Association between pre-heart transplant kidney function and post-transplant outcomes in Black and White adults.

BACKGROUND: It remains unknown whether estimated glomerular filtration rate (eGFR) using the refit Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation without a term for race is associated with mortality and the need for kidney replacement therapy (KRT) differentially between Black and White heart transplant recipients. METHODS: We studied 25,900 adults included in the Scientific Registry of Transplant Recipients. We classified recipients into six categories of eGFR (< 30, 30 to < 45, 45 to < 60, 60 to < 90, 90 to < 120, ≥ 120 ml/min/1.73 m2) using the race-neutral CKD-EPI refit equation, and assessed survival with multivariable adjusted Cox proportional hazards regression. RESULTS: The association between pre-transplant race-neutral eGFR and mortality varied by race (Pinteraction = 0.006). Compared to White patients with an eGFR of 90-120 ml/min/1.73 m2, the mortality rates were 57% (95% CI 1.25, 1.98), 29% (95% CI 1.11, 1.51), 34% (95% CI 1.19, 1.52), and 19% (95% CI 1.06, 1.33) higher in Black patients with an eGFR less than 30, 30-45, 45-60, and 60-90 ml/min/1.73m2, respectively; and 53% (95% CI 1.28, 1.82), 49% (95% CI 1.33, 1.66), and 23% (95% CI 1.11, 1.35) higher among White patients with an eGFR less than 30, 30-45, and 45-60 ml/min/1.73 m2, respectively. The association between pre-transplant eGFR and the need for KRT during follow-up was similar between Black and White patients (Pinteraction = 0.57). CONCLUSIONS: Worsening pre-transplant eGFR using the new race-neutral CKD-EPI refit equation was associated with a higher rate of post-heart transplant mortality and KRT in Black and White recipients. The racial disparity in post-heart transplant mortality was narrower in the setting of severe kidney dysfunction.

Naltrexone augmented with prazosin for alcohol use disorder: results from a randomized controlled proof-of-concept trial.

AIMS: We conducted a proof-of-concept randomized controlled trial of the mu-opioid receptor antagonist, naltrexone, augmented with the alpha-1 adrenergic receptor antagonist, prazosin, for alcohol use disorder in veterans. We sought a signal that the naltrexone plus prazosin combination regimen would be superior to naltrexone alone. METHODS: Thirty-one actively drinking veterans with alcohol use disorder were randomized 1:1:1:1 to naltrexone plus prazosin (NAL-PRAZ [n = 8]), naltrexone plus placebo (NAL-PLAC [n = 7]), prazosin plus placebo (PRAZ-PLAC [n = 7]), or placebo plus placebo (PLAC-PLAC [n = 9]) for 6 weeks. Prazosin was titrated over 2 weeks to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS. Naltrexone was administered at 50 mg QD. Primary outcomes were the Penn Alcohol Craving Scale (PACS), % drinking days (PDD), and % heavy drinking days (PHDD). RESULTS: In the NAL-PRAZ condition, % reductions from baseline for all three primary outcome measures exceeded 50% and were at least twice as large as % reductions in the NAL-PLAC condition (PACS: 57% vs. 26%; PDD: 51% vs. 22%; PHDD: 69% vs. 15%) and in the other two comparator conditions. Standardized effect sizes between NAL-PRAZ and NAL-PLAC for each primary outcome measure were >0.8. All but one participant assigned to the two prazosin containing conditions achieved the target prazosin dose of 16 mg/day and maintained that dose for the duration of the trial. CONCLUSION: These results suggest that prazosin augmentation of naltrexone enhances naltrexone benefit for alcohol use disorder. These results strengthen rationale for an adequately powered definitive randomized controlled trial.

Continuous quality improvement in a community-wide TB screening and prevention programme in Papua New Guinea.

SETTING: Daru Island in Papua New Guinea (PNG) has a high prevalence of TB and multidrug-resistant TB (MDR-TB). OBJECTIVE: To evaluate the early implementation of a community-wide project to detect and treat TB disease and infection, outline the decision-making processes, and change the model of care. DESIGN: A continuous quality improvement (CQI) initiative used a plan-do-study-act (PDSA) framework for prospective implementation. Care cascades were analysed for case detection, treatment, and TB preventive treatment (TPT) initiation. RESULTS: Of 3,263 people screened for TB between June and December 2023, 13.7% (447/3,263) screened positive (CAD4TB or symptoms), 77.9% (348/447) had Xpert Ultra testing, 6.9% (24/348) were diagnosed with TB and all initiated treatment. For 5-34-year-olds without active TB (n = 1,928), 82.0% (1,581/1,928) had tuberculin skin testing (TST), 96.1% (1,519/1,581) had TST read, 23.0% (350/1,519) were TST-positive, 95.4% (334/350) were TPT eligible, and 78.7% (263/334) initiated TPT. Three PDSA review cycles informed adjustments to the model of care, including CAD4TB threshold and TPT criteria. Key challenges identified were meeting screening targets, sputum unavailability from asymptomatic individuals with high CAD4TB scores, and consumable stock-outs. CONCLUSION: CQI improved project implementation by increasing the detection of TB disease and infection and accelerating the pace of screening needed to achieve timely community-wide coverage.

