The Effect of Tibiotalar Joint Line Level Alterations on Tibiotalar Range of Motion Following Total Ankle Arthroplasty.

BACKGROUND: The effect of tibiotalar joint line level (TTJL) on patient outcomes following total ankle arthroplasty (TAA) remains unclear. It was previously reported that patients with end-stage ankle arthritis have an elevated TTJL compared with nonarthritic ankles, and the TTJL post-TAA remains elevated compared with nonarthritic ankles. The objectives of this study were to (1) propose a reliable radiographic method to measure the TTJL absolute value and (2) determine the effect of TTJL alterations on tibiotalar range of motion (ROM) following TAA. METHODS: A retrospective review was performed on patients who underwent TAA between January 2018 and April 2021 with a minimum of 1-year postoperative follow-up and complete perioperative ROM radiographs. Radiographic TTJL and ROM measurements were performed by 2 observers. The proposed TTJL measuring technique computes 4 measurements: high, low, center of the talus (center), and center of the axis (axis). Reliability of measurements and correlation between TTJL measurements and ROM were assessed. RESULTS: A total of 33 patients were included. Postoperatively, 22 patients had a lowered TTJL compared to 11 patients with an elevated TTJL (2.2 ± 1.3 mm lowered vs 1.9 ± 1.2 mm elevated; P < .0001). Of the 4 TTJL measurements, 3 (low, center, axis) demonstrated a significant positive correlation between lowering the TTJL and improved tibiotalar dorsiflexion and 2 (low, axis) for total ROM (all P < .05). Plantarflexion was not significantly affected by TTJL alterations. Compared to patients with an elevated TTJL, patients with a lowered TTJL had improved tibiotalar dorsiflexion (8.8 vs 2.5 degrees; P = .0015) and total ROM (31.0 vs 22.9 degrees; P = .0191), respectively. The interrater reliability was nearly perfect (intraclass correlation r = 0.96-0.99). CONCLUSION: In this small series, we found that lowering the TTJL level may more closely reestablish the native TTJL and correlates with improved tibiotalar dorsiflexion and total ROM following TAA. LEVEL OF EVIDENCE: Level IV, case series.

The effects of policy changes and human mobility on the COVID-19 epidemic in the Dominican Republic, 2020-2021.

Recent advances in technology can be leveraged to enhance public health research and practice. This study aimed to assess the effects of mobility and policy changes on COVID-19 case growth and the effects of policy changes on mobility using data from Google Mobility Reports, information on public health policy, and COVID-19 testing results. Multiple bivariate regression analyses were conducted to address the study objectives. Policies designed to limit mobility led to decreases in mobility in public areas. These policies also decreased COVID-19 case growth. Conversely, policies that did not restrict mobility led to increases in mobility in public areas and led to increases in COVID-19 case growth. Mobility increases in public areas corresponded to increases in COVID-19 case growth, while concentration of mobility in residential areas corresponded to decreases in COVID-19 case growth. Overall, restrictive policies were effective in decreasing COVID-19 incidence in the Dominican Republic, while permissive policies led to increases in COVID-19 incidence.

Fatal Primary Amebic Meningoencephalitis in Nebraska: Case Report and Environmental Investigation, August 2022.

Primary amebic meningoencephalitis (PAM) is a rare and lethal infection caused by Naegleria fowleri. We report an epidemiological and environmental investigation relating to a case of PAM in a previously healthy boy age 8 years. An interview of the patient's family was conducted to determine the likely exposure site and to assess risk factors. Data from the United States Geological Survey site at Waterloo, NE, on the Elkhorn River were used to estimate water temperature and streamflow at the time and site of exposure. Data from the National Weather Service were used to estimate precipitation and ambient air temperature at the time and site of exposure. Despite conventional treatment, the patient died 2 days after hospital admission. The patient participated in recreational water activities in the Elkhorn River in northeastern Nebraska 5 days before symptom onset. In the week before exposure, water and ambient air high temperatures reached annual highs, averaging 32.4°C and 35.8°C, respectively. The day before infection, 2.2 cm of precipitation was reported. Streamflow was low (407 ft3/s). Infections in several northern states, including Nebraska, suggest an expanding geographic range of N. fowleri transmission, which may lead to increased incidence of PAM in the United States. Similar environmental investigations at suspected exposure sites of future cases will allow data aggregation, enabling investigators to correlate environmental factors with infection risk accurately.

Cranioplasty in the deployed environment: experience for host-country nationals.

OBJECTIVE: Decompressive craniectomy (DC) is the definitive neurosurgical treatment for managing refractory malignant cerebral edema and intracranial hypertension due to combat-related severe traumatic brain injury (TBI). To date, the long-term outcomes and sequelae of this procedure on host-country national (HCN) populations during Operation Iraqi Freedom (Iraq, 2003-2011), Operation Enduring Freedom (Afghanistan, 2001-2014), and Operation Freedom's Sentinel (Afghanistan, 2015-2021) have not been described, specifically the process and results of delayed custom synthetic cranioplasty. The Joint Trauma System's Clinical Practice Guidelines (JTS-CPG) for severe head injury counsels surgeons to discard the cranial osseous explant when treating coalition service members. Ongoing political and healthcare system instabilities often preclude opportunities for delayed cranioplasty by host-country assets. Various surgical options (such as hinge craniectomy) are inadequate in the setting of complicated cranial comminution from blast or missile injuries, severe cerebral edema, grossly contaminated wounds, complex polytrauma, and tissue devitalization. Delayed cranioplasty with a custom synthetic implant is a viable but logistically challenging alternative. In this retrospective review, the authors present the first patient series describing delayed custom synthetic cranioplasty in an HCN population performed during active military conflict. METHODS: Patients were identified through the Joint Trauma System/Theater Medical Data Store, and subgroup analyses were performed to include mechanisms of injury, surgical complications, and clinical outcomes. RESULTS: Twenty-five patients underwent DC between 2012 and 2020 to treat penetrating, blast, and high-energy closed head injuries per JTS-CPG criteria. The average time from injury to surgery was 1.4 days, although 6 patients received delayed care (3-6 days) due to protracted evacuation from local hospitals. Delayed care correlated with an increased rate of intracranial abscess and empyema. The average time to cranioplasty was 134 days due to a lack of robust mechanisms for patient follow-up, tracking, and access to NATO hospitals. HCN patients who recovered from DC demonstrated overall benefit from custom synthetic cranioplasty, although formal statistical analysis was impeded by a lack of long-term follow-up. CONCLUSIONS: This review demonstrates that cranioplasty with a custom synthetic implant is a safe and feasible treatment for vulnerable HCN patients who survive their index DC surgery. This unique paradigm of care highlights the capabilities of deployed neurosurgical healthcare teams working in partnership with the prosthetics laboratory at Walter Reed National Military Medical Center.

The mediating effects of barriers to vaccination on the relationship between race/ethnicity and influenza vaccination status in a rural Southeastern Louisiana medical center.

Introduction: Persistent disparities in influenza vaccination rates exist between racial/ethnic minorities and Whites. The mechanisms that define this relationship are under-researched. Methods: Surveys assessing barriers to vaccination were administered to outpatients in a rural medical center in Southeastern Louisiana. Survey responses were matched to patient medical records. Likert-style statements were used to measure barriers to vaccination. A mediation analysis assessing the relationship between race and influenza vaccination mediated by vaccination barriers was conducted. Results: The self-reported influenza vaccination rate in those surveyed was 40.4%. Whites (45.5%) were more likely than racial/ethnic minorities (36.3%) to report receipt of an influenza vaccination (p = 0.02). Racial/ethnic minorities reported significantly higher vaccination barrier scores (p < 0.01). The relationship between race/ethnicity and vaccination was mediated by vaccination barriers, when controlling for provider recommendation and having at least one comorbid medical condition (natural indirect effect [NIE] p-value = 0.02, proportion mediated = 0.71). Conclusions: Barriers to vaccination mediates the relationship between race/ethnicity and vaccination status. Providers should focus on minimizing fears that the vaccine will cause illness and emphasize that the vaccine is safe and effective at preventing severe influenza-associated illness. Additional efforts should be made to improve accessibility of the influenza vaccine, including addressing costs of vaccination and expanding the number and types of settings where the vaccine is offered.

Discovery of Anthranilic Acid Derivatives as Difluoromethylornithine Adjunct Agents That Inhibit Far Upstream Element Binding Protein 1 (FUBP1) Function.

Polyamine biosynthesis is regulated by ornithine decarboxylase (ODC), which is transcriptionally activated by c-Myc. A large library was screened to find molecules that potentiate the ODC inhibitor, difluoromethylornithine (DFMO). Anthranilic acid derivatives were identified as DFMO adjunct agents. Further studies identified the far upstream binding protein 1 (FUBP1) as the target of lead compound 9. FUBP1 is a single-stranded DNA/RNA binding protein and a master controller of specific genes including c-Myc and p21. We showed that 9 does not inhibit 3H-spermidine uptake yet works synergistically with DFMO to limit cell growth in the presence of exogenous spermidine. Compound 9 was also shown to inhibit the KH4 FUBP1-FUSE interaction in a gel shift assay, bind to FUBP1 in a ChIP assay, reduce both c-Myc mRNA and protein expression, increase p21 mRNA and protein expression, and deplete intracellular polyamines. This promising hit opens the door to new FUBP1 inhibitors with increased potency.

Failure in Adult Spinal Deformity Surgery: A Comprehensive Review of Current Rates, Mechanisms, and Prevention Strategies.

STUDY DESIGN: Literature review. OBJECTIVE: The aim of this review is to summarize recent literature on adult spinal deformity (ASD) treatment failure as well as prevention strategies for these failure modes. SUMMARY OF BACKGROUND DATA: There is substantial evidence that ASD surgery can provide significant clinical benefits to patients. The volume of ASD surgery is increasing, and significantly more complex procedures are being performed, especially in the aging population with multiple comorbidities. Although there is potential for significant improvements in pain and disability with ASD surgery, these procedures continue to be associated with major complications and even outright failure. METHODS: A systematic search of the PubMed database was performed for articles relevant to failure after ASD surgery. Institutional review board approval was not needed. RESULTS: Failure and the potential need for revision surgery generally fall into 1 of 4 well-defined phenotypes: clinical failure, radiographic failure, the need for reoperation, and lack of cost-effectiveness. Revision surgery rates remain relatively high, challenging the overall cost-effectiveness of these procedures. CONCLUSION: By consolidating the key evidence regarding failure, further research and innovation may be stimulated with the goal of significantly improving the safety and cost-effectiveness of ASD surgery.

Assessing influenza vaccination coverage and predictors in persons living with HIV/AIDS in Louisiana, June 2002-June 2013.

Background: Despite the burden of disease and increased risk of influenza-associated morbidity and mortality among PLWHA, influenza vaccination has been understudied in this population. Methods: We built an 11-year cohort of HIV-infected adults from medical records of PLWHA seeking care within the Louisiana State University medical system from June 2002-June 2013. Influenza vaccination uptake among PLWHA was calculated overall and for each medical facility for each influenza season. Linear regression was used to assess influenza vaccination uptake over time, both overall and by facility. Data were restricted to the final influenza season (2012-13) to assess predictors of PLWHA vaccination. Individuals were nested within medical facilities in order to assess the amount of variability in influenza vaccination rates across medical facilities. Results: Influenza vaccination uptake among PLWHA increased over the study period (p < 0.01). The overall proportion of PLWHA vaccinated during the 2012-13 influenza season was 33.7%. 37.9% of the variability in the model occurred at the facility-level. Conclusions: Although there was an increase in influenza vaccination within the PLWHA cohort over the course of the study, vaccination rates remained low overall. Special efforts must be made to increase vaccination uptake among PLWHA, with particular focus on those within the population who are likely to be at highest risk. The substantial variability at the facility-level indicates that there are unmeasured facility-level factors that contribute significantly to PLWHA vaccination.

Kickstand Rod With Asymmetric Pedicle Subtraction Osteotomy for Treatment of Adult Kyphoscoliosis With Severe Coronal Imbalance.

