Exercise blood pressure and heart rate responses to graded exercise testing in intermediate versus morning chronotypes with obesity.

Exaggerated exercise blood pressure (BP) is linked to cardiovascular disease (CVD). Although evening chronotypes have greater CVD risk than morning (Morn) types, it is unknown if exercise BP differs in intermediate (Int) types. Adults with obesity were classified as either Morn [n = 23 (18 females), Morning-Eveningness Questionnaire (MEQ) = 63.96 ± 1.0, 54.74 ± 1.4 yr, 33.7 ± 0.6 kg/m2] or Int [n = 23 (19 females), MEQ = 51.36 ± 1.1, 55.96 ± 1.8 yr, 37.2 ± 1.2 kg/m2] chronotype per MEQ. A graded, incremental treadmill test to maximal aerobic capacity (V̇o2max) was conducted. Systolic (SBP) and diastolic (DBP) blood pressure and mean arterial pressure (MAP), rate pressure product (RPP), heart rate (HR), and rate of perceived intensity (RPE) were determined at baseline, 4 min, 6 min, and maximal stages. HR recovery (HRR; maximum postexercise) was determined at 1 and 2 min postexercise. Preexercise fasted aortic waveforms (applanation tonometry), plasma leptin, nitrate/nitrite (nitric oxide bioavailability), and body composition (dual X-ray, DXA) were also collected. Int had lower V̇o2max and plasma nitrate (both P ≤ 0.02) than Morn. No difference in preexercise BP, aortic waveforms, or body composition were noted between groups, although higher plasma leptin was seen in Int compared with Morn (P = 0.04). Although Int had higher brachial DBP and MAP across exercise stages (both P ≤ 0.05) and higher HR, RPE, and RPP at 6 min of exercise (all P ≤ 0.05), covarying for V̇o2max nullified the BP, but not HR or RPE, difference. HRR was greater in Morn independent of V̇o2max (P = 0.046). Fasted leptin correlated with HR at exercise stage 4 (r = 0.421, P = 0.041) and 6 min (r = 0.593, P = 0.002). This observational study suggests that Int has exaggerated BP and HR responses to exercise compared with Morn, although fitness abolished BP differences.NEW & NOTEWORTHY This study compares blood pressure and heart rate responses with graded, incremental exercise between morning and intermediate chronotype adults with obesity. Herein, blood pressure responses to exercise were elevated in intermediate compared with morning chronotype, although V̇o2max abolished this observation. However, heart rate responses to exercise were higher in intermediate vs. morning chronotypes independent of fitness. Collectively, this exercise hemodynamic response among intermediate chronotype may be related to reduced aerobic fitness, altered nitric oxide metabolism, and/or elevated aortic waveforms.

Predicting daily emergency department visits using machine learning could increase accuracy.

OBJECTIVE: Administrators and clinicians alike have attempted to predict emergency department visits for many years. The ability to predict or "forecast" ED visit volume can allow for more efficient resource allocation, including up-staffing or down-staffing, changing OR schedules, and predicting the need for significant resources. The goal of this study is to examine combinations of variables via machine learning to increase prediction accuracy and determine the factors that are most predictive of overall ED visits. As compared to a simple univariate time series model, we hypothesize that machine learning models will predict St. Joseph Mercy Ann Arbor's patient visit load for the emergency department (ED) with higher accuracy than a simple univariate time series model. METHODS: Univariate time series models for daily ED visits, including ARIMA, Exponential Smoothing (ETS), and Facebook Inc.'s prophet algorithm were estimated as a baseline comparison. Machine learning models, including random forests and gradient boosted machines (GBM), were trained using data from 2017 to 2018. After final models were created, they were applied to the 2019 data to determine how well these models predicted actual ED patient volumes in data not utilized during the model fitting process. The accuracy of the machine learning and time series models were assessed based on out-of-sample predictive accuracy, compared using root mean squared error (RMSE). RESULTS: Using root mean squared error (RMSE) to assess out-of-sample predictive accuracy of the models, the results showed that the random forest model was the most accurate at predicting daily ED visits in the 2019 test set, followed by the GBM model. These performed only slightly better than the simple exponential smoothing model predictions. The ARIMA model performed poorly in comparison. The day of the week (likely capturing differences between weekdays and weekends) was found to be the most important predictor of patient volumes. Weather-related features such as maximum temperature and SFC pressure appeared to capture some of the seasonality trends related to changes in patient volumes. CONCLUSIONS: Machine learning models perform better at predicting daily patient volumes as compared to simple univariate time series models, though not by a substantial amount. Further research can help confirm these limited initial results. Gathering more training data and additional feature engineering could also be beneficial to training the models and potentially improving predictive accuracy.

