Cost-Effectiveness Analysis of a Regional Program for Identifying and Treating Children with Correctable Refractive Error in Indonesia.

PURPOSE: Indonesia is a rapidly growing county with over 262 million inhabitants, but among highly populated countries it has one of the lowest concentrations of eye care providers. This study evaluated the cost-effectiveness of a program implemented in South Sulawesi, Indonesia that trained school teachers to conduct vision screenings, organized in-school evaluations by opticians, and provided free eyeglasses to school children with refractive error (RE). METHODS: Schoolteachers across 6 districts in South Sulawesi were trained to screen children with possible RE for subsequent evaluation by opticians. All costs associated with designing and implementing the program (administration, training personnel, labor, service delivery, etc.) were assessed. Expenditures and outcomes data were utilized to calculate the cost per disability-adjusted-life-year (DALY) averted using both 2010 and 2016 Global Burden of Disease (GBD) weights. RESULTS: 521 teachers screened 41,212 students across 172 schools in South Sulawesi. 4,506 (10.9%) students failed screening, 2,652 were seen by optometrists, and 2,038 received glasses.The total program cost was US$97,380, with glasses (39.6%) and labor (23.3%) accounting for the two biggest expenditures. In districts with school-based refraction services, the costs per student screened, refracted, and receiving glasses were $2.57, $31.33, and $41.40, respectively; costs were $2.04, $59.80, and $73.22 when district services were instead provided centrally. The estimated cost per DALY averted was US$89.04 based on GBD 2010 weights. CONCLUSION: Treating children with correctable RE in limited resource settings can be done cost-effectively through a school-based model.

Retinal manifestations in autosomal recessive MPDZ maculopathy: report of two cases and literature review.

BACKGROUND: To present the retinal and systemic findings in two siblings with compound heterozygous MPDZ variants that were found to have different chorioretinal manifestations. Materials and Methods: Two sibling patients underwent comprehensive ophthalmic examination, including ophthalmoscopy, fundus photography, optical coherence tomography (OCT), and genetic testing by whole exome sequencing. RESULTS: A 4-year-old male presented with intermittent exotropia and decreased vision in both eyes. Ophthalmologic examination was notable for macular colobomas and far temporal chorioretinal atrophy in both eyes. OCT of the macula in both eyes demonstrated a caldera with severe retinal and choroidal thinning. Fluorescein angiography of the central macula showed hypofluorescence with persistence of deep choroidal vessels. An ocular gene panel was nondiagnostic, but subsequent whole-exome sequencing noted compound heterozygous, likely pathogenic MPDZ variants (c.3100C>T p.(Arg1034*) from father and c.747 + 2T>G p.(?) from mother). His older brother, a 9-year-old male, had a history of macrocephaly but had not undergone further workup. On exam, he had a visual acuity of 20/25 in the right eye and 20/40 in the left eye and was found to have subtle changes in the foveal reflex of both eyes. OCT revealed thinning of the outer nuclear layer (ONL) temporal to the fovea bilaterally. Sanger sequencing revealed he was positive for the same two MPDZ variants. CONCLUSIONS: MPDZ variants have been described in cases of congenital hydrocephalus with varying ophthalmologic manifestations. We present a case series describing retinal phenotypes associated with MPDZ variants in a single family through multimodal imaging.

COVID-19 related disruptions to medical education and perceived clinical capability of new resident physicians: a nationwide study of over 1200 first-year residents.

The COVID-19 pandemic transformed the final year of undergraduate medical education for thousands of medical students across the globe. Out of concern for spreading SARS-CoV-2 and conserving personal protective equipment, many students experienced declines in bedside clinical exposures. The perceived competency of this class within the context of the pandemic is unclear. We designed and distributed a survey to measure the degree to which recent medical school graduates from the USA felt clinically prepared on 13 core clinical skills. Of the 1283 graduates who matched at HCA Healthcare facilities, 90% (1156) completed the survey. In this national survey, most participants felt they were competent in their clinical skills. However, approximately one out of four soon-to-be residents felt they were clinically below where they should be with regard to calling consultations, performing procedures, and performing pelvic and rectal exams. One in five felt they were below where they should be with regard to safely transitioning care. These perceived deficits in important skill sets suggest the need for evaluation and revised educational approaches in these areas, especially when traditional in-person practical skills teaching and practice are disrupted.

