Impact of Cerebral Embolic Protection Devices on Disabling Stroke after Transcatheter Aortic Valve Replacement: Updated Results from the STS/ACC TVT Registry.

Background: Cerebral embolic protection devices (EPDs) were developed to mitigate the risk of stroke during transcatheter aortic valve replacement (TAVR), but their benefit remains unproven. In the PROTECTED-TAVR trial, EPD use did not reduce periprocedural stroke (primary study outcome) but led to a 62% reduction in the secondary endpoint of disabling stroke. Given these results, the impact of EPDs during TAVR remains unclear. Methods: We used STS/ACC TVT registry data to examine the association between EPD use and a proxy for disabling stroke among transfemoral TAVR patients between 1/2018-6/2023. The primary outcome was in-hospital disabling stroke-defined as stroke associated with either in-hospital death or discharge to a non-home location. We evaluated the association between EPD use and disabling stroke using instrumental variable (IV) analysis with site-level preference for EPD use as the instrument-a quasi-experimental approach that can support causal inference. In addition, we performed a propensity-score based comparison using overlap weighting as a secondary analysis. Results: The study population consisted of 414,649 patients of whom 53,389 (12.9%) received an EPD. The unadjusted rate of in-hospital disabling stroke was 0.7% among the EPD group and 0.9% in the no EPD group. EPD use was associated with a reduction in disabling stroke in both IV analysis (RR 0.87; 95% CI: 0.73-1.00) and propensity-weighted (PW) analysis (OR 0.79; 95% CI: 0.70-0.90) but was not associated with a reduction in non-disabling stroke. In subgroup analyses, the benefit of EPD was greater among those with versus without prior stroke (interaction p<0.05 for IV and PW). Conclusions: In the largest study to date, among patients undergoing TAVR, EPD use was associated with a small, borderline significant reduction in stroke associated with death or a discharge to a non-home location (a proxy for disabling stroke) that is likely to be causal in nature. Taken together with previous mechanistic and clinical studies, these findings provide credible evidence that EPDs benefit patients undergoing TAVR.

Procedure Volume and Outcomes With WATCHMAN Left Atrial Appendage Occlusion.

BACKGROUND: Procedure volumes are associated with outcomes for many cardiovascular procedures, leading to guidelines on minimum volume thresholds for certain procedures; however, the volume-outcome relationship with left atrial appendage occlusion is poorly understood. As such, we sought to determine the relationship between hospital and physician volume and WATCHMAN left atrial appendage occlusion procedural success overall and with the new generation WATCHMAN FLX device. METHODS: We performed an analysis of WATCHMAN procedures (January 2019 to October 2021) from the National Cardiovascular Data Registry LAAO Registry. Three-level hierarchical generalized linear models were used to assess the adjusted relationship between procedure volume and procedural success (device released with peridevice leak <5 mm, no in-hospital major adverse events). RESULTS: Among 87 480 patients (76.2±8.0 years; 58.8% men; mean CHA2DS2-VASc score, 4.8±1.5) from 693 hospitals, the procedural success rate was 94.2%. With hospital volume Q4 (greatest volume) as the reference, the likelihood of procedural success was significantly less among Q1 (odds ratio [OR], 0.66 [CI, 0.57-0.77]) and Q2 (OR, 0.78 [CI, 0.69-0.90]) but not Q3 (OR, 0.95 [CI, 0.84-1.07]). With physician volume Q4 (greatest volume) as the reference, the likelihood of procedural success was significantly less among Q1 (OR, 0.72 [CI, 0.63-0.82]), Q2 (OR, 0.79 [CI, 0.71-0.89]), and Q3 (OR, 0.88 [CI, 0.79-0.97]). Among WATCHMAN FLX procedures, there was attenuation of the volume-outcome relationships, with statistically significant but modest absolute differences of only ≈1% across volume quartiles. CONCLUSIONS: In this contemporary national analysis, greater hospital and physician WATCHMAN volumes were associated with increased procedure success. The WATCHMAN FLX transition was associated with increased procedural success and less heterogeneity in outcomes across volume quartiles. These findings indicate the importance of understanding the volume-outcome relationship for individual left atrial appendage occlusion devices.

Comparison of Transcatheter Edge-to-Edge Mitral Valve Repair for Primary Mitral Regurgitation Outcomes to Hospital Volumes of Surgical Mitral Valve Repair.

