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The Innovator - Summer 2024
Get PDFhttps://scholarlycommons.libraryinfo.bhs.org/facultyaffairs_newsletters/1013/thumbnail.jp
Reward neurocircuitry predicts longitudinal changes in alcohol use following trauma exposure
No full textBackground: Trauma is a risk factor for developing maladaptive alcohol use. Preclinical research has shown that stress alters the processing of midbrain and striatal reward and incentive signals. However, little research has been conducted on alterations in reward-related neurocircuitry post-trauma in humans. Neuroimaging markers may be particularly useful as they can provide insight into the mechanisms that may make an individual vulnerable to developing trauma-related psychopathologies. This study aimed to identify reward-related neural correlates associated with changes in alcohol use after trauma exposure.
Methods: Participants were recruited from U.S. emergency departments for the AURORA study (N=286, 178 female). Trauma-related change in alcohol use at 8 weeks post-trauma relative to pre-trauma was quantified as a change in 30-day total drinking per the PhenX Toolkit Alcohol 30-Day Quantity and Frequency Measure. Reward-related neurocircuitry activation and functional connectivity (FC) were assessed 2 weeks post-trauma using fMRI during a monetary reward task using region of interest and whole-brain voxelwise analyses.
Results: Greater increase in alcohol use from pre-trauma to 8 weeks post-trauma was predicted by (1) greater ventral tegmental area (VTA) and (2) greater cerebellum activation during Gain\u3eLoss trials measured 2 weeks post-trauma and (3) greater seed-based FC between the VTA and lateral occipital cortex and precuneus.
Conclusions: Altered VTA activation and FC early post-trauma may be associated with reward-seeking and processing, contributing to greater alcohol use post-trauma. These data provide novel evidence of neural correlates that underlie increased alcohol use early post-trauma that may be targeted via early interventions to prevent the development of maladaptive alcohol use
Medication Dosing for Children With Overweight and Obesity
No full textApproximately 14.7 million US children aged 2 to 19 years are obese. This creates significant challenges to dosing medications that are primarily weight based (mg/kg) and in predicting pharmacokinetics parameters in pediatric patients. Obese individuals generally have a larger volume of distribution (Vd) for lipophilic medications. Conversely, the Vd of hydrophilic medications may be increased or decreased owing to increased lean body mass, blood volume, and decreased percentage of total body water. They may also experience decreased hepatic clearance secondary to fatty infiltrates of the liver. Hence, obesity may affect loading dose, dosage interval, plasma half-life, and time to reach steady-state concentration for various medications. Weight-based dosing is also a cause for potential medication errors. This position statement of the Pediatric Pharmacy Association recommends that weight-based dosing should be used in patients ages \u3c18 years who weigh \u3c40 kg; weight-based dosing should be used in patients ≥40 kg, unless the recommended adult dose for the specific indication is exceeded; clinicians should use pharmacokinetic analysis for adjusting medications in children diagnosed with overweight and obesity; and research efforts continue to evaluate dosing of medications in children diagnosed with overweight and obesity.
Keywords: drug dosage calculations; drug therapy; obese; overweight; pediatrics; pharmacokinetics; therapeutic drug monitoring
Approval, Evidence, and Off-Label Device Utilization: The Patent Foramen Ovale Closure Story
No full textBackground: Following regulatory approval, medical devices may be used off-label. Patent foramen ovale (PFO) closure is indicated to reduce recurrent stroke but has been proposed for other indications, including migraine, transient ischemic attack, and diving decompression illness. We sought to evaluate PFO closure rates and indications relative to the timing of regulatory approval and publication of key randomized trials.
Methods: We performed a retrospective cohort study using the OptumLabs Data Warehouse of US commercial insurance enrollees from 2006 to 2019. We quantified PFO closure among individuals with ≥2 years of preprocedure coverage to establish indications, classified hierarchically as stroke/systemic embolism, migraine, transient ischemia attack, or other.