BACKGROUND: The kickstand rod has been described for the treatment of severe coronal imbalance. We present a modified description that combines an asymmetric pedicle subtraction osteotomy (PSO) for correction of severe kyphoscoliosis. OBJECTIVE: To describe the use of a temporary kickstand rod. METHODS: Type 1 osteotomies were performed across the main and fractional curves. An asymmetric PSO was performed at the apex of the main curve, and a kickstand rod placed on the concavity anchored from the ilium to a temporary connector above the main curve. Distraction was applied across the kickstand rod because the PSO was closed on the convexity. A permanent rod was placed contralateral to the kickstand, followed by replacement of the kickstand with a permanent rod and bilateral accessory rods. RESULTS: A 66-year-old man presented with kyphoscoliosis causing severe coronal and sagittal imbalance. He underwent L4-S1 anterior lumbar interbody fusion followed by T4-pelvis instrumented fusion the following day. Type 1 osteotomies were performed from T6-T12 to L3-S1 and an asymmetric PSO at L2. A temporary kickstand rod was used to distract across the concavity because the PSO was closed on the convexity. The patient achieved excellent clinical and radiographical results. CONCLUSION: When used in conjunction with appropriate osteotomies, the kickstand rod can aid in correction of severe coronal imbalance. Use of a temporary kickstand rod is technically easier and allows for correction of the main and fractional curves when used with an asymmetric PSO.

An Optimized Dihydrodibenzothiazepine Lead Compound (SBI-0797750) as a Potent and Selective Inhibitor of Plasmodium falciparum and P. vivax Glucose 6-Phosphate Dehydrogenase 6-Phosphogluconolactonase.

In Plasmodium, the first two and rate-limiting enzymes of the pentose phosphate pathway, glucose 6-phosphate dehydrogenase (G6PD) and the 6-phosphogluconolactonase, are bifunctionally fused to a unique enzyme named GluPho, differing structurally and mechanistically from the respective human orthologs. Consistent with the enzyme's essentiality for malaria parasite proliferation and propagation, human G6PD deficiency has immense impact on protection against severe malaria, making PfGluPho an attractive antimalarial drug target. Herein we report on the optimized lead compound N-(((2R,4S)-1-cyclobutyl-4-hydroxypyrrolidin-2-yl)methyl)-6-fluoro-4-methyl-11-oxo-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide (SBI-0797750), a potent and fully selective PfGluPho inhibitor with robust nanomolar activity against recombinant PfGluPho, PvG6PD, and P. falciparum blood-stage parasites. Mode-of-action studies have confirmed that SBI-0797750 disturbs the cytosolic glutathione-dependent redox potential, as well as the cytosolic and mitochondrial H2O2 homeostasis of P. falciparum blood stages, at low nanomolar concentrations. Moreover, SBI-0797750 does not harm red blood cell (RBC) integrity and phagocytosis and thus does not promote anemia. SBI-0797750 is therefore a very promising antimalarial lead compound.

Discovery of small molecule guanylyl cyclase A receptor positive allosteric modulators.

The particulate guanylyl cyclase A receptor (GC-A), via activation by its endogenous ligands atrial natriuretic peptide (ANP) and b-type natriuretic peptide (BNP), possesses beneficial biological properties such as blood pressure regulation, natriuresis, suppression of adverse remodeling, inhibition of the renin-angiotensin-aldosterone system, and favorable metabolic actions through the generation of its second messenger cyclic guanosine monophosphate (cGMP). Thus, the GC-A represents an important molecular therapeutic target for cardiovascular disease and its associated risk factors. However, a small molecule that is orally bioavailable and directly targets the GC-A to potentiate cGMP has yet to be discovered. Here, we performed a cell-based high-throughput screening campaign of the NIH Molecular Libraries Small Molecule Repository, and we successfully identified small molecule GC-A positive allosteric modulator (PAM) scaffolds. Further medicinal chemistry structure-activity relationship efforts of the lead scaffold resulted in the development of a GC-A PAM, MCUF-651, which enhanced ANP-mediated cGMP generation in human cardiac, renal, and fat cells and inhibited cardiomyocyte hypertrophy in vitro. Further, binding analysis confirmed MCUF-651 binds to GC-A and selectively enhances the binding of ANP to GC-A. Moreover, MCUF-651 is orally bioavailable in mice and enhances the ability of endogenous ANP and BNP, found in the plasma of normal subjects and patients with hypertension or heart failure, to generate GC-A-mediated cGMP ex vivo. In this work, we report the discovery and development of an oral, small molecule GC-A PAM that holds great potential as a therapeutic for cardiovascular, renal, and metabolic diseases.

Reduced proximal junctional failure with ligament augmentation in adult spinal deformity: a series of 242 cases with a minimum 1-year follow-up.