BACKGROUND: Transcatheter edge-to-edge mitral valve (MV) repair (TEER) is an effective treatment for patients with primary mitral regurgitation at prohibitive risk for surgical MV repair (MVr). High-volume MVr centers and high-volume TEER centers have better outcomes than low-volume centers, respectively. However, whether MVr volume predicts TEER outcomes remains unknown. We hypothesized that high-volume MV surgical centers would have superior risk-adjusted outcomes for TEER than low-volume centers. METHODS: We combined data from the American College of Cardiology/Society of Thoracic Surgeons Transcatheter Valve Therapy registry and the Society of Thoracic Surgeons adult cardiac surgery database. MVr was defined as leaflet resection or artificial chords with or without annuloplasty and was evaluated as a continuous variable and as predefined categories (<25, 25-49, and ≥50 MV repairs/year). A generalized linear mixed model was used to evaluate risk-adjusted in-hospital/30-day mortality, 30-day heart failure readmission, and TEER success (mitral regurgitation ≤2+ and gradient <5 mm Hg). RESULTS: The study comprised 41 834 patients from 500 sites of which 332 (66.4%) were low, 102 (20.4%) intermediate, and 66 (13.2%) high-volume surgical centers (P<0.001). TEER success was 54.6% and was not statistically significantly different across MV surgical site volumes (P=0.4271). TEER mortality at 30 days was 3.5% with no significant difference across MVr volume on unadjusted (P=0.141) or adjusted (P=0.071) analysis of volume as a continuous variable. One-year mortality was 15.0% and was lower for higher MVr volume centers when adjusted for clinical and demographic variables (P=0.027). Heart failure readmission at 1 year was 9.4% and was statistically significantly lower in high-volume centers on both unadjusted (P=0.017) or adjusted (P=0.015) analysis. CONCLUSIONS: TEER can be safely performed in centers with low volumes of MV repair. However, 1-year mortality and heart failure readmission are superior at centers with higher MVr volume.

Transcatheter Edge-to-Edge Repair in COAPT-Ineligible Patients With Functional Mitral Regurgitation.

BACKGROUND: Mitral valve transcatheter edge-to-edge repair (MTEER) was approved in the United States for treatment of functional mitral regurgitation (FMR) based on results from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial. OBJECTIVES: The authors sought to analyze outcomes of MTEER in FMR patients who would have been excluded from COAPT. METHODS: MTEER procedures performed for FMR in the TVT (Transcatheter Valve Therapy) Registry between January 1, 2013, and April 30, 2020, were categorized as "trial-ineligible" if any of the following were present: cardiogenic shock, inotropic support, left ventricular ejection fraction <20%, left ventricular end-systolic dimension >7 cm, home oxygen use, or severe tricuspid regurgitation. Trial-ineligible and trial-eligible groups were compared through 1 year using multivariable models. The primary endpoint was 1-year death or heart failure hospitalization (HFH). RESULTS: Of 6,675 patients who underwent MTEER for FMR, 3,721 (55.7%) were trial-eligible and 2,954 (44.3%) were trial-ineligible. Trial-ineligible patients had lower rates of technical procedural success (86.9% vs 92.6%; P < 0.001) and more frequent in-hospital complications (11.8% vs 5.7%; P < 0.001) compared with trial-eligible patients. A clinically meaningful improvement in health status at 30 days was observed in 78.9% and 77.0% of patients in the trial-ineligible and trial-eligible groups, respectively. There was a higher risk of 1-year death or HFH (HR: 1.73; 95% CI: 1.57-1.91; P < 0.001) in trial-ineligible patients. CONCLUSIONS: Among patients who underwent MTEER for FMR in the TVT Registry, nearly one-half would have been ineligible for the COAPT trial. Health status improvement at 30 days was similar in COAPT-ineligible and COAPT-eligible patients, but trial-ineligible patients had higher 1-year rates of death or HFH.

Interventions to Improve Long-Term Adherence to Physical Rehabilitation: A Systematic Review.

OBJECTIVE: To evaluate the impact of physical rehabilitation interventions, supplemented with one or more adherence-enhancing components, on outcomes among adults with hip or knee osteoarthritis or chronic lower back pain. DESIGN: Primary literature search from inception of each database to July 27, 2021, guided by relevant search terms and keywords to search titles and abstracts. All articles meeting eligibility criteria were included for data abstraction. DATA SOURCES: MEDLINE, CINAHL Complete, and Embase. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomized and nonrandomized trials evaluating adherence-focused intervention components conducted in addition to an index usual care or usual care-like physical rehabilitation program among adults with hip or knee osteoarthritis or chronic low back pain. Eligible studies included a comparator group of the same index physical rehabilitation intervention without the adjunctive adherence components. Included studies measured outcomes at least 3 months after the rehabilitation course. RESULTS: Of the 10 studies meeting inclusion criteria, 6 interventions were delivered concurrent to an index rehabilitation program and 4 were delivered sequentially. Of the 3 studies that reported a positive effect on long-term adherence, only 1 was a low risk of bias study. There is very limited evidence of a beneficial treatment effect of adjunct adherence interventions on long-term physical function, self-efficacy, or adverse events. CONCLUSION: We found inadequate evidence evaluating adherence-enhancing interventions for the specific promotion of long-term adherence to home rehabilitation programs. Future studies should consider testing interventions specifically built to target behavioral maintenance of home rehabilitation programs.

