Greater Neighborhood Disadvantage Is Associated with Alterations in Fetal Functional Brain Network Structure.

OBJECTIVE: To determine the association between neighborhood disadvantage (ND) and functional brain development of in utero fetuses. STUDY DESIGN: We conducted an observational study using Social Vulnerability Index (SVI) scores to assess the impact of ND on a prospectively recruited sample of healthy pregnant women from Washington, DC. Using 79 functional magnetic resonance imaging scans from 68 healthy pregnancies at a mean gestational age of 33.12 weeks, we characterized the overall functional brain network structure using a graph metric approach. We used linear mixed effects models to assess the relationship between SVI and gestational age on 5 graph metrics, adjusting for multiple scans. RESULTS: Exposure to greater ND was associated with less well integrated functional brain networks, as observed by longer characteristic path lengths and diminished global efficiency (GE), as well as diminished small world propensity (SWP). Across gestational ages, however, the association between SVI and network integration diminished to a negligible relationship in the third trimester. Conversely, SWP was significant across pregnancy, but the relationship changed such that there was a negative association with SWP earlier in the second trimester that inverted around the transition to the third trimester to a positive association. CONCLUSIONS: These data directly connect ND and altered functional brain maturation in fetuses. Our results suggest that, even before birth, proximity to environmental stressors in the wider neighborhood environment are associated with altered brain development.

Common Mutation in the HFE Gene Modifies Recovery After Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is characterized by bleeding into the brain parenchyma. During an ICH, iron released from the breakdown of hemoglobin creates a cytotoxic environment in the brain through increased oxidative stress. Interestingly, the loss of iron homeostasis is associated with the pathological process of other neurological diseases. However, we have previously shown that the H63D mutation in the homeostatic iron regulatory (HFE) gene, prevalent in 28% of the White population in the United States, acts as a disease modifier by limiting oxidative stress. The following study aims to examine the effects of the murine homolog, H67D HFE, on ICH. METHODS: An autologous blood infusion model was utilized to create an ICH in the right striatum of H67D and wild-type mice. The motor recovery of each animal was assessed by rotarod. Neurodegeneration was measured using fluorojade-B and mitochondrial damage was assessed by immunofluorescent numbers of CytC+ (cytochrome C) neurons and CytC+ astrocytes. Finally, the molecular antioxidant response to ICH was quantified by measuring Nrf2 (nuclear factor-erythroid 2 related factor), GPX4 (glutathione peroxidase 4), and FTH1 (H-ferritin) levels in the ICH-affected and nonaffected hemispheres via immunoblotting. RESULTS: At 3 days post-ICH, H67D mice demonstrated enhanced performance on rotarod compared with wild-type animals despite no differences in lesion size. Additionally, H67D mice displayed higher levels of Nrf2, GPX4, and FTH1 in the ICH-affected hemisphere; however, these levels were not different in the contralateral, non-ICH-affected hemisphere. Furthermore, H67D mice showed decreased degenerated neurons, CytC+ Neurons, and CytC+ astrocytes in the perihematomal area. CONCLUSIONS: Our data suggest that the H67D mutation induces a robust antioxidant response 3 days following ICH through Nrf2, GPX4, and FTH1 activation. This activation could explain the decrease in degenerated neurons, CytC+ neurons, and CytC+ astrocytes in the perihematomal region, leading to the improved motor recovery. Based on this study, further investigation into the mechanisms of this neuroprotective response and the effects of the H63D HFE mutation in a population of patients with ICH is warranted.

Tropical forests are approaching critical temperature thresholds.

