urinary irritative (1 year: -13.4 [-17.6, -9.2], P < 0.001; 5 year: -5.0 [-8.7, -1.3], P = 0.008), and better urinary incontinence function (1 year: 15.1 [11.0, 19.2], P < 0.001; 5 years: 13.3 [7.7, 18.9], P < 0.001) through 5 years. Men reported similar frequency of moderate to big problem with urinary function between treatment groups through 5 years (1 year: 12% RP vs. 15% EBRT-LDR, P = 0.52; 5 years: 13% vs. 15%, P = 0.50). EBRT-LDR was associated with clinically meaningful better sexual function through 1 year (12 [6.5, 17.5]; P < 0.001 at 1 year), however, sexual function was not clinically different at subsequent timepoints (6.7 [-0.1, 13.4], P = 0.05 at 5 years). There were no clinically meaningful differences between treatment groups in physical functioning, emotional well-being, or energy and fatigue. There was no difference in treatment-related regret between groups at 5 years.Compared to RP, EBRT-LDR was associated with clinically meaningful worse urinary irritative and bowel function and better urinary incontinence function through 5 years after treatment. These patient-reported functional outcomes may clarify treatment expectations and help men make informed treatment choices for their localized prostate cancer.

Early objective adherence to hypoglossal nerve stimulation therapy.

To assess early adherence to therapy with hypoglossal nerve stimulation therapy. This is a prospective study of consecutive patients with moderate to severe obstructive sleep apnea who underwent implantation of hypoglossal nerve stimulation therapy within a single academic practice and attended a follow-up appointment after greater than 30 days of therapy use. Objective adherence data were extracted from an objective monitoring database and compared to patient characteristics. The study population was 79 participants who were 29.1% female with a mean age of 58.7 ± 12.8 years old, body mass index of 28.9 ± 3.4 kg/m2, and baseline apnea-hypopnea index of 33.8 ± 17.6 events/h. In the first 7 days after device activation, average use was 7.8 h/night, with 91.9% of nights with greater than 4 hours of therapy use and an average of 0.2 pauses in therapy per night. These figures remained stable after 30 days of use: 7.7 h/night, 91.0% of nights longer than 4 hours, and 0.3 pauses per night. Objective evidence of difficulty with acclimatization was associated with age less than 60 years (odds ratio 2.8, 95% confidence interval 1.1-7.1, P = .03) and a history of prior upper airway surgery (3.9, 1.2-11.9, P = .015). Insomnia was present in 31 patients and was not associated with objective evidence of difficulty tolerating therapy. Early adherence to hypoglossal nerve stimulation is excellent (92.4% >4 hours on >70% of nights), suggesting that the acclimatization period is straightforward in most. Younger age and a history of prior upper airway surgery appear to be associated with an increased risk of difficulty with acclimatization. Huyett P. Early objective adherence to hypoglossal nerve stimulation therapy. J Clin Sleep Med. 2022;18(2):631-636.

Closing the Gap: Insights into the Epidemiology of Heart Failure Care from the Critical Care Cardiology Trials Network

There is no field in greater need of high-quality prospective evidence and comparative effectiveness research than that of cardiovascular critical care. The stakes are high, fueled by a high proportion of lives lost. The resources consumed are substantial. Variability in care is striking and practice is often driven by institutional experience and preferences in the absence of robust evidence. Within the domain of critical care cardiology, management of cardiogenic shock and severely decompensated heart failure (HF) is emblematic of this need. As the composition of the population in cardiac intensive care units (CICUs) has shifted away from acute coronary syndromes, 1 Bohula EA Katz JN van Diepen S Alviar CL Baird-Zars VM Park JG et al. Critical Care Cardiology Trials Network. Demographics, care patterns, and outcomes of patients admitted to cardiac intensive care units: the Critical Care Cardiology Trials Network Prospective North American Multicenter Registry of Cardiac Critical Illness. JAMA Cardiol. 2019; 4: 928-935 Crossref PubMed Scopus (47) Google Scholar patients with severe manifestations of HF have become a focal point of practice in the CICU and major gaps in evidence regarding their management have become even more apparent.

