Citations

We examined the effects of acute β‐adrenergic blockade on central artery hemodynamics and wave reflection characteristics in young healthy humans. High‐fidelity radial artery waveforms were recorded non‐invasively by applanation tonometry before and after intravenous propranolol (0.25 mg/kg bolus for 5 min followed by a maintenance infusion of 0.004/mg/kg/min for 20–30 min) in fourteen subjects (9 F/5M; 27 ± 2 years). Radial blood pressure (BP) was calibrated from the brachial BP (arterial catheter). Aortic augmentation index (AI a ; a measure of amplitude and timing of arterial pressure wave reflection) and roundtrip travel time of the reflected wave to and from the periphery (Δt p ; inverse of pulse wave velocity) were calculated from the generated aortic pressure waveform and are indices of central arterial stiffness. Systemic β‐blockade reduced heart rate (HR; 60 ± 2 vs. 53 ± 2 bpm, P < 0.001) and increased AI a (9.9 ± 4.3% vs. 4.3 ± 4.4%, P < 0.05), but did not alter Δt p (156 ± 4 msec vs. 152 ± 2 msec, P = 0.34). The AI a normalized to a HR of 75bpm (AI a @75) was not increased following β‐blockade (P = 0.67). Taken together, our data indicate that the increase in AI a following systemic β‐blockade is a result of a slower HR and not due to changes in β‐ mediated vascular tone. Supported by NIH K23 DK‐082424 (TBC), AHA 2170087(ECH) and CTSA RR‐024150

We examined the relationship between flow restoration and vascular resistance in the exercising forearm during hypoperfusion caused by balloon inflation in the brachial artery. 75 trials (with and without nitric oxide synthase (NOS) inhibition) were analyzed. Each included forearm exercise (10% or 20% of max), exercise with inflation, and exercise after deflation (3 min each). FBF (ultrasound), local (brachial artery; BAP), and systemic arterial pressure (SAP) were measured. FBF restoration during balloon inflation was calculated as (steady state inflation plus exercise value – nadir)/[steady state exercise (control) value‐nadir] and expressed as % recovery of FBF. Balloon resistance [(SAP‐BAP)/flow] and vascular resistance (BAP/flow) were expressed as the % change from onset of inflation to end inflation. The % recovery of FBF was strongly related to the drop in vascular resistance for all trials (r = 0.664, P <0.001). This relationship was unaffected by NOS inhibition (n= 27; r = 0.623, P < 0.001 vs. control n = 48; r = 0.685, P < 0.001). The relationship was also stronger with increasing exercise intensity (r = 0.57 vs. 0.704). The % recovery of FBF was unrelated to changes in balloon resistance under any condition. Thus, flow restoration is determined primarily by the fall in local vascular resistance during forearm exercise with hypoperfusion. Supported by NIH HL‐46493 (MJJ), AR‐55819 (DPC) and RR‐024150.

Purpose Development of appropriate reimbursement models for breast reconstruction in the United States requires an understanding of relevant economic trends. The purpose of this study is to evaluate longitudinal patterns in Medicare reimbursement for frequently performed breast reconstruction procedures between 2000 and 2019. Methods Reimbursement data for 15 commonly performed breast reconstruction procedures were analyzed using the Centers for Medicare & Medicaid Services Physician Fee Schedule Look-Up Tool for each Current Procedural Terminology code. By utilizing changes to the US consumer price index, monetary data were adjusted for inflation to 2019 US dollars. Inflation-adjusted trends were used to calculate average annual and total percentage changes in reimbursement over time. Results From 2000 to 2019, average adjusted reimbursement for all procedures fell by 13.32%. All procedures demonstrated a negative adjusted reimbursement rate other than immediate insertion of breast prosthesis, which increased by 55.37%. The largest mean decrease was observed in breast reconstruction with other technique (−28.63%), followed by single pedicle transverse rectus abdominis myocutaneous flap (−26.02%), single pedicle transverse rectus abdominis myocutaneous flap with microvascular anastomosis (−23.33%), latissimus dorsi flap (−19.65%), and free flap reconstruction (−19.36%). Conclusions There has been a steady yet substantial decline in Medicare reimbursement for the majority of breast reconstruction procedures over the last 20 years. Given increasing medical costs and the financial uncertainty of the US health care system, an understanding of Medicare reimbursement trends is vital for policymakers, administrators, and physicians to develop agreeable reimbursement models that facilitate growth and economic vitality of breast reconstruction in the United States.