The critical temperature beyond which photosynthetic machinery in tropical trees begins to fail averages approximately 46.7 °C (Tcrit)1. However, it remains unclear whether leaf temperatures experienced by tropical vegetation approach this threshold or soon will under climate change. Here we found that pantropical canopy temperatures independently triangulated from individual leaf thermocouples, pyrgeometers and remote sensing (ECOSTRESS) have midday peak temperatures of approximately 34 °C during dry periods, with a long high-temperature tail that can exceed 40 °C. Leaf thermocouple data from multiple sites across the tropics suggest that even within pixels of moderate temperatures, upper canopy leaves exceed Tcrit 0.01% of the time. Furthermore, upper canopy leaf warming experiments (+2, 3 and 4 °C in Brazil, Puerto Rico and Australia, respectively) increased leaf temperatures non-linearly, with peak leaf temperatures exceeding Tcrit 1.3% of the time (11% for more than 43.5 °C, and 0.3% for more than 49.9 °C). Using an empirical model incorporating these dynamics (validated with warming experiment data), we found that tropical forests can withstand up to a 3.9 ± 0.5 °C increase in air temperatures before a potential tipping point in metabolic function, but remaining uncertainty in the plasticity and range of Tcrit in tropical trees and the effect of leaf death on tree death could drastically change this prediction. The 4.0 °C estimate is within the 'worst-case scenario' (representative concentration pathway (RCP) 8.5) of climate change predictions2 for tropical forests and therefore it is still within our power to decide (for example, by not taking the RCP 6.0 or 8.5 route) the fate of these critical realms of carbon, water and biodiversity3,4.

What is the best procedure for determining removal rate coefficients in horizontal flow treatment wetlands: influent and effluent concentrations or longitudinal concentration profiles?

First-order removal rate coefficients (k) are used in predictive equations for estimating effluent concentrations from horizontal flow (HF) wetlands. Due to limited resources, influent and effluent concentration data from existing systems are frequently used in the estimation of k values from operating systems, but another choice is to use concentration data along the longitudinal profile of the HF wetland. Based on a dataset with 41 HF wetlands/studies obtained from a literature survey, with chemical oxygen demand (COD) measurements at different sampling points, volumetric (kV) and areal (kA) removal rate coefficients for the Tanks-In-Series (TIS) model have been obtained using the two estimation methods. In general, removal rate coefficients derived from longitudinal profiles of concentrations were higher than those obtained by using data from influent and effluent concentrations, reflecting the fact that constituent removal is mostly accomplished before the wastewater reaches the outlet zone. Deriving coefficients from longitudinal profiles is more comprehensive, providing a better explanation of the internal removal taking place in the treatment wetland. However, the more widely used approach of calculating kV and kA from influent/effluent concentrations may lead to a safer design of horizontal flow wetlands, because of underestimation of the actual removal rate coefficients.

Variation in Carotid Artery Stenosis Measurements Among Facilities Seeking Carotid Stenting Facility Accreditation.

BACKGROUND: Based on the inclusion criteria of clinical trials, the degree of cervical carotid artery stenosis is often used as an indication for stent placement in the setting of extracranial carotid atherosclerotic disease. However, the rigor and consistency with which stenosis is measured outside of clinical trials are unclear. In an agreement study using a cross-sectional sample, we compared the percent stenosis as measured by real-world physician operators to that measured by independent expert reviewers. METHODS: As part of the carotid stenting facility accreditation review, images were obtained from 68 cases of patients who underwent carotid stent placement. Data collected included demographics, stroke severity measures, and the documented degree of stenosis, termed operator-reported stenosis (ORS), by 34 operators from 14 clinical sites. The ORS was compared with reviewer-measured stenosis (RMS) as assessed by 5 clinicians experienced in treating carotid artery disease. RESULTS: The median ORS was 90.0% (interquartile range, 80.0%-90.0%) versus a median RMS of 61.1% (interquartile range, 49.8%-73.6%), with a median difference of 21.8% (interquartile range, 13.7%-34.4%), P<0.001. The median difference in ORS and RMS for asymptomatic versus symptomatic patients was not statistically different (24.6% versus 19.6%; P=0.406). The median difference between ORS and RMS for facilities granted initial accreditation was smaller compared with facilities whose accreditation was delayed (17.9% versus 25.5%, P=0.035). The intraclass correlation between ORS and RMS was 0.16, indicating poor agreement. If RMS measurements were used, 72% of symptomatic patients and 10% of asymptomatic patients in the population examined would meet the Centers for Medicare and Medicaid Services criteria for stent placement. CONCLUSIONS: Real-world operators tend to overestimate carotid artery stenosis compared with external expert reviewers. Measurements from facilities granted initial accreditation were closer to expert measurements than those from facilities whose accreditation was delayed. Since decisions regarding carotid revascularization are often based on percent stenosis, such measuring discrepancies likely lead to increased procedural utilization.

