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Sinus tachycardia (ST) is ubiquitous, but its presence outside of normal physiological triggers in otherwise healthy individuals remains a commonly encountered phenomenon in medical practice. In many cases, ST can be readily explained by a current medical condition that precipitates an increase in the sinus rate, but ST at rest without physiological triggers may also represent a spectrum of normal. In other cases, ST may not have an easily explainable cause but may represent serious underlying pathology and can be associated with intolerable symptoms. The classification of ST, consideration of possible etiologies, as well as the decisions of when and how to intervene can be difficult. ST can be classified as secondary to a specific, usually treatable, medical condition (eg, pulmonary embolism, anemia, infection, or hyperthyroidism) or be related to several incompletely defined conditions (eg, inappropriate ST, postural tachycardia syndrome, mast cell disorder, or post-COVID syndrome). While cardiologists and cardiac electrophysiologists often evaluate patients with symptoms associated with persistent or paroxysmal ST, an optimal approach remains uncertain. Due to the many possible conditions associated with ST, and an overlap in medical specialists who see these patients, the inclusion of experts in different fields is essential for a more comprehensive understanding. This article is unique in that it was composed by international experts in Neurology, Psychology, Autonomic Medicine, Allergy and Immunology, Exercise Physiology, Pulmonology and Critical Care Medicine, Endocrinology, Cardiology, and Cardiac Electrophysiology in the hope that it will facilitate a more complete understanding and thereby result in the better care of patients with ST.

BackgroundPediatric anesthesiology has been greatly impacted by COVID-19 in the delivery of care to patients and to the individual providers. With this study, we sought to survey pediatric centers and highlight the variations in care related to perioperative medicine during the COVID-19 pandemic, including the availability of protective equipment, the practice of pediatric anesthesia, and economic impact.AimThe aim of the survey was to determine how COVID-19 directly impacted pediatric anesthesia practices during the study period.MethodsA survey concerning four major domains (testing, safety, clinical management/policy, economics) was developed. It was pilot tested for clarity and content by members of the Pediatric Anesthesia COVID-19 Collaborative. The survey was administered by email to all Pediatric Anesthesia COVID-19 Collaborative members on September 1, 2020. Respondents had six weeks to complete the survey and were instructed to answer the questions based on their institution's practice during September 1 - October 13, 2020.ResultsSixty-three institutions (100% response rate) participated in the COVID-19 Pediatric Anesthesia Survey. Forty-one hospitals (65%) were from the United States, and 35% included other countries. N95 masks were available to anesthesia teams at 91% of institutions (n = 57) (95% CI: 80%-96%). COVID-19 testing criteria of anesthesia staff and guidelines to return to work varied by institution. Structured simulation training aimed at improving COVID-19 safety and patient care occurred at 62% of institutions (n = 39). Pediatric anesthesiologists were economically affected by a reduction in their employer benefits and restriction of travel due to employer imposed quarantine regulations.ConclusionOur data indicate that the COVID-19 pandemic has impacted the testing, safety, clinical management, and economics of pediatric anesthesia practice. Further investigation into the long-term consequences for the specialty is indicated.

BACKGROUND: A subset of patients with postural tachycardia syndrome (POTS) are thought to have a primary hyperadrenergic cause. We assessed clinical biomarkers to identify those that would benefit from sympatholytic therapy. METHODS: We measured sympathetic function (supine muscle sympathetic nerve activity, upright plasma norepinephrine, and blood pressure responses to the Valsalva maneuver) in 28 patients with POTS (phenotyping cohort) to identify clinical biomarkers that are associated with responsiveness to the central sympatholytic guanfacine in a separate uncontrolled treatment cohort of 38 patients that had received guanfacine clinically for suspected hyperadrenergic POTS (HyperPOTS). RESULTS: In the phenotyping cohort, an increase in diastolic blood pressure (DBP) >17 mm Hg during late phase 2 of the Valsalva maneuver identified patients with the highest quartile of resting muscle sympathetic nerve activity (HyperPOTS) with 71% sensitivity and 85% specificity. In the treatment cohort, patients with HyperPOTS, identified by this clinical biomarker, more often reported clinical improvement (85% versus 44% in nonhyperadrenergic; P=0.016), had better orthostatic tolerance (∆Orthostatic Hypotension Daily Activities Scale: −1.9±0.9 versus 0.1±0.5; P=0.032), and reported less chronic fatigue (∆PROMIS Fatigue Short Form 7a: −12.9±2.7 versus −2.2±2.2; P=0.005) in response to guanfacine. CONCLUSIONS: These results are consistent with the concept that POTS is caused by a central sympathetic activation in a subset of patients, which can be identified clinically by an exaggerated DBP increase during phase 2 of the Valsalva maneuver and improved by central sympatholytic therapy. These results support further clinical trials to determine the safety and efficacy of guanfacine in patients with POTS enriched for the presence of this clinical biomarker. [ABSTRACT FROM AUTHOR]

