Chemical Immobilization Effects on Cougar (Felis concolor) Movement.

Capturing and handling wildlife is a common practice for both management and research. As telemetry use has become common, the need to capture and chemically immobilize wildlife has increased. Understanding how long the effects of immobilizing agents last after releasing the animal is often poorly understood but needed to ensure that analyses use data that reflect natural behavior. Between 2016 and 2021, 87 cougars (Puma concolor) were chemically immobilized with medetomidine, zolazepam, and tiletamine (MZT) and collared across west-central Alberta, Canada, 27 of which were individuals being recollared. We examined the distance an individual traveled per day and compared equivalent periods before and after the recollaring event to determine whether postcapture movement rates were significantly different from precapture rates. Within 1 d of the recollaring, daily movement rates had returned to precapture rates (t20=2.09, P=0.18). Our results provide insight on how MZT used in cougars affects their postcapture movement and thus may be helpful in interpreting movement data after release.

Pharmacist Initiated Interventions Using RxChange Message Communication with Prescribers for Electronic Prescriptions: A Retrospective Descriptive Study.

BACKGROUND: RxChange messages improve patient medication management by enhancing pharmacist-prescriber communication, but their usage patterns in the United States are not well-documented. OBJECTIVE: To determine intervention characteristics by pharmacists and prescribers using RxChange messages. METHODS: A retrospective analysis of electronic prescription and RxChange messages from 2022 and 2023, using data from Surescripts, LLC, was conducted. This included NewRx messages and RxChange Responses, categorized by seven RxChange use cases and Anatomical Therapeutic Chemical level 4 medication classes. Descriptive statistics and non-parametric tests were used for statistical analysis. RESULTS: The study analyzed 1,361,528 RxChange messages. Therapeutic interchange was the predominant use case (76.14%). Direct approvals accounted for 10.44% of requests, approvals with changes for 42.55%, and denials for 47.01%. Script clarification had the highest approval rate (64.21%), while prior authorization faced the most frequent denials (73.38%). The top denial reason was "Request addressed through alternate methods such as phone or fax" (41.50%). The most frequent drug classes observed in the data were selective beta-2 adrenoreceptor agonists, extended-spectrum penicillins, selective serotonin reuptake inhibitors, and glucagon-like peptide 1 analogues. Time from new e-prescription issuance to RxChange request submission was longer than from request to response, with a significant statistical difference (median 1.57 vs 0.27 days, p-value < 0.05). CONCLUSION: This study highlights interventions pharmacists make using RxChange with electronic prescriptions to improve patient care and medication safety. It underlined the need for improved RxChange message content and data on the effectiveness of RxChange messages in improving medication use.

Sustained 3-Year Improvement of Glucose Control With Hybrid Closed Loop in Children With Type 1 Diabetes While Going Through Puberty.

OBJECTIVE: To evaluate the impact of prolonged hybrid closed loop (HCL) use in children with type 1 diabetes (T1D) on glucose control and BMI throughout pubertal progression. RESEARCH DESIGN AND METHODS: We used a prospective multicenter extension study following the Free-Life Kid AP (FLKAP) HCL trial. The 9-month previously reported FLKAP trial included 119 prepubertal children (aged 6-12 years). During the extension study, participants could continue to use HCL for 30 months (M9 to M39). HbA1c values were collected every 3 months up to M39, while continuous glucose monitoring metrics, BMI Z scores, and Tanner stages were collected up to M24. Noninferiority tests were performed to assess parameter sustainability over time. RESULTS: One hundred seventeen children completed the extension study, with mean age 10.1 years (min-max 6.8-14.0) at the beginning. Improvement of HbA1c obtained in the FLKAP trial was significantly sustained during extension (median [interquartile range], M9: 7.0% [6.8-7.4], and M39: 7.0% [6.6-7.4], P < 0.0001 for noninferiority test) and did not differ between children who entered puberty at M24 (Tanner ≥ stage 2; 54% of the patients) and patients who remained prepubertal. BMI Z score also remained stable (M9: 0.41 [-0.29 to 1.13] and M24: 0.48 [-0.11 to 1.13], P < 0.0001, for noninferiority test). No severe hypoglycemia and one ketoacidosis episode not related to the HCL system occurred. CONCLUSIONS: Prolonged use of HCL can safely and effectively mitigate impairment of glucose control usually associated with pubertal progression without impact on BMI in children with T1D.

Design, Fabrication, and Validation of a Portable Perturbation Treadmill for Balance Recovery Research.

Trips and falls are a major concern for older adults. The resulting injury and loss of mobility can have a significant impact on quality of life. An emerging field of study, known as Perturbation Training, has been shown to reduce injury rates associated with trips and falls in older adults. Treadmills traditionally used for Perturbation Training are large, expensive, and immobile, forcing users to travel long distances to receive care. A portable treadmill would serve a larger portion of the at-risk population than current methods. We developed a portable, low-cost, twin-belt perturbation treadmill capable of high-intensity Perturbation Training. Belt speeds are controlled by a custom mechanical and software interface, allowing operators with no programming experience to control the device. The treadmill can accommodate users up to 118 kg and provides a maximum acceleration and speed of 12 m/s2 and 3.3 m/s, respectively, under full load. The total weight is 180 kg, and the treadmill can be moved like a wheelbarrow, with handles in the back and wheels in the front. The prototype was validated with mechanical and human participant testing, showing it as a viable device for Perturbation Training. In this paper, we will go over the design, fabrication, and validation processes used to create the Portable Perturbation Treadmill.

Methylprednisolone dosing for pediatric critical asthma: a single-center cohort study.

OBJECTIVE: We aimed to characterize intravenous (IV) methylprednisolone (MP) dosing regimens and clinical outcomes for children hospitalized for critical asthma (CA). METHODS: A single-center, retrospective review was performed of children admitted to the pediatric intensive care unit (PICU) for CA between September 2015 and October 2019. Patients 5-to 17-year-olds, initiated on continuous nebulized albuterol, and prescribed at least one dose of IV MP were included. The primary outcome was to characterize PICU MP dosing. Cohorts were then compared by MP dosing: conservative-dose methylprednisolone (CDMP, ≤ 0.5 mg/kg/dose every 6 h) and standard-dose methylprednisolone (SDMP, > 0.5 mg/kg/dose every 6 h). Clinical efficacy endpoints were the duration of continuous nebulized albuterol and PICU length of stay (LOS). Safety endpoints included corticosteroid-related adverse events. RESULTS: Of 168 children studied, 50 (29.8%) were prescribed CDMP and 118 (70.2%) SDMP. The overall mean MP dose was 31.3 ± 19.6 mg (weight-adjusted: 0.77 ± 0.32 mg/kg/dose). Compared to those prescribed SDMP, those prescribed CDMP had a shorter median duration of continuous nebulized albuterol (12.8 [IQR: 10.5-20] versus 17.3 [IQR: 11.3-29.7] hours, p = 0.019) and median PICU LOS (0.9 [IQR: 0.7-1.4] versus 1.2 [IQR: 0.9-1.8] days, p = 0.012). No corticosteroid-related adverse events were observed. In adjusted models, weight-adjusted IV MP dose was not associated with PICU LOS or duration of continuous nebulized albuterol. CONCLUSIONS: Intravenous MP dosing for pediatric CA varied widely in our study sample. Prospective, controlled trials are required to validate our observations including clinical efficacy and safety endpoints.

Testosterone levels increase following bariatric surgery - validation of preceding literature in a large-scale population analysis.

BACKGROUND: The effects of bariatric surgery on testosterone levels in men with obesity and hypogonadism have not been thoroughly explored yet. OBJECTIVES: To investigate the possible effects of bariatric surgery on T levels in obese hypogonadal men by comparing T levels before and after surgery using a comprehensive claims database. MATERIALS AND METHODS: The TriNetX US Collaborative Network database was used to identify men ages 18-80 who underwent a bariatric procedure and had a serum T value of < 350 ng/dL prior to surgery. Men who received testosterone therapy before/or after surgery were excluded. We conducted a retrospective self-matched cohort analysis to examine the difference in serum T levels before and after bariatric surgery. A sub-analysis was carried out to explore differences between men who reached eugonadal status or maintained low T levels following surgery. Descriptive statistics detailed sociodemographic and clinical characteristics, with continuous and categorical data compared using unpaired t-tests and chi-square analysis, respectively. Changes in T levels and body mass index (BMI) before and after surgery were compared using an unpaired t-test with a < 0.05 set for significance. All analyses were conducted using the TriNetX platform which utilizes both Python and R software. RESULTS: The study analyzed 69 hypogonadal men who underwent bariatric surgery and had T levels assessed before and after the procedure. The mean (standard deviation) pre-surgery serum T level was 208 ± 79 ng/dL, which post-surgery increased to 371 ± 164 ng/dL, marking an average increase of 163 ± 164 ng/dL. Likewise, the mean (standard deviation) body mass index decreased from 42.9 ± 9.0 to 38.8 ± 5.7 kg/m2. Post-surgery, 45% (31 men) achieved eugonadal status, while 55% (38 men) continued to have low T levels. A comparison between the post-surgery eugonadal cohort and the persistent low T cohort revealed that the former had higher pre-surgery serum T levels (235 ± 71 ng/dL vs. 184 ± 80.4 ng/dL, p = 0.007), a higher pre-surgery body mass index (45.5 ± 4.5 kg/m2 vs. 41.1 ± 11.5 kg/m2, p = 0.041), and a significantly greater reduction in body mass index post-surgery (7.3 ± 7.2 kg/m2 vs. 2.0 ± 12.8 kg/m2, p = 0.04). Notably, the increase in T was significantly higher in the eugonadal cohort compared to the persistent low testosterone cohort (257 ± 143 ng/dL vs. 95 ± 178 ng/dL, p < 0.0001). CONCLUSION: This study provides evidence of bariatric surgery's positive effect on serum T levels in obese men with baseline low T. Almost one out of two men with low T reached normal T levels after bariatric surgery. As the most comprehensive study to date, it validates and substantiates previous work suggesting that weight loss can improve T levels physiologically.

When Perfect Is the Enemy of Good: Results of a RAND Appropriateness Panel on Treat to Target in Asymptomatic IBD.

BACKGROUND: A treat-to-target strategy for inflammatory bowel disease (IBD) recommends iterative treatment adjustments to achieve clinical and endoscopic remission. In asymptomatic patients with ongoing endoscopic activity, the risk/benefit balance of this approach is unclear, particularly with prior exposure to advanced therapies. METHODS: Using the RAND/UCLA Appropriateness Method, 9 IBD specialists rated appropriateness of changing therapy in 126 scenarios of asymptomatic patients with ulcerative colitis (UC) and Crohn's disease (CD) and active endoscopic disease. Disease extent and behavior, prior treatment, prior complications, and recent disease progression were considered, as were factors that might influence decision-making, including age and pregnancy. Ratings were collected via anonymous survey, discussed at an in-person meeting, and finalized in a second anonymous survey. RESULTS: Panelists rated change in therapy as appropriate (i.e., expected benefit sufficiently outweighs potential harms from continuing therapy) in 96/126 scenarios, generally in patients with progressive, complicated, and/or extensive disease, while changing therapy was rated uncertain in 27 scenarios of mild and/or stable disease. Changing therapy was rated inappropriate in UC patients with mild and stable disease previously exposed to ≥3 therapies or with improved endoscopic activity, and in CD patients with only scattered aphthous ulcers. The validated threshold for disagreement was not crossed for any scenario. Patient age >65 years and a plan for pregnancy in the next year might influence decision-making in some settings. CONCLUSION: Appropriateness ratings can help guide clinical decision-making about changing therapy to achieve endoscopic remission in asymptomatic patients with IBD until data from ongoing randomized studies are available.

Trends and Factors Associated With Peripheral Vascular Interventions for the Treatment of Claudication From 2011 to 2022: A National Medicare Cohort Study.

BACKGROUND: Previous cross-sectional studies have identified wide practice pattern variations in the use of peripheral vascular interventions (PVIs) for the treatment of claudication. However, there are limited data on longitudinal practice patterns. We aimed to describe the temporal trends and charges associated with PVI use for claudication over the past 12 years in the United States. METHODS AND RESULTS: We conducted a retrospective analysis using 100% Medicare fee-for-service claims data to identify all patients who underwent a PVI for claudication between January 2011 and December 2022. We evaluated the trends in utilization and Medicare-allowed charges of PVI according to anatomic level, procedure type, and intervention settings using generalized linear models. Multinomial logistic regressions were used to evaluate factors associated with different levels and types of PVI. We identified 599 197 PVIs performed for claudication. The proportional use of tibial PVI increased 1.0% per year, and atherectomy increased by 1.6% per year over the study period. The proportion of PVIs performed in ambulatory surgical centers/office-based laboratories grew at 4% per year from 12.4% in 2011 to 55.7% in 2022. Total Medicare-allowed charges increased by $11 980 035 USD/year. Multinomial logistic regression identified significant associations between race and ethnicity and treatment setting with use of both atherectomy and tibial PVI. CONCLUSIONS: The use of tibial PVI and atherectomy for the treatment of claudication has increased dramatically in in ambulatory surgical center/office-based laboratory settings, non-White patients, and resulting in a significant increase in health care charges. There is a critical need to improve the delivery of value-based care for the treatment of claudication.

Customized passive-dynamic ankle-foot orthoses can improve walking economy and speed for many individuals post-stroke.

BACKGROUND: Passive-dynamic ankle-foot orthoses (PD-AFOs) are often prescribed to address plantar flexor weakness during gait, which is commonly observed after stroke. However, limited evidence is available to inform the prescription guidelines of PD-AFO bending stiffness. This study assessed the extent to which PD-AFOs customized to match an individual's level of plantar flexor weakness influence walking function, as compared to No AFO and their standard of care (SOC) AFO. METHODS: Mechanical cost-of-transport, self-selected walking speed, and key biomechanical variables were measured while individuals greater than six months post-stroke walked with No AFO, with their SOC AFO, and with a stiffness-customized PD-AFO. Outcomes were compared across these conditions using a repeated measures ANOVA or Friedman test (depending on normality) for group-level analysis and simulation modeling analysis for individual-level analysis. RESULTS: Twenty participants completed study activities. Mechanical cost-of-transport and self-selected walking speed improved with the stiffness-customized PD-AFOs compared to No AFO and SOC AFO. However, this did not result in a consistent improvement in other biomechanical variables toward typical values. In line with the heterogeneous nature of the post-stroke population, the response to the PD-AFO was highly variable. CONCLUSIONS: Stiffness-customized PD-AFOs can improve the mechanical cost-of-transport and self-selected walking speed in many individuals post-stroke, as compared to No AFO and participants' standard of care AFO. This work provides initial efficacy data for stiffness-customized PD-AFOs in individuals post-stroke and lays the foundation for future studies to enable consistently effective prescription of PD-AFOs for patients post-stroke in clinical practice. TRIAL REGISTRATION: NCT04619043.

The Impact of Undermining Coparenting on the Mental and Physical Health Outcomes of Black Fathers: The Role of Depression and Restrictive Emotionality.

The parenting literature has established the coparenting relationship as central to the parenting behaviors and outcomes of men. The construct of coparenting encompasses supportive efforts among individuals that facilitate the rearing of children and unsupportive actions that can undermine parenting efforts (Merrifield & Gamble, 2013). Few studies have examined undermining coparenting as an experience that shapes Black men's health outcomes. In this study, we apply the social determinants of health framework to examine the impact of Black fathers' perceptions of undermining coparenting on their self-reported ratings of mental and physical health. Using a nationally representative sample of Black men (n = 255), correlational analyses revealed perceptions of undermining coparenting to be a significant predictor of higher levels of anger and poorer perceptions of physical health. These relationships were found to be mediated by depressive symptoms and moderated by restrictive emotionality. It is recommended that the negative impact of undermining coparenting on health be considered as a potential comorbidity contributing to negative health outcomes for Black men. This study adds to the literature on coparenting, Black men's health, and Black fatherhood more generally and urges policymakers and practitioners to consider undermining as an often overlooked, but significant, social determinant of health impacting the well-being of Black men. We also offer recommendations for promoting Black men's health by educating families on the effects of undermining and offering the supports necessary for achieving positive coparenting dynamics.

Infrapopliteal Endovascular Interventions for Claudication Are Associated with Poor Long-Term Outcomes in Medicare-Matched Registry Patients.

BACKGROUND: There are limited data supporting or opposing the use of infrapopliteal peripheral vascular interventions (PVI) for the treatment of claudication. OBJECTIVES: We aimed to evaluate the association of infrapopliteal PVI with long-term outcomes compared with isolated femoropopliteal PVI for the treatment of claudication. METHODS: We conducted a retrospective analysis of all patients in the Medicare-matched Vascular Quality Initiative database who underwent an index infrainguinal PVI for claudication from January 2004-December 2019 using Cox proportional hazards models. RESULTS: Of 14,261 patients (39.9% female; 85.6% age ≥65 years, 87.7% non-Hispanic white) who underwent an index infrainguinal PVI for claudication, 16.6% (N=2,369) received an infrapopliteal PVI. The median follow-up after index PVI was 3.7 years (IQR 2.1-6.1). Compared to patients who underwent isolated femoropopliteal PVI, patients receiving any infrapopliteal PVI had a higher 3-year cumulative incidence of conversion to CLTI (33.3% vs. 23.8%; P<0.001); repeat PVI (41.0% vs. 38.2%; P<0.01); and amputation (8.1% vs. 2.8%; P<0.001). After risk-adjustment, patients undergoing infrapopliteal PVI had a higher risk of conversion to CLTI (aHR 1.39, 95% CI, 1.25-1.53); repeat PVI (aHR 1.10, 95% CI, 1.01-1.19); and amputation (aHR 2.18, 95% CI, 1.77-2.67). Findings were consistent after adjusting for competing risk of death; in a 1:1 propensity-matched analysis; and in subgroup analyses stratified by TASC disease, diabetes, and end-stage kidney disease. CONCLUSIONS: Infrapopliteal PVI is associated with worse long-term outcomes than femoropopliteal PVI for claudication. These risks should be discussed with patients.

Persistent spatial clustering and predictors of pediatric La Crosse virus neuroinvasive disease risk in eastern Tennessee and western North Carolina, 2003-2020.

The combined region of eastern Tennessee and western North Carolina has a persistently high risk of pediatric La Crosse virus neuroinvasive disease (LACV-ND). To guide public health intervention in this region, the objectives of this retrospective ecological study were to investigate the geographic clustering and predictors of pediatric LACV-ND risk at the ZIP code tabulation area (ZCTA) level. Data on pediatric cases of LACV-ND reported between 2003 and 2020 were obtained from Tennessee Department of Health and North Carolina Department of Health and Human Services. Purely spatial and space-time scan statistics were used to identify ZCTA-level clusters of confirmed and probable pediatric LACV-ND cases from 2003-2020, and a combination of global and local (i.e., geographically weighted) negative binomial regression models were used to investigate potential predictors of disease risk from 2015-2020. The cluster investigation revealed spatially persistent high-risk and low-risk clusters of LACV-ND, with most cases consistently reported from a few high-risk clusters throughout the entire study period. Temperature and precipitation had positive but antagonistic associations with disease risk from 2015-2020, but the strength of those relationships varied substantially across the study area. Because LACV-ND risk clustering in this region is focally persistent, retroactive case surveillance can be used to guide the implementation of targeted public health intervention to reduce the disease burden in high-risk areas. Additional research on the role of climate in LACV transmission is warranted to support the development of predictive transmission models to guide proactive public health interventions.

Supratubercle Anterior Closing Wedge Osteotomy: No Changes in Patellar Height and Significant Decreases in Anterior Tibial Translation at 6 Months Postoperatively.

BACKGROUND: Because of the increased prevalence of revision anterior cruciate ligament (ACL) reconstruction, there has been a desire to understand the role of posterior tibial slope on increased anterior tibial translation and increased ACL graft forces. One potential concern in supratubercle anterior closing wedge proximal tibial osteotomy (ACW-PTO) for decreasing the posterior tibial slope is the risk of altering the patellar height. PURPOSE: To radiographically assess changes in (1) patellar height, (2) anterior tibial translation, and (3) posterior tibial slope after supratubercle ACW-PTO. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients who underwent supratubercle ACW-PTO by a single surgeon between July 2019 and June 2023 were included. Standardized lateral knee weightbearing radiographs to assess patellar height (via the Caton-Deschamps index), anterior tibial translation of the lateral tibial plateau relative to the lateral femoral condyle, and posterior tibial slope were obtained at 4 time points (preoperatively and 1 day, 3 months, and 6 months postoperatively). Paired t test was used to compare differences between preoperative, 1-day, and 3- and 6-month values for patellar height as measured using the Caton-Deschamps index and for posterior tibial slope. Paired t test was also used to compare differences in the preoperative and 6-month postoperative values for anterior tibial translation. RESULTS: In 20 patients after ACW-PTO, the Caton-Deschamps index demonstrated a significant increase in patellar height on postoperative day 1 (P < .001) but no significant differences at 3 (P = .057) and 6 (P = .176) months postoperatively. Anterior tibial translation on standing lateral knee radiographs was significantly decreased by a mean of 8.9 mm from preoperatively to 6 months postoperatively (P < .001). Posterior tibial slope was significantly decreased by a mean of 11.2° from preoperatively to 6 months postoperatively (P < .001). CONCLUSION: Supratubercle ACW-PTO performed for ACL reconstruction failure in the setting of an increased posterior tibial slope did not induce significant changes in patellar height postoperatively. Furthermore, after ACW-PTO, there was a significant decrease in anterior tibial translation and posterior tibial slope.

Investigating Unconscious Race Bias and Bias Awareness Among Vascular Surgeons.

Background: Implicit bias can influence behavior and decision-making. In clinical settings, implicit bias may influence treatment decisions and contribute to health disparities. Given documented Black-White disparities in vascular care, the purpose of this study was to examine the prevalence and degree of unconscious bias and awareness of bias among vascular surgeons treating peripheral artery disease (PAD). Methods: The sampling frame included all vascular surgeons who participate in the Vascular Quality Initiative (VQI). Participants completed a survey which included demographic questions, the race implicit association test (IAT) to measure magnitude of unconscious bias, and six bias awareness questions to measure conscious bias. The magnitude of unconscious bias was no preference; or slight, moderate, or strong in the direction of pro-White or pro-Black. Data from participants were weighted to account for nonresponse bias and known differences in the characteristics of surgeons who chose to participate compared to the full registry. We stratified unconscious and conscious findings by physician race/ethnicity, physician sex, and years of experience. Finally, we examined the relationship between unconscious and conscious bias. Results: There were 2,512 surgeons in the VQI registry, 304 of whom completed the survey, including getting IAT results. Most participants (71.6%) showed a pro-White bias with 73.0% of this group in the moderate and strong categories. While 77.5% of respondents showed conscious awareness of bias, of those whose conscious results showed lack of awareness, 67.8% had moderate or strong bias, compared to 55.7% for those with awareness. Bias magnitude varied based on physician race/ethnicity and years of experience. Women were more likely than men to report awareness of biases and potential impact of bias on decision-making. Conclusions: Most people have some level of unconscious bias, developed from early life reinforcements, social stereotypes, and learned experiences. Regarding health disparities, however, these are important findings in a profession that takes care of patients with PAD due to heavy burden of comorbid conditions and high proportion of individuals from structurally vulnerable groups. Given the lack of association between unconscious and conscious awareness of biases, awareness may be an important first step in mitigation to minimize racial disparities in healthcare.

Infrapopliteal Peripheral Vascular Interventions for Claudication are Performed Frequently in the USA and Are Associated with Poor Long Term Outcomes.

OBJECTIVE: Infrapopliteal peripheral vascular interventions (PVIs) for claudication are still performed in the USA. This study aimed to evaluate whether infrapopliteal PVI is associated with worse long term outcomes than isolated femoropopliteal PVI for treatment of claudication. METHODS: A retrospective analysis of fee for service claims in a national administrative database was conducted using 100% of the Medicare fee for service claims between 2017 and 2019 to capture all Medicare beneficiaries who underwent an index infra-inguinal PVI for claudication. Hierarchical Cox proportional hazards models were performed to assess the association of infrapopliteal PVI with conversion to chronic limb threatening ischaemia (CLTI), repeat PVI, and major amputation. RESULTS: In total, 36 147 patients (41.1% female; 89.7% age ≥ 65 years; 79.0% non-Hispanic White ethnicity) underwent an index PVI for claudication, of whom 32.6% (n = 11 790) received an infrapopliteal PVI. Of these, 61.4% (n = 7 245) received a concomitant femoropopliteal PVI and 38.6% (n = 4 545) received an isolated infrapopliteal PVI. The median follow up time was 3.5 years (interquartile range 2.7, 4.3). Patients receiving infrapopliteal PVI had a higher three year cumulative incidence of conversion to CLTI (26.0%; 95% confidence interval [CI] 24.9 - 27.2% vs. 19.9%; 95% CI 19.1 - 20.7%), repeat PVI (56.0%; 95% CI 54.8 - 57.3% vs. 45.7%; 95% CI 44.9 - 46.6%), and major amputation (2.2%; 95% CI 1.8 - 2.6% vs. 1.3%; 95% CI 1.1 - 1.5%) compared with patients receiving isolated femoropopliteal PVI. After adjusting for patient and physician level characteristics, the risk of conversion to CLTI (adjusted hazard ratio [aHR] 1.31, 95% CI 1.23 - 1.39), repeat PVI (aHR 1.12, 95% CI 1.05 - 1.20), and major amputation (aHR 1.72, 95% CI 1.42 - 2.07) remained significantly higher for patients receiving infrapopliteal PVI. An increasing number of infrapopliteal vessels treated during the index intervention was associated with increasingly poor outcomes (p < .001 for trend). CONCLUSION: Infrapopliteal PVI for claudication is associated with worse long term outcomes relative to isolated femoropopliteal PVI.

Recommendations for Broadening Eligibility Criteria in Inflammatory Bowel Disease Clinical Trials.

BACKGROUND: Clinical trial recruitment for patients with inflammatory bowel disease (IBD) has become more challenging over time. We aimed to develop recommendations for broadening IBD clinical trial eligibility to improve the inclusion of a more representative patient population in a more efficient timeline. METHODS: We applied the RAND/UCLA Appropriateness Method focused on broadening IBD clinical trial eligibility. A literature review was performed for 7 domains, each representing a different area related to trial recruitment. Based on these domains, 32 statements were developed. A questionnaire was sent to IBD specialists to anonymously vote on each statement with regards to its appropriateness and feasibility. After the first round of voting, participants met for a moderated discussion to review all statements. At the end of the discussion a second round of anonymous voting led to the final recommendations. RESULTS: The final round of voting resulted in 26 statements. All were rated as feasible and 25 of 26 rated as appropriate. Recommendations generally are to be more inclusive of complicated disease phenotypes, more liberal around safety criteria, to recognize the importance of non-invasive imaging and biomarkers, to minimize the washout period and to not enforce a minimum or maximum number of prior medications, to allow a recently recorded colonoscopy to count as a baseline study, and to be less restrictive of age. CONCLUSION: Recommendations to broaden clinical trial eligibility were found to be both appropriate and feasible with a high degree of agreement amongst an international group of IBD specialists.

Transcriptional control of a metabolic switch regulating cellular methylation reactions is part of a common response to stress in divergent bee species.

Recent global declines in bee health have elevated the need for a more complete understanding of the cellular stress mechanisms employed by diverse bee species. We recently uncovered the biomarker lethal (2) essential for life [l(2)efl] genes as part of a shared transcriptional program in response to a number of cell stressors in the western honey bee (Apis mellifera). Here, we describe another shared stress-responsive gene, glycine N-methyltransferase (Gnmt), which is known as a key metabolic switch controlling cellular methylation reactions. We observed Gnmt induction by both abiotic and biotic stressors. We also found increased levels of the GNMT reaction product sarcosine in the midgut after stress, linking metabolic changes with the observed changes in gene regulation. Prior to this study, Gnmt upregulation had not been associated with cellular stress responses in other organisms. To determine whether this novel stress-responsive gene would behave similarly in other bee species, we first characterized the cellular response to endoplasmic reticulum (ER) stress in lab-reared adults of the solitary alfalfa leafcutting bee (Megachile rotundata) and compared this with age-matched honey bees. The novel stress gene Gnmt was induced in addition to a number of canonical gene targets induced in both bee species upon unfolded protein response (UPR) activation, suggesting that stress-induced regulation of cellular methylation reactions is a common feature of bees. Therefore, this study suggests that the honey bee can serve as an important model for bee biology more broadly, although studies on diverse bee species will be required to fully understand global declines in bee populations.

An evaluation of consumer smartphones for generating bolus and surface mould applicators for radiation oncology.