Hospital Strain and Variation in Sepsis ICU Admission Practices and Associated Outcomes.

To understand how strain-process-outcome relationships in patients with sepsis may vary among hospitals. DESIGN: Retrospective cohort study using a validated hospital capacity strain index as a within-hospital instrumental variable governing ICU versus ward admission, stratified by hospital. SETTING: Twenty-seven U.S. hospitals from 2013 to 2018. PATIENTS: High-acuity emergency department patients with sepsis who do not require life support therapies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean predicted probability of ICU admission across strain deciles ranged from 4.9% (lowest ICU-utilizing hospital for sepsis without life support) to 61.2% (highest ICU-utilizing hospital for sepsis without life support). The difference in the predicted probabilities of ICU admission between the lowest and highest strain deciles ranged from 9.0% (least strain-sensitive hospital) to 45.2% (most strain-sensitive hospital). In pooled analyses, emergency department patients with sepsis (n = 90,150) experienced a 1.3-day longer median hospital length of stay (LOS) if admitted initially to the ICU compared with the ward, but across the 27 study hospitals (n = 517-6,564), this effect varied from 9.0 days shorter (95% CI, -10.8 to -7.2; p < 0.001) to 19.0 days longer (95% CI, 16.7-21.3; p < 0.001). Corresponding ranges for inhospital mortality with ICU compared with ward admission revealed odds ratios (ORs) from 0.16 (95% CI, 0.03-0.99; p = 0.04) to 4.62 (95% CI, 1.16-18.22; p = 0.02) among patients with sepsis (pooled OR = 1.48). CONCLUSIONS: There is significant among-hospital variation in ICU admission rates for patients with sepsis not requiring life support therapies, how sensitive those ICU admission decisions are to hospital capacity strain, and the association of ICU admission with hospital LOS and hospital mortality. Hospital-level heterogeneity should be considered alongside patient-level heterogeneity in critical and acute care study design and interpretation.

Associations Between New York Heart Association Classification, Objective Measures, and Long-term Prognosis in Mild Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial.

Importance: Heart failure (HF) treatment recommendations are centered on New York Heart Association (NYHA) classification, such that most apparently asymptomatic patients are not eligible for disease-modifying therapies. Objectives: To assess within-patient variation in NYHA classification over time, the association between NYHA class and an objective measure of HF severity (N-terminal pro-B-type natriuretic peptide [NT-proBNP] level), and their association with long-term prognosis in the PARADIGM-HF trial. Design, Setting, and Participants: All patients in PARADIGM-HF were in NYHA class II or higher at baseline and were treated with sacubitril-valsartan during a 6- to 10-week run-in period before randomization. Patients classified as NYHA class I, II, and III in PARADIGM-HF were compared at randomization. Exposures: NYHA class at randomization after 6 to 10 weeks of the run-in period. Main Outcomes and Measures: Primary outcome was cardiovascular death or first HF hospitalization. Logistic regression models, areas under the receiver operating characteristic curve (AUC), kernel density estimation overlaps, and Cox proportional hazards models were used. Results: The analysis included 8326 patients with known NYHA classification at randomization. Of 389 patients in NYHA class I, 228 (58%) changed functional class during the first year after randomization. Level of NT-proBNP was a poor discriminator of NYHA classification: for NYHA class I vs II, the AUC was 0.51 (95% CI, 0.48-0.54). For NT-proBNP level, estimated kernel density overlap was 93% between NYHA class I vs II, 79% between NYHA I vs III, and 83% between NYHA II vs III. Patients classified as NYHA III displayed a distinctively higher rate of cardiovascular events (NYHA III vs I, hazard ratio [HR], 1.84; 95% CI, 1.44-2.37; NYHA III vs II, HR, 1.49; 95% CI, 1.35-1.64). Patients in NYHA class I and II revealed lower event rates (NYHA II vs I, HR, 1.24; 95% CI, 0.97-1.58). Stratification by NT-proBNP level (<1600 pg/mL or ≥1600 pg/mL) identified subgroups with distinctive risk, such that NYHA class I patients with high NT-proBNP levels (n = 175) had a numerically higher event rate than patients with low NT-proBNP levels from any NYHA class (vs I, HR, 3.43; 95% CI, 2.03-5.87; vs II, HR, 2.12; 95% CI, 1.58-2.86; vs III, HR, 1.37; 95% CI, 1.00-1.88). Conclusions and Relevance: In this study, patients in NYHA class I and II overlapped substantially in objective measures and long-term prognosis. Physician-defined "asymptomatic" functional class concealed patients who were at substantial risk for adverse outcomes. NYHA classification might be limited to differentiate mild forms of HF. Trial Registration: ClinicalTrials.gov Identifier: NCT01035255.

Rivaroxaban in patients with symptomatic peripheral artery disease after lower extremity bypass surgery with venous and prosthetic conduits.

BACKGROUND: Patients with peripheral artery disease (PAD) requiring lower extremity revascularization (LER) have a high risk of adverse limb and cardiovascular events. The results from the VOYAGER PAD (efficacy and safety of rivaroxaban in reducing the risk of major thrombotic vascular events in subjects with symptomatic peripheral artery disease undergoing peripheral revascularization procedures of the lower extremities) trial have demonstrated that rivaroxaban significantly reduced this risk with an overall favorable net benefit for patients undergoing surgical revascularization. However, the efficacy and safety for those treated by surgical bypass, including stratification by bypass conduit (venous or prosthetic), has not yet been described. METHODS: In the VOYAGER PAD trial, patients who had undergone surgical and endovascular infrainguinal LER to treat PAD were randomized to rivaroxaban 2.5 mg twice daily or placebo on top of background antiplatelet therapy (aspirin 100 mg to be used in all and clopidogrel in some at the treating physician's discretion) and followed up for a median of 28 months. The primary end point was a composite of acute limb ischemia, major amputation of vascular etiology, myocardial infarction, ischemic stroke, and cardiovascular death. The principal safety outcome was major bleeding using the TIMI (thrombolysis in myocardial infarction) scale. The index procedure details, including conduit type (venous vs prosthetic), were collected at baseline. RESULTS: Among 6564 randomized patients, 2185 (33%) had undergone surgical LER. Of these 2185 patients, surgical bypass had been performed for 1448 (66%), using a prosthetic conduit for 773 patients (53%) and venous conduit for 646 patients (45%). Adjusting for the baseline differences and anatomic factors, the risk of unplanned limb revascularization in the placebo arm was 2.5-fold higher for those receiving a prosthetic conduit vs a venous conduit (adjusted hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.65-3.90; P < .001), and the risk of acute limb ischemia was three times greater (adjusted HR, 3.07; 95% CI, 1.84-5.11; P < .001). The use of rivaroxaban reduced the primary outcome for the patients treated with bypass surgery (HR, 0.78; 95% CI, 0.62-0.98), with consistent benefits for those receiving venous (HR, 0.66; 95% CI, 0.49-0.96) and prosthetic (HR, 0.87; 95% CI, 0.66-1.15) conduits (Pinteraction = .254). In the overall trial, major bleeding using the TIMI scale was increased with rivaroxaban. However, the numbers for those treated with bypass surgery were low (five with rivaroxaban vs nine with placebo; HR, 0.55; 95% CI, 0.18-1.65) and not powered to show statistical significance. CONCLUSIONS: Surgical bypass with a prosthetic conduit was associated with significantly higher rates of major adverse limb events relative to venous conduits even after adjustment for patient and anatomic characteristics. Adding rivaroxaban 2.5 mg twice daily to aspirin or dual antiplatelet therapy significantly reduced this risk, with an increase in the bleeding risk, but had a favorable benefit risk for patients treated with bypass surgery, regardless of conduit type. Rivaroxaban should be considered after lower extremity bypass for symptomatic PAD to reduce ischemic complications of the heart, limb, and brain.

