Pediatric Obesity: Influence on Drug Dosing and Therapeutics

Obesity is an ongoing global health concern and has only recently been recognized as a chronic disease of energy homeostasis and fuel partitioning. Obesity afflicts 17% of US children and adolescents. Severe obesity (³120% of the 95th percentile of BMI-for-age, or a BMI of ³35 kg/m2) is the fastest growing subgroup and now approaches 6% of all US youth. Health consequences (e.g., type 2 diabetes, coronary heart disease) are related in a dose-dependent manner to severity of obesity. Since therapeutic interventions are less effective in severe obesity, prevention is a high priority. Treatment plans involving combinations of behavioral therapy, nutrition and exercise achieve limited success. Only one drug, orlistat, is FDA-approved for long-term obesity management in adolescents 12 years and older. As part of comprehensive medication management, clinicians should consider the propensity for a given drug to aggravate weight gain and to consider alternatives that minimize weight impact. Medication management must take into account developmental changes as well as pathophysiology of obesity and comorbidities. Despite expanding insight into obesity pathophysiology, there are gaps in its translation to therapeutic application. The historical construct of obesity as simply a fat storage disorder is fundamentally inaccurate. The approach to adjusting doses based solely on body size and extrapolating from therapeutic knowledge of adult obesity may be based on assumptions that are not fully substantiated. Classes of drugs commonly prescribed for comorbidities associated with obesity should be prioritized for clinical research evaluations aimed at optimizing dosing regimens in pediatric obesity

Seeing Clearly: Telescope Assembly Instruction Redesign

The ME telescopes are over 60 lb mounts that must be secured to permanent piers that have been cemented onto the roof of COAS. The astronomy students have to learn to assemble these telescopes during their labs each semester. We have been working in tandem with the astronomy department to simplify their assembly manuals for the ME, Mx, and Mx+ telescopes. Feedback from ERAU students indicated that they were struggling to clearly understand the assembly process and reported the current instruction set to be cumbersome to use. Through a review of human factors and educational literature, a set of best practices was developed to create a template for a new instruction set that breaks down each step and pairs it with two images per page. The language was simplified into bulleted direct command statements rather than paragraphs. Once the ME manual was completed, we ran a pilot study where two teaching assistants and a professor walked through the manual during assembly. Currently we are making the necessary changes based on the pilot. The next steps will be to conduct a full usability study with naïve students and to apply the template to the other telescope models

Dosing Common Medications in Hospitalized Pediatric Patients with Obesity: A Review

Medication management in children and adolescents with obesity is challenging since both developmental and pathophysiologic changes may impact drug disposition and response. Evidence to date indicates an effect of obesity on drug disposition for certain drugs used in this population. This work identified published studies evaluating drug dosing, pharmacokinetics, and effect in pediatric patients with obesity, focusing on 70 common medications used in a pediatric network of 42 U.S. medical centers. A PubMed search revealed 33 studies providing pharmacokinetic and/or effectiveness data for 23% (16/70) of medications, 44% of which have just one study and can be considered exploratory. This work appraising 4 decades of literature shows several promising approaches: greater use of pharmacokinetic models applied to prospective clinical studies, dosing recommendations derived from both pharmacokinetics and safety, and multi-year effectiveness data on drugs for chronic conditions (e.g., asthma). Most studies make dose recommendations, but are weakened by retrospective study design, small study populations, and no controls or historic controls. Dosing decisions continue to rely on extrapolating knowledge, including targeting systemic drug exposure typically achieved in adults. Optimal weight-based dosing strategies vary by drug and warrant prospective, controlled studies incorporating pharmacokinetics and modeling and simulation to complement clinical assessment

Renal and hemodynamic responses to bumetanide in hypertension: Effects of nitrendipine

Renal and hemodynamic responses to bumetanide in hypertension: Effects of nitrendipine. The effects of a calcium antagonist on the response to a loop diuretic were tested in eight hypertensive patients while they received 120mmol · 24hr-1 of dietary Na. Nitrendipine (N; 20 mg) or placebo (P) was administered twice daily for five days and bumetanide (B; 1 mg, i.v.) for the last three days of each period. Cardiac index (CI) was measured during tilt. B alone significantly (P < 0.05; N = 7) reduced CI and increased total peripheral resistance; N prevented these effects of B. Neither drug altered BP consistently. Although three days of B increased plasma renin activity (PRA) during P and N, it increased plasma aldosterone (PAldo) only during P (P, 4.4 ± 1.3 to 7.6 ± 1.0; P < 0.05. N, 5.7 ± 1.3 to 6.0 ± 1.3; pg · liter-1; NS). B increased Na excretion without changing GFR or RPF; this was followed by 18 hours of decreased renal Na excretion. These actions were unchanged by N. N did not change the cumulative excretion of B (P, 268 ± 35 vs. N, 217 ± 21 µg) or the relationship between Na excretion and the log of B excretion. However, Na excretion was increased (P < 0.05) by 40 to 60% in the six hour period following the first two doses of N. Therefore, the cumulative Na balance was more negative during five days of N (P, -47 ± 17 vs. N, -108 ± 24 mmol; P < 0.05). The effect of N and B on Na balance were independent. In conclusion, short-term administration of N: 1) increases CI and reduces TPRI in the post-diuretic state; 2) blunts B-induced increase in PAldo without modifying the rise in PRA; 3) does not change B kinetics or dynamics or the post-diuretic period of renal Na retention; 4) causes negative Na balance which is additive with that produced by B

Redesigning for Efficiency: Adding a Homepage to Canvas Courses

With the increase in online learning, learning management systems (LMS) such as Canvas are increasing in importance for disseminating information from professors to students. An initial focus group was conducted to assess students’ perceptions of their current Canvas course organization. Results indicate that students report a lack of consistency and clear organization, which leads to significant time searching for information and frustration. In an effort to help students create a clear mental model of a Canvas course, we developed a template homepage that contains a main navigation menu including an FAQ, Course Resources, Start Here, Grades, and Syllabus link. The homepage also includes a course overview schedule made with links to individual modules and assignment due dates. We are currently evaluating the new design in terms of efficiency and student perceptions. Our hypothesis is that the homepage design will help students get to the information they want faster and provide a better overview of the course than the traditional home page design

von Willebrand factor levels in the diagnosis of von Willebrand disease: a systematic review and meta-analysis

Von Willebrand Disease (VWD) is associated with significant morbidity as a result of excessive mucocutaneous bleeding symptoms. Patients with VWD can experience easy bruising, epistaxis, gastrointestinal and oral cavity bleeding, as well as heavy menstrual bleeding and bleeding after dental work, surgical procedures, and childbirth. Early diagnosis and treatment is important to prevent and treat these symptoms. We systematically reviewed the accuracy of diagnostic tests using different cut-off values of VWF:Ag and platelet-dependent VWF activity assays in the diagnosis of VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity and reported patient important outcomes when relevant. This review included 21 studies that evaluated VWD diagnosis, including the approach to patients with VWF levels that have normalized with age (6 studies), VWF cut-off levels for the diagnosis of Type 1 VWD (9 studies), and platelet-dependent VWF activity/VWF:Ag ratio cut-off levels for the diagnosis of Type 2 VWD (6 studies). The results showed low certainty in the evidence for a net health benefit from reconsidering the diagnosis of VWD versus simply removing the disease in patients with VWF levels that have normalized with age. For the diagnosis of Type 1 VWD, in patients with VWF:A

Acute ischaemic stroke associated with SARS-CoV-2 infection in North America

BACKGROUND: To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS: Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS: A total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age \u3e60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p\u3c0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome. CONCLUSION: There is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction