One-tailed Research Articles

Optimal antithrombotic therapy in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis: study protocol for a randomized controlled trial.

The addition of antiplatelet therapy to anticoagulant therapy in patients with stroke with non-valvular atrial fibrillation (NVAF) and atherothrombotic disease may increase bleeding risk without reducing recurrent stroke risk. To evaluate the clinical benefits of anticoagulant monotherapy compared to combination therapy with anticoagulants and antiplatelet agents. This is an investigator-initiated prospective multicenter, randomized, open-label, parallel-group clinical trial. Patients with NVAF and atherothrombotic disease who have had a recent ischemic stroke or transient ischemic attack will be eligible to participate in this trial. The primary outcome is a composite of ischemic cardiovascular events, including cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization, and major bleeding events within 2 years after randomization. This study will enroll 400 patients, 200 receiving anticoagulant monotherapy and 200 receiving combination therapy. This sample size will provide 90% power (one-sided p = 0.025) to detect a risk reduction in outcome events within 2 years, assuming event rates of 13 and 27% for each group, respectively, and a 10% loss to follow-up at a 2.5% significance level with one-sided log-rank tests at an interim analysis and a final analysis. This will be the first study to assess the net clinical benefit of oral anticoagulant monotherapy in ischemic stroke patients with NVAF and atherothrombosis. https://clinicaltrials.gov/study/NCT03062319, NCT03062319; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000029222, UMIN000025392; https://jrct.niph.go.jp/latest-detail/jRCTs051180202, jRCTs051180202.

Proactive control for conflict resolution is intact in subclinical obsessive-compulsive individuals.

BackgroundObsessive-compulsive (OC) traits (i.e., tendency to implement stereotyped behaviors to avoid negative consequences) are transversally observed in psychiatric disorders largely differing in terms of clinical manifestations and etiopathogenesis. Interestingly, OC traits were also extensively found in the prodromal phases of the full-blown psychopathology and in healthy relatives of affected individuals. Moreover, OC traits were found to be associated—and possibly underlain by—cognitive control impairments. Nonetheless, the role of such interplay in the onset of OC disorders is yet to be understood. We hypothesized that OC traits are associated with abnormalities in proactively implement cognitive control for solving conflict.MethodsWe administered healthy individuals (n = 104) with the perifoveal spatial Stroop task to measure their ability of solving conflict in a proactive fashion, and with Obsessive-Compulsive Inventory (OCI) to stratify population according to the severity of OC traits.ResultsAnalysis of response times by means of Linear Mixed-effect models revealed that proactive control performance was not associated with and the severity of OC traits. Furthermore, an equivalence test (Two One-Sided Test) revealed that the association between OCI scores and task performance was equivalent to zero.ConclusionThese results suggest that the interplay between OC traits and proactive control abnormalities might not contribute to the development of OC-related disorders. Therefore, the role of other cognitive endophenotypes should be scrutinized for exploiting alternative prevention and intervention strategies.

Perioperative management of antithrombotic therapy in elderly patients undergoing lumbar discectomy: a retrospective study on 163 patients.

The prevalence of lumbar disc herniation (LDH) has risen alongside the aging population, often necessitating neurosurgical intervention. However, managing antithrombotic medications in elderly patients with a history of major cardiovascular events (MACE) presents challenges, as treatment may require modification or cessation. This study aims to compare surgical outcomes among elderly patients receiving antithrombotic drugs and assess their impact and potential complications. The findings aim to inform the management of elderly patients with cardiovascular and spinal conditions undergoing neurosurgery. This retrospective, observational study was conducted at a single center. A total of 163 patients aged 60 or above who underwent lumbar discectomy for LDH were included. Patients were categorized into three groups based on their antithrombotic drug management: Group A (46 patients) replaced antiplatelet agents with low-dose aspirin for secondary prevention, Group B (54 patients) discontinued antiplatelet agents for primary prevention one week preoperatively and replaced them with LMWH, and Group C (63 patients) did not receive antithrombotic medication. Intraoperative blood loss, surgical time, and postoperative hospitalization were analyzed across all three groups. Continuous variables were compared between groups using the two-tailed Mann-Whitney test, with significance set at p < 0.05. No significant differences were found in intraoperative blood loss or surgical time among groups A, B, and C. Similarly, no significant differences were observed between groups B and C across all analyzed variables. No early or delayed hemorrhagic complications occurred perioperatively or during the 3-month postoperative follow-up period. The study suggests that elective discectomy surgery in patients receiving anticoagulant and antiplatelet therapies may proceed without early complications and can be safely continued perioperatively. These findings have implications for the management of elderly patients requiring neurosurgical intervention in the context of cardiovascular comorbidities.