CONTEXTE: L'île de Daru en Papouasie-Nouvelle-Guinée (PNG) présente une forte prévalence de la TB et de la TB multirésistante (MDR-TB). OBJECTIF: Évaluer la mise en œuvre précoce d'un projet à l'échelle de la communauté pour détecter et traiter la TB et l'infection, décrire les processus de prise de décision et changer le modèle de soins. CONCEPTION: Une initiative d'amélioration continue de la qualité (CQI, pour l'anglais « continuous quality improvement ¼) a utilisé un cadre de planification, d'action, d'étude, d'action (PDSA, pour l'anglais «plan-do-study-act ¼) pour la mise en œuvre prospective. Les cascades de soins ont été analysées pour la détection des cas, le traitement et l'initiation du traitement préventif de la TB. RÉSULTATS: Sur 3 263 personnes dépistées pour la TB entre juin et décembre 2023, 13,7% (447/3 263) ont été dépistées positives (CAD4TB ou symptômes), 77,9% (348/447) ont subi un test Xpert Ultra, 6,9% (24/348) ont reçu un diagnostic de TB et toutes ont commencé un traitement. Chez les 5 à 34 ans sans TB active (n = 1 928), 82,0% (1 581/1 928) ont subi un test cutané à la tuberculine (TCT), 96,1% (1 519/1 581) ont eu un test de dépistage du TCT, 23,0% (350/1 519) étaient positifs au TCT, 95,4% (334/350) étaient éligibles au TPT et 78,7% (263/334) ont initié le TPT. Trois cycles d'examen PDSA ont permis d'ajuster le modèle de soins, y compris le seuil CAD4TB et les critères TPT. Les principaux défis identifiés étaient l'atteinte des objectifs de dépistage, l'indisponibilité des expectorations chez les personnes asymptomatiques avec des scores CAD4TB élevés et les ruptures de stock de consommables. CONCLUSION: L'ACQ a amélioré la mise en œuvre du projet en augmentant la détection de la TB et de l'infection et en accélérant le rythme de dépistage nécessaire pour atteindre une couverture à l'échelle de la communauté en temps opportun.

Incidence of de novo malignancy and all-cause mortality among heart transplant recipients.

BACKGROUND: Heart transplant recipients develop cancer at two-times the rate compared to the general population. However, the incidence and mortality rates and the adjusted association between cancer and mortality remains unclear. METHODS: We estimated the incidence and mortality rates and the adjusted association between developing cancer (any, skin, hematologic, and solid tumor subtypes) and the all-cause mortality rates among adult heart transplant recipients from the Scientific Registry of Transplant Recipients from October 1, 1987, until June 28, 2020. RESULTS: Among 51,597 adult heart transplant recipients, 13,191 (25.6%) were diagnosed with de novo malignancy throughout the follow-up period. The cumulative incidence cancer at years 1, 5, 10, and 20 was 3%, 16.4%, 32.8%, and 56.6%, respectively. Among those with cancer, the cumulative mortality was 17.5%, 42.3%, 65%, and 91% at years 1, 5, 10, and 20, respectively. The incidence rate of any de novo malignancy was 38.7 cases per 1000 person-years and the mortality rate (for those with cancer) was 115.2 cases per 1000 person-years. Compared to those without cancer, those with cancer had a higher adjusted mortality association [HR: 2.14 (2.07, 2.21)]. The strongest associations were estimated for pancreatic [10.63 (8.34, 13.54)], leukemia [8.06 (4.33, 15.00)], and esophagus [6.94 (5.43, 8.87)] malignancies. The association between de novo malignancies and mortality was higher in the earlier years of follow-up. CONCLUSION: Compared to not developing cancer, those with de novo malignancy have a 2-fold higher mortality rate, on average. The strength of the association varies by cancer subtype and by follow-up time.

iStent insertion orientation and impact on trabecular meshwork motion resolved by optical coherence tomography imaging.