Results: We identified 5315 patients undergoing PFO closure (51.8% female, 29.2%≥60 years old), which increased from 4.75 per 100 000 person-years in 2006 to 6.60 per 100 000 person-years in 2019. Patients aged ≥60 years accounted for 29.2% of closures. Procedure volumes corresponded weakly with supportive clinical publications and device approval. Among patients with PFO closure, 58.6% underwent closure for stroke/systemic embolism, 10.2% for transient ischemia attack, 8.8% for migraine, and 22.4% for other indications; 17.6% of patients had atrial fibrillation at baseline; and 11.9% developed atrial fibrillation postprocedure. Those aged ≥60 years and male were less likely to undergo closure for migraine than stroke/systemic embolism.
Conclusions: From 2006 to 2019, PFO closure use was consistently low and corresponded weakly with clinical trial publications and regulatory status. Nearly half of patients underwent PFO closure for indications unapproved by the Food and Drug Administration. Regulators and payers should coordinate mechanisms to promote utilization for approved indications to ensure patient safety and should facilitate clinical trials for other possible indications.
Keywords: adult; cardiology; device approval; health services; patent foramen ovale
Influence of Patient and Clinician Gender on Emergency Department HEART Scores: A Secondary Analysis of a Prospective Observational Trial
No full textStudy objective: Clinical decision aids can decrease health care disparities. However, many clinical decision aids contain subjective variables that may introduce clinician bias. The HEART score is a clinical decision aid that estimates emergency department (ED) patients\u27 cardiac risk. We sought to explore patient and clinician gender\u27s influence on HEART scores.
Methods: In this secondary analysis of a prospective observational trial, we examined a convenience sample of adult ED patients at one institution presenting with acute coronary syndrome symptoms. We compared ED clinician-generated HEART scores with researcher-generated HEART scores blinded to patient gender. The primary outcome was agreement between clinician and researcher HEART scores by patient gender overall and stratified by clinician gender. Analyses used difference-in-difference (DiD) for continuous score and prevalence-adjusted, bias-adjusted Kappa (PABAK) for binary (low versus moderate/high risk) score comparison.
Results: All 336 clinician-patient pairs from the original study were included. In total, 47% (158/336) of patients were women, and 52% (174/336) were treated by a woman clinician. The DiD between clinician and researcher HEART scores among men versus women patients was 0.24 (95% CI -0.01 to 0.48). Compared with researchers, men clinicians assigned a higher score to men versus women patients (DiD 0.51 [95% CI 0.16 to 0.87]), whereas women clinicians did not (DiD 0.00 [95% CI -0.33 to 0.33]). Agreement was the highest among women clinicians (PABAK 0.72; 95% CI 0.61 to 0.81) and lowest among men clinicians assessing men patients (PABAK 0.47; 95% CI 0.29 to 0.66).
Conclusion: Patient and clinician gender may influence HEART scores. Researchers should strive to understand these influences in developing and implementing this and other clinical decision aids
Pediatricians\u27 Career Satisfaction and Wellbeing by Sex Before and During the COVID-19 Pandemic
No full textObjective: To compare pediatrician career satisfaction and wellbeing by sex during the coronavirus disease 2019 pandemic with prepandemic years using longitudinal survey data.
Methods: Data from a cohort study, the American Academy of Pediatrics Pediatrician Life and Career Experience Study, were used to examine career satisfaction and wellbeing from 2012 to 2021 among 2002-2004 and 2009-2011 residency graduates (n = 1760). Mixed effects logistic regression, including key pediatrician characteristics, examined career satisfaction and wellbeing measures for sex (female vs male), pandemic year (2012-2019 vs 2020-2021), and their interaction effect. Adjusted predicted percentage values (PVs) were determined.