Maternal sensitivity and child attachment security in a low SES Peruvian sample: longitudinal relationships

ABSTRACT We tested the generalizability of the sensitivity-security link in a sample of 35 preschooler-mother dyads from a low socioeconomic district in Lima, Peru. We first describe maternal sensitivity and attachment security at two timepoints during early childhood. Second, we investigated the stability of attachment security and maternal sensitivity over a time span of one year. Third, we tested the association between sensitivity and security at each timepoint. Finally, we investigated whether changes in maternal sensitivity predict changes in child security. The results indicated that sensitivity and security were lower than scores reported in the literature for middle-class samples. T2 maternal sensitivity scores were significantly higher than T1 sensitivity scores, and no significant differences were found between T1 and T2 security. Sensitivity and security were associated at both timepoints, after controlling for socio-demographic variables. One-tail test indicated that changes in maternal sensitivity were associated with changes in child security.

Tranexamic Acid for reduction of intra- and postoperative TRansfusion requirements in elective Abdominal surgery (TATRA): study protocol for an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized superiority trial with two parallel groups

BackgroundIntra- and postoperative hemorrhage is a relevant problem in major abdominal surgery, leading to acute anemia and necessitating transfusion of packed red blood cells. It is estimated that in 30% of abdominal surgeries, intra- or postoperative transfusion is required. Transfusion potentially has detrimental health effects and poses a considerable socioeconomic burden. Tranexamic acid, a lysine analog inhibiting plasminogen activation and providing clot stability, has been used to reduce hemorrhage. While there is ample evidence in other surgical disciplines, it is almost completely lacking in abdominal surgery.MethodsThis multicenter double-blind parallel group randomized superiority trial will compare tranexamic acid (loading dose 1000 mg over 10 min prior to skin incision, maintenance dose 125 mg/h continuously until skin closure or until 1000 mg have been administered) to placebo in patients ≥ 18 years undergoing elective esophagectomy, gastrectomy, colectomy, rectal resection, pancreatic resection, or hepatectomy. The primary efficacy endpoint is the intra- or postoperative transfusion of at least one unit of packed red blood cells. Key secondary endpoints are the number of transfused units per patient, estimated intraoperative blood loss, postoperative complications/mortality, length of hospital stay, operation/anesthesia time, D-dimer levels, and quality of life. Sample size calculation is based on the assumption that in the control group, 30% of patients require transfusion while the intervention achieves a risk reduction of 33%, reducing the probability to 20%. With a type one error of 5% and a power of 90%, using a two-sided χ2 test, this results in 412 patients per group. Accounting for non-compliance, 425 patients are to be randomized per group. The total trial duration will be 30 months with a recruitment period of 18 months.DiscussionIf the proposed trial yielded positive results, the routine use of tranexamic acid in major abdominal surgery would be supported. This would avoid acute anemia with detrimental effects such as tissue hypoxia and organ injury, as well as the negative immediate and delayed effects of transfusions.Trial registrationEU CT Nr: 2023–509970-43–01, NCT06414031. Registered on 10 May 2024.

A randomized controlled trial of a “Small Changes” behavioral weight loss treatment delivered in cardiac rehabilitation for patients with atrial fibrillation and obesity: study protocol for the BE-WEL in CR-AF study