Malignant teratoid intraocular ciliary body medulloepithelioma in a 5-year-old male with corresponding somatic copy number alteration profile of aqueous humor cell-free DNA.

BACKGROUND: Intraocular, ciliary body, medulloepithelioma (CBME) is a rare tumor of the nonpigmented ciliary body epithelium, typically presenting in childhood. We describe a case of CBME. MATERIALS AND METHODS: Ocular examination and imaging guided diagnostic and treatment decisions. Aqueous humor (AH) liquid biopsy was collected from the affected eye at eventual enucleation. Whole genome sequencing (WGS) was employed to determine somatic copy number alterations (SCNA) in AH cell-free DNA (cfDNA). Tumor sample was analyzed using various assays to evaluate for oncogenic mutations and SCNAs. Histopathology determined diagnosis. RESULTS: A 5-year-old male with glaucoma and cataract in the left eye (OS) experienced worsening left eye pain and redness. There was no light perception OS and the eye was hypotonus. Anterior segment exam showed complete cataract and rubeosis iridis. Ocular B-scan ultrasound OS revealed an intraocular lesion with calcifications and retinal detachment. Orbital MRI suggested left globe hypercellularity. An infiltrative lesion involving the ciliary body was seen in the left eye on examination under anesthesia. Left eye enucleation was performed in the setting of pain, blindness, and tumor, with anterior chamber paracentesis for AH liquid biopsy collection. SCNA profile of AH cfDNA demonstrated loss of copy of chromosomes 4, 6, and 9. Tumor was negative for clinically significant mutations or SCNAs. Histopathology diagnosed malignant teratoid CBME. CONCLUSIONS: We present a case of CBME and include the unique SCNA profile of AH cfDNA from the enucleated eye. This case suggests utility of AH liquid biopsy in distinguishing between differential diagnoses for intraocular mass lesions.

Misdiagnosis of Orbital Foreign Body as Glaucoma Drainage Device.

BACKGROUND: Sight-threatening complications from retained orbital and intraocular foreign bodies are frequently reported in literature. Delays in diagnosis can result in severe complications, including choroidal neovascularization, infection, and irreversible vision loss. Therefore, it is imperative that emergency physicians consider the possibility of orbital and intraocular foreign bodies when evaluating patients with acute facial trauma. CASE REPORT: A 91-year-old woman with a history of laser-treated glaucoma and cataracts presented to an outside emergency department after a ground-level fall. A maxillofacial noncontrast computed tomography scan showed no facial fractures or hemorrhage, but a 41 mm × 4 mm foreign body within the intraconal compartment of the right orbit was identified. The object was presumed to be an implanted glaucoma drainage device, and the patient was discharged without antibiotics. One day after discharge, the patient developed right periorbital swelling and erythema with increasing purulent discharge and skin thickening, ultimately requiring transfer to our facility for management of complex right orbital cellulitis, orbital compartment syndrome, and surgical foreign body removal. Despite globe exploration and surgical intervention, the patient developed a frozen globe with no light perception in the right eye. Why Should an Emergency Physician Be Aware of This? Subtle ophthalmologic emergencies such as sight-threatening foreign bodies can be challenging to diagnose on imaging, particularly with the advent of implantable ocular technology. When an orbital foreign body is discovered in the context of facial trauma, early ophthalmology consultation should be considered.

Assessment of Disparities Associated With a Crisis Standards of Care Resource Allocation Algorithm for Patients in 2 US Hospitals During the COVID-19 Pandemic.