Significance: The iStent is a popular device designed for glaucoma treatment, functioning by creating an artificial fluid pathway in the trabecular meshwork (TM) to drain aqueous humor. The assessment of iStent implantation surgery is clinically important. However, current tools offer limited information. Aim: We aim to develop innovative assessment strategies for iStent implantation using optical coherence tomography (OCT) to evaluate the position and orientation of the iStent and its biomechanical impact on outflow system dynamics. Approach: We examined four iStents in the two eyes of a glaucoma patient. Three-dimensional (3D) OCT structural imaging was conducted for each iStent, and a semi-automated algorithm was developed for iStent segmentation and visualization, allowing precise measurement of position and orientation. In addition, phase-sensitive OCT (PhS-OCT) imaging was introduced to measure the biomechanical impact of the iStent on the outflow system quantified by cumulative displacement (CDisp) of pulse-dependent trabecular TM motion. Results: The 3D structural image processed by our algorithm definitively resolved the position and orientation of the iStent in the anterior segment, revealing substantial variations in relevant parameters. PhS-OCT imaging demonstrated significantly higher CDisp in the regions between two iStents compared to locations distant from the iStents in both OD ( p = 0.0075 ) and OS ( p = 0.0437 ). Conclusions: Our proposed structural imaging technique improved the characterization of the iStent's placement. The imaging results revealed inherent challenges in achieving precise control of iStent insertion. Furthermore, PhS-OCT imaging unveiled potential biomechanical alterations induced by the iStent. This unique methodology shows potential as a valuable clinical tool for evaluating iStent implantation.

The Mosquito Fauna of Arizona: Species Composition and Public Health Implications.

Arizona is home to many mosquito species, some of which are known vectors of infectious diseases that harm both humans and animals. Here, we provide an overview of the 56 mosquito species that have been identified in the State to date, but also discuss their known feeding preference and the diseases they can (potentially) transmit to humans and animals. This list is unlikely to be complete for several reasons: (i) Arizona's mosquitoes are not systematically surveyed in many areas, (ii) surveillance efforts often target specific species of interest, and (iii) doubts have been raised by one or more scientists about the accuracy of some collection records, which has been noted in this article. There needs to be an integrated and multifaceted surveillance approach that involves entomologists and epidemiologists, but also social scientists, wildlife ecologists, ornithologists, representatives from the agricultural department, and irrigation and drainage districts. This will allow public health officials to (i) monitor changes in current mosquito species diversity and abundance, (ii) monitor the introduction of new or invasive species, (iii) identify locations or specific populations that are more at risk for mosquito-borne diseases, and (iv) effectively guide vector control.

Golfers are physically more active and have greater health associated quality of life than non-golfers following lower limb arthroplasty.

Background: The health benefits of physical activity are well recognised. This study assessed whether golfers were more physically active after lower limb arthroplasty when compared to those that did not play golf (primary outcome). In addition pre and postoperative changes in health-associated quality of life (HAQoL) and joint specific outcomes between golfers and none golfers were assessed (secondary outcomes). Methods: There were 304 patients [THA (n = 155) or TKA (n = 149)] prospectively registered during a 4-month period undergoing lower limb arthroplasty. The mean age was 70.0 (range 37-92, standard deviation 10.2) years and included 188 (61%) females and 120 (39%) males. They completed pre and postoperative questionnaires assessing recreational activity, physical activity, HAQoL (EuroQol [EQ]), joint specific health (Oxford scores), and satisfaction. Results: Golfers (n = 33, 10.9%) were more likely to achieve longer than 3 hours of moderate activity during a week (48.5% vs 38.0%, odds ratio (OR) 3.4, p = 0.045) and achieved their recommended activity level (96.8% vs 77.7%, OR 8.6, p = 0.015) compared to non-golfers following arthroplasty. Postoperative EQ5D (p = 0.034) and EQVAS (p = 0.019) were significantly greater in golfers. The joint specific Oxford hip score was greater in golfers compared to non-golfers (mean difference 5.6, p = 0.022), however no difference was observed in the Oxford knee score following TKA (p = 0.495). Conclusion: Golfers were more likely to achieve their weekly recommended level of physical activity and had a greater HAQoL relative to those that did not play golf following lower limb arthroplasty. More specifically after THA golfers also had a greater postoperative joint specific outcome, but no such advantage was observed in those following TKA. Evidence Level: Level II, diagnostic study.

Short-term air pollution levels and sickle cell disease hospital encounters in South Carolina: A case-crossover analysis.

BACKGROUND: Sickle cell disease (SCD) is a genetic disorder and symptoms may be sensitive to environmental stressors. Although it has been hypothesized that exposure to outdoor air pollution could trigger acute SCD events, evidence is limited. METHODS: We obtained SCD administrative data on hospital encounters in South Carolina from 2002 to 2019. We estimated outdoor air pollutant (particulate matter<2.5 µm (PM2.5), ozone (O3), and PM2.5 elemental carbon (EC) concentrations at residential zip codes using spatio-temporal models. Using a random bi-directional, fixed-interval case-crossover study design, we investigated the relationship between air pollution exposure over 1-, 3-, 5-, 9-, and14-day periods with SCD hospital encounters. RESULTS: We studied 8410 patients with 144,129 hospital encounters. We did not observe associations among all patients with SCD and adults for PM2.5, O3, and EC. We observed positive associations among children for 9- and 14-day EC (OR: 1.05 (95% confidence interval (CI): 1.02, 1.08) and OR: 1.05 (95% CI: 1.02, 1.09), respectively) and 9- and 14-day O3 (OR: 1.04 (95%CI: 1.00, 1.08)) for both. CONCLUSIONS: Our findings suggest that short-term (within two-weeks) levels of EC and O3 and may be associated with SCD hospital encounters among children. Two-pollutant model results suggest that EC is more likely responsible for effects on SCD than O3. More research is needed to confirm our findings.