Characterizing Acute Low Back Pain in a Community-Based Cohort.

Acute low back pain (LBP) is a common experience, however, the associated pain severity, pain frequency, and characteristics of individuals with acute LBP in community settings have yet to be well understood. In this manuscript, three acute LBP severity categorization definitions were used based on LBP frequency combined with either 1) pain impact frequency (impact-based) or 2) pain intensity (intensity-based), as well as LBP pain interference frequency (interference only-based) severity categories. The purpose of this manuscript is to describe and then compare these acute LBP severity groups in the following characteristics: 1) sociodemographic, 2) general and physical health, and 3) psychological. This cross-sectional study used baseline data from 131 community-based participants with acute LBP (<4 weeks duration before screening and ≥30 pain-free days before acute LBP onset). Descriptive associations were calculated as prevalence ratios for categorical variables and Hedges' g for continuous variables. Our analyses identified several large associations for impact-based and intensity-based categories with global mental health, global physical health, STarT Back Screening Tool risk category, and general health. Larger associations were found with social constructs (racially and ethnically minoritized, performance of social roles, and isolation) when using the intensity-based versus impact-based categorization. The interference-based category did not capture as much variability between acute LBP severity categories. This study adds to the literature by providing standard ways to characterize community-based individuals experiencing acute LBP. The robust differences observed between these categorization approaches suggest that how we define acute LBP severity is consequential; these different approaches may be used to improve the early identification of factors potentially contributing to the development of chronic LBP.

Association Between Polyvascular Disease and Transcatheter Aortic Valve Replacement Outcomes: Insights From the STS/ACC TVT Registry.

BACKGROUND: Atherosclerotic cardiovascular disease is highly prevalent in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). Polyvascular disease (PVD), defined as involvement of ≥2 vascular beds (VBs), that is, coronary, cerebrovascular, or peripheral, portends a poor prognosis in patients with atherosclerotic cardiovascular disease; however, data on the association of PVD with outcomes of patients undergoing TAVR are limited. METHODS: The Society of Thoracic Surgeons and the American College of Cardiology Transcatheter Valve Therapy Registry was analyzed to identify patients who underwent TAVR from November 2011 to March 2022. The exposure of interest was PVD. The primary outcome was all-cause mortality. Secondary outcomes included major vascular complications, major/life-threatening bleeding, myocardial infarction, transient ischemic attack/stroke, and valve- and non-valve-related readmissions. Outcomes were assessed at 30 days and 1 year. RESULTS: Of 443 790 patients who underwent TAVR, PVD was present in 150 823 (34.0%; 111 425 [25.1%] with 2VB-PVD and 39 398 [8.9%] with 3VB-PVD). On multivariable analysis, PVD was associated with increased all-cause mortality at 1 year (hazard ratio, 1.17 [95% CI, 1.14-1.20]). There was an incremental increase in 1-year mortality with an increasing number of VBs involved (no PVD [reference]; 2VB-PVD: hazard ratio, 1.12 [95% CI, 1.09-1.15]: and 3VB-PVD: hazard ratio, 1.31 [95% CI, 1.26-1.36]). Patients with versus without PVD had higher rates of major vascular complications, major/life-threatening bleeding, transient ischemic attack/stroke, and non-valve-related readmissions at 30 days and 1 year. CONCLUSIONS: PVD is associated with worse outcomes after TAVR, and the risk is highest in patients with 3VB-PVD.

The effects of a 6-month weight loss intervention on physical function and serum biomarkers in older adults with and without osteoarthritis.

Objective: To examine the effects of a 6-month weight loss intervention on physical function, inflammatory biomarkers, and metabolic biomarkers in both those with and without osteoarthritis (OA). Design: 59 individuals ≥60 years old with obesity and a functional impairment were enrolled into this IRB approved clinical trial and randomized into one of two 6-month weight loss arms: a higher protein hypocaloric diet or a standard protein hypocaloric diet. All participants were prescribed individualized 500-kcal daily-deficit diets, with a goal of 10% weight loss. Additionally, participants participated in three, low-intensity, exercise sessions per week. Physical function, serum biomarkers and body composition data were assessed at the baseline and 6-month timepoints. Statistical analyses assessed the relationships between biomarkers, physical function, body composition, and OA status as a result of the intervention. Results: No group effects of dietary intervention were detected on any outcome measures (multiple p â€‹> â€‹0.05). During the 6-month trial, participants lost 6.2 â€‹± â€‹4.0% of their bodyweight (p â€‹< â€‹0.0001) and experienced improved physical function on the Short-Performance-Physical-Battery (p â€‹< â€‹0.0001), 8-foot-up-and-go (p â€‹< â€‹0.0001), and time to complete 10-chair-stands (p â€‹< â€‹0.0001). Adiponectin concentrations (p â€‹= â€‹0.0480) were elevated, and cartilage oligomeric matrix protein (COMP) concentrations (p â€‹< â€‹0.0001) were reduced; further analysis revealed that reductions in serum COMP concentrations were greater in OA-negative individuals. Conclusions: These results suggest that weight loss in older adults with and without OA may provide a protective effect to cartilage and OA. In particular, OA-negative individuals may be able to mitigate changes associated with OA through weight loss.