BACKGROUND: The use of Computed Tomography (CT) imaging data to create 3D printable patient-specific devices for radiation oncology purposes is already well established in the literature and has shown to have superior conformity than conventional methods. Using non-ionizing radiation imaging techniques such as photogrammetry or laser scanners in-lieu of a CT scanner presents many desirable benefits including reduced imaging dose and fabrication of the device can be completed prior to simulation. With recent advancements in smartphone-based technology, photographic and LiDAR-based technologies are more readily available than ever before and to a high level of quality. As a result, these non-ionizing radiation imaging methods are now able to generate patient-specific devices that can be acceptable for clinical use. PURPOSE: In this work, we aim to determine if smartphones can be used by radiation oncologists or other radiation oncology staff to generate bolus or brachytherapy surface moulds instead of conventional CT with equivalent or comparable accuracy. METHODS: This work involved two separate studies: a phantom and participant study. For the phantom study, a RANDO anthropomorphic phantom (limited to the nose region) was used to generate 3D models based on three different imaging techniques: conventional CT, photogrammetry & LiDAR which were both acquired on a smartphone. Virtual boli were designed in Blender and 3D printed from PLA plastic material. The conformity of each printed boli was assessed by measuring the air gap volume and approximate thickness between the phantom & bolus acquired together on a CT. For the participant study, photographs, and a LiDAR scan of four volunteers were captured using an iPhone 13 Pro™ to assess their feasibility for generating human models. Each virtual 3D model was visually assessed to identify any issues in their reconstruction. The LiDAR models were registered to the photogrammetry models where a distance to agreement analysis was performed to assess their level of similarity. Additionally, a 3D virtual bolus was designed and printed using ABS material from all models to assess their conformity onto the participants skin surface using a verbal feedback method. RESULTS: The photogrammetry derived bolus showed comparable conformity to the CT derived bolus while the LiDAR derived bolus showed poorer conformity as shown by their respective air gap volume and thickness measurements. The reconstruction quality of both the photogrammetry and LiDAR models of the volunteers was inadequate in regions of facial hair and occlusion, which may lead to clinically unacceptable patient-specific device that are created from these areas. All participants found the photogrammetry 3D printed bolus to conform to their nose region with minimal room to move while three of the four participants found the LiDAR was acceptable and could be positioned comfortably over their entire nose. CONCLUSIONS: Smartphone-based photogrammetry and LiDAR software show great potential for future use in generating 3D reference models for radiation oncology purposes. Further investigations into whether they can be used to fabricate clinically acceptable patient-specific devices on a larger and more diverse cohort of participants and anatomical locations is required for a thorough validation of their clinical usefulness.

The use of accelerometers to improve estimation of the thermic effect of food in whole room calorimetry studies.

We tested whether spontaneous physical activity (SPA) from accelerometers could be used in a whole room calorimeter to estimate thermic effect of food (TEF). Eleven healthy participants (n = 7 females; age: 27 ± 4 yr; body mass index: 22.8 ± 2.6 kg/m2) completed two 23-h visits in randomized order: one "fed" with meals provided and one "fasted" with no food. SPA was measured by ActivPAL and Actigraph accelerometers. Criterion TEF was calculated as the difference in total daily energy expenditure (TDEE) between fed and fasted visits and compared with three methods of estimating TEF: 1) SPA-adjusted TEF (adjTEF)-difference in TDEE without SPA between visits, 2) Wakeful TEF-difference in energy expenditure obtained from linear regression and basal metabolic rate during waking hours, 3) 24-h TEF-increase in TDEE above SPA and sleeping metabolic rate. Criterion TEF was 9.4 ± 4.5% of TDEE. AdjTEF (difference in estimated vs. criterion TEF: activPAL: -0.3 ± 3.3%; Actigraph: -1.8 ± 8.0%) and wakeful TEF (activPAL: -0.9 ± 6.1%; Actigraph: -2.8 ± 7.6%) derived from both accelerometers did not differ from criterion TEF (all P > 0.05). ActivPAL-derived 24-h TEF overestimated TEF (6.8 ± 5.4%, P = 0.002), whereas Actigraph-derived 24-h TEF was not significantly different (4.3 ± 9.4%, P = 0.156). TEF estimations using activPAL tended to show better individual-level agreement (i.e., smaller coefficients of variation). Both accelerometers can be used to estimate TEF in a whole room calorimeter; wakeful TEF using activPAL is the most viable option given strong group-level accuracy and reasonable individual agreement.NEW & NOTEWORTHY Two research-grade accelerometers can effectively estimate spontaneous physical activity and improve the estimation of thermic effect of food (TEF) in whole room calorimeters. The activPAL demonstrates strong group-level accuracy and reasonable individual-level agreement in estimating wakeful TEF, whereas a hip-worn Actigraph is an acceptable approach for estimating 24-h TEF. These results highlight the promising potential of accelerometers in advancing energy balance research by improving the assessment of TEF within whole room calorimeters.