Phonation Resistance Training Exercises (PhoRTE) With and Without Expiratory Muscle Strength Training (EMST) For Patients With Presbyphonia: A Noninferiority Randomized Clinical Trial.

OBJECTIVES: Presbyphonia negatively impacts quality of life in patients with age-related voice changes. A proof-of-concept study showed promise for high vocal intensity exercise to treat presbyphonia, which became the basis for a novel intervention for age-related voice changes known as Phonation Resistance Training Exercises (PhoRTE). Expiratory Muscle Strength Training (EMST) has also been proposed as an additional intervention to target and strengthen the aging respiratory system; however, EMST has undergone limited evaluation as an adjunct treatment for elderly patients undergoing voice therapy for presbyphonia. This study determined if the addition of EMST to PhoRTE voice therapy (PhoRTE + EMST) is at least as effective at voice improvement as PhoRTE alone. STUDY DESIGN: Prospective, randomized, controlled, single-blinded, non-inferiority. MATERIALS AND METHODS: Participants aged 55 years or older with a diagnosis of vocal fold atrophy were randomized to complete PhoRTE therapy or PhoRTE + EMST. The primary outcome was change in Voice Handicap Index-10 (VHI-10). Secondary outcomes included the Aging Voice Index, maximum expiratory pressure, and acoustic and aerodynamic measures of voice. Repeated measures linear mixed models were constructed to analyze outcomes at a significance level of α = 0.10. RESULTS: Twenty-six participants were recruited for the study, and 24 participants were randomized to either treatment arm. Sixteen participants completed the entire study. Both treatment arms showed statistically significant and clinically meaningful improvements in VHI-10 (PhoRTE mean [M] = -8.20, P < 0.001; PhoRTE + EMST M = -9.58, P < 0.001), and PhoRTE + EMST was noninferior to PhoRTE alone (P = 0.069). Both groups experienced a statistically significant pre-post treatment decrease (improvement) in AVI scores (PhoRTE M = -18.40, P = 0.004; PhoRTE + EMST M = -16.28, P = 0.005). PhoRTE+EMST had statistically significantly greater changes in maximum expiratory pressure compared to PhoRTE alone (PhoRTE M = 8.24 cm H2O, PhoRTE + EMST M = 32.63 cm H2O; P= 0.015). Some secondary acoustic and aerodynamic outcomes displayed trends toward improvement. CONCLUSION: This study demonstrates that voice therapy targeting high vocal intensity exercise (eg, PhoRTE) and EMST can play a role in improving voice outcomes for patients with presbyphonia.

Analyzing Impact of Multimorbidity on Long-Term Outcomes after Emergency General Surgery: A Retrospective Observational Cohort Study.

BACKGROUND: Little is known about the impact of multimorbidity on long-term outcomes for older emergency general surgery patients. STUDY DESIGN: Medicare beneficiaries, age 65 and older, who underwent operative management of an emergency general surgery condition were identified using Centers for Medicare & Medicaid claims data. Patients were classified as multimorbid based on the presence of a Qualifying Comorbidity Set (a specific combination of comorbid conditions known to be associated with increased risk of in-hospital mortality in the general surgery setting) and compared with those without multimorbidity. Risk-adjusted outcomes through 180 days after discharge from index hospitalization were calculated using linear and logistic regressions. RESULTS: Of 174,891 included patients, 45.5% were identified as multimorbid. Multimorbid patients had higher rates of mortality during index hospitalization (5.9% vs 0.7%, odds ratio [OR] 3.05, p < 0.001) and through 6 months (17.1% vs 3.4%, OR 2.33, p < 0.001) after discharge. Multimorbid patients experienced higher rates of readmission at 1 month (22.9% vs 11.4%, OR 1.48, p < 0.001) and 6 months (38.2% vs 21.2%, OR 1.48, p < 0.001) after discharge, lower rates of discharge to home (42.5% vs 74.2%, OR 0.52, p < 0.001), higher rates of discharge to rehabilitation/nursing facility (28.3% vs 11.3%, OR 1.62, p < 0.001), greater than double the use of home oxygen, walker, wheelchair, bedside commode, and hospital bed (p < 0.001), longer length of index hospitalization (1.33 additional in-patient days, p < 0.001), and higher costs through 6 months ($5,162 additional, p < 0.001). CONCLUSIONS: Older, multimorbid patients experience worse outcomes, including survival and independent function, after emergency general surgery than nonmultimorbid patients through 6 months after discharge from index hospitalization. This information is important for setting recovery expectations for high-risk patients to improve shared decision-making.