Using Randomized Controlled Trials to Estimate the Effect of Community Interventions for Childhood Asthma.

INTRODUCTION: The Centers for Disease Control and Prevention's Controlling Childhood Asthma and Reducing Emergencies initiative aims to prevent 500,000 emergency department (ED) visits and hospitalizations within 5 years among children with asthma through implementation of evidence-based interventions and policies. Methods are needed for calculating the anticipated effects of planned asthma programs and the estimated effects of existing asthma programs. We describe and illustrate a method of using results from randomized control trials (RCTs) to estimate changes in rates of adverse asthma events (AAEs) that result from expanding access to asthma interventions. METHODS: We use counterfactual arguments to justify a formula for the expected number of AAEs prevented by a given intervention. This formula employs a current rate of AAEs, a measure of the increase in access to the intervention, and the rate ratio estimated in an RCT. RESULTS: We justified a formula for estimating the effect of expanding access to asthma interventions. For example, if 20% of patients with asthma in a community with 20,540 annual asthma-related ED visits were offered asthma self-management education, ED visits would decrease by an estimated 1,643; and annual hospitalizations would decrease from 2,639 to 617. CONCLUSION: Our method draws on the best available evidence from RCTs to estimate effects on rates of AAEs in the community of interest that result from expanding access to asthma interventions.

Mediators of Improvement in TAVR Outcomes Over Time: Insights From the STS-ACC TVT Registry.

BACKGROUND: Over the past decade, there has been substantial improvement in outcomes after transcatheter aortic valve replacement. Many patient and procedural factors have also changed over that time, making it challenging to untangle the drivers of those improvements. METHODS: Among patients who underwent transcatheter aortic valve replacement from 2012 to 2018 within the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry, we examined the relative contribution of changes in patient factors, device modifications, improving experience/skill, and advances in periprocedural care to the observed improvement in outcomes after transcatheter aortic valve replacement. Mediator clusters included demographics, noncardiovascular comorbidities, cardiovascular comorbidities, device-related factors, and nondevice-related procedural factors. Using logistic regression, we serially adjusted for the mediator clusters to examine the contribution of each to the observed improvement in outcomes over time. RESULTS: Among 161 196 patients treated with transcatheter aortic valve replacement at 596 sites, outcomes improved steadily from 2012 to 2018, including 30-day mortality (6.7% to 2.4%), 30-day composite adverse events (25.3% to 10.5%), and 1-year mortality (19.9% to 10.1%; all P<0.001). In sequential models, the unadjusted odds ratio for 30-day mortality was 0.82 per year (95% CI, 0.80-0.84), which was progressively attenuated with addition of each covariate cluster. Most of the improvement was explained by device factors and nondevice procedural factors. Results were similar for 30-day composite adverse events, although the observed temporal improvement was not fully explained by measured factors, suggesting improved technical skill as an additional mediator. In contrast to 30-day outcomes, each cluster of patient and procedural factors contributed similarly to the temporal improvement in 1-year mortality, indicating a greater impact of patient factors on longer-term outcomes. CONCLUSIONS: While US patients undergoing transcatheter aortic valve replacement have become younger, healthier, and lower risk over time, the most important factors contributing to improvements in short-term outcomes relate to advances in device technology and procedural factors, whereas changing patient characteristics had a greater impact on improvement in 1-year outcomes.

Modeling the Association of Volume vs Composite Outcome Thresholds With Outcomes and Access to Transcatheter Aortic Valve Implantation in the US.

