Publications

The day-to-day regularity of sleep-wake timing refers to time-varying patterns of behavioral cycles, which co-occur with temporally associated environmental exposures and circadian rhythms. Introduced in 2017, the Sleep Regularity Index (SRI) has enabled rigorous study of the health and performance implications of the day-to-day regularity of sleep-wake timing. Since its introduction, multiple open-source calculators have been published to facilitate SRI scoring from timestamped sleep-wake data; however, the comparability of these calculators had not previously been evaluated. Here, we sought to (1) estimate SRI usage and method of calculation in peer-reviewed studies published since its establishment; (2) compare SRI scores calculated by two widely used SRI calculators, sleepreg and GGIR; (3) compare results from prospective assessments of the relationship between sleepreg SRI scores versus GGIR SRI scores and previously examined health outcomes. We found that amidst increasing use of the SRI, non-disclosure and heterogeneity in the method of SRI calculation are common. Additionally, among more than 70 000 adults with accelerometer-derived sleep-wake data, SRI scores calculated by two widely used open-source packages differed markedly, both in absolute and relative values. Applied to prospective clinical outcome models for all-cause mortality, incident type 2 diabetes, and incident atrial fibrillation or atrial flutter, the method of calculation alone meaningfully changed results and interpretations. In light of these findings, we developed and introduced a 14-item RIRI statement (Reporting Items for Regularity Indices) to standardize reporting and promote reproducibility in research involving the SRI or complementary regularity indices.

BACKGROUND: Symptomatic peripheral artery disease (PAD) is prevalent and guideline-recommended therapies include optimal medical therapy (OMT), supervised exercise therapy (SET), and revascularization (stenting). The Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) trial examined longitudinal patient-reported outcomes to assess response to OMT, SET, and stenting. The predictors of symptomatic improvement have not been fully assessed.

METHODS: This is a secondary analysis of the CLEVER trial, which randomized patients with claudication to OMT alone, OMT plus SET, or OMT plus stenting. The primary outcome was a change in the Peripheral Artery Questionnaire (PAQ) summary score by 10 points or more from baseline to 6 and 18 months. Multivariate logistic regression was used to identify predictors of response.

RESULTS: Of the 103 participants (66 men, median age 63 years), 65 (63%) had a response to therapy at 6 months. Of 98 participants who completed the 18-month PAQ, 52 (53%) had a symptomatic response. On binary logistic regression, when compared to OMT, SET (6 months: odds ratio [OR] 4.25, 95% CI: 1.33-13.58; 18 months: OR 3.92, 95% CI: 1.04-14.70) and ST (6 months: OR 5.19, 95% CI: 1.58-17.03; 18 months: OR 11.50, 95% CI: 2.89-45.72) were associated with an increase in PAQ at 6 and 18 months.

CONCLUSION: Among randomized patients in the CLEVER trial, treatment with either SET or stenting was predictive of clinically meaningful change in the PAQ summary score from baseline to 6 and 18 months. These interventions, with a prioritization of SET, should be more widely available to patients with PAD. This study adds to the findings of the CLEVER trial by denoting that SET and stenting are beneficial in patients with PAD, independent of comorbidities.

BACKGROUND: National guidelines recommend forearm arteriovenous fistulas (AVFs) over upper arm AVFs as the initial permanent vascular access for hemodialysis if consistent with the end-stage kidney disease (ESKD) Life-Plan, but comparative outcomes are underexplored. Our objective was to assess longitudinal outcomes of forearm vs upper arm AVFs in patients with advanced kidney disease.

METHODS: Using multicenter data from three prospective studies (Hemodialysis Fistula Maturation [HFM] Study, PATENCY-1 [A Study of PRT-201 Administered Immediately After Radiocephalic Arteriovenous Fistula (AVF) Creation in Patients With Chronic Kidney Disease], and PATENCY-2), we conducted a cohort study of 1516 patients who underwent upper extremity AVF creation (2014-2019). Demographic factors, comorbidities, procedural details, and 3 years of longitudinal follow-up were captured. Outcomes included primary, primary-assisted, and secondary patency at 3 years, successful AVF use, and access-related hand ischemia (ARHI) interventions. Forearm vs upper arm AVF outcomes were compared using Cox regression and logistic regression models. Subgroup analyses included outcomes stratified by site volume using model interaction terms.