Increased [18F]Fluorodeoxyglucose Uptake in the Left Pallidum in Military Veterans with Blast-Related Mild Traumatic Brain Injury: Potential as an Imaging Biomarker and Mediation with Executive Dysfunction and Cognitive Impairment.

Blast-related mild traumatic brain injury (blast-mTBI) can result in a spectrum of persistent symptoms leading to substantial functional impairment and reduced quality of life. Clinical evaluation and discernment from other conditions common to military service can be challenging and subject to patient recall bias and the limitations of available assessment measures. The need for objective biomarkers to facilitate accurate diagnosis, not just for symptom management and rehabilitation but for prognostication and disability compensation purposes is clear. Toward this end, we compared regional brain [18F]fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET) intensity-scaled uptake measurements and motor, neuropsychological, and behavioral assessments in 79 combat Veterans with retrospectively recalled blast-mTBI with 41 control participants having no lifetime history of TBI. Using an agnostic and unbiased approach, we found significantly increased left pallidum [18F]FDG-uptake in Veterans with blast-mTBI versus control participants, p < 0.0001; q = 3.29 × 10-9 [Cohen's d, 1.38, 95% confidence interval (0.96, 1.79)]. The degree of left pallidum [18F]FDG-uptake correlated with the number of self-reported blast-mTBIs, r2 = 0.22; p < 0.0001. Greater [18F]FDG-uptake in the left pallidum provided excellent discrimination between Veterans with blast-mTBI and controls, with a receiver operator characteristic area under the curve of 0.859 (p < 0.0001) and likelihood ratio of 21.19 (threshold:SUVR ≥ 0.895). Deficits in executive function assessed using the Behavior Rating Inventory of Executive Function-Adult Global Executive Composite T-score were identified in Veterans with blast-mTBI compared with controls, p < 0.0001. Regression-based mediation analyses determined that in Veterans with blast-mTBI, increased [18F]FDG-uptake in the left pallidum-mediated executive function impairments, adjusted causal mediation estimate p = 0.021; total effect estimate, p = 0.039. Measures of working and prospective memory (Auditory Consonant Trigrams test and Memory for Intentions Test, respectively) were negatively correlated with left pallidum [18F]FDG-uptake, p < 0.0001, with mTBI as a covariate. Increased left pallidum [18F]FDG-uptake in Veterans with blast-mTBI compared with controls did not covary with dominant handedness or with motor activity assessed using the Unified Parkinson's Disease Rating Scale. Localized increased [18F]FDG-uptake in the left pallidum may reflect a compensatory response to functional deficits following blast-mTBI. Limited imaging resolution does not allow us to distinguish subregions of the pallidum; however, the significant correlation of our data with behavioral but not motor outcomes suggests involvement of the ventral pallidum, which is known to regulate motivation, behavior, and emotions through basal ganglia-thalamo-cortical circuits. Increased [18F]FDG-uptake in the left pallidum in blast-mTBI versus control participants was consistently identified using two different PET scanners, supporting the generalizability of this finding. Although confirmation of our results by single-subject-to-cohort analyses will be required before clinical deployment, this study provides proof of concept that [18F]FDG-PET bears promise as a readily available noninvasive biomarker for blast-mTBI. Further, our findings support a causative relationship between executive dysfunction and increased [18F]FDG-uptake in the left pallidum.

CSF ß-Amyloid and Tau Biomarker Changes in Veterans With Mild Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Moderate-to-severe traumatic brain injuries (TBI) have been reported to increase the risk of Alzheimer disease (AD). Whether mild TBI (mTBI) in veterans confers a similar increased risk of AD is less known. This study investigated early AD changes using CSF biomarkers in veterans with blast mTBI. METHODS: This was a cross-sectional case-control study of veterans with mTBI and non-mTBI veterans and civilians from 2 study sources. Blast-mTBI veterans had at least 1 war zone blast or combined blast/impact mTBI meeting Veterans Affairs (VA) and Department of Defense (DoD) criteria for mTBI. Non-mTBI participants had no lifetime history of TBI. All participants underwent standardized clinical and neuropsychological assessments and lumbar puncture for collection of the CSF. CSF biomarkers were measured using MesoScale Discovery assays for Aß40 and Aß42 and INNOTEST ELISAs for phosphorylated tau181 (p-tau181) and total tau (t-tau). RESULTS: Our sample comprised 51 participants with mTBI and 85 non-mTBI participants with mean (SD) ages 34.0 (10.1) and 33.5 years (8.9), respectively. All participants but 1 (99%) were male. Differences in CSF AD biomarkers between mTBI and non-mTBI groups were age dependent and most pronounced at older ages (omnibus test p ≤ 0.08). At age 50 years, the mTBI group had lower mean [95% CI] CSF Aß42 and Aß40 than the non-mTBI group by 154 [-12 to 319] and 1864 [610-3,118] pg/mL, respectively. By contrast, CSF p-tau181 and t-tau mean levels remained relatively constant with age in participants with mTBI, while tending to be higher at older ages for the non-mTBI group. The mTBI group also demonstrated poorer cognitive performance at older ages (omnibus p < 0.08): at age 50 years, the mean TMT-B time was higher by 34 seconds [10-58] and the mean CVLT-II short-delay recall was lower by 4.2 points [1.9-6.6]. Poorer verbal memory and verbal fluency performance were associated with lower CSF Aß42 (p ≤ 0.05) in older participants. DISCUSSION: CSF Aß levels decreased in middle-aged veterans with blast-related mTBI. These data suggest that chronic neuropathologic processes associated with blast mTBI share properties in common with pathogenic processes known to portend AD onset, thus raising concern that veterans with blast-related mTBI may develop a dementing disorder later in life.

Statin Twitter: Human and Automated Bot Contributions, 2010 to 2022.

BACKGROUND: Many individuals eligible for statin therapy decline treatment, often due to fear of adverse effects. Misinformation about statins is common and drives statin reluctance, but its prevalence on social media platforms, such as Twitter (now X) remains unclear. Social media bots are known to proliferate medical misinformation, but their involvement in statin-related discourse is unknown. This study examined temporal trends in volume, author type (bot or human), and sentiment of statin-related Twitter posts (tweets). METHODS AND RESULTS: We analyzed original tweets with statin-related terms from 2010 to 2022 using a machine learning-derived classifier to determine the author's bot probability, natural language processing to assign each tweet a negative or positive sentiment, and manual qualitative analysis to identify statin skepticism in a random sample of all tweets and in highly influential tweets. We identified 1 155 735 original statin-related tweets. Bots produced 333 689 (28.9%), humans produced 699 876 (60.6%), and intermediate probability accounts produced 104 966 (9.1%). Over time, the proportion of bot tweets decreased from 47.8% to 11.3%, and human tweets increased from 43.6% to 79.8%. The proportion of negative-sentiment tweets increased from 27.8% to 43.4% for bots and 30.9% to 38.4% for humans. Manually coded statin skepticism increased from 8.0% to 19.0% for bots and from 26.0% to 40.0% for humans. CONCLUSIONS: Over the past decade, humans have overtaken bots as generators of statin-related content on Twitter. Negative sentiment and statin skepticism have increased across all user types. Twitter may be an important forum to combat statin-related misinformation.

Influence of antigen density and TLR ligands on preclinical efficacy of a VLP-based vaccine against peanut allergy.

BACKGROUND: Virus-like particle (VLP) Peanut is a novel immunotherapeutic vaccine candidate for the treatment of peanut allergy. The active pharmaceutical ingredient represents cucumber mosaic VLPs (CuMVTT -VLPs) that are genetically fused with one of the major peanut allergens, Ara h 2 (CuMVTT -Ara h 2). We previously demonstrated the immunogenicity and the protective capacity of VLP Peanut-based immunization in a murine model for peanut allergy. Moreover, a Phase I clinical trial has been initiated using VLP Peanut material manufactured following a GMP-compliant manufacturing process. Key product characterization studies were undertaken here to understand the role and contribution of critical quality attributes that translate as predictive markers of immunogenicity and protective efficacy for clinical vaccine development. METHOD: The role of prokaryotic RNA encapsulated within VLP Peanut on vaccine immunogenicity was assessed by producing a VLP Peanut batch with a reduced RNA content (VLP Peanut low RNA). Immunogenicity and peanut allergen challenge studies were conducted with VLP Peanut low RNA, as well as with VLP Peanut in WT and TLR 7 KO mice. Furthermore, mass spectrometry and SDS-PAGE based methods were used to determine Ara h 2 antigen density on the surface of VLP Peanut particles. This methodology was subsequently applied to investigate the relationship between Ara h 2 antigen density and immunogenicity of VLP Peanut. RESULTS: A TLR 7 dependent formation of Ara h 2 specific high-avidity IgG antibodies, as well as a TLR 7 dependent change in the dominant IgG subclass, was observed following VLP Peanut vaccination, while total allergen-specific IgG remained relatively unaffected. Consistently, a missing TLR 7 signal caused only a weak decrease in allergen tolerability after vaccination. In contrast, a reduced RNA content for VLP Peanut resulted in diminished total Ara h 2 specific IgG responses, followed by a significant impairment in peanut allergen tolerability. The discrepant effect on allergen tolerance caused by an absent TLR 7 signal versus a reduced RNA content is explained by the observation that VLP Peanut-derived RNA not only stimulates TLR 7 but also TLR 3. Additionally, a strong correlation was observed between the number of Ara h 2 antigens displayed on the surface of VLP Peanut particles and the vaccine's immunogenicity and protective capacity. CONCLUSIONS: Our findings demonstrate that prokaryotic RNA encapsulated within VLP Peanut, including antigen density of Ara h 2 on viral particles, are key contributors to the immunogenicity and protective capacity of the vaccine. Thus, antigenicity and RNA content are two critical quality attributes that need to be determined at the stage of manufacturing, providing robust information regarding the immunogenicity and protective capacity of VLP Peanut in the mouse which has translational relevance to the human setting.

Transforaminal lumbar interbody fusion with placement of steerable banana cage: A single-center retrospective analysis of radiographic parameters of success.

INTRODUCTION: The transforaminal lumbar interbody fusion (TLIF) is among the most utilized methods for the surgical treatment of lumbar degenerative disc disease. The TLIF has advanced significantly with several iterative changes since its inception in the early 1980s, with the advent of several generations of interbody types, shapes, and materials. Steerable curvilinear interbodies are among the most recent innovations in this space and may offer biomechanical advantages, namely in preservation of lumbar and segmental lordosis. While radiographic parameters have been investigated for other cage shapes and lumbar interbody fusion techniques, no study has investigated postoperative radiographic outcomes specific to TLIFs done with curvilinear interbodies. METHODS: This study is a retrospective review of TLIFs performed with curvilinear interbodies between 2019 and 2022 at a single institution. Upright radiographs were obtained preoperatively and at several timepoints postoperatively. Radiographic variables including interspace height and segmental lordosis were collected. RESULTS: 26 surgeries with 32 curvilinear interbodies were performed across 3 years. There was significant increase in segmental lordosis at the L4-L5 (p = 0.0183) and L5-S1 levels (p = 0.004) as well as interspace height postoperatively at levels L3-L4 (p = 0.011) and L4-L5 (p = 0.002). Pain as measured with the numeric rating scale significantly improved in the overall cohort postoperatively (p<0.001). CONCLUSIONS: TLIF with curvilinear interbody placement increases segmental lordosis and interspace height at the L4-L5 and L5-S1 levels, and increased interspace height at the L3-L4 and L4-L5 levels. Further investigation into additional radiographic parameters is warranted and expanded cohort size would benefit deeper analysis of other spinal levels. IMPLICATIONS FOR PRACTICE: As an increasing number of cage designs and materials are brought to market, studies such as this allow for better understanding of cage specific outcomes allowing for better informed device selection.

Nitrogen offset potential in a multiyear farmlet-scale study: Milk and herbage production from grazed perennial ryegrass-white clover swards.

The objective of this study was to quantify the farm gate nitrogen (N) offset potential of perennial ryegrass (Lolium perenne L.; PRG) white clover (Trifolium repens L.; WC) swards by comparing the herbage and milk production from dairy farmlets that were simulations of full farming systems. A study was established where 120 cows were randomly assigned to 4 farmlets of 10.9 ha (stocking rate: 2.75 cow/ha), composed of 20 paddocks each. Cows were fed 526 kg of DM of concentrate on average each year. The 4 grazing treatments were PRG-only at 150 or 250 kg of N/ha and PRG-WC at 150 or 250 kg of N/ha. Cows remained in their treatment group for an entire grazing season and were re-randomized as they calved across treatments each year. As cows calved in the spring as standard practice in Ireland, they were rotationally grazed from early February both day and night (weather permitting) to mid-November, to a target postgrazing sward height of 4.0 cm. Mean sward WC content was 18.1% and 15.4% for the 150 and 250 kg of N/ha PRG-WC treatments, respectively over the 3-yr period. When WC was included, lowering the N rate did not reduce pregrazing yield, pregrazing height, or herbage removed, but those factors decreased significantly when WC was absent. Total annual herbage DM production was 13,771, 15,242, 14,721, and 15,667 kg of DM/ha for PRG-only swards receiving 150 or 250 kg of N/ha and PRG-WC swards receiving 150 or 250 kg of N/ha, respectively. In addition, when WC was present, compressed postgrazing sward heights were lower (4.10 vs. 4.21 cm) and herbage allowance (approximately 17 kg/cow feed allocation per cow per day) higher than the high-N control (+ 0.7 kg of DM/cow per day). There was a significant increase in milk production, both per cow and per hectare, when WC was included in PRG swards. Over the 3-yr study, cows grazing PRG-WC had greater milk (+304 kg) and milk solids (+31 kg of fat + protein) yields than cows grazing PRG-only swards. This significant increase in milk production suggests that the inclusion of WC in grazing systems can be effectively used to increase milk production per cow and per hectare and help offset nitrogen use. This result shows the potential to increase farm gate N use efficiency and reduce the N surplus compared with PRG-dominant sward grazing systems receiving 250 kg of N/ha, without negatively affecting milk solids yield or herbage production, thus increasing farm profit by €478/ha.

