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BackgroundNoninvasive telemonitoring and nurse telephone coaching (NTM-NTC) is a promising postdischarge strategy in heart failure (HF). Comorbid conditions and disease burden influence health outcomes in HF, but how comorbidity burden modulates the effectiveness of NTM-NTC is unknown. This study aims to identify patients with HF who may benefit from postdischarge NTM-NTC based on their burden of comorbidity.Methods and resultsIn the Better Effectiveness After Transition - Heart Failure trial, patients hospitalized for acute decompensated HF were randomized to postdischarge NTM-NTC or usual care. In this secondary analysis of 1313 patients with complete data, comorbidity burden was assessed by scoring complication and coexisting diagnoses from index admissions. Clinical outcomes included 30-day and 180-day readmissions, mortality, days alive, and combined days alive and out of the hospital. Patients had a mean of 5.7 comorbidities and were stratified into low (0-2), moderate (3-8), and high comorbidity (≥9) subgroups. Increased comorbidity burden was associated with worse outcomes. NTM-NTC was not associated with readmission rates in any comorbidity subgroup. Among high comorbidity patients, NTM-NTC was associated with significantly lower mortality at 30 days (hazard ratio 0.25, 95% confidence interval 0.07-0.90) and 180 days (hazard ratio 0.51, 95% confidence interval 0.27-0.98), as well as more days alive (160.1 vs 140.3, P = .029) and days alive out of the hospital (152.0 vs 133.2, P = .044) compared with usual care.ConclusionsPostdischarge NTM-NTC improved survival among patients with HF with a high comorbidity burden. Comorbidity burden may be useful for identifying patients likely to benefit from this management strategy.

The sympathetic nervous system fight-or-flight response is characterized by a rapid increase in heart rate, which is mediated by an increase in the spontaneous action potential (AP) firing rate of pacemaker cells in the sinoatrial node. Sympathetic neurons stimulate sinoatrial myocytes (SAMs) by activating β adrenergic receptors (βARs) and increasing cAMP. The funny current (If) is among the cAMP-sensitive currents in SAMs. If is critical for pacemaker activity, however, its role in the fight-or-flight response remains controversial. In this study, we used AP waveform analysis, machine learning, and dynamic clamp experiments in acutely isolated SAMs from mice to quantitatively define the AP waveform changes and role of If in the fight-or-flight increase in AP firing rate. We found that while βAR stimulation significantly altered nearly all AP waveform parameters, the increase in firing rate was only correlated with changes in a subset of parameters (diastolic duration, late AP duration, and diastolic depolarization rate). Dynamic clamp injection of the βAR-sensitive component of If showed that it accounts for ∼41% of the fight-or-flight increase in AP firing rate and 60% of the decrease in the interval between APs. Thus, If is an essential contributor to the fight-or-flight increase in heart rate.

Background Despite optimal medical therapy, a significant proportion of patients' blood pressure remains uncontrolled. Catheter‐based renal denervation (RDN) has been proposed as a potential intervention for uncontrolled hypertension. We conducted an updated meta‐analysis to assess the efficacy and safety of RDN in patients with uncontrolled hypertension, with emphasis on the differential effect of RDN in patients on and off antihypertensive medications. Methods and Results Online databases were searched to identify randomized clinical trials comparing efficacy and safety of RDN versus control in patients with uncontrolled hypertension. Subgroup analyses were conducted for sham‐controlled trials and studies that used RDN devices that have gained or are currently seeking US Food and Drug Administration approval. Fifteen trials with 2581 patients (RDN, 1723; sham, 858) were included. In patients off antihypertensive medications undergoing RDN, a significant reduction in 24‐hour ambulatory (−3.70 [95% CI, −5.41 to −2.00] mm Hg), office (−4.76 [95% CI, −7.57 to −1.94] mm Hg), and home (−3.28 [95% CI, −5.96 to −0.61] mm Hg) systolic blood pressures was noted. In patients on antihypertensive medications, a significant reduction was observed in 24‐hour ambulatory (−2.23 [95% CI, −3.56 to −0.90] mm Hg), office (−6.39 [95% CI, −11.49 to −1.30]), home (−6.08 [95% CI, −11.54 to −0.61] mm Hg), daytime (−2.62 [95% CI, −4.14 to −1.11]), and nighttime (−2.70 [95% CI, −5.13 to −0.27]) systolic blood pressures, as well as 24‐hour ambulatory (−1.16 [95% CI, −1.96 to −0.35]), office (−3.17 [95% CI, −5.54 to −0.80]), and daytime (−1.47 [95% CI, −2.50 to −0.27]) diastolic blood pressures. Conclusions RDN significantly lowers blood pressure in patients with uncontrolled hypertension, in patients off and on antihypertensive medications, with a favorable safety profile. The efficacy of RDN was consistent in sham‐controlled trials and contemporary trials using US Food and Drug Administration–approved devices.