Abstract Objectives The study aimed to understand potential barriers to the adoption of health information technology projects that are released as free and open source software (FOSS). Methods We conducted a survey of research consortia participants engaged in genomic medicine implementation to assess perceived institutional barriers to the adoption of three systems: ClinGen electronic health record (EHR) Toolkit, DocUBuild, and MyResults.org. The survey included eight barriers from the Consolidated Framework for Implementation Research (CFIR), with additional barriers identified from a qualitative analysis of open-ended responses. Results We analyzed responses from 24 research consortia participants from 18 institutions. In total, 14 categories of perceived barriers were evaluated, which were consistent with other observed barriers to FOSS adoption. The most frequent perceived barriers included lack of adaptability of the system, lack of institutional priority to implement, lack of trialability, lack of advantage of alternative systems, and complexity. Conclusion In addition to understanding potential barriers, we recommend some strategies to address them (where possible), including considerations for genomic medicine. Overall, FOSS developers need to ensure systems are easy to trial and implement and need to clearly articulate benefits of their systems, especially when alternatives exist. Institutional champions will remain a critical component to prioritizing genomic medicine projects.

There is a need for multimodal strategies to keep research participants informed about study results. Our aim was to characterize preferences of genomic research participants from two institutions along four dimensions of general research result updates: content, timing, mechanism, and frequency. Methods: We conducted a web-based cross-sectional survey that was administered from 25 June 2018 to 5 December 2018. Results: 397 participants completed the survey, most of whom (96%) expressed a desire to receive research updates. Preferences with high endorsement included: update content (brief descriptions of major findings, descriptions of purpose and goals, and educational material); update timing (when the research is completed, when findings are reviewed, when findings are published, and when the study status changes); update mechanism (email with updates, and email newsletter); and update frequency (every three months). Hierarchical cluster analyses based on the four update preferences identified four profiles of participants with similar preference patterns. Very few participants in the largest profile were comfortable with budgeting less money for research activities so that researchers have money to set up services to send research result updates to study participants. Conclusion: Future studies may benefit from exploring preferences for research result updates, as we have in our study. In addition, this work provides evidence of a need for funders to incentivize researchers to communicate results to participants.

Abstract Background: A positive association between circulating C-reactive protein (CRP) and colorectal cancer survival was reported in observational studies, which are susceptible to unmeasured confounding and reverse causality. We used a Mendelian randomization approach to evaluate the association between genetically predicted CRP concentrations and colorectal cancer–specific survival. Methods: We used individual-level data for 16,918 eligible colorectal cancer cases of European ancestry from 15 studies within the International Survival Analysis of Colorectal Cancer Consortium. We calculated a genetic-risk score based on 52 CRP-associated genetic variants identified from genome-wide association studies. Because of the non-collapsibility of hazard ratios from Cox proportional hazards models, we used the additive hazards model to calculate hazard differences (HD) and 95% confidence intervals (CI) for the association between genetically predicted CRP concentrations and colorectal cancer–specific survival, overall and by stage at diagnosis and tumor location. Analyses were adjusted for age at diagnosis, sex, body mass index, genotyping platform, study, and principal components. Results: Of the 5,395 (32%) deaths accrued over up to 10 years of follow-up, 3,808 (23%) were due to colorectal cancer. Genetically predicted CRP concentration was not associated with colorectal cancer–specific survival (HD, −1.15; 95% CI, −2.76 to 0.47 per 100,000 person-years; P = 0.16). Similarly, no associations were observed in subgroup analyses by stage at diagnosis or tumor location. Conclusions: Despite adequate power to detect moderate associations, our results did not support a causal effect of circulating CRP concentrations on colorectal cancer–specific survival. Impact: Future research evaluating genetically determined levels of other circulating inflammatory biomarkers (i.e., IL6) with colorectal cancer survival outcomes is needed.

Abstract Background Incidence of early-onset (younger than 50 years of age) colorectal cancer (CRC) is increasing in many countries. Thus, elucidating the role of traditional CRC risk factors in early-onset CRC is a high priority. We sought to determine whether risk factors associated with late-onset CRC were also linked to early-onset CRC and whether association patterns differed by anatomic subsite. Methods Using data pooled from 13 population-based studies, we studied 3767 CRC cases and 4049 controls aged younger than 50 years and 23 437 CRC cases and 35 311 controls aged 50 years and older. Using multivariable and multinomial logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess the association between risk factors and early-onset CRC and by anatomic subsite. Results Early-onset CRC was associated with not regularly using nonsteroidal anti-inflammatory drugs (OR = 1.43, 95% CI = 1.21 to 1.68), greater red meat intake (OR = 1.10, 95% CI = 1.04 to 1.16), lower educational attainment (OR = 1.10, 95% CI = 1.04 to 1.16), alcohol abstinence (OR = 1.23, 95% CI = 1.08 to 1.39), and heavier alcohol use (OR = 1.25, 95% CI = 1.04 to 1.50). No factors exhibited a greater excess in early-onset compared with late-onset CRC. Evaluating risks by anatomic subsite, we found that lower total fiber intake was linked more strongly to rectal (OR = 1.30, 95% CI = 1.14 to 1.48) than colon cancer (OR = 1.14, 95% CI = 1.02 to 1.27; P = .04). Conclusion In this large study, we identified several nongenetic risk factors associated with early-onset CRC, providing a basis for targeted identification of those most at risk, which is imperative in mitigating the rising burden of this disease.