Importance: Significant concern has been raised that crisis standards of care policies aimed at guiding resource allocation may be biased against people based on race/ethnicity. Objective: To evaluate whether unanticipated disparities by race or ethnicity arise from a single institution's resource allocation policy. Design, Setting, and Participants: This cohort study included adults (aged ≥18 years) who were cared for on a coronavirus disease 2019 (COVID-19) ward or in a monitored unit requiring invasive or noninvasive ventilation or high-flow nasal cannula between May 26 and July 14, 2020, at 2 academic hospitals in Miami, Florida. Exposures: Race (ie, White, Black, Asian, multiracial) and ethnicity (ie, non-Hispanic, Hispanic). Main Outcomes and Measures: The primary outcome was based on a resource allocation priority score (range, 1-8, with 1 indicating highest and 8 indicating lowest priority) that was assigned daily based on both estimated short-term (using Sequential Organ Failure Assessment score) and longer-term (using comorbidities) mortality. There were 2 coprimary outcomes: maximum and minimum score for each patient over all eligible patient-days. Standard summary statistics were used to describe the cohort, and multivariable Poisson regression was used to identify associations of race and ethnicity with each outcome. Results: The cohort consisted of 5613 patient-days of data from 1127 patients (median [interquartile range {IQR}] age, 62.7 [51.7-73.7]; 607 [53.9%] men). Of these, 711 (63.1%) were White patients, 323 (28.7%) were Black patients, 8 (0.7%) were Asian patients, and 31 (2.8%) were multiracial patients; 480 (42.6%) were non-Hispanic patients, and 611 (54.2%) were Hispanic patients. The median (IQR) maximum priority score for the cohort was 3 (1-4); the median (IQR) minimum score was 2 (1-3). After adjustment, there was no association of race with maximum priority score using White patients as the reference group (Black patients: incidence rate ratio [IRR], 1.00; 95% CI, 0.89-1.12; Asian patients: IRR, 0.95; 95% CI. 0.62-1.45; multiracial patients: IRR, 0.93; 95% CI, 0.72-1.19) or of ethnicity using non-Hispanic patients as the reference group (Hispanic patients: IRR, 0.98; 95% CI, 0.88-1.10); similarly, no association was found with minimum score for race, again with White patients as the reference group (Black patients: IRR, 1.01; 95% CI, 0.90-1.14; Asian patients: IRR, 0.96; 95% CI, 0.62-1.49; multiracial patients: IRR, 0.81; 95% CI, 0.61-1.07) or ethnicity, again with non-Hispanic patients as the reference group (Hispanic patients: IRR, 1.00; 95% CI, 0.89-1.13). Conclusions and Relevance: In this cohort study of adult patients admitted to a COVID-19 unit at 2 US hospitals, there was no association of race or ethnicity with the priority score underpinning the resource allocation policy. Despite this finding, any policy to guide altered standards of care during a crisis should be monitored to ensure equitable distribution of resources.

Do all cardiac surgery patients benefit from antifibrinolytic therapy?

BACKGROUND: In trauma patients, the recognition of fibrinolysis phenotypes has led to a re-evaluation of the risks and benefits of antifibrinolytic therapy (AF). Many cardiac patients also receive AF, but the distribution of fibrinolytic phenotypes in that population is unknown. The purpose of this hypothesis-generating study was to fill that gap. METHODS: Seventy-eight cardiac surgery patients were retrospectively reviewed. Phenotypes were defined as hypofibrinolytic (LY30 <0.8%), physiologic (0.8%-3.0%), and hyperfibrinolytic (>3%) based on thromboelastogram. RESULTS: The population was 65 ± 10-years old, 74% male, average body mass index of 29 ± 5 kg/m2 . Fibrinolytic phenotypes were distributed as physiologic = 45% (35 of 78), hypo = 32% (25 of 78), and hyper = 23% (18 of 78). There was no obvious effect of age, gender, race, or ethnicity on this distribution; 47% received AF. For AF versus no AF, the time with chest tube was longer (4 [1] vs. 3 [1] days, p = .037), and all-cause morbidity was more prevalent (51% vs. 25%, p = .017). However, when these two groups were further stratified by phenotypes, there were within-group differences in the percentage of patients with congestive heart failure (p = .022), valve disease (p = .024), on-pump surgery (p < .0001), estimated blood loss during surgery (p = .015), transfusion requirement (p = .015), and chest tube output (p = .008), which highlight other factors along with AF that might have affected all-cause morbidity. CONCLUSION: This is the first description of the prevalence of three different fibrinolytic phenotypes and their potential influence on cardiac surgery patients. The use of AF was associated with increased morbidity, but because of the small sample size and treatment allocation bias, additional confirmatory studies are necessary. We hope these present findings open the dialog on whether it is safe to administer AFs to cardiac surgery patients who are normo- or hypofibrinolytic.