Introduction: Foot and ankle pathology in patients with diabetes mellitus is prevalent in the United States and may be associated with significant morbidity. Patient outcomes can be improved by optimal medical management; deformity management and correction to limit the development of infection and ulceration; and timely, appropriate treatment of infection and ulceration when it occurs. Orthopaedic foot and ankle surgeons are well-qualified to treat these patients, either individually or as members of a healthcare professional team. However, there are some healthcare professionals and members of the public who are under the impression that orthopaedic foot and ankle surgeon are either unwilling or uninterested in treating this patient population. The authors hypothesized that this impression was a misconception and this study was designed to address this question. Methods: An online survey was sent to 1376 AOFAS members practicing in the United States. There were six questions, two of which were demographic and one that asked for additional comments. The survey was completed by 297 (22%) members from 45 states and the District of Columbia. Results: Nonoperative treatment of foot and ankle disorders in patients with diabetes mellitus was performed by 98.7% of responders including 98.7% for fractures; 97.6% for common disorders (e.g., bunions, hammer toes, flatfeet, plantar fasciitis, osteoarthritis, tendon disorders); 89.9% for Charcot arthropathy; 77.1% for infections; and 69.0% for ulcers. Operative treatment of foot and ankle disorders in patients with diabetes mellitus was performed by 98.7% of responders including 97.0% for fracture fixation; 96.3% for gastrocnemius recession and/ or Achilles tendon lengthening; 94.6% for arthrodesis for osteoarthritis; 94.3% for hammer toe surgery; 92.6% for bunion surgery; 89.6% for Charcot exostectomy; 83.8% for Charcot reconstruction; 83.5% for amputations within foot; 81.1% for below knee amputations; 74.8% for operative debridement of infections/ ulcers; and 57.9% for total ankle replacement. When asked which healthcare professionals treat diabetic patients in their community, 96.6% listed podiatrists; 91.3% listed orthopaedic foot and ankle surgeons; 69.0% listed other MD/ DO surgeons (e.g. general, plastics, vascular); 64.0% listed nurses (e.g., APRN, wound care specialist); 37.4% listed other orthopaedic surgeons; 31.7% listed non- surgeon MD/ DO physicians; 32.3% listed physician assistants; and 2% listed other. Conclusion: The vast majority of orthopaedic foot and ankle surgeons practicing in the United States who responded to the survey provide operative and nonoperative treatment to patients with diabetes mellitus and foot and ankle disorders. Given the extensive medical education and training of orthopaedic foot and ankle surgeons, their knowledge and surgical skill, and the benefits patients with diabetes receive from appropriate and timely foot and ankle care, efforts should be made to educate the public and other healthcare professionals of the availability of most orthopaedic foot and ankle surgeons to provide this care.

Given the growing number of prediction algorithms developed to predict COVID-19 mortality, we evaluated the transportability of a mortality prediction algorithm using a multi-national network of healthcare systems. We predicted COVID-19 mortality using baseline commonly measured laboratory values and standard demographic and clinical covariates across healthcare systems, countries, and continents. Specifically, we trained a Cox regression model with nine measured laboratory test values, standard demographics at admission, and comorbidity burden pre-admission. These models were compared at site, country, and continent level. Of the 39,969 hospitalized patients with COVID-19 (68.6% male), 5717 (14.3%) died. In the Cox model, age, albumin, AST, creatine, CRP, and white blood cell count are most predictive of mortality. The baseline covariates are more predictive of mortality during the early days of COVID-19 hospitalization. Models trained at healthcare systems with larger cohort size largely retain good transportability performance when porting to different sites. The combination of routine laboratory test values at admission along with basic demographic features can predict mortality in patients hospitalized with COVID-19. Importantly, this potentially deployable model differs from prior work by demonstrating not only consistent performance but also reliable transportability across healthcare systems in the US and Europe, highlighting the generalizability of this model and the overall approach.

Despite demonstrated efficacy of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), widespread hesitancy to vaccination persists. Improved knowledge regarding frequency, severity, and duration of vaccine-associated symptoms may help reduce hesitancy. In this prospective observational study, we studied 1032 healthcare workers who received both doses of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine and completed post-vaccine symptom surveys both after dose 1 and after dose 2. We defined appreciable post-vaccine symptoms as those of at least moderate severity and lasting at least 2 days. We found that symptoms were more frequent following the second vaccine dose than the first (74% vs. 60%, P 80% of all symptoms resolving within 2 days. The most common symptom was injection site pain, followed by fatigue and malaise. Overall, 20% of participants experienced appreciable symptoms after dose 1 and 30% after dose 2. In multivariable analyses, female sex was associated with greater odds of appreciable symptoms after both dose 1 (OR, 95% CI 1.73, 1.19-2.51) and dose 2 (1.76, 1.28-2.42). Prior COVID-19 was also associated with appreciable symptoms following dose 1, while younger age and history of hypertension were associated with appreciable symptoms after dose 2. We conclude that most post-vaccine symptoms are reportedly mild and last