OBJECTIVE: Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are well-recognized complications of long-segment spinal fusion. Previous studies have suggested that ligament augmentation can decrease rates of PJF by reducing junctional stress and strengthening upper instrumented vertebrae (UIVs) and adjacent segments. However, there is a paucity of long-term data on the efficacy of ligament augmentation in preventing PJF. In this study, the authors sought to determine the effect of ligament augmentation on rates of PJF in a cohort of adult spinal deformity patients with at least 1 year of follow-up. METHODS: They conducted a retrospective analysis of ligament augmentation in a consecutive series of surgical patients with adult spinal deformity. Data on patient demographics, surgical characteristics, and surgery for PJF were collected. The minimum follow-up was 12 months. Univariate and multivariate analyses were performed to identify factors associated with reoperation for PJF. RESULTS: The authors identified a total of 242 patients (166 women [68.6%]) with ligament augmentation whose mean age was 66 years. The mean number of fused levels was 10, with a UIV distribution as follows: 90 upper thoracic UIVs (37.2%) and 152 lower thoracic UIVs (62.8%). Compared to a historical cohort of 77 patients treated before implementation of ligament augmentation, reoperation for PJF was significantly lower with ligament augmentation (15.6% vs 3.3%, p < 0.001). In a multivariate model, only ligament augmentation (OR 0.184, 95% CI 0.071-0.478, p = 0.001) and number of fused levels (OR 0.762, 95% CI 0.620-0.937, p = 0.010) were associated with reductions in reoperation for PJF. CONCLUSIONS: Ligament augmentation was associated with significant reductions in the rate of reoperation for PJF at 12 months in a cohort of adult spinal deformity patients. The most dramatic reduction was seen among patients with lower thoracic UIV. These data suggest that in appropriately selected patients, ligament augmentation may be a valuable adjunct for PJF reduction; however, long-term follow-up is needed.

Optimization of a urea-containing series of nicotinamide phosphoribosyltransferase (NAMPT) activators.

NAD+ is a crucial cellular factor that plays multifaceted roles in wide ranging biological processes. Low levels of NAD+ have been linked to numerous diseases including metabolic disorders, cardiovascular disease, neurodegeneration, and muscle wasting disorders. A novel strategy to boost NAD+ is to activate nicotinamide phosphoribosyltransferase (NAMPT), the putative rate-limiting step in the NAD+ salvage pathway. We previously showed that NAMPT activators increase NAD+ levels in vitro and in vivo. Herein we describe the optimization of our NAMPT activator prototype (SBI-0797812) leading to the identification of 1-(4-((4-chlorophenyl)sulfonyl)phenyl)-3-(oxazol-5-ylmethyl)urea (34) that showed far more potent NAMPT activation and improved oral bioavailability.

Effect of Achilles Tendon Lengthening and Gastrocnemius Recession on Radiographic Tibiotalar Motion Following Total Ankle Replacement.

BACKGROUND: Surgeons frequently add an Achilles tendon lengthening or gastrocnemius recession to increase dorsiflexion following total ankle replacement. Previous studies have looked at the effects of these procedures on total tibiopedal motion. However, tibiopedal motion includes motion of the midfoot and hindfoot as well as the ankle replacement. The current study examined the effects of Achilles tendon lengthening and gastrocnemius recession on radiographic tibiotalar motion at the level of the prosthesis only. METHODS: Fifty-four patients with an average of 25 months follow-up after total ankle replacement were divided into 3 groups: (1) patients who underwent Achilles tendon lengthening, (2) patients who had a gastrocnemius recession, (3) patients with no lengthening procedure. Tibiotalar range of motion was measured on lateral dorsiflexion-plantarflexion radiographs using reference lines on the surface of the implants. RESULTS: Both Achilles tendon lengthening and gastrocnemius recession significantly increased tibiotalar dorsiflexion when compared to the group without lengthening. However, the total tibiotalar range of motion among the 3 groups was the same. Interestingly, the Achilles tendon lengthening group lost 11.7 degrees of plantarflexion compared to the group without lengthening, which was significant. CONCLUSION: Both Achilles tendon lengthening and gastrocnemius recession increased radiographic tibiotalar dorsiflexion following arthroplasty. Achilles tendon lengthening had the unexpected effect of significantly decreasing plantarflexion. Gastrocnemius recession may be a better choice when faced with a tight ankle replacement because it increases dorsiflexion without a compensatory loss of plantarflexion. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Outcomes in single-level posterior cervical spine surgeries performed in the sitting and prone positions.