Sacubitril/valsartan versus ramipril for patients with acute myocardial infarction: win-ratio analysis of the PARADISE-MI trial.

AIM: The win ratio can incorporate different types of outcomes and enhance statistical power, making it a useful method for analysing composite outcomes in cardiovascular trials. The application of this approach to the PARADISE-MI trial provides an additional perspective into understanding the effects of sacubitril/valsartan in patients with acute myocardial infarction. METHODS AND RESULTS: We conducted a post-hoc analysis of the PARADISE-MI trial, which randomly assigned patients with acute myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril/valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to guideline-recommended therapy. The principal composite outcome was analysed in the hierarchical order of death due to cardiovascular causes, first hospitalization for heart failure, and first outpatient episode of symptomatic heart failure. We included events confirmed by the clinical events classification (CEC) committee as well as events identified by investigators that did not meet study definitions. Results were analysed by the unmatched win-ratio method. A win ratio that exceeds 1.00 reflects a better outcome. A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril/valsartan and 2831 to receive ramipril. The hierarchical analysis of the principal composite outcome demonstrated a larger number of wins (1 265 767 [15.7%]) than losses (1 079 502 [13.4%]) in the sacubitril/valsartan group (win ratio of 1.17, 95% confidence interval [CI] 1.03-1.33; p = 0.015). Sensitivity analyses using alternative definitions of the composite outcome showed results similar to those of the principal analysis, except for analysis restricted to events that met CEC definitions (win ratio of 1.11, 95% CI 0.96-1.30; p = 0.16). CONCLUSION: In this post-hoc analysis of the PARADISE-MI trial using the win ratio and including investigator-identified events not having CEC confirmation, sacubitril/valsartan was superior to ramipril among high-risk survivors of acute myocardial infarction.

Radiographic Analysis of the Lateral Column Lengthening Procedure in Stage II Adult Acquired Flatfoot Deformity.

Adult acquired flat foot deformity (AAFD) is a progressive, tri-planar deformity involving collapse of the medial longitudinal arch, valgus deformity of the rear foot, and abduction of the mid-foot on the rear foot. There are a wide variety of surgical treatment options for this deformity, including lateral column lengthening (LCL) which results in tri-planar correction of AAFD. We retrospectively reviewed weightbearing preoperative radiographs and weight-bearing 6-week postoperative radiographs of 34 patients with stage II AAFD who underwent LCL (with and without concurrent procedures) with a minimum of 1-year of follow up. Outcomes, including complications and postoperative differences in 6 types of angle measurements were evaluated. Radiographic evaluation showed statistically significant differences in preoperative and postoperative measures in the following angles: calcaneal inclination, Meary's, Simmons, talocalcaneal, and metatarsus adductus (each p ≤ .05). Postoperative Engel's angle difference did not reach statistical significance (p = .07). Paired t tests showed TN coverage angles increased greater with LCL plus a Cotton osteotomy as compared to isolated LCL. Additionally, there was no significant difference in TN coverage angle based on LCL graft size (p = .20). Furthermore, the distance of the osteotomy from the calcaneocuboid joint on anteroposterior and lateral radiographs did not significantly predict TN coverage angle change. Our study suggests that LCL corrects AAFD in three planes while decreasing the metatarsus adductus angle. LCL appears to be more effective when performed with a Cotton osteotomy. Wedge size (6 mm, 8 mm, 10 mm) and osteotomy location did not demonstrate a relationship with postoperative TN coverage angle or incidence of lateral column overload.

First Tarsometatarsal Joint Arthrodesis for Hallux Valgus With and Without Intermetatarsal Screw Fixation: A Comparison of Correction and Maintenance of Correction.