Importance: Professional societies and the Centers for Medicare & Medicaid Services suggest volume thresholds to ensure quality in transcatheter aortic valve implantation (TAVI). Objective: To model the association of volume thresholds vs spoke-and-hub implementation of outcome thresholds with TAVI outcomes and geographic access. Design, Setting, and Participants: This cohort study included patients who enrolled in the US Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy registry. Site volume and outcomes were determined from a baseline cohort of adults undergoing TAVI between July 1, 2017, and June 30, 2020. Exposures: Within each hospital referral region, TAVI sites were categorized by volume (<50 or ≥50 TAVIs per year) and separately by risk-adjusted outcome on the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy 30-day TAVI composite during the baseline period (July 2017 to June 2020). Outcomes of patients undergoing TAVIs from July 1, 2020, to March 31, 2022, were then modeled as though the patients had been treated at (1) the nearest higher volume (≥50 TAVIs per year) or (2) the best outcome site within the hospital referral region. Main Outcomes and Measures: The primary outcome was the absolute difference in events between the adjusted observed and modeled 30-day composite of death, stroke, major bleeding, stage III acute kidney injury, and paravalvular leak. Data are presented as the number of events reduced under the above scenarios with 95% bayesian credible intervals (CrIs) and median (IQR) driving distance. Results: The overall cohort included 166 248 patients with a mean (SD) age of 79.5 (8.6) years; 74 699 (47.3%) were female and 6657 (4.2%) were Black; 158 025 (95%) were treated in higher-volume sites (≥50 TAVIs) and 75 088 (45%) were treated in best-outcome sites. Modeling a volume threshold, there was no significant reduction in estimated adverse events (-34; 95% CrI, -75 to 8), while the median (IQR) driving time from the existing site to the alternate site was 22 (15-66) minutes. Transitioning care to the best outcome site in a hospital referral region resulted in an estimated 1261 fewer adverse outcomes (95% CrI, 1013-1500), while the median (IQR) driving time from the original site to the best site was 23 (15-41) minutes. Directionally similar findings were observed for Black individuals, Hispanic individuals, and individuals from rural areas. Conclusions and Relevance: In this study, compared with the current system of care, a modeled outcome-based spoke-and-hub paradigm of TAVI care improved national outcomes to a greater extent than a simulated volume threshold, at the cost of increased driving time. To improve quality while maintaining geographic access, efforts should focus on reducing site variation in outcomes.

Facilitating Shared Decision Making Among Black Patients at Risk for Sudden Cardiac Arrest : A Randomized Clinical Trial.

BACKGROUND: Racial disparities in implantable cardioverter-defibrillator (ICD) implantation are multifactorial and are partly explained by higher refusal rates. OBJECTIVE: To assess the effectiveness of a video decision support tool for Black patients eligible for an ICD. DESIGN: Multicenter, randomized clinical trial conducted between September 2016 and April 2020. (ClinicalTrials.gov: NCT02819973). SETTING: Fourteen academic and community-based electrophysiology clinics in the United States. PARTICIPANTS: Black adults with heart failure who were eligible for a primary prevention ICD. INTERVENTION: An encounter-based video decision support tool or usual care. MEASUREMENTS: The primary outcome was the decision regarding ICD implantation. Additional outcomes included patient knowledge, decisional conflict, ICD implantation within 90 days, the effect of racial concordance on outcomes, and the time patients spent with clinicians. RESULTS: Of the 330 randomly assigned patients, 311 contributed data for the primary outcome. Among those randomly assigned to the video group, assent to ICD implantation was 58.6% compared with 59.4% in the usual care group (difference, -0.8 percentage point [95% CI, -13.2 to 11.1 percentage points]). Compared with usual care, participants in the video group had a higher mean knowledge score (difference, 0.7 [CI, 0.2 to 1.1]) and a similar decisional conflict score (difference, -2.6 [CI, -5.7 to 0.4]). The ICD implantation rate within 90 days was 65.7%, with no differences by intervention. Participants randomly assigned to the video group spent less time with their clinician than those in the usual care group (mean, 22.1 vs. 27.0 minutes; difference, -4.9 minutes [CI, -9.4 to -0.3 minutes]). Racial concordance between video and study participants did not affect study outcomes. LIMITATION: The Centers for Medicare & Medicaid Services implemented a requirement for shared decision making for ICD implantation during the study. CONCLUSION: A video-based decision support tool increased patient knowledge but did not increase assent to ICD implantation. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute.

Complications of Intravenous Tenecteplase Versus Alteplase for the Treatment of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Prior systematic reviews have compared the efficacy of intravenous tenecteplase and alteplase in acute ischemic stroke, assigning their relative complications as a secondary objective. The objective of the present study is to determine whether the risk of treatment complications differs between patients treated with either agent. METHODS: We performed a systematic review including interventional studies and prospective and retrospective, observational studies enrolling adult patients treated with intravenous tenecteplase for ischemic stroke (both comparative and noncomparative with alteplase). We searched MEDLINE, Embase, the Cochrane Library, Web of Science, and the www. CLINICALTRIALS: gov registry from inception through June 3, 2022. The primary outcome was symptomatic intracranial hemorrhage, and secondary outcomes included any intracranial hemorrhage, angioedema, gastrointestinal hemorrhage, other extracranial hemorrhage, and mortality. We performed random effects meta-analyses where appropriate. Evidence was synthesized as relative risks, comparing risks in patients exposed to tenecteplase versus alteplase and absolute risks in patients treated with tenecteplase. RESULTS: Of 2226 records identified, 25 full-text articles (reporting 26 studies of 7913 patients) were included. Sixteen studies included alteplase as a comparator, and 10 were noncomparative. The relative risk of symptomatic intracranial hemorrhage in patients treated with tenecteplase compared with alteplase in the 16 comparative studies was 0.89 ([95% CI, 0.65-1.23]; I2=0%). Among patients treated with low dose (<0.2 mg/kg; 4 studies), medium dose (0.2-0.39 mg/kg; 13 studies), and high dose (≥0.4 mg/kg; 3 studies) tenecteplase, the RRs of symptomatic intracranial hemorrhage were 0.78 ([95% CI, 0.22-2.82]; I2=0%), 0.77 ([95% CI, 0.53-1.14]; I2=0%), and 2.31 ([95% CI, 0.69-7.75]; I2=40%), respectively. The pooled risk of symptomatic intracranial hemorrhage in tenecteplase-treated patients, including comparative and noncomparative studies, was 0.99% ([95% CI, 0%-3.49%]; I2=0%, 7 studies), 1.69% ([95% CI, 1.14%-2.32%]; I2=1%, 23 studies), and 4.19% ([95% CI, 1.92%-7.11%]; I2=52%, 5 studies) within the low-, medium-, and high-dose groups. The risks of any intracranial hemorrhage, mortality, and other studied outcomes were comparable between the 2 agents. CONCLUSIONS: Across medium- and low-dose tiers, the risks of complications were generally comparable between those treated with tenecteplase versus alteplase for acute ischemic stroke.