Influenza vaccination and use of lipid lowering therapies in adults with atherosclerotic cardiovascular disease: An analysis of the Behavioral Risk Factor Surveillance System (BRFSS).

BACKGROUND: Influenza vaccination and lipid lowering therapy (LLT) are evidence-based interventions with substantial benefit for individuals with established atherosclerotic cardiovascular disease (ASCVD). However, levels of influenza immunization and LLT use are low, possibly due to pervasive fear-based misinformation uniquely targeting vaccines and LLT. Whether being unvaccinated for influenza predicts lower utilization of LLT is unknown. OBJECTIVES: We tested the hypothesis that American adults with ASCVD who are unvaccinated for influenza have lower use of LLT even after accounting for traditional factors associated with underuse of preventive therapies. METHODS: We pooled 2017, 2019, and 2021 survey data from the Behavioral Risk Factor Surveillance System (BRFSS), and selected respondents aged 40 to 75 years with self-reported ASCVD. We used logistic regression models adjusted for potential confounders to examine the association between influenza vaccination and self-reported LLT use. We performed a sensitivity analysis with multiple imputation to account for missing data. All analyses accounted for complex survey weighting. RESULTS: Of 66,923 participants with ASCVD, 55% reported influenza vaccination in the last year and 76% reported using LLT. Being unvaccinated for influenza was associated with lower odds of LLT use (OR 0.54; 95% CI 0.50, 0.58; P< .001). In a multivariable regression model adjusting for demographics and comorbidities, this association remained statistically significant (aOR 0.58, 95% CI 0.52, 0.64, P < .001). After additional adjustment for preventive care engagement, health care access, and use patterns of other cardiovascular medications this association persisted (aOR 0.66; 95% CI 0.60, 0.74; P < .001). There were no significant differences across subgroups, including those with and without hyperlipidemia. CONCLUSIONS: Unvaccinated status for influenza was independently associated with 34% lower odds of LLT use among American adults with ASCVD after adjustment for traditional factors linked to underuse of preventive therapies. This finding identifies a population with excess modifiable ASCVD risk, and supports investigation into nontraditional mechanisms driving underuse of preventive therapies, including fear-based misinformation.

Induction immunosuppression and post-transplant diabetes mellitus: a propensity-matched cohort study.

Introduction: Post-transplant diabetes mellitus (PTDM) is a common complication among cardiac transplant recipients, causing diabetes-related complications and death. While certain maintenance immunosuppressive drugs increase PTDM risk, it is unclear whether induction immunosuppression can do the same. Therefore, we evaluated whether induction immunosuppression with IL-2 receptor antagonists, polyclonal anti-lymphocyte antibodies, or Alemtuzumab given in the peri-transplant period is associated with PTDM. Methods: We used the Scientific Registry of Transplant Recipients database to conduct a cohort study of US adults who received cardiac transplants between January 2008-December 2018. We excluded patients with prior or multiple organ transplants and those with a history of diabetes, resulting in 17,142 recipients. We created propensity-matched cohorts (n=7,412) using predictors of induction immunosuppression and examined the association between post-transplant diabetes and induction immunosuppression by estimating hazard ratios using Cox proportional-hazards models. Results: In the propensity-matched cohort, the average age was 52.5 (SD=13.2) years, 28.7% were female and 3,706 received induction immunosuppression. There were 867 incident cases of PTDM during 26,710 person-years of follow-up (32.5 cases/1,000 person-years). There was no association between induction immunosuppression and post-transplant diabetes (Hazard Ratio= 1.04, 95% confidence interval 0.91 - 1.19). Similarly, no associations were observed for each class of induction immunosuppression agents and post-transplant diabetes. Conclusion: The use of contemporary induction immunosuppression in cardiac transplant patients was not associated with post-transplant diabetes.

Infestation rates of lice Lepeophtheirus salmonis and Caligus elongatus on Atlantic salmon in fixed and towed sentinel cages.

Sea lice are a key limitation to sustainable salmon aquaculture, and effective monitoring strategies are critical for the management of these parasites. Sentinel cages are an established means of assessing infestation pressure at fixed locations, but as smolts move through systems they will be exposed to varying lice densities. As a means of assessing infestation pressure along trajectories, we describe the development and application of towed sentinel cages (TSCs) in a Scottish sea loch containing salmonid aquaculture. Trial deployments took place over 3 yr (2016-2018), and levels of sea lice infestation were compared between methodologies. Oceanographic data was collected alongside TSCs to put the results into the environmental context that smolts and sea lice experienced during the tows. The sea lice infestation rates found from TSCs were comparable to those on contemporaneously deployed fixed sentinel cages. Thus, due to their practicability and consistency with other surveillance methods, TSCs could be used to improve the assessment of exposure risk along wild salmonid smolt migration trajectories, where these are known.