BackgroundAtrial fibrillation (AF) represents a global epidemic. Although international AF practice guidelines indicate weight loss for patients with AF and comorbid obesity (BMI ≥ 30 kg/m2) to alleviate symptom burden and improve prognosis, few cardiac rehabilitation (CR) programs include targeted weight loss treatment.AimsThis RCT protocol will evaluate the efficacy of a “Small Changes” behavioral weight loss treatment (BWLT) to produce clinically relevant (≥ 10%) weight loss among patients with AF and obesity undergoing CR, relative to CR alone. Secondary aims are to establish efficacy of CR + BWLT for improving AF symptoms, AF risk factors, and health-related quality of life.MethodsAdults (18 +) with AF and obesity will be recruited and randomized to receive CR + BWLT (intervention) or CR-only (control). Controls will receive CR consisting of supervised exercise and risk factor self-management for 12 weeks. The intervention group will receive CR plus BWLT (12 weekly, group-based virtual sessions, followed by 12 weeks of follow-up support). Weight and AF-risk factors will be assessed at pre-randomization, 12 weeks, 24 weeks, and 52 weeks. AF burden will be assessed using 30-s ECGs recorded bidaily and with AF symptoms. The primary endpoint of weight loss will be calculated from baseline to 52 weeks as a percentage of starting weight. Intention-to-treat analyses will compare the proportion in each group achieving ≥ 10% weight loss. Assuming success rates of 5% and 30% among controls and intervention groups, respectively, and a 30% loss to follow-up, 120 patients (60 per group) will provide 80% power to detect a difference using a two-sided independent test of proportions (alpha = 5%).ImpactThis clinical trial will be the first to demonstrate that adding BWLT to CR promotes clinically meaningful weight loss among patients with AF and comorbid obesity. Findings will inform design and execution of a large efficacy trial of long-term (e.g., 5-year) clinical endpoints (e.g., AF severity, mortality). Implementing weight control interventions designed to target the AF substrate in CR could dramatically reduce morbidity and enhance quality of life among patients living with AF in Canada.Trial registrationClinicalTrials.gov registration number: NCT05600829. Registered October 31, 2022.

Statistical Model of Ocular Wavefronts With Accommodation.

The purpose of this study was to determine the minimum number of orthonormal basis functions, applying Principal Component Analysis (PCA), to represent the most wavefront aberrations at different accommodation stages. The study also aims to generate synthetic wavefront data using these functions. Monocular wavefront data from 191 subjects (26.15 ± 5.56years old) were measured with a Hartmann-Shack aberrometer, simulating accommodation from 0 diopters (D) to 5 D in 1 D steps. The wavefronts for each accommodative demand were rescaled for different pupil sizes: 4.66, 4.76, 4.40, 4.09, 4.07, and 3.68mm. PCA was applied to 150 wavefront parameters (25 Zernike coefficients × 6 accommodation levels) to obtain eigenvectors for dimensional reduction. A total of 49 eigenvectors were modeled as a sum of 2 multivariate Gaussians, from which 1000 synthetic data sets were generated. The first 49 eigenvectors preserved 99.97% of the original data variability. No significant differences were observed between the mean values and standard deviation of the generated and original 49 eigenvectors (two one-sided test [TOST], P > 0.05/49) and (F-test, P > 0.05/49), both with Bonferroni correction. The mean values of the generated parameters (1000) were statistically equal to those of the original data (TOST, P > 0.05/150). The variability of the generated data was similar to the original data for the most important Zernike coefficients (F-test, P > 0.05/150). PCA significantly reduces the dimensionality of wavefront aberration data across 6 accommodative demands, reducing the variable space by over 66%. The synthetic data generated by the proposed wavefront model for accommodation closely resemble the original clinical data.

Using QI to develop a sustainable method for titrating taxane infusions to reduce hypersensitivity reactions.

To develop a sustainable three-step method for titrating first and second taxane exposures through integration of best practices in patient and environmental safety; and to evaluate the impact on immediate hypersensitivity rates. A quality improvement study was initiated at a large, NCI-designated comprehensive cancer center in the U.S. to determine a sustainable method of slow, upward titration for reducing taxane-related hypersensitivity reactions. Multidisciplinary collaboration led to the incorporation of best practices for safe preparation and administration of high risk, hazardous drugs. Retrospective data from the electronic health records of 690 patients who received 1221 taxane doses were analyzed. Non-titrated infusions were compared with infusions titrated using a method initially tested for efficacy; and infusions titrated using a method revised for greater compliance with safety standards. Two-sided Fisher's exact tests at a 0.1 level of significance were used to detect differences in the rate of HSR between the three groups. A method of taxane titration that incorporated standardized, preprogrammed infusion rates and tubing primed with inert IV fluid showed a significant reduction in HSR incidence in comparison to non-titrated infusions (6% v. 19%, P = 0.001) and a similar decrease in the rate of HSR (6%) to the initial method previously studied (7%) (P = 0.659) which was not sustainable due to patient and environmental safety concerns. A three-step titration method using standardized, preprogrammed infusion rates and tubing primed with inert IV fluid reduced taxane-related HSRs and was adopted as sustainable practice in ambulatory cancer care.