The Impact of Hearing Loss and Its Treatment on Health-Related Quality of Life Utility: a Systematic Review with Meta-analysis.

BACKGROUND: Hearing loss significantly impacts health-related quality of life (QoL), yet the effects of current treatments on QoL utility remain uncertain. Our objective was to describe the impact of untreated and treated hearing loss on QoL utility to inform hearing healthcare policy. METHODS: We searched databases for articles published through 02/01/2021. Two independent reviewers screened for articles that reported elicitation of general QoL utility values for untreated and treated hearing loss health states. We extracted data and quality indicators from 62 studies that met the inclusion criteria. RESULTS: Included studies predominately used observational pre/post designs (61%), evaluated unilateral cochlear implantation (65%), administered the Health Utilities Index 3 (HUI3; 71%), and were conducted in Europe and North America (84%). In general, treatment of hearing loss improved post-treatment QoL utility when measured by most methods except the Euro-QoL 5 dimension (EQ-5D). In meta-analysis, hearing aids for adult mild-to-moderate hearing loss compared to no treatment significantly improved HUI3-estimated QoL utility (3 studies; mean change=0.11; 95% confidence interval (CI): 0.07 to 0.14) but did not impact EQ-5D-estimated QoL (3 studies; mean change=0.0; 95% CI: -0.03 to 0.04). Cochlear implants improved adult QoL utility 1-year post-implantation when measured by the HUI3 (7 studies; mean change=0.17; 95% CI: 0.11 to 0.23); however, pediatric VAS-estimated QoL utility was non-significant (4 studies; mean change=0.12; 95% CI: -0.02 to 0.25). The quality of included studies was limited by failure to report missingness of data and low survey response rates. Our study was limited by heterogeneous study populations and designs. FINDINGS: Treatment of hearing loss significantly improves QoL utility, and the HUI3 and VAS were most sensitive to improvements in hearing. Improved access to hearing healthcare should be prioritized. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42021253314.

Impact of Diabetes on Pathologic Response to Multimodality Therapy for Esophageal Cancer.

BACKGROUND: The incidence of esophageal cancer has increased faster than that of most cancers. Evidence from other malignant neoplasms suggests that diabetic patients have a worse response to multimodality therapy. We hypothesized that diabetic patients with esophageal cancer will have a decreased response to neoadjuvant chemotherapy and radiation therapy compared with nondiabetic patients. METHODS: A retrospective study of The Society of Thoracic Surgeons General Thoracic Surgery Database identified all patients who had an esophagectomy after neoadjuvant therapy for esophageal cancer between 2012 and 2019. Patients were compared on the basis of the presence of diabetes. A pathologic complete response (pCR) was defined as ypT0 N0. The χ2 and Wilcoxon rank sum tests were used to compare patients' demographic and clinical characteristics between those with and those without diabetes. Multivariable logistic regression was used to evaluate the predictors of response to neoadjuvant therapy. RESULTS: Of the 9171 patients who met inclusion criteria, 2011 (22%) patients were diabetic and 7160 (78%) patients were nondiabetic. Patients with diabetes were older, more likely to be male, and more likely to have all comorbidities. Univariate analysis revealed that diabetic patients were less likely to have pCR (16% vs 18%; P = .026). Although multivariable analysis showed a trend toward diabetic patients' having lower odds of achieving pCR, diabetes was not independently associated with pCR (odds ratio, 0.89; 95% CI, 0.78-1.01; P = .075). CONCLUSIONS: Diabetic patients may be less likely than nondiabetic patients to achieve pCR after neoadjuvant treatment of esophageal cancer. This suggests the need for further exploration as diabetic patients with esophageal cancer can potentially benefit from different treatment paradigms compared with their nondiabetic counterparts.