Compliance-Adjusted Estimates of Aspirin Effects Among Older Persons in the ASPREE Randomized Trial.

The Aspirin in Reducing Events in the Elderly (ASPREE) Trial recruited 19,114 participants across Australia and the United States during 2010-2014. Participants were randomized to receive either 100 mg of aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open-label aspirin use. In the placebo group, 35% and 11% ceased using study medication and commenced open-label aspirin use, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank-preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people, along with an elevated risk of clinically significant bleeding.

Politically related stress and low-birth-weight infants among Arab, Asian, Hispanic, non-Hispanic Black, and non-Hispanic White women in Michigan.

BACKGROUND: Despite the high cost of low birth weight and the persistent challenge of racial inequities affecting the Arab American community, there has been limited research to identify and examine risk factors for these inequities with validated data on Arab American ethnicity and recent population stressors. OBJECTIVES: This study examined whether the 2016 presidential election is associated with low birth weight among non-Hispanic White, Arab American, Hispanic, and non-Hispanic Black women. DESIGN: This population-based study of singleton births in Michigan (2008-2017) used an algorithm to identify mothers who were of Arab descent. METHODS: We used logistic regression to estimate odds ratios and 95% confidence intervals for the association between race/ethnicity and the odds of low birth weight. We examined whether these associations differed before and after the 2016 presidential election and according to maternal education. RESULTS: There were 1,019,738 births, including 66,272 (6.5%) classified as low birth weight. The odds of having a low-birth-weight infant were higher among all minority women compared to non-Hispanic White women. The association was similar before and after the 2016 presidential election and stronger among women with higher levels of education. CONCLUSION: This is the first study to estimate low birth weight among Arab American women in the context of political events. There are opportunities for future studies to discuss this issue in depth.

Randomized controlled pilot trial of prazosin for prophylaxis of posttraumatic headaches in active-duty service members and veterans.

OBJECTIVE: Evaluate the efficacy and tolerability of prazosin for prophylaxis of headaches following mild traumatic brain injury in active-duty service members and military veterans. BACKGROUND: Prazosin is an alpha-1 adrenoreceptor antagonist that reduces noradrenergic signaling. An open-label trial in which prazosin reduced headache frequency in veterans following mild traumatic brain injury provided the rationale for this pilot study. METHODS: A 22-week parallel-group randomized controlled trial  which included 48 military veterans and active-duty service members with mild traumatic brain injury-related headaches was performed. The study design was based on International Headache Society consensus guidelines for randomized controlled trials for chronic migraine. Following a pre-treatment baseline phase, participants with at least eight qualifying headache days per 4 weeks were randomized 2:1 to prazosin or placebo. After a 5-week titration to a maximum possible dose of 5 mg (morning) and 20 mg (evening), participants were maintained on the achieved dose for 12 weeks. Outcome measures were evaluated in 4-week blocks during the maintenance dose phase. The primary outcome measure was change in 4-week frequency of qualifying headache days. Secondary outcome measures were percent participants achieving at least 50% reduction in qualifying headache days and change in Headache Impact Test-6 scores. RESULTS: Intent-to-treat analysis of randomized study participants (prazosin N = 32; placebo N = 16) demonstrated greater benefit over time in the prazosin group for all three outcome measures. In prazosin versus placebo participants, reductions from baseline to the final rating period for 4-week headache frequency were -11.9 ± 1.0 (mean ± standard error) versus -6.7 ± 1.5, a prazosin minus placebo difference of -5.2 (-8.8, -1.6 [95% confidence interval]), p = 0.005 and for Headache Impact Test-6 scores were -6.0 ± 1.3 versus +0.6 ± 1.8, a difference of -6.6 (-11.0, -2.2), p = 0.004. The mean predicted percent of participants at 12 weeks with ≥50% reduction in headache days/4 weeks, baseline to final rating, was 70 ± 8% for prazosin (21/30) versus 29 ± 12% for placebo (4/14), odds ratio 5.8 (1.44, 23.6), p = 0.013. The trial completion rate of 94% in the prazosin group (30/32) and 88% in the placebo group (14/16) indicated that prazosin was generally well tolerated at the administered dose regimen. Morning drowsiness/lethargy was the only adverse effect that differed significantly between groups, affecting 69% of the prazosin group (22/32) versus 19% of the placebo group (3/16), p = 0.002. CONCLUSIONS: This pilot study provides a clinically meaningful efficacy signal for prazosin prophylaxis of posttraumatic headaches. A larger randomized controlled trial is needed to confirm and extend these promising results.