RESULTS: The study population included 1059 forearm AVFs and 457 upper arm AVFs; mean age was 56.2 ± 13.4 years and 25.2% were female. The overall primary, primary-assisted, and secondary patency rates at 3 years was 26.2% (95% confidence interval [CI], 23.6%-29.1%), 57.6% (95% CI, 54.6%-60.9%), and 66.5% (95% CI, 63.6%-69.5%), respectively, with no significant differences between forearm and upper arm AVFs. Successful AVF use at 12 months was also similar between forearm (66.1%) and upper arm AVFs (70.0%) (odds ratio, 1.02; 95% CI, 0.71-1.48; P = .91). Forearm AVFs had lower risk of ARHI interventions (hazard ratio [HR], 0.36; 95% CI, 0.18-0.71; P = .003) compared with upper arm AVFs. Subgroup analyses showed that compared with upper arm AVFs, patients who received forearm AVFs at low volume sites (≤30 access creations per year) were at greater risk for loss of primary-assisted (HR, 2.03; 95% CI, 1.21-3.41; P < .001) and secondary patency (HR, 2.53; 95% CI, 1.33-4.83; P < .001). Patients receiving forearm AVFs at low volume sites also had lower AVF use at 12 months (odds ratio, 0.52; 95% CI, 0.21-1.31; P value of interaction = .03).

CONCLUSIONS: Although forearm AVFs demonstrate similar long-term patency and usability as upper arm AVFs, they are associated with lower rates of ARHI. However, outcomes for forearm AVFs seem to have associations with institutional volume-significantly poorer results are seen at low-volume centers. System-level efforts are needed to improve outcomes for forearm AVFs, which serve as a critical lifeline for end-stage kidney disease patients.

OBJECTIVE: This first in human study evaluated the six month angiographic and one year clinical outcomes of a novel thin strut, sirolimus eluting, resorbable scaffold for symptomatic below the knee peripheral arterial disease (PAD). RESOLV I is an international, prospective, multicentre, single arm study assessing the performance of the MAGNITUDE drug eluting resorbable scaffold (DRS) for the treatment of below the knee lesions in patients with symptomatic PAD.

METHODS: Angiographic and duplex ultrasound evaluations were performed by independent core labs at baseline, post-DRS implantation, and at six months follow up. Binary re-stenosis (> 50% diameter stenosis) was determined via quantitative vascular angiography or duplex ultrasound when quantitative vascular angiography was unavailable. Peri-operative death, major adverse limb events, and functional status were evaluated up to one year.

RESULTS: Thirty five patients (mean age 74.5 ± 6.0 years) were enrolled: six (17%) had chronic total occlusion lesions and 25 (71%) had a baseline Rutherford-Becker classification of stage 5. The mean lesion length was 30.1 ± 12.0 mm. The binary re-stenosis rate at six months was 10% (3/31) (angiographic patency of 90%) and mean in segment late lumen loss was 0.75 ± 0.74 mm. Improved Rutherford class at 12 months follow up was achieved in 88% (29/33) of patients and most were asymptomatic (Rutherford-Becker class 0). No amputation or clinically driven target lesion revascularisation events were seen through 12 months.

CONCLUSION: Early results of the RESOLV I study showed that implantation of a thin strut MAGNITUDE DRS achieved low binary re-stenosis rates at six months, as well as improvement in functional status, with no clinically driven target lesion revascularisation at one year.

BACKGROUND: Based on the landmark PLATO (Platelet Inhibition and Patient Outcomes) and TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction) trials, current guidelines recommend ticagrelor and prasugrel over clopidogrel for acute coronary syndrome. However, subsequent studies have failed to replicate the reported benefits of ticagrelor, raising concerns about the validity of the PLATO trial's findings.

METHODS: Randomized trials published until January 2025 were searched on PubMed and Embase and included if they compared 2 of the 3 standard dual antiplatelet therapies: 12 months aspirin plus clopidogrel, prasugrel, or ticagrelor. We constructed a network with and without PLATO to assess its impact on the synthesized risk estimates on major adverse cardiovascular events, patient mortality, myocardial infarction, and stent thrombosis, as well as major bleeding and major or minor bleeding.

RESULTS: Twelve trials, enrolling 52 415 patients (clopidogrel: 23 557; ticagrelor: 13 344, prasugrel: 15 514) were included. The analysis with PLATO showed lower hazard ratios for ticagrelor versus clopidogrel than the analysis without PLATO in major adverse cardiovascular events, mortality, myocardial infarction, and bleeding outcomes (e.g., cardiovascular mortality; hazard ratio [HR], 0.83 [95% CI, 0.72-0.96] when PLATO was included; HR, 0.96 [95% CI, 0.73-1.25] when PLATO was excluded). Ticagrelor and prasugrel were associated with higher incidences of major bleeding and major or minor bleeding for analyses including and excluding PLATO, altohugh the point estimates for ticagrelor were lower when PLATO was included.

CONCLUSIONS: The pooled estimates with PLATO favored ticagrelor compared with estimates without PLATO in several studied outcomes, potentially suggesting the substantial impacts of PLATO's findings on the pooled risk estimates; therefore, additional evidence may be needed given the large number of patients worldwide treated with dual antiplatelet therapy.