Telehealth for the Longitudinal Management of Chronic Conditions: Systematic Review.

BACKGROUND: Extensive literature support telehealth as a supplement or adjunct to in-person care for the management of chronic conditions such as congestive heart failure (CHF) and type 2 diabetes mellitus (T2DM). Evidence is needed to support the use of telehealth as an equivalent and equitable replacement for in-person care and to assess potential adverse effects. OBJECTIVE: We conducted a systematic review to address the following question: among adults, what is the effect of synchronous telehealth (real-time response among individuals via phone or phone and video) compared with in-person care (or compared with phone, if synchronous video care) for chronic management of CHF, chronic obstructive pulmonary disease, and T2DM on key disease-specific clinical outcomes and health care use? METHODS: We followed systematic review methodologies and searched two databases (MEDLINE and Embase). We included randomized or quasi-experimental studies that evaluated the effect of synchronously delivered telehealth for relevant chronic conditions that occurred over ≥2 encounters and in which some or all in-person care was supplanted by care delivered via phone or video. We assessed the bias using the Cochrane Effective Practice and Organization of Care risk of bias (ROB) tool and the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation. We described the findings narratively and did not conduct meta-analysis owing to the small number of studies and the conceptual heterogeneity of the identified interventions. RESULTS: We identified 8662 studies, and 129 (1.49%) were reviewed at the full-text stage. In total, 3.9% (5/129) of the articles were retained for data extraction, all of which (5/5, 100%) were randomized controlled trials. The CHF study (1/5, 20%) was found to have high ROB and randomized patients (n=210) to receive quarterly automated asynchronous web-based review and follow-up of telemetry data versus synchronous personal follow-up (in-person vs phone-based) for 1 year. A 3-way comparison across study arms found no significant differences in clinical outcomes. Overall, 80% (4/5) of the studies (n=466) evaluated synchronous care for patients with T2DM (ROB was judged to be low for 2, 50% of studies and high for 2, 50% of studies). In total, 20% (1/5) of the studies were adequately powered to assess the difference in glycosylated hemoglobin level between groups; however, no significant difference was found. Intervention design varied greatly from remote monitoring of blood glucose combined with video versus in-person visits to an endocrinology clinic to a brief, 3-week remote intervention to stabilize uncontrolled diabetes. No articles were identified for chronic obstructive pulmonary disease. CONCLUSIONS: This review found few studies with a variety of designs and interventions that used telehealth as a replacement for in-person care. Future research should consider including observational studies and studies on additional highly prevalent chronic diseases.

In vivo fluid transport in human intervertebral discs varies by spinal level and disc region.

Background: The lumbar discs are large, dense tissues that are primarily avascular, and cells residing in the central region of the disc are up to 6-8 mm from the nearest blood vessel in adults. To maintain homeostasis, disc cells rely on nutrient transport between the discs and adjacent vertebrae. Thus, diminished transport has been proposed as a factor in age-related disc degeneration. Methods: In this study, we used magnetic resonance imaging (MRI) to quantify diurnal changes in T2 relaxation time, an MRI biomarker related to disc hydration, to generate 3D models of disc fluid distribution and determine how diurnal changes in fluid varied by spinal level. We recruited 10 participants (five males/five females; age: 21-30 years; BMI: 19.1-29.0 kg/m2) and evaluated the T2 relaxation time of each disc at 8:00 AM and 7:00 PM, as well as degeneration grade (Pfirrmann). We also measured disc height, volume, and perimeter in a subset of individuals as a preliminary comparison of geometry and transport properties. Results: We found that the baseline (AM) T2 relaxation time and the diurnal change in T2 relaxation time were greatest in the cranial lumbar discs, decreasing along the lumbar spine from cranial to caudal. In cranial discs, T2 relaxation times decreased in each disc region (nucleus pulposus [NP], inner annulus fibrosus [IAF], and outer annulus fibrosus [OAF]), whereas in caudal discs, T2 relaxation times decreased in the NP but increased in the AF. Conclusions: Fluid transport varied by spinal level, where transport was greatest in the most cranial lumbar discs and decreased from cranial to caudal along the lumbar spine. Future work should evaluate what level-dependent factors affect transport.

Cardiac resynchronization therapy outcomes with left ventricular lead concordant with latest mechanical activation: A meta-analysis.