The US Food and Drug Administration (FDA) and National Organization for Rare Disease (NORD) convened a public workshop titled "Immune Responses to Enzyme Replacement Therapies: Role of Immune Tolerance Induction" to discuss the impact of anti-drug antibodies (ADAs) on efficacy and safety of enzyme replacement therapies (ERTs) intended to treat patients with lysosomal storage diseases (LSDs). Participants in the workshop included FDA staff, clinicians, scientists, patients, industry, and advocacy group representatives. The risks and benefits of implementing prophylactic immune tolerance induction (ITI) to reduce the potential clinical impact of antibody development were considered. Complications due to immune responses to ERT are being recognized with increasing experience and lengths of exposure to ERTs to treat several LSDs. Strategies to mitigate immune responses and to optimize therapies are needed. Discussions during the workshop resulted in the identification of knowledge gaps and future areas of research, as well as the following proposals from the participants: (1) systematic collection of longitudinal data on immunogenicity to better understand the impact of ADAs on long-term clinical outcomes; (2) development of disease-specific biomarkers and outcome measures to assess the effect of ADAs and ITI on efficacy and safety; (3) development of consistent approaches to ADA assays to allow comparisons of immunogenicity data across different products and disease groups, and to expedite reporting of results; (4) establishment of a system to widely share data on antibody titers following treatment with ERTs; (5) identification of components of the protein that are immunogenic so that triggers and components of the immune responses can be targeted in ITI; and (6) consideration of early ITI in patients who are at risk of developing clinically relevant ADA that have been demonstrated to worsen treatment outcomes.

Known disparities exist in pain treatment between African American, Latino, and White children. A recent study described 'adultification' of Black children, with Black children being less likely to have a parent present at induction of anesthesia and less likely to receive an anxiolytic premedication before proceeding to the operating room. The aim of this study is to identify differences based on race and socioeconomic status when treating children and their families for anesthetic induction. We hypothesize that differences exist such that certain populations are less likely to receive sedative premedication and less likely to have parents present at induction of anesthesia. This was a retrospective cohort study. Demographic data were obtained along with type of surgical procedure, type of anesthesia induction, use of premedication, and involvement of child life services (including the plan for parental presence at induction) for all pediatric patients presenting for anesthetics from February 2019 to March 2020. Statistical analysis consisted of fitting logistic mixed effects models for caregiver presence or for midazolam use during induction, with fixed effects for sex, race, ethnicity, language, public/private insurance, and anesthetic risk, and with the provider as a random effect. A total of 7,753 patients were included in our statistical analyses, and parental presence focused on 4,102 patients with documentation from child life specialists. Females were less likely than males to have parents present at induction (odds ratio [OR] 0.77, confidence interval [CI] [0.67, 0.89]). When looking at race, American Indian/Alaskan Native patients (OR 0.23 [CI 0.093, 0.47]) and Black/African American patients OR 0.64 [CI 0.47, 0.89]) were less likely to have a parent present induction than White patients. Patients with private insurance were more likely to have parents present than patients with public insurance (OR 0.63 CI [0.5, 0.78]). These findings held true in age-separated sensitivity analysis. Asian patients were less likely to receive midazolam premedication (OR 0.65 CI [0.49, 0.86]). This study supports previous work showing differential use of parental presence at induction based on race. Additionally, it also shows different treatment based on sex and public insurance status, a surrogate for socioeconomic status. [ABSTRACT FROM AUTHOR]

BackgroundThe clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results.MethodsWe randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy.ResultsAt 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], -0.2; 95% confidence interval, -3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy.ConclusionsGenotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. (Funded by the National Heart, Lung, and Blood Institute and others; COAG ClinicalTrials.gov number, NCT00839657.).

Tobacco use among youth remains one of our nation's most significant public health problems, and yet available evidence from prevention and cessation person-centered approaches has been mixed. Given these disappointing outcomes, some have recommended more public health approaches, and these include tobacco sales-to-minors and possession-use-purchase laws. While community members and police officials have endorsed these types of public health initiatives, many within the public health community have been either guarded or even oppositional to such approaches. The primary reasons for this controversy are reviewed in this article. Outcome studies indicate that sales-to-minors laws can be an effective step toward the reduction of youth access to commercial sources of tobacco. However, even with these laws in place, many youth indicate that they continue to have easy access to tobacco, often by means of social sources. Advocates of these approaches have argued that more comprehensive public health interventions are needed, such as programs that combine youth access and possession-use-purchase laws. This article reviews the ongoing debate behind these types of public health efforts, and examines the evidence of such programs to reduce youth tobacco use.

Several valerian-containing products sold in pharmacies were evaluated to verify the presence of Valeriana officinalis by identifying the presence of valerenic acid found only in species of Valeriana. The content of valerenic acid was found to vary considerably in the products analyzed, thus emphasizing the importance of standardizing herbal medicinal products.