12422 Linsitinib Inhibits Proliferation And Induces Apoptosis Of IGF-1R And TSH-R Expressing Cells

Abstract Disclosure: M. Luffy: None. A. Ganz: None. J. Ropertz: None. R. Douglas: Employee; Self; Sling Therapeutics. R. Zeidan: Employee; Self; Sling Therapeutics. J. Kent: Employee; Self; Sling Therapeutics. J. Wolf: None. G.J. Kahaly: Grant Recipient; Self; Sling Therapeutics. Background: The insulin-like growth factor 1 receptor (IGF-1R) and the thyrotropin receptor (TSH-R) are expressed on orbital target cells and thyrocytes. Targeting these pathways effectively improves thyroid eye disease (TED). Methods: The inhibitory effect of Linsitinib, a small molecule targeting the IGF-1R (Sling Therapeutics, Ann Arbor, MI, USA), on cell proliferation was investigated in an IGF-1R expressing cell line, NCI-H295R (ATCC, Manassas, VA, USA) and a Chinese Hamster Ovary (CHO) cell line overexpressing the TSH-R (QuidelOrtho, San Diego, CA, USA). An IGF-1R antagonist, Teprotumumab (BioVision, Milpitas, CA, USA) served as control. Both cell lines were plated in a 96-well format and treated with four concentrations of both compounds for 24 hours. After addition of tetrazolium, absorbance was measured (GloMax luminometer, Promega, Madison, WI, USA). Furthermore, the half-maximal inhibitory concentration (IC50) of TSH-R-Ab induced stimulation (stimulatory monoclonal antibody, mAb, M22, RSR, Cardiff, UK) of the TSH-R cell line was evaluated with a cell-based bioassay for blocking TSH-R-Ab (Thyretain TBI, QuidelOrtho). Cells were treated with ten rising concentrations of either Linsitinib, Linsitinib + Metformin, Teprotumumab, or a blocking TSH-R mAb (K1-70, RSR). The Kruskal-Wallis and/or the two-tailed Mann-Whitney tests were used for statistical comparisons. Results: Linsitinib strongly inhibited the proliferation of both cell lines at the following concentrations: 31,612.5 ng/mL (-78%, P=0.0031, IGF-1R cell line and -75%, P=0.0059, TSH-R cell line), as well as at 63,225 ng/mL (-73%, P=0.0073, IGF-1R cell line and -73%, P=0.0108, TSH-R cell line). Linsitinib induced morphologically confirmed apoptosis of both cell lines across all tested concentrations (Luna-FL cell counter, Logos Biosystems, Annandale, VA, USA). Compared to Teprotumumab, Linsitinib inhibited markedly more the proliferation of the IGF-1R cell line at all concentrations (Linsitinib versus Teprotumumab, P=0.0286). Teprotumumab inhibition ranged from -21 to -31% of the IGF-1R cell line across all concentrations, while it was significant only at 15,806.25 ng/mL with the TSH-R cell line (-15%, P=0.0396). In addition, in the TSH-R-Ab blocking bioassay, all tested compounds demonstrated strong inhibition across all ten dilutions (100%). The IC50 of Linsitinib was lower than Teprotumumab (147.1 ng/mL versus 160.6 ng/mL). Combining Metformin to Linsitinib did not further lower the IC50. Not surprisingly, the TSH-R blocking mAb K1-70 had the lowest IC50 of 20.57 ng/mL. Conclusions: Linsitinib effectively induces apoptosis and inhibits proliferation of both IGF-1R and TSH-R expressing target cells, also displaying a lower IC50 in the blocking TSH-R-Ab bioassay compared to Teprotumumab, hence demonstrating its therapeutic potential for TED. Presentation: 6/2/2024

12481 Evaluating The Device Handling And Preference Assessment Questionnaire For Growth Hormone Deficiency: Results From Content Validation Interviews