Nitric oxide regulation of cellular metabolism: Adaptive tuning of cellular energy.

Nitric oxide can interact with a wide range of proteins including many that are involved in metabolism. In this review we have summarized the effects of NO on glycolysis, fatty acid metabolism, the TCA cycle, and oxidative phosphorylation with reference to skeletal muscle. Low to moderate NO concentrations upregulate glucose and fatty acid oxidation, while higher NO concentrations shift cellular reliance toward a fully glycolytic phenotype. Moderate NO production directly inhibits pyruvate dehydrogenase activity, reducing glucose-derived carbon entry into the TCA cycle and subsequently increasing anaploretic reactions. NO directly inhibits aconitase activity, increasing reliance on glutamine for continued energy production. At higher or prolonged NO exposure, citrate accumulation can inhibit multiple ATP-producing pathways. Reduced TCA flux slows NADH/FADH entry into the ETC. NO can also inhibit the ETC directly, further limiting oxidative phosphorylation. Moderate NO production improves mitochondrial efficiency while improving O2 utilization increasing whole-body energy production. Long-term bioenergetic capacity may be increased because of NO-derived ROS, which participate in adaptive cellular redox signaling through AMPK, PCG1-α, HIF-1, and NF-κB. However, prolonged exposure or high concentrations of NO can result in membrane depolarization and opening of the MPT. In this way NO may serve as a biochemical rheostat matching energy supply with demand for optimal respiratory function.

Advancing the Real-World Evidence for Medical Devices through Coordinated Registry Networks.

Objectives: Generating and using real-world evidence (RWE) is a pragmatic solution for evaluating health technologies. RWE is recognized by regulators, health technology assessors, clinicians, and manufacturers as a valid source of information to support their decision-making. Well-designed registries can provide RWE and become more powerful when linked with electronic health records and administrative databases in coordinated registry networks (CRNs). Our objective was to create a framework of maturity of CRNs and registries, so guiding their development and the prioritization of funding. Design setting and participants: We invited 52 stakeholders from diverse backgrounds including patient advocacy groups, academic, clinical, industry and regulatory experts to participate on a Delphi survey. Of those invited, 42 participated in the survey to provide feedback on the maturity framework for CRNs and registries. An expert panel reviewed the responses to refine the framework until the target consensus of 80% was reached. Two rounds of the Delphi were distributed via Qualtrics online platform from July to August 2020 and from October to November 2020. Main outcome measures: Consensus on the maturity framework for CRNs and registries consisted of seven domains (unique device identification, efficient data collection, data quality, product life cycle approach, governance and sustainability, quality improvement, and patient-reported outcomes), each presented with five levels of maturity. Results: Of 52 invited experts, 41 (79.9%) responded to round 1; all 41 responded to round 2; and consensus was reached for most domains. The expert panel resolved the disagreements and final consensus estimates ranged from 80.5% to 92.7% for seven domains. Conclusions: We have developed a robust framework to assess the maturity of any CRN (or registry) to provide reliable RWE. This framework will promote harmonization of approaches to RWE generation across different disciplines and health systems. The domains and their levels may evolve over time as new solutions become available.

Complete Genome of Aeromonas encheleia Strain SOD01 Isolated from an Urban Freshwater Stream.

We isolated Aeromonas encheleia strain SOD01 from an urban freshwater stream in Providence, RI. De novo assembly of PacBio RSII data followed by polishing with Illumina MiSeq data generated a complete 4,450,115 bp genome with 61.8% GC content. PGAP annotation predicted 3,877 protein-coding genes, 127 tRNA, and 31 rRNA.