Gut-Induced Inflammation during Development May Compromise the Blood-Brain Barrier and Predispose to Autism Spectrum Disorder.

Recently, the gut microbiome has gained considerable interest as one of the major contributors to the pathogenesis of multi-system inflammatory disorders. Several studies have suggested that the gut microbiota plays a role in modulating complex signaling pathways, predominantly via the bidirectional gut-brain-axis (GBA). Subsequent in vivo studies have demonstrated the direct role of altered gut microbes and metabolites in the progression of neurodevelopmental diseases. This review will discuss the most recent advancements in our understanding of the gut microbiome's clinical significance in regulating blood-brain barrier (BBB) integrity, immunological function, and neurobiological development. In particular, we address the potentially causal role of GBA dysregulation in the pathophysiology of autism spectrum disorder (ASD) through compromising the BBB and immunological abnormalities. A thorough understanding of the complex signaling interactions between gut microbes, metabolites, neural development, immune mediators, and neurobiological functionality will facilitate the development of targeted therapeutic modalities to better understand, prevent, and treat ASD.

Quantification of Retinal Nonperfusion and Neovascularization With Ultrawidefield Fluorescein Angiography in Patients With Diabetes and Associated Characteristics of Advanced Disease.

Importance: Quantification of nonperfusion (NP) and neovascularization (NV) in diabetic retinopathy (DR) may identify better biomarkers of disease progression. Objective: To identify demographic risk factors and markers of advanced DR that are associated with increased areas of NP and NV in eyes with disease ranging from no DR but diagnosed as having diabetes to proliferative DR (PDR) and to calculate a threshold total area of NP that may be associated with an increased risk of PDR. Design, Setting, and Participants: This retrospective case series was performed on ultrawidefield fluorescein angiography (UWF FA) images from January 2009 to May 2018 at the University of Michigan Kellogg Eye Center. A total of 363 participants (651 eyes) diagnosed as having type 1 or 2 diabetes receiving UWF FA were included. Exclusion criteria included previous panretinal photocoagulation (PRP) and poor-quality images (eg, vitreous hemorrhage and significant cataract). Main Outcomes and Measures: The surface areas in millimeters squared of the foveal avascular zone; total NP; NP at posterior pole, midperiphery, and far periphery; total NV; NV at posterior pole, midperiphery, and far periphery were measured. Results: Of 363 patients, most were male (205 patients [56.5%]) and white (247 [68%]) or black (77 [21.2%]). The mean (SD) age was 59.4 (13.7) years. Seventy-six eyes with no DR, 92 with mild NPDR, 144 with moderate NPDR, 101 with severe NPDR, 220 with PDR, and 18 with DR of unknown severity were included. Male sex had a positive association with total NP (difference, 15.72; 95% CI, 4.83-26.61; P = .005); black race/ethnicity with total NV (difference, 2.32; 95% CI, 0.09-4.55; P = .04); and vitreous hemorrhage with total NP (difference, 30.00; 95% CI, 5.26-54.75; P = .02). A threshold total NP area of 77.48 mm2 (95% CI, 54.24-92.66 mm2) was identified, at greater than which patients may have an increased risk of developing PDR (sensitivity of 59.5% and specificity of 73.6%). Conclusions and Relevance: Our results indicate NP and NV can be quantified on UWF FA. These biomarkers interpreted with demographic risk factors may help predict disease progression. Conclusions are limited by ascertainment and information biases because the results are from retrospective data.