OBJECTIVE: The sitting or semisitting position in neurosurgery allows for several technical advantages, including improved visualization of the surgical field. However, it has also been associated with an increased risk of venous air embolisms and positioning-related complications that limit its commonplace adoption. The authors report a large, single-center series of cervical spine procedures performed with patients in the sitting or prone position in order to assess the perceived risk of intraoperative and postoperative complications associated with the sitting position. METHODS: Noninstrumented, single-level posterior cervical spine procedures performed with patients in the sitting/semisitting or prone position from 2000 to 2016 at a single institution were reviewed. Institutional abstraction tools (DataMart and Chart Plus) were used to collect data from the medical records. The two positions were compared with regard to preoperative factors, intraoperative variables, and postoperative outcomes. Multivariable logistic regression models were fitted for 30-day readmission, 30-day return to the operating room, and complication rates. RESULTS: A total of 750 patients (sitting, n = 480; prone, n = 270) were analyzed. The median age was 53 years for those who underwent surgery in the prone position and 50 years for those who underwent surgery in the sitting position (IQRs 45-62 years and 43-60 years, respectively), and 35% of the patients were female. Sitting cases were associated with significantly longer anesthetic times (221 minutes [range 199-252 minutes] vs 205 minutes [range 179-254 minutes]) and operative times (126 minutes [range 101-163 minutes] vs 149 minutes [120-181 minutes]). Cardiorespiratory events in the postanesthesia care unit (PACU) were comparable between the two groups, with the exception of episodes of apnea (2.6% vs 0.6%, p = 0.041) and hypoventilation (4.4% vs 0.8%, p < 0.003), which were more frequent in the prone-position cohort. On multivariable analysis, the effect of the sitting versus the prone position was not significant for 30-day readmission (OR 0.77, 95% CI 0.34-1.71, p = 0.52) or reoperation (OR 0.71, 95% CI 0.31-1.60, p = 0.40). The sitting position was associated with lower odds of developing any complication (OR 0.31, 95% CI 0.16-0.62, p < 0.001). CONCLUSIONS: Based on the intraoperative and postoperative complications chosen in this study, the sitting position confers a similar safety profile to the prone position. This can be explained by a more anatomic positioning accounting for reduced temporary neurological deficits and reduced PACU-associated hypoventilation noted in this series. Nevertheless, the findings may also reflect institutional familiarity, experience, and mastery of this position type, and outcomes may not reflect practices in general.

ß-Arrestin-Biased Allosteric Modulator of NTSR1 Selectively Attenuates Addictive Behaviors.

Small molecule neurotensin receptor 1 (NTSR1) agonists have been pursued for more than 40 years as potential therapeutics for psychiatric disorders, including drug addiction. Clinical development of NTSR1 agonists has, however, been precluded by their severe side effects. NTSR1, a G protein-coupled receptor (GPCR), signals through the canonical activation of G proteins and engages ß-arrestins to mediate distinct cellular signaling events. Here, we characterize the allosteric NTSR1 modulator SBI-553. This small molecule not only acts as a ß-arrestin-biased agonist but also extends profound ß-arrestin bias to the endogenous ligand by selectively antagonizing G protein signaling. SBI-553 shows efficacy in animal models of psychostimulant abuse, including cocaine self-administration, without the side effects characteristic of balanced NTSR1 agonism. These findings indicate that NTSR1 G protein and ß-arrestin activation produce discrete and separable physiological effects, thus providing a strategy to develop safer GPCR-targeting therapeutics with more directed pharmacological action.

Parasitic infections represent a significant health threat among recent immigrants in Chicago.