Encoding laboratory testing data: case studies of the national implementation of HHS requirements and related standards in five laboratories.

OBJECTIVE: Assess the effectiveness of providing Logical Observation Identifiers Names and Codes (LOINC®)-to-In Vitro Diagnostic (LIVD) coding specification, required by the United States Department of Health and Human Services for SARS-CoV-2 reporting, in medical center laboratories and utilize findings to inform future United States Food and Drug Administration policy on the use of real-world evidence in regulatory decisions. MATERIALS AND METHODS: We compared gaps and similarities between diagnostic test manufacturers' recommended LOINC® codes and the LOINC® codes used in medical center laboratories for the same tests. RESULTS: Five medical centers and three test manufacturers extracted data from laboratory information systems (LIS) for prioritized tests of interest. The data submission ranged from 74 to 532 LOINC® codes per site. Three test manufacturers submitted 15 LIVD catalogs representing 26 distinct devices, 6956 tests, and 686 LOINC® codes. We identified mismatches in how medical centers use LOINC® to encode laboratory tests compared to how test manufacturers encode the same laboratory tests. Of 331 tests available in the LIVD files, 136 (41%) were represented by a mismatched LOINC® code by the medical centers (chi-square 45.0, 4 df, P < .0001). DISCUSSION: The five medical centers and three test manufacturers vary in how they organize, categorize, and store LIS catalog information. This variation impacts data quality and interoperability. CONCLUSION: The results of the study indicate that providing the LIVD mappings was not sufficient to support laboratory data interoperability. National implementation of LIVD and further efforts to promote laboratory interoperability will require a more comprehensive effort and continuing evaluation and quality control.

ASH Research Collaborative: a real-world data infrastructure to support real-world evidence development and learning healthcare systems in hematology.

The ASH Research Collaborative is a nonprofit organization established through the American Society of Hematology's commitment to patients with hematologic conditions and the science that informs clinical care and future therapies. The ASH Research Collaborative houses 2 major initiatives: (1) the Data Hub and (2) the Clinical Trials Network (CTN). The Data Hub is a program for hematologic diseases in which networks of clinical care delivery sites are developed in specific disease areas, with individual patient data contributed through electronic health record (EHR) integration, direct data entry through electronic data capture, and external data sources. Disease-specific data models are constructed so that data can be assembled into analytic datasets and used to enhance clinical care through dashboards and other mechanisms. Initial models have been built in multiple myeloma (MM) and sickle cell disease (SCD) using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) and Fast Healthcare Interoperability Resources (FHIR) standards. The Data Hub also provides a framework for development of disease-specific learning communities (LC) and testing of health care delivery strategies. The ASH Research Collaborative SCD CTN is a clinical trials accelerator that creates efficiencies in the execution of multicenter clinical trials and has been initially developed for SCD. Both components are operational, with the Data Hub actively aggregating source data and the SCD CTN reviewing study candidates. This manuscript describes processes involved in developing core features of the ASH Research Collaborative to inform the stakeholder community in preparation for expansion to additional disease areas.

Early Use of the Palliative Approach to Improve Patient Outcomes in HIV Disease: Insights and Findings From the Care and Support Access (CASA) Study 2013-2019.

Young men of color who have sex with men (yMSM) living with human immunodeficiency virus (HIV) in syndemic environments have been difficult-to-retain in care resulting in their being at-risk for poor health outcomes despite availability of effective once-daily antiretroviral treatment (ART). Multiple methods have been implemented to improve outcomes for this cohort; none with sustainable results. Outpatient HIV staff themselves may be a contributing factor. We introduced multidisciplinary staff to the concept of using a palliative approach early (ePA) in outpatient HIV care management to enable them to consider the patient-level complexity of these young men. Young MSM (18-35 years of age) enrolled in and cared for at the intervention site of the Care and Support Access Study (CASA), completed serial surveys over 18 months. Patients' Global and Summary quality of life (QoL) increased during the study at the intervention site (IS) where staff learned about ePA, compared with patients attending the control site (CS) (p=.021 and p=.018, respectively). Using serial surveys of staff members, we found that in the era of HIV disease control, outpatient staff are stressed more by environmental factors than by patients' disease status seen historically in the HIV epidemic. A Community Advisory Panel of HIV stakeholders contributed to all phases of this study and altered language used in educational activities with staff members to describe the patient cohort.