Results: In total, 73.4% of participants identified as female. Adjusting for key pediatrician characteristics, differences were found by sex for satisfaction and 4 of 5 wellbeing measures, by pandemic year for 2 wellbeing measures, and the interaction of sex and pandemic year for 3 wellbeing measures. Female pediatricians reported higher levels of anxiety, sadness, and work stress, with greater differences during the pandemic. For example, female pediatricians (PV = 22.6, confidence interval [CI] = 21.0-24.3) were more likely than male pediatricians (PV = 14.2, CI = 12.0-16.4) to report anxiety during pre-pandemic years, and the difference between female pediatricians (PV = 29.3, CI = 26.7-32.0) and male pediatricians (PV = 12.4, CI = 9.3-15.5) increased during pandemic years (sex by pandemic year interaction, P \u3c .001).
Conclusions: Compared with male pediatricians, female pediatricians reported worse anxiety, sadness, and stress at work, and the differences were more pronounced during the pandemic
Feasibility of His Bundle Pacing and Atrioventricular Junction Ablation with Left Bundle Branch Area Pacing as Back-up
No full textKeywords: AV junction ablation; Atrial fibrillation; His bundle pacing; left bundle branch area pacing
Unveiling the Chilaiditi Syndrome: A Case Report and Management Implications
No full textThe Chilaiditi syndrome is when the radiologic Chilaiditi sign, defined by the interpositioning of the colon between the liver and diaphragm, becomes complicated by clinical symptoms such as respiratory insufficiency or bowel obstruction. We present the case of a 70-year-old male with a history of depression, anxiety, gastroesophageal reflux disease (GERD), and post-polio syndrome, who presented with left shoulder pain, chronic weakness, and dizziness. Initial evaluation revealed hypotension and elevated lactic acid, attributed to dehydration. Further imaging identified a Chilaiditi sign, thus raising suspicion of small bowel obstruction and the Chilaiditi syndrome. Despite conservative management, the patient continued to experience elevated lactic acid levels, prompting a computed tomography (CT) angiogram to rule out bowel ischemia. No acute intra-abdominal pathology was identified, and the patient improved with hydration and bowel rest. This case highlights the challenges in diagnosing and managing the Chilaiditi syndrome in the setting of chronic comorbidities.
Keywords: chilaiditi syndrome; colonic interposition; computed tomography; lactic acidosis; radiologic finding
Differential Impact of Systolic and Diastolic Heart Failure on In-Hospital Treatment, Outcomes, and Cost of Patients Admitted for Pneumonia
No full textBackground: Patients admitted with pneumonia and heart failure (HF) have increased mortality and cost compared to those without HF, but it is not known whether outcomes differ between systolic and diastolic HF. Management of concomitant pneumonia and HF is complicated because HF treatments can worsen complications of pneumonia.
Methods: This is a retrospective cohort study from the Premier Database among patients admitted with pneumonia between 2010-2015. Patients were categorized based on systolic, diastolic, and combined HF using ICD-9 codes. The primary outcome was in-hospital mortality. Secondary outcomes included use of HF medications, length of stay, cost, intensive care unit (ICU) admission, as well as use of invasive mechanical ventilation (IMV), vasopressors and inotropes. Multivariable logistic regression was used to describe associations of these outcomes with type of HF.
Results: Of 123,211 patients with pneumonia and HF, 41,196 (33.4%) had systolic HF, 69,982 (56.8%) diastolic HF, and 12,033 (9.8%) had combined HF. Compared to patients with diastolic HF, after multivariable adjustment systolic HF was associated with higher in-hospital mortality (OR 1.15; 95% CI:1.11-1.20), ICU admission, and use of IMV and vasoactive agents, but not with increased length of stay or cost. Among patients with systolic HF, 80% received a loop diuretic, 72% a beta blocker, 48% angiotensin converting enzyme inhibitor or angiotensin receptor blocker, and 12.5% a mineralocorticoid receptor antagonist.
Conclusion: Systolic HF is associated with added risk in pneumonia compared to diastolic HF. There may also be an opportunity to optimize medications in systolic HF prior to discharge.
Keywords: diastolic heart failure; pneumonia; systolic heart failure