A Data-Driven Social Network Intervention for Improving Organ Donation Awareness Among Minorities: Analysis and Optimization of a Cross-Sectional Study.

BACKGROUND: Increasing the number of organ donors may enhance organ transplantation, and past health interventions have shown the potential to generate both large-scale and sustainable changes, particularly among minorities. OBJECTIVE: This study aimed to propose a conceptual data-driven framework that tracks digital markers of public organ donation awareness using Twitter and delivers an optimized social network intervention (SNI) to targeted audiences using Facebook. METHODS: We monitored digital markers of organ donation awareness across the United States over a 1-year period using Twitter and examined their association with organ donation registration. We delivered this SNI on Facebook with and without optimized awareness content (ie, educational content with a weblink to an online donor registration website) to low-income Hispanics in Los Angeles over a 1-month period and measured the daily number of impressions (ie, exposure to information) and clicks (ie, engagement) among the target audience. RESULTS: Digital markers of organ donation awareness on Twitter are associated with donation registration (beta=.0032; P<.001) such that 10 additional organ-related tweets are associated with a 3.20% (33,933/1,060,403) increase in the number of organ donor registrations at the city level. In addition, our SNI on Facebook effectively reached 1 million users, and the use of optimization significantly increased the rate of clicks per impression (beta=.0213; P<.004). CONCLUSIONS: Our framework can provide a real-time characterization of organ donation awareness while effectively delivering tailored interventions to minority communities. It can complement past approaches to create large-scale, sustainable interventions that are capable of raising awareness and effectively mitigate disparities in organ donation.

Use of Predictive Equations for Energy Prescription Results in Inaccurate Estimation in Trauma Patients.

BACKGROUND: Overfeeding and underfeeding are associated with poor clinical outcomes. In the absence of indirect calorimetry (IC), the Society of Critical Care Medicine/ASPEN recommend prescribing 25-30 kcal/kg. The Harris-Benedict equation (HBE) multiplied by a stress factor is commonly applied in critically ill patients. We describe the difference between estimated and actual energy needs in critically injured patients. METHODS: From March to November 2018, we collected demographics and energy needs determined by continuous IC (started within 4 days) in intubated adults. Ideal or adjusted body weight was used for 25-30 kcal/kg, and HBE was multiplied by a 1.3 stress factor (1.3HBE). Daily requirements up to 14 days, extubation, or death were calculated using all 3 methods and compared with IC. RESULTS: Fifty-five subjects were included. Median age was 38 [27-58] years, 38 (69%) were male, body mass index was 28 [25-33] kg/m2 , and Acute Physiology and Chronic Health Evaluation II score was 17 [14-24] Mechanism of injury was blunt (38, 69%), penetrating (9, 16%), and burn (8, 15%). By day 14, compared with measured energy requirements by IC, the other methods could result in a cumulative 1827-kcal (+7%) surplus (1.3HBE), a 1313-kcal (-5%) deficit (25 kcal/kg), or a 3950-kcal (+14%) surplus (30 kcal/kg) per patient over a median 9 days. CONCLUSION: In critically injured patients, predictive equations for energy needs do not account for dynamic metabolic changes over time and could result in underfeeding or overfeeding. Adjusting daily prescription based on continuous IC may result in better individualized treatment.

Gene therapy for neurological disorders: challenges and recent advancements.

Major advancements in targeted gene therapy have opened up avenues for the treatment of major neurological disorders through a range of versatile modalities varying from expression of exogenous to suppression of endogenous genes. Recent technological innovations for improved gene sequence delivery have focussed on highly specific viral vector designs, plasmid transfection, nanoparticles, polymer-mediated gene delivery, engineered microRNA and in vivo clustered regulatory interspaced short palindromic repeats (CRISPR)-based therapeutics. These advanced techniques have profound applications in treating highly prevalent neurological diseases and neurodevelopmental disorders including Parkinson's disease, Alzheimer's disease and autism spectrum disorder, as well as rarer diseases such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy, lysosomal storage diseases, X-linked adrenoleukodystrophy and oncological diseases. In this article, we present an overview of the latest advances in targeted gene delivery and discuss the challenges and future direction of gene therapy in the treatment of neurological disorders.

Continuous Indirect Calorimetry in Critically Injured Patients Reveals Significant Daily Variability and Delayed, Sustained Hypermetabolism.

BACKGROUND: Previous studies have used using Indirect Calorimetry (IC) with solitary or sparse measurements of resting energy expenditure (REE). This "snapshot" may not capture the dynamic nature of metabolic requirements. Using continuous IC, we describe the variation of REE during the first days in the intensive care unit. METHODS: Injured adults (≥18 years) requiring mechanical ventilation from March 2018 to September 2018 were enrolled. IC was initiated within 4 days of admission and continuous REE recorded until 14 days, extubation, or death. Multiple 10-minute periods collected during steady state were used to calculate daily REE maximum, minimum, average, and variability [(REEmax - REEmin/2)/average REE]. RESULTS: We included 55 patients. Median age was 38 [27-58] years, 38 (69%) were male, body mass index was 28 [25-33] kg/m2 , and Acute Physiology and Chronic Health Evaluation II was 17 [14-24]. Mechanism of injury was: blunt (n = 38, 69%), penetrating (n = 9, 16%), and burn (n = 8, 15%). Average REE increased gradually from 1,663 kcal [1,435-2,143] to a maximum of 2,080 [1,701-2,336] on day 7, a relative 25% increase, which was sustained through day 14. REE variability ranged 8%-13% and was not reliably predicted by fever, tachycardia, elevated intracranial pressures, hypertension, or hypotension. CONCLUSION: In critically injured patients, steady-state REE measurements display fluctuations over a 24-hour period and demonstrate a gradual rise over the first few days after injury. Continuous REE, if available, is recommended for more precise matching of energy delivery to metabolic requirements.

The Effect of Financial Incentives on Patient Decisions to Undergo Low-value Head Computed Tomography Scans.

BACKGROUND: Excessive diagnostic testing and defensive medicine contribute to billions of dollars in avoidable costs in the United States annually. Our objective was to determine the influence of financial incentives, accompanied with information regarding test risk and benefit, on patient preference for diagnostic testing. METHODS: We conducted a cross-sectional survey of patients at the University of Michigan emergency department (ED). Each participant was presented with a hypothetical scenario involving an ED visit following minor traumatic brain injury. Participants were given information regarding potential benefit (detecting brain hemorrhage) and risk (developing cancer) of head computed tomography scan, as well as an incentive of $0 or $100 to forego testing. We used 0.1 and 1% for test benefit and risk, and values for risk, benefit, and financial incentive varied across participants. Our primary outcome was patient preference to undergo testing. We also collected demographic and numeracy information. We then used logistic regression to estimate odds ratios (ORs), which were adjusted for multiple potential confounders. Our sample size was designed to find at least 300 events (preference for testing) to allow for inclusion of up to 30 covariates in fully adjusted models. We had 85% to 90% power to detect a 10% absolute difference in testing rate across groups, assuming a 95% significance level. RESULTS: We surveyed 913 patients. Increasing test benefit from 0.1% to 1% significantly increased test acceptance (adjusted OR [AOR] = 1.6, 95% confidence interval [CI] = 1.2 to 2.1) and increasing test risk from 0.1% to 1% significantly decreased test acceptance (AOR = 0.70, 95% CI = 0.52 to 0.93). Finally, a $100 incentive to forego low-value testing significantly reduced test acceptance (AOR = 0.6; 95% CI = 0.4 to 0.8). CONCLUSIONS: Providing financial incentives to forego testing significantly decreased patient preference for testing, even when accounting for test benefit and risk. This work is preliminary and hypothetical and requires confirmation in larger patient cohorts facing these actual decisions.

Electrical Burns During Fruit Harvesting.

Electrocutions during tree trimming or fruit harvesting are occasionally reported in the public media, but the actual incidence is unknown. Some fruit trees (eg, mango and avocado) can exceed 30 feet, with dense foliage concealing the fruit and overlying power lines so burns associated with harvesting these fruits are often exacerbated with falls. However, there are limited data on this subject. To fill this gap, we provide some of the first information on this unique injury pattern. All electrocutions from 2013 to 2018 were retrospectively reviewed at an ABA-verified burn center. Demographics, injury patterns, and complications were analyzed. Of 97 electrocutions, 22 (23%) were associated with fruit procurement. This population was aged 43 ± 14 years, 95% (n = 21) male, injury severity score of 15 ± 13, and total body surface area burned 4% [1%-9%]. Third-degree burns were present in 36% (n = 8). ICU admission was required in 59% (n = 13) and 39% of the survivors required operative interventions for the burn. Compartment syndrome occurred in 18% (n = 4) and 14% (n = 3) patients required amputations. Falls complicated the care in 50% (n = 11), with associated head, chest, and/or extremity trauma. Mortality was 32% (n = 7), with three patients presenting dead on arrival. All but 3 injuries occurred between June and December, coinciding with mango and avocado season. Electrocution during fruit picking is a seasonal injury often exacerbated by falls. Management is challenging, and favorable outcome depends on recognition of the complexity of the polytrauma.

Patient Preferences for Diagnostic Testing in the Emergency Department: A Cross-sectional Study.

BACKGROUND: Diagnostic testing is common during emergency department (ED) visits. Little is understood about patient preferences for such testing. We hypothesized that a patient's willingness to undergo diagnostic testing is influenced by the potential benefit, risk, and personal cost. METHODS: We conducted a cross sectional survey among ED patients for diagnostic testing in two hypothetical scenarios: chest pain (CP) and mild traumatic brain injury (mTBI). Each scenario defined specific risks, benefits, and costs of testing. The odds of a participant desiring diagnostic testing were calculated using a series of nested multivariable logistic regression models. RESULTS: Participants opted for diagnostic testing 68.2% of the time, including 69.7% of CP and 66.7% of all mTBI scenarios. In the CP scenario, 81% of participants desired free testing versus 59% when it was associated with a $100 copay (difference = 22%, 95% confidence interval [CI] = 16% to 28%). Similarly, in the mTBI scenario, 73% of adult participants desired free testing versus 56% when charged a $100 copayment (difference = 17%, 95% CI = 11% to 24%). Benefit and risk had mixed effects across the scenarios. In fully adjusted models, the association between cost and desire for testing persisted in the CP (odds ratio [OR] = 0.33, 95% CI = 0.23 to 0.47) and adult mTBI (OR = 0.47, 95% CI = 0.33 to 0.67) scenarios. CONCLUSIONS: In this ED-based study, patient preferences for diagnostic testing differed significantly across levels of risk, benefit, and cost of diagnostic testing. Cost was the strongest and most consistent factor associated with decreased desire for testing.

Effect of patient-reported smoking status on short-term bariatric surgery outcomes.

INTRODUCTION: Preoperative patient screening is a major contributor to the remarkable safety of bariatric surgery. Smoking status is a modifiable patient risk factor, and smoking cessation is associated with improved outcomes in surgical patients. However, the length of smoking cessation necessary to optimize bariatric surgery patient outcomes is not yet defined. We sought to explore the relationship between patient-reported smoking status and short-term bariatric surgery outcomes. METHODS: Using prospectively collected data from the MBSC registry, we evaluated the effects of patient-reported length of tobacco abstinence on 30-day surgical outcomes. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) patients (n = 49,772) were divided into three categories based on smoking status: never smoker, former smoker, and recent smoker. We compared risk-adjusted complication rates using multivariable logistic regression models and compared excess body weight loss using a one-way ANOVA test. RESULTS: The risk-adjusted rate of severe complications among RYGB patients in the recent smoker group was significantly increased relative to patients who had never smoked (OR 1.34; 95% CI, 1.01-1.77), but not among SG patients (OR 1.18; 95% CI 0.87-1.62). In the same populations, differences in overall complication rate were not significant for either RYGB (OR, 1.11; 95% CI 0.94-1.31) or LSG (OR 1.04; 95% CI 0.86-1.25). CONCLUSIONS: Recent smokers suffer detrimental effects of smoking on serious postoperative complications following RYGB surgery, but may not suffer an elevated risk of complications attributable to smoking for sleeve gastrectomy. An evaluation of the effect on long-term outcomes is necessary to further define the risks of smoking on bariatric surgery outcomes.

Risk, Benefit, and Cost Thresholds for Emergency Department Testing: A Cross-sectional, Scenario-based Study.

BACKGROUND: While diagnostic testing is common in the emergency department, the value of some testing is questionable. The purpose of this study was to assess how varying levels of benefit, risk, and costs influenced an individual's desire to have diagnostic testing. METHODS: A survey through Amazon Mechanical Turk presented hypothetical clinical situations: low-risk chest pain and minor traumatic brain injury. Each scenario included three given variables (benefit, risk, and cost), that was independently randomly varied over four possible values (0.1, 1, 5, and 10% for benefit and risk and $0, $100, $500, and $1,000 for the individual's personal cost for receiving the test). Benefit was defined as the probability of finding the target disease (traumatic intracranial hemorrhage or acute coronary syndrome). RESULTS: One-thousand unique respondents completed the survey. With an increased benefit from 0.1% to 10%, the percentage of respondents who accepted a diagnostic test went from 28.4% to 53.1%. (odds ratio [OR] = 3.42; 95% confidence interval [CI] = 2.57-4.54). As risk increased from 0.1% to 10%, this number decreased from 52.5% to 28.5%. (OR = 0.33; 95% CI = 0.25-0.44). Increasing cost from $0 to $1,000 had the greatest change of those accepting the test from 61.1% to 21.4%, respectively (OR = 0.15; 95% CI = 0.11-0.2). CONCLUSIONS: The desire for testing was strongly sensitive to the benefits, risks, and costs. Many participants wanted a test when there was no added cost, regardless of benefit or risk levels, but far fewer elected to receive the test as cost increased incrementally. This suggests that out-of-pocket costs may deter patients from undergoing diagnostic testing with low potential benefit.

NanoLuc reporter for dual luciferase imaging in living animals.

Bioluminescence imaging is widely used for cell-based assays and animal imaging studies in biomedical research and drug development, capitalizing on the high signal to background of this technique. A relatively small number of luciferases are available for imaging studies, substantially limiting the ability to image multiple molecular and cellular events, as done commonly with fluorescence imaging. To advance dual reporter bioluminescence molecular imaging, we tested a recently developed, adenosine triphosphate­independent luciferase enzyme from Oplophorus gracilirostris (NanoLuc [NL]) as a reporter for animal imaging. We demonstrated that NL could be imaged in superficial and deep tissues in living mice, although the detection of NL in deep tissues was limited by emission of predominantly blue light by this enzyme. Changes in bioluminescence from NL over time could be used to quantify tumor growth, and secreted NL was detectable in small volumes of serum. We combined NL and firefly luciferase reporters to quantify two key steps in transforming growth factor ß signaling in intact cells and living mice, establishing a novel dual luciferase imaging strategy for quantifying signal transduction and drug targeting. Our results establish NL as a new reporter for bioluminescence imaging studies in intact cells and living mice that will expand imaging of signal transduction in normal physiology, disease, and drug development.