Abstract Disclosure: J. Neergaard: Employee; Self; Novo Nordisk. S. Akhtar: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. B. Berg: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. S. Hamilton: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. E. Hildebrand: Consulting Fee; Self; Novo Nordisk. J. Medina: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. G. Ter-Borch: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. N. Rasmussen: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. Background: Patient experiences with injection devices may affect treatment adherence, and hence it is important to ensure patient-reported outcomes (PRO) instruments used to assess experience are supported by evidence of validity. As part of a study that compared patient preference and ease of use between the devices used to administer Somapacitan (Sogroya®, Novo Nordisk A/S) and Somatrogon (Ngenla®, Pfizer), we assessed relevance, comprehensiveness and comprehension of a PRO instrument, the Device Handling and Preference Assessment Questionnaire (DHPAQ), in adolescent patients with growth hormone deficiency (GHD) and their caregivers. Methods: We recruited 33 adolescent patients with GHD and 37 caregivers across five sites in the US for an open label, randomized, crossover study in which participants simulated an injection with each device using an injection pad or mannequin. The DHPAQ was used to assess patients’ device preference. Two-sided statistical tests with 5% significance levels were performed using DHPAQ responses. After completing the DHPAQ, a random subgroup of 10 adolescents and 10 caregivers were offered additional compensation to participate in a cognitive interview (CI). The CIs were conducted in accordance with the US Food and Drug Administration 2022 Principles for PRO Instruments and 2009 PRO Guidance for Industry. Trained interviewers used a structured guide to evaluate questions, statements, tasks and response options in the DHPAQ. Participants’ interview responses for each question were coded and added to summary tables. These summary tables were evaluated by the study team to determine the relevance, comprehensiveness and participant comprehension of instructions, item stems and response options. Results: When asked if any questions in the DHPAQ did not seem relevant to their device experience, all 20 CI participants answered “no”. Questions on “learning how to use the device”, “selecting the correct dose” and “injecting the dose” were ranked as most relevant. Participants responses from the CIs supported perceived comprehensiveness of all DHPAQ items. All CI participants reported comprehension of all test items in the DHPAQ, and only three items did not receive a “no difficulty” response from all 20 participants. In the main study, the number of participants who preferred the somapacitan device was significantly greater than those who preferred the somatrogon device (84.3% vs 12.9%, p&amp;lt;0.0001). More participants found the somapacitan device easy or very easy to use compared with the somatrogon device (98.6% vs 74.3%). Conclusions: The results from the CIs indicated that the instructions, item stems and response options of the DHPAQ were relevant, comprehensive and fully comprehended by all participants. In the main study, patients with GHD and their caregivers were found to prefer the somapacitan device to the somatrogon device. Presentation: 6/2/2024

Long-term course of gastrostomy nutritional management in patients with Duchenne muscular dystrophy: A retrospective cohort study

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease that commonly requires gastrostomy due to dysphagia. This study aimed to investigate the proportion of patients with DMD requiring gastrostomy and to assess the timing and outcomes of gastrostomy in patients with DMD to optimize perioperative care and improve long-term management. We conducted a retrospective cohort study by reviewing the medical records of patients with DMD treated between March 1991 and November 2023 at Kobe University Hospital. To identify risk factors for gastrostomy, Fisher’s two-tailed test and logistic analysis were used to compare the gastrostomy (group G) and comparison group without gastrostomy (group C) groups. We identified patients >18 years with DMD. We excluded those without medical records from the last decade and those on nasogastric tube feeding. Among the 135 eligible patients, five (median age, 23 years) underwent percutaneous endoscopic gastrostomy (PEG; uptake rate, 3.7 %), and their data were analyzed for perioperative outcomes. Complications included ventilatory disturbances, aspiration pneumonia, and hemorrhagic shock. Two patients experienced significant postoperative complications, underscoring the high-risk nature of PEG in this population. Participants’ postoperative weight changes varied significantly. The presence or absence of ventilatory management, cardiomyopathy treatment, scoliosis, and steroid treatment were examined as risk factors between groups G and C, but no significant differences were observed. This study highlights low gastrostomy usage among patients with DMD, with varying outcomes. Meticulous planning and early consideration of gastrostomy are crucial to enhance the quality of life and nutritional outcomes in these patients.

Nurses' perceptions of medical service robots in negative-pressure isolated wards and in general wards: A cross-sectional survey.