Tarsometatarsal joint arthrodesis is a commonly accepted procedure for hallux valgus associated with severe deformity and first ray hypermobility or medial column instability. This study evaluates the correction of hallux valgus deformity and the maintenance of correction with and without the use of a stabilization screw between the first and second metatarsal bases. Through retrospective review of first tarsometatarsal joint arthrodesis within our institution we evaluated 63 patients. Twenty-seven patients did not have a first to second metatarsal base screw and were placed into the no screw cohort. Thirty-six patients did have a first to second metatarsal base screw and were placed into the screw cohort. This study population had an osseous union rate of 95%. Clinical and radiographic recurrence occurred in 5 of 63 patients (8%). At 1-y postop the measurements demonstrated that the screw cohort had an average intermetatarsal angle correction of 11.6 degrees while the no screw cohort had an average correction of 7.8 degrees. Additionally, at 1-y postop the screw cohort had greater maintenance of the intermetatarsal angle correction with an average change of 0.5 degrees compared to 2.3 degrees in the no screw cohort. We conclude that the addition of the stabilization screw improves the first tarsometatarsal joint arthrodesis construct resulting in a greater degree of realignment and maintenance of correction.

Changes in Valganciclovir Use Among Infants with Congenital Cytomegalovirus Diagnosis in the United States, 2009-2015 and 2016-2019.

From 2009-2015 to 2016-2019, the proportion of infants in the US with congenital cytomegalovirus treated with valganciclovir roughly doubled for infants enrolled with employer-sponsored insurance (from 16% to 29%) and Medicaid (from 16% to 36%). The proportion treated with valganciclovir increased for all congenital cytomegalovirus disease severity groups.

Geochemistry of selenium, barium, and iodine in representative soils of the Brazilian Amazon rainforest.

The Amazon rainforest is a heterogeneous ecosystem and its soils exhibit geographically variable concentrations of trace elements. In this region, anthropic activities - e.g., agriculture and mining - are numerous and varied, and even natural areas are at risk of contamination by trace elements, either of geogenic or anthropogenic origin. A reliable dataset of benchmark values for selenium (Se), barium (Ba), and iodine (I) concentrations in soils is needed for use as a reference in research and public policies in the region. In this study, 9 selected sites in the Brazilian Amazon rainforest within areas represented by Oxisols and Ultisols were assessed for relevant soil physicochemical characteristics, along with the concentrations of total Se (SeTot), total Ba (BaTot), and sequentially-extracted soluble Se (SeSol) and adsorbed Se (SeAd) in 3 different soil layers (0-20, 20-40, and 40-60 cm). In addition, organically bound-Se (SeOrg) and total I (ITot) concentrations in the surface layer (0-20 cm) were measured. Soil Se concentrations (SeTot) were considered safe and are likely a result of contributions of sedimentary deposits from the Andes. Available Se (SeSol + SeAd) accounted for 4.5% of SeTot, on average, while SeOrg in the topsoil accounted for more than 50% of SeTot. Barium in the western Amazon (state of Acre) and central Amazon (Anori, state of Amazonas) exceeded national prevention levels (PVs). Furthermore, the average ITot in the studied topsoils (5.4 mg kg-1) surpassed the worldwide mean. Notwithstanding, the close relationship found between the total content of the elements (Se, Ba, and I) and soil texture (clay, silt, and sand) suggests their geogenic source. Finally, our data regarding SeTot, BaTot, and ITot can be used to derive regional quality reference values for Amazon soils and also for updating prevention (PV) and investigation (IV) values established for selected elements by the Brazilian legislation.

Foraging ecology of critically endangered Eastern Pacific hawksbill sea turtles (Eretmochelys imbricata) in the Gulf of California, Mexico.