Parasitic infections are likely under-recognized among immigrant populations in the USA. We conducted a cross-sectional study to evaluate if such infections have health impacts among recent immigrants in Chicago and to identify predictive factors for parasitic infections. A total of 133 recent immigrants were enrolled, filling out a standardized medical questionnaire and providing blood and stool samples. Appriximately 12% of subjects (15/125) who provided a blood or stool sample for testing were found to have evidence of current or prior infection with a pathogenic parasite, of which Toxocara spp. (8 subjects, 6.4%) and Strongyloides stercoralis (5 subjects, 4%) were most commonly identified. Parasitic infection was more likely among subjects who had immigrated within the previous 2 years and those with a self-reported history of worms in the stool. The most useful surrogate markers identified for parasitic infections were an elevated immunoglobulin E level (seen in 46.7% (7/15) of subjects with parasitic infections and 20% (22/110) of uninfected individuals, p = 0.04) and the presence of Blastocystis hominis cysts on Ova & Parasite exam (detected in 38.5% (5/13) of subjects with parasitic infections who provided a stool sample and 5.1% (5/98) of uninfected subjects, p = 0.002). Our study found that parasitic infections may be common in recent US immigrants, which highlights an important health disparity among a vulnerable population that merits further study. Additionally, clinical risk factors, symptoms, and laboratory findings traditionally thought to be associated with parasites were commonly found but not predictive of infection in this study population.

Assessment of Emergency Department Antibiotic Discharge Prescription Dosing Errors for Pediatric Patients in a Community Hospital Health System.

OBJECTIVES: We quantify and describe emergency department antibiotic discharge prescription dosing errors for pediatric patients in a community hospital health system. METHODS: This was a retrospective chart review evaluating emergency department discharge prescriptions written between July 1, 2014, and June 30, 2015. Pediatric patients who received a prescription for an oral antibiotic were included in error analysis if they had a weight updated in the electronic medical record during the encounter. We used a predefined threshold of +10% variance from the recommended dose to quantify error. Prescriber, environmental, and antibiotic specific data were also collected to identify variables associated with high incidence of error. RESULTS: Among the 1934 prescriptions included in our error analysis, we detected 776 (40%) dosing errors. Of the prescriptions reviewed, 288 (15%) contained an overdosing error and 488 (25%) contained an underdosing error. There were 208 underdosing errors written for amoxicillin to treat acute otitis media. These errors represented 43% of the total underdosing errors and had a greater magnitude of variance from the recommended dose compared with overall underdosing errors. CONCLUSIONS: Underdosing of amoxicillin in acute otitis media was a dosing error that occurred frequently throughout our community health system. Further research is needed to identify the clinical impact these errors have on pediatric patients.

The Relationship Between Social Vulnerability and COVID-19 Incidence Among Louisiana Census Tracts.

Objective: To examine the association between the Centers for Disease Control and Prevention (CDC)'s Social Vulnerability Index (SVI) and COVID-19 incidence among Louisiana census tracts. Methods: An ecological study comparing the CDC SVI and census tract-level COVID-19 case counts was conducted. Choropleth maps were used to identify census tracts with high levels of both social vulnerability and COVID-19 incidence. Negative binomial regression with random intercepts was used to compare the relationship between overall CDC SVI percentile and its four sub-themes and COVID-19 incidence, adjusting for population density. Results: In a crude stratified analysis, all four CDC SVI sub-themes were significantly associated with COVID-19 incidence. Census tracts with higher levels of social vulnerability were associated with higher COVID-19 incidence after adjusting for population density (adjusted RR: 1.52, 95% CI: 1.41-1.65). Conclusions: The results of this study indicate that increased social vulnerability is linked with COVID-19 incidence. Additional resources should be allocated to areas of increased social disadvantage to reduce the incidence of COVID-19 in vulnerable populations.

Discovery of small molecule antagonists of chemokine receptor CXCR6 that arrest tumor growth in SK-HEP-1 mouse xenografts as a model of hepatocellular carcinoma.

The chemokine system plays an important role in mediating a proinflammatory microenvironment for tumor growth in hepatocellular carcinoma (HCC). The CXCR6 receptor and its natural ligand CXCL16 are expressed at high levels in HCC cell lines and tumor tissues and receptor expression correlates with increased neutrophils in these tissues contributing to poor prognosis in patients. Availability of pharmacologcal tools targeting the CXCR6/CXCL16 axis are needed to elucidate the mechanism whereby neutrophils are affected in the tumor environment. We report the discovery of a series of small molecules with an exo-[3.3.1]azabicyclononane core. Our lead compound 81 is a potent (EC50 = 40 nM) and selective orally bioavailable small molecule antagonist of human CXCR6 receptor signaling that significantly decreases tumor growth in a 30-day mouse xenograft model of HCC.