Robot-assisted Versus Open Radical Cystectomy in Bladder Cancer: An Economic Evaluation Alongside a Multicentre Comparative Effectiveness Study

BackgroundOpen radical cystectomy (ORC) is regarded as the standard treatment for muscle-invasive bladder cancer, but robot-assisted radical cystectomy (RARC) is increasingly used in practice. A recent study showed that RARC resulted in slightly fewer minor but slightly more major complications, although the difference was not statistically significant. Some differences were found in secondary outcomes favouring either RARC or ORC. RARC use is expected to increase in coming years, which fuels the debate about whether RARC provides value for money. ObjectiveTo assess the cost-effectiveness of RARC compared to ORC in bladder cancer. Design, setting, and participantsThis economic evaluation was performed alongside a prospective multicentre comparative effectiveness study. We included 348 bladder cancer patients (ORC, n = 168; RARC, n = 180) from 19 Dutch hospitals. Outcome measurements and statistical analysisOver 1 yr, we assessed the incremental cost per quality-adjusted life year (QALY) gained from both healthcare and societal perspectives. We used single imputation nested in the bootstrap percentile method to assess missing data and uncertainty, and inverse probability of treatment weighting to control for potential bias. Deterministic sensitivity analyses were performed to explore the impact of various parameters on the cost difference. Results and limitationsThe mean healthcare cost per patient was €17 141 (95% confidence interval [CI] €15 791–€18 720) for ORC and €21 266 (95% CI €19 163–€23 650) for RARC. The mean societal cost per patient was €18 926 (95% CI €17 431–€22 642) for ORC and €24 896 (95% CI €21 925–€31 888) for RARC. On average, RARC patients gained 0.79 QALYs (95% CI 0.74–0.85) compared to 0.81 QALYs (95% CI 0.77–0.85) for ORC patients, resulting in a mean QALY difference of −0.02 (95% CI −0.05 to 0.02). Using a cost-effectiveness threshold of €80 000, RARC was cost-effective in 0.6% and 0.2% of the replications for the healthcare and societal perspectives, respectively. ConclusionsRARC shows no difference in terms of QALYs, but is more expensive than ORC. Hence, RARC does not seem to provide value for money in comparison to ORC. Patient summaryThis study assessed the relation between costs and effects of robot-assisted surgery compared to open surgery for removal of the bladder in 348 Dutch patients with bladder cancer. We found that after 1 year, the two approaches were similarly effective according to a measure called quality-adjusted life years, but robot-assisted surgery was much more expensive.This trial was prospectively registered in the Netherlands Trial Register as NTR5362 (https://www.trialregister.nl/trial/5214).

Support for the Reliability and Validity of the National Institutes of Health Impact Stratification Score in a Sample of Active-Duty U.S. Military Personnel with Low Back Pain

Evaluate the Impact Stratification Score (ISS) measure of low back pain impact that assesses physical function, pain interference, and pain intensity. Secondary analyses of a prospective comparative effectiveness trial of active-duty military personnel with low back pain. A Naval hospital at a military training site (Pensacola, Florida) and two military medical centers: 1) Walter Reed National Military Medical Center (Bethesda, Maryland); and 2) San Diego Naval Medical Center. The 749 active-duty military personnel had an average age of 31, 76% were male and 67% white. Participants completed questionnaires at baseline, 6-weeks later, and 12-weeks later. Measures included the ISS, Roland-Morris Disability Questionnaire (RMDQ), PROMIS-29 v1.0 satisfaction with social role participation scale, and single-item ratings of average pain, feeling bothered by low back pain in the past week, and a rating of change in low back pain. Internal consistency reliability for the ISS was 0.92-0.93 at the three time points. The ISS correlated 0.75 to 0.84 with the RMDQ, 0.51 to 0.78 with the single-item ratings, and -0.64 to -0.71 with satisfaction with social role participation. The ISS was responsive to change on the three single items. The area under the curve for the ISS predicting improvement on the rating of change from baseline to 6-weeks later was 0.83. This study provides support for the reliability and validity of the ISS as a patient-reported summary measure for acute, subacute, and chronic low back pain. The ISS is a useful indicator of low back impact.

Five-year outcomes from a prospective comparative effectiveness study evaluating external-beam radiotherapy with or without low-dose-rate brachytherapy boost for localized prostate cancer.