Use of data from the Vascular Quality Initiative registry to support regulatory decisions yielded a high return on investment.

BACKGROUND: Real-world data (RWD) from the Society for Vascular Surgery Vascular Quality Initiative (VQI) registry has been used to support US Food and Drug Administration (FDA) regulatory decisions regarding vascular devices. The variables of cost and time needed for these registry-based studies have not been previously compared to traditional, independent, industry studies that would otherwise have been conducted to support regulatory decisions. OBJECTIVES: To determine the potential value (cost and time saving and return on investment) created by device evaluation studies using the VQI registry infrastructure. METHODS: We compared studies that used data from the VQI registry with estimated costs of independent industry studies (counterfactual studies) using an established model using design specifications determined by FDA reviewers. RESULTS: We analyzed the initial six studies evaluating vascular devices for regulatory decisions using data from the VQI registry that generated evidence for four device manufacturers. Return on investment for these studies was estimated to be 143% and cost saving as 59% based on an actual per patient (with 5-year follow-up) cost of US$11K using VQI data versus US$26K from the counterfactual when averaged across all studies. Significant enrollment time savings (45%-71%) were also realized compared with industry-based estimates. CONCLUSIONS: The use of RWD from the VQI registry in this study and the transcatheter valve treatment coordinated registry network in a prior study indicates that substantial value was added to device evaluation projects by the reuse of registry data, with additional potential savings if linked claims data can be used instead of costly long-term in-person follow-up.

Possible exercised-induced rhabdomyolysis associated with terbinafine.

Introduction. Terbinafine is reported to be associated with rhabdomyolysis. We present a patient taking terbinafine who may have developed exercise-induced rhabdomyolysis. Case Report. A healthy 40-year-old female developed onychomycosis of the right first toe for which she was taking terbinafine. After an increase in her exercise regimen, she began experiencing notable myalgias of the triceps. During outpatient evaluation, the patient was found to have elevated and worsening creatine kinase (CK) and aspartate transaminase. At evaluation in the emergency department, CK was <5000 IU/L and had decreased. She did not have electrolyte abnormalities, kidney injury or kidney failure. Discussion. Patients may be at risk for exercise-induced rhabdomyolysis while on terbinafine and may need to be cautioned regarding the intensity of exercise.

Determining value of Coordinated Registry Networks (CRNs): a case of transcatheter valve therapies.

BACKGROUND: The Transcatheter Valve Therapy (TVT) Coordinated Registry Network (CRN) supported 23 regulatory decisions and ensured evidence-based evaluation of the application of TVT technology. However, there are cost concerns that require value assessment of the TVT CRN compared with traditional study designs. OBJECTIVES: We aimed to determine the value created by the TVT CRN based on (1) Return on investment (ROI), (2) Time saved (TS) in conducting necessary regulatory studies. METHODS: For both ROI and TS analyses, we compared studies that used the TVT CRN with those that would have been required if the registry did not exist (counterfactual studies). To estimate ROI, we accounted for the costs of investment and gain from investment. Both the counterfactual costs and length of studies were projected using design specifications determined by US Food and Drug Administration (FDA) reviewers. RESULTS: We identified 21 studies using the TVT CRN (supporting 23 FDA decisions) that generated evidence on TVT for three device manufacturers. ROI is estimated to be greater than 550%. TS by using the CRN ranged from months to years. CONCLUSIONS: The CRN method to evidence generation creates value for manufacturers and the broader device ecosystem, demonstrated with this example of the TVT CRN. The public health benefits of evidence created by this CRN outweighs the difference in data quality between traditional clinical studies and the CRN method.

The HAS-Choice study: Utilizing the HEART score, an ADP, and shared decision-making to decrease admissions in chest pain patients.