To evaluate nurses' workload during the coronavirus disease 2019 (COVID-19) pandemic and to identify their perception of medical serviced robots (MSRs) that may help with or replace the tasks of nurses in negative-pressure isolated wards and general wards. Cross-sectional survey. A researcher-made questionnaire was applied that assessed nurses' current workload and their attitudes towards and perceptions of MSRs. A visual analogue scale (VAS) from 1 to 10 was used to assess workload. Perceptions evaluated on a 5-point Likert scale ranging from one point for 'strongly disagree' to five points for 'strongly agree'. A higher VAS score indicated a higher workload. On the other hands, a higher Likert score indicated a more positive perception and three points was neutral. The questionnaire was conducted on 150 nurses in negative-pressure isolated wards for the management of COVID-19 and 150 nurses in general wards. Quota sampling technique was used as sampling technique. Data analysis was performed through independent t-tests, chi-square tests and two-tailed tests. The p-value <0.05 was interpreted to statistically significant. Two hundred eighty-two participants responded and 142 belonged to the negative-pressure isolated ward. The overall response rate was 94%, and 94.7% in the negative isolated ward. The mean score ± standard deviation for nursing-related psychological stress at the current work site was 7.18 ± 1.58 points, and the mean score for physical workload was 7.65 ± 1.48. The need for MSRs was rated as 3.66 ± 0.86 out of 5. Overall, a positive attitude towards MSRs was confirmed, with no difference between ward groups. The overall ratings were 3.14 ± 1.15 for perceived availability and 3.26 ± 1.13 for perceived efficiency. Both nurse groups perceived that MSRs were most available and efficient for monitoring and measurements. Nurses in negative-pressure isolated wards perceived MSRs more positively than did nurses in general wards regarding setting of alarms (p = 0.003) and delivery of medical devices/materials (p = 0.013). Based on these results, functional development of MSRs associated with monitoring, measurements, setting of alarms and delivery should be prioritized. No patient or public contribution.

Reducing Patient Care Delays in Radiation Oncology Via Optimization of Insurance Preauthorization

Purpose/ObjectivesDifficulties and delays in insurance pre-authorization (pre-auth) can negatively impact patient care, resulting in postponing, modifying, or even cancelling radiation therapy for patients. We aimed to perform a root cause analysis for pre-auth delays in our department and implement solutions to optimize our workflow. Our primary objectives were to decrease mean time for clinical treatment plan (CTP) completion, and for number of cases delayed/denied, by 50% each. Materials/MethodsWe performed a root cause analysis for pre-auth delays, and used the PDSA & A3 quality improvement methods. We sampled ∼2 cases per disease site (19 cases from July – Aug 2022) to determine the baseline. Countermeasures included: 1) optimizing our CTP templates per disease site to contain the specific clinical information required for pre-auth, 2) formalizing earlier completion of CTPs in our Care Path®, and 3) formalizing the pre auth workflow in our Care Path®. We tracked various metrics, including mean time for CTP completion, % usage of our Care Path®, % usage of revised CTP templates, mean time until pre-auth initiated & completed, and % of cases delayed/denied. Two-tailed T-tests and Chi-squared tests were used to generate p-values comparing mean values and percentages, respectively. Results495 patients completed CT simulation in our department between October 2022 and February 2023. Mean time for CTP completion (Day 0 = day of CT simulation scheduling) improved from 16 days at baseline to 4 days (p<0.001). Care Path® usage improved from 16% to 97% (p<0.001), as did usage of our revised CTP templates, from 0% to 97% (p<0.001). The mean time from insurance pre-auth initiation to completion improved from 5 days to 1 day. The percent of cases that were delayed/denied was reduced significantly from 32% to 8% (p<0.001). ConclusionsImproving timeliness and details of CTP documentation and pre-auth by using our Care Path® and optimizing CTP templates improved efficiency of insurance pre-auth completion and reduced the number of cases delayed/denied.

Prospective selective embedding of radical prostatectomy specimens is not inferior to full embedding regarding established and new prognostic parameters.

The histopathological examination of radical prostatectomy specimens is essential for assessing critical tumor characteristics, including stage, grade, and margins, all of which impact patient prognosis. However, the extent of embedding the prostate has long been a subject of debate, with some advocating partial/selective embedding and others favoring complete embedding. This study establishes a standardized and time-efficient protocol for processing radical prostatectomy specimens with limited embedding while maintaining diagnostic accuracy. Two hundred twenty-six prostatectomy specimens were analyzed, and the results of a highly standardized selective embedding protocol, systematically embedding the apex, the base, the transition to the seminal vesicles, and selected horizontal sections, were compared with full embedding as the gold standard. Non-inferiority testing was conducted by one-sided binomial tests and Pearson-Clopper confidence intervals. Selective embedding provided consistent and accurate diagnostic information with up to 90-98% concordance in pT, margins, ISUP-grade groups, and presence of IDC-P and cribriform tumor growth. In summary, this study establishes an economical standardized protocol for selective embedding of radical prostatectomy specimens with only minimal loss of information.

Quantitative assessment of residual tumor is a strong and independent predictor of survival in methylated glioblastoma following radiochemotherapy with CCNU/