To inform patients who are in the process of selecting prostate cancer treatment, the authors compared disease-specific function after external-beam radiotherapy (EBRT) alone versus EBRT plus a low-dose-rate (LDR) brachytherapy boost (EBRT-LDR). For this prospective study, men who had localized prostate cancer in 2011 and 2012 were enrolled. Assessments at baseline, 0.5, 1, 3, and 5 years included the patient-reported Expanded Prostate Index Composite, the 36-item Medical Outcomes Study Short-Form Health Survey, and treatment-related regret. Regression models were adjusted for baseline function and for patient and treatment characteristics. The minimum clinically important difference in scores on the Expanded Prostate Index Composite 26-item instrument was from 5 to 7 for urinary irritation and from 4 to 6 for bowel function. Six-hundred ninety-five men met inclusion criteria and received either EBRT (n = 583) or EBRT-LDR (n = 112). Patients in the EBRT-LDR group were younger (median age, 66 years [interquartile range [IQR], 60-71 years] vs 69 years [IQR, 64-74 years]; P < .001), were less likely to receive pelvic radiotherapy (10% vs 18%; P = .040), and had higher baseline 36-item Medical Outcomes Study Short-Form Health Survey physical function scores (median score, 95 [IQR, 86-100] vs 90 [IQR, 70-100]; P < .001). Over a 3-year period, compared with EBRT, EBRT-LDR was associated with worse urinary irritative scores (adjusted mean difference at 3 years, -5.4; 95% CI, -9.3, -1.6) and bowel function scores (-4.1; 95% CI, -7.6, -0.5). The differences were no longer clinically meaningful at 5 years (difference in urinary irritative scores: -4.5; 95% CI, -8.4, -0.5; difference in bowel function scores: -2.1; 95% CI, -5.7, -1.4). However, men who received EBRT-LDR were more likely to report moderate or big problems with urinary function bother (adjusted odds ratio, 3.5; 95% CI, 1.5-8.2) and frequent urination (adjusted odds ratio, 2.6; 95% CI, 1.2-5.6) through 5 years. There were no differences in survival or treatment-related regret between treatment groups. Compared with EBRT alone, EBRT-LDR was associated with clinically meaningful worse urinary irritative and bowel function over 3 years after treatment and more urinary bother at 5 years. In men with prostate cancer who received external-beam radiation therapy (EBRT) with or without a brachytherapy boost (EBRT-LDR), EBRT-LDR was associated with clinically worse urinary irritation and bowel function through 3 years but resolved after 5 years. Men who received EBRT-LDR continued to report moderate-to-big problems with urinary function bother and frequent urination through 5 years. There was no difference in treatment-related regret or survival between patients who received EBRT and those who received EBRT-LDR. These intermediate-term estimates of function may facilitate counseling for men who are selecting treatment.

In-hospital Growth of Very Low Birth Weight Preterm Infants: Comparative Effectiveness of 2 Human Milk Fortifiers.

Amidst a high prevalence of prematurity, limited research on the growth of very low birth weight (VLBW) preterm infants and the availability of a reformulated fortifier c(RF), the study aimed to compare in-hospital growth of such infants receiving exclusively human milk fortified with either of 2 different formulations in a tertiary South African hospital. In a prospective comparative effectiveness design, intakes and growth of VLBW infants on the Original Fortifier (OF; 2016-2017) were compared with those receiving RF (2017-2018). Daily intake was calculated using published composition of preterm and mature milk with fortifier (OF: 0.2 g protein, 3.5kcal/g powder; RF: 0.4 g protein, 4.4 kcal/g powder). Change in z scores from start to end of fortification for weight (WFAZ), length (LFAZ), and head circumference (HCFAZ) for age was the primary outcome. Additionally, weight gain velocity (g · kg-1 · day-1) and gain in length and head circumference (HC) (cm/week) were calculated. Fifty-eight infants (52% girls; gestational age: 30 ± 2 weeks; birth weight: 1215 ± 187 g) received OF for 16 days and 59 infants (56% girls; gestational age: 29 ± 2 weeks; birth weight 1202 ± 167 g) received RF for 15 days. Protein intake of RF (3.7 ± 0.4 g · kg-1 · day-1) was significantly higher (P < 0.001) than of OF (3.4 ± 0.2 g · kg-1 · day-1). Protein-to-energy ratio of RF (2.6 ± 0.2 g/100 kcal) was significantly higher (P < 0.001) than of OF (2.3 ± 0.1 g/100 kcal). In both groups, WFAZ and LFAZ decreased; HCFAZ improved slightly. No significant differences (P > 0.05) were noted between the 2 groups for change in z scores, weight gain velocity, length or HC gain. Despite a modest increase in protein intake and protein-to-energy ratio, the growth of VLBW infants on RF was not better than on OF during their hospital stay.