OBJECTIVE: The HAS-Choice pathway utilizes the HEART Score, an accelerated diagnostic protocol (ADP), and shared decision-making using a visual aid in the evaluation of chest pain patients. We seek to determine if our intervention can improve resource utilization in a community emergency department (ED) setting while maintaining safe patient care. METHODS: This was a single-center prospective cohort study with historical that included ED patients ≥21years old presenting with a primary complaint of chest pain in two time periods. The primary outcome was patient disposition. Secondary outcomes focused on 30-day ED bounce back and major adverse cardiac events (MACE). We used multivariate logistic regression to estimate the odds ratio (OR) and its 95% confidence interval (CI). RESULTS: In the pre-implementation period, the unadjusted disposition to inpatient, observation and discharge was 6.5%, 49.1% and 44.4%, respectively, whereas in the post period, the disposition was 4.8%, 41.5% and 53.7%, respectively (chi-square p<0.001). The adjusted odds of a patient being discharged was 40% higher (OR=1.40; 95% CI, 1.30, 1.51; p<0.001) in the post-implementation period. The adjusted odds of patient admission was 30% lower (OR=0.70; 95% CI, 0.60, 0.82; p<0.001) in the post-implementation period. The odds of 30-day ED bounce back did not statistically differ between the two periods. MACE rates were <1% in both periods, with a significant decrease in mortality in the post-implementation period. CONCLUSION: Our study suggests that implementation of a shared decision-making tool that integrates an ADP and the HEART score can safely decrease hospital admissions without an increase in MACE.

Implementation of HIV Palliative Care: Interprofessional Education to Improve Patient Outcomes in Resource-Constrained Settings, 2004-2012.

Palliative care (PC), introduced early in the management of chronic illness, improves patient outcomes. Early integration of a palliative approach for persons with HIV has been documented to be effective in identifying and managing patient-level concerns over the past decade in African settings. The experience of implementing PC in multiple African and other resource-constrained settings (RCSs) emphasizes the need for essential palliative competencies that can be integrated with chronic disease management for patients and their families facing life-limiting illness. This article is an historical description of how basic palliative competencies were observed to be acceptable for health workers providing outpatient HIV care and treatment during eight years of U.S. implementation of "care and support," a term coined to represent PC for persons living with HIV in RCS. The need for team building and interprofessional education is highlighted. The model is currently being tested in one U.S. city and may represent a mechanism for expanding the palliative approach into management of chronic disease. Such competencies may play a role in the development of the patient-centered medical home, a critical component of U.S. health care reform.

Pain Management for Persons Living With HIV Disease: Experience With Interprofessional Education in Nigeria.

CONTEXT: Pain management (PM) has not been routinely incorporated into HIV/AIDS care and treatment in resource-constrained settings. OBJECTIVES: We describe training for multidisciplinary teams tasked with integrating care management into HIV clinics to address pain for persons living with HIV in Nigeria. METHODS: Education on PM was provided to mixed-disciplinary teams including didactic and iterative sessions following home and hospital visits. Participants identified challenges and performed group problem solving. RESULTS: HIV trainers identified barriers to introducing PM reflecting views of the patient, providers, culture, and the health environment. Implementation strategies included (1) building upon existing relationships; (2) preliminary advocacy; (3) attention to staff needs; and (4) structured data review. CONCLUSION: Implementing PM in Nigerian HIV clinics requires recognition of cultural beliefs.

Diagnoses of human immunodeficiency virus (HIV) infection among foreign-born persons living in the District of Columbia.

This study characterizes available surveillance data for HIV infected foreign-born residents in the District of Columbia (DC) to inform local HIV prevention and care efforts. HIV surveillance data were reviewed for adults and adolescents (ages ≥13 years) living with HIV in 2008. Variables analyzed included demographics, region of origin (for persons born outside of the U.S.), insurance coverage, linkage to and continuous HIV care. Of the 16,513 DC residents living with HIV diagnoses, 1,391 (8.4%) were foreign-born. Of foreign-born infected, 71.9% were male; 33.3% were from Africa and 20.8% from Central America; 80.6% were exposed through sex; 36.3% had health coverage at diagnosis. While 100% of foreign-born persons had documented linkage to HIV care, only 18.0% had documentation of continued HIV care. These data suggest that strengthening continuous HIV care support after successful care linkage is warranted for foreign-born persons living with HIV in DC.

Perspectives on the role of patient-centered medical homes in HIV Care.

To strengthen the quality of HIV care and achieve improved clinical outcomes, payers, providers, and policymakers should encourage the use of patient-centered medical homes (PCMHs), building on the Ryan White CARE Act Program established in the 1990s. The rationale for a PCMH with HIV-specific expertise is rooted in clinical complexity, HIV's social context, and ongoing gaps in HIV care. Existing Ryan White HIV/AIDS Program clinicians are prime candidates to serve HIV PCMHs, and HIV-experienced community-based organizations can play an important role. Increasingly, state Medicaid programs are adopting a PCMH care model to improve access and quality to care. Stakeholders should consider several important areas for future action and research with regard to development of the HIV PCMH.

Site migration in seeking care services from multiple providers is associated with worse clinical outcomes among HIV-infected individuals in Washington, DC.

Washington, DC, is a metropolitan city with a severe HIV epidemic and faces challenges in retaining people living with HIV (PLWH) in quality care. This study assessed site migration in seeking care services and its correlates among PLWH in DC. PLWH diagnosed before 2008 and living through the end of 2010 were analyzed. Six scenarios of site migration were examined as patients visited =2, =3, and =4 different providers for their CD4 cell count and/or viral load (VL) tests in the past 3 years from 2008 to 2010 and 2 years from 2009 to 2010, respectively. Of 6480 patients analyzed from 2008 to 2010, 18.4% had CD4 < 200 cells/mm(3), 30.5% had VL > 400 copies/mL, and 76.6% were retained in same care sites; 23.4%, 5.0%, and 0.9% visited =2, =3, and =4 sites in the past 3 years from 2008 to 2010, respectively. Of 5954 patients analyzed from 2009 to 2010, 16.8% had CD4 < 200 cells/mm(3), 29.4% had VL > 400 copies/mL, and 81.9% were retained in same care sites; 18.1%, 3.1%, and 0.6% visited =2, =3, and =4 sites in the past 2 years from 2009 to 2010, respectively. Multivariable logistic regression analyses revealed that migration across six scenarios are consistently associated with CD4 < 200 cells/mm(3) and VL > 400 copies/mL. Site migration was common and associated with lower CD4 and higher VL among PLWH in DC. Frequent migration might be a factor in achieving optimal health outcomes for a subset of patients. Site migration might potentially limit effective delivery of high quality care and treatment services. The preliminary findings underscore the need for further research to assess the predictors of migration and its impact on stage of care.

Forward to AIDS 2014: Now is the Time to Unite for the Global HIV/AIDS Epidemic.

As AIDS activists, advocates, researchers, practitioners, scientists, and policy makers from around the world prepare for the forthcoming 20th International AIDS Conference (AIDS 2014) which takes place from 20-25 July in Melbourne, Australia, Gregory Pappas, MD, PhD, former Executive Director of the Washington DC's local Host Committee, International AIDS Society (IAS) organizing committee member, and Director, HIV/AIDS Program in the District of Columbia, Washington, DC, USA, reflects, for the first time, on his experiences hosting the world conference and bringing AIDS conference to United States after 22 years. He shares some of the key challenges and opportunities confronting program planners, policy makers and advocates in the efforts to address the global epidemic.

Cost-utility analysis of a female condom promotion program in Washington, DC.

A retrospective economic evaluation of a female condom distribution and education program in Washington, DC. was conducted. Standard methods of cost, threshold and cost-utility analysis were utilized as recommended by the U.S. Panel on cost-effectiveness in health and medicine. The overall cost of the program that distributed 200,000 female condoms and provided educational services was $414,186 (at a total gross cost per condom used during sex of $3.19, including educational services). The number of HIV infections that would have to be averted in order for the program to be cost-saving was 1.13 in the societal perspective and 1.50 in the public sector payor perspective. The cost-effectiveness threshold of HIV infections to be averted was 0.46. Overall, mathematical modeling analyses estimated that the intervention averted approximately 23 HIV infections (even with the uncertainty inherent in this estimate, this value appears to well exceed the necessary thresholds), and the intervention resulted in a substantial net cost savings.