BACKGROUND: For cardiac resynchronization therapy (CRT), image-guided approaches targeting left ventricular (LV) lead placement at the site of latest mechanical activation had inconsistent outcomes. We examined evidence for improved CRT outcomes when LV lead placement concordant with latest mechanical activation occurred. METHODS: A review of EMBASE and PubMed was performed for randomized controlled trials or prospective observational studies from October 2008 through October 2020 comparing outcomes with concordant versus discordant LV lead placement. Meta-analyses were performed to assess the association between concordance and death, death or heart failure (HF) hospitalization, ≥ 15% reduction in LV end systolic volume (LVESV), and changes in LVESV or ejection fraction (LVEF). RESULTS: From 5897 citations, nine publications (eight studies) with 1355 patients were selected; 975 with a concordant LV lead and 380 with a discordant lead. Mean age was 66-68 years, 82% were male, and 64% had ischemic cardiomyopathy. Meta-analyses demonstrated a statistically significant reduction in death/HF hospitalization at 2 years (OR 0.38; 95% CI 0.16, 0.92) and LVESV at 6 months (mean difference [MD] -13.4%; 95% CI -6.7%, -20.0%), and an increase in LVEF (MD 4.03; 95% CI 0.77, 7.30) with the concordant LV lead. There were trends toward decreased death at 2 years (OR 0.49; 95% CI 0.19, 1.23) and ≥ 15% reduction in LVESV at 6 months (OR 3.81; 95% CI 0.24, 61.24) with concordant LV lead placement. CONCLUSION: A concordant LV lead was associated with better CRT outcomes. Further study of feasible methods to achieve LV lead concordance is needed.

Outcomes of Cardiac Resynchronization Therapy with Image-Guided Left Ventricular Lead Placement at the Site of Latest Mechanical Activation: A Systematic Review and Meta-Analysis.

Aim: To assess evidence for an image-guided approach for cardiac resynchronization therapy (CRT) that targets left ventricular (LV) lead placement at the segment of latest mechanical activation. Methods: A systematic review of EMBASE and PubMed was performed for randomized controlled trials (RCTs) and prospective observational studies from October 2008 through October 2020 that compared an image-guided CRT approach with a non-image-guided approach for LV lead placement. Meta-analyses were performed to assess the association between the image-guided approach and NYHA class improvement or changes in end-systolic volume (LVESV), end-diastolic volume (LVEDV), and ejection fraction (LVEF). Results: From 5897 citations, 5 RCTs including 818 patients (426 image-guided and 392 non-image-guided) were identified. The mean age ranged from 66 to 71 years, 76% were male, and 53% had ischemic cardiomyopathy. Speckle tracking echocardiography was the primary image-guided method in all studies. LV lead placement within the segment of the latest mechanical activation (concordant) was achieved in the image-guided arm in 45% of the evaluable patients. There was a statistically significant improvement in the NYHA class at 6 months (odds ratio 1.66; 95% confidence interval (CI) [1.02, 2.69]) with the image-guided approach, but no statistically significant change in LVESV (MD -7.1%; 95% CI [-16.0, 1.8]), LVEDV (MD -5.2%; 95% CI [-15.8, 5.4]), or LVEF (MD 0.68; 95% CI [-4.36, 5.73]) versus the non-image-guided approach. Conclusion: The image-guided CRT approach was associated with improvement in the NYHA class but not echocardiographic measures, possibly due to the small sample size and a low rate of concordant LV lead placement despite using the image-guided approach. Therefore, our meta-analysis was not able to identify consistent improvement in CRT outcomes with an image-guided approach.

Risk of Each of the Five Lung Lobectomies: A Society of Thoracic Surgeons Database Analysis.

BACKGROUND: The perioperative risk of pulmonary lobectomy as a solitary procedure has been extensively studied, yet the differences in outcomes between lobes, which have unique anatomy and a different amount of lung parenchyma, are entirely unknown. The purpose of this study was to define the risk of each of the 5 lobectomies. METHODS: The Society of Thoracic Surgeons Database was queried for patients undergoing lobectomy between 2008 and 2018. Patient and disease characteristics, operative variables, major morbidity, and 30-day mortality were examined. A multivariable logistic regression model (using the same variables in the current Society of Thoracic Surgeons lobectomy risk model) was developed to assess the contribution of lobectomy site to adverse outcomes. RESULTS: There were 65 006 patients analyzed. Adjusted perioperative mortality rate is lowest for right middle lobe (RML), 0.63%; intermediate for right upper lobe (RUL), left upper lobe (LUL), and left lower lobe (LLL), 1.08 to 1.24%; and highest for right lower lobe (RLL), 1.63%. The adjusted major morbidity rate is lowest for RML, 5.36%; intermediate for LLL and LUL, 7.82% to 8.33%; and highest for RUL and RLL, 8.94% to 9.32%. Adjusted intraoperative transfusion rate is lowest for RML, 1.37%; intermediate for RLL and LLL, 1.81% to 1.94%; and highest for RUL and LUL, 2.47% to 2.72%. CONCLUSIONS: There are clear differences in postoperative outcomes by lobectomy location. Mortality, major morbidity, and transfusion rate are lowest for RML but vary across other lobectomies. These differences should be appreciated in evaluating risk of operation, deciding on best therapy, counseling patients, and comparing outcomes.