The Eastern Pacific hawksbill sea turtle population is one of the most endangered of all sea turtle species. Here, we examine the foraging ecology of 47 hawksbill turtles (40.5-90.3 cm CCL, mean = 54.1 ± 10.1 cm) around Isla San José, Gulf of California, Mexico by integrating information from passive acoustic telemetry, behavior recordings, fecal analysis, and habitat surveys. Tagged hawkbill turtles exhibited high site fidelity over months and years (tracking duration 1-1490 days, mean = 255 ± 373 days) to the location and benthic habitat where individuals were initially caught. Diet was dominated by benthic invertebrates and algae including sponges, algae, tunicates, and mangrove roots. The mean percent cover of these benthic food items was significantly greater in the mangrove estuary than in adjacent rocky and sandy reef habitats. The Isla San José foraging ground is a high-use area for hawksbills and should be granted national protection status.

Economic evaluation of Zika Contraception Access Network in Puerto Rico during the 2016-17 Zika virus outbreak.

OBJECTIVE: During the 2016-2017 Zika virus (ZIKV) outbreak, the prevention of unintended pregnancies was identified as a primary strategy to prevent birth defects. This study estimated the cost-effectiveness of the Zika Contraception Access Network (Z-CAN), an emergency response intervention that provided women in Puerto Rico with access to the full range of reversible contraception at no cost and compared results with a preimplementation hypothetical cost-effectiveness analysis (CEA). STUDY DESIGN: We evaluated costs and outcomes of Z-CAN from a health sector perspective compared to no intervention using a decision tree model. Number of people served, contraception methods mix, and costs under Z-CAN were from actual program data and other input parameters were from the literature. Health outcome measures included the number of Zika-associated microcephaly (ZAM) cases and unintended pregnancies. The economic benefits of the Z-CAN intervention were ZIKV-associated direct costs avoided, including lifetime medical and supportive costs associated with ZAM cases, costs of monitoring ZIKV-exposed pregnancies and infants born from Zika-virus infected mothers, and the costs of unintended pregnancies prevented during the outbreak as a result of increased contraception use through the Z-CAN intervention. RESULTS: The Z-CAN intervention cost a total of $26.1 million, including costs for the full range of reversible contraceptive methods, contraception related services, and programmatic activities. The program is estimated to have prevented 85% of cases of estimated ZAM cases and unintended pregnancies in the absence of Z-CAN. The intervention cost was projected to have been more than offset by $79.9 million in ZIKV-associated costs avoided, 96% of which were lifetime ZAM-associated costs, as well as $137.0 million from avoided unintended pregnancies, with total net savings in one year of $216.9 million. The results were consistent with the previous CEA study. CONCLUSION: Z-CAN was likely cost-saving in the context of a public health emergency response setting.

Multi-elemental Analysis and Health Risk Assessment of Commercial Yerba Mate from Brazil.

Consumption of yerba mate occurs mostly in the form of hot infusion (chimarrão). Water solubility of elements found in commercialized yerba mate is needed to establish nutritional value and risks associated with potentially toxic elements. In this study, yerba mate products marketed in three Brazilian states (Paraná, Santa Catarina, and Rio Grande do Sul) for chimarrão were analyzed. Total (dry product) and hot water-soluble concentrations of Al, As, B, Ba, Ca, Cd, Co, Cs, Cu, Fe, K, Li, Mg, Mn, Mo, Ni, P, Pb, Rb, S, Se, Sr, Ti, V, and Zn were determined by inductively coupled plasma mass spectroscopy (ICP-MS). Total concentrations of the ten top elements followed the order of K>Ca>Mg>Mn>P>S>Al>Fe>Ba>Zn. The most soluble elements were B, Cs, Ni, Rb, and K, with values greater than 80%. The lowest water-soluble elements were V, Fe, and Ti (values <10%), followed by Ba, Cd, Al, As, Sr, Ca, and Pb with solubility between 10 and 20%. Although total Cd levels in yerba mate products were often above those permitted by South America legislation, estimated daily consumption intake indicated no risk associated with the chimarrão beverage. Manganese was the micronutrient with the highest total and soluble levels in yerba mate, which surpassed recommended daily intake values when considering a consumption amount of 50 g day-1 of yerba mate as chimarrão. The consumption of yerba mate is safe and contributes to intake of nutrients. The Cd and Pb reference values of yerba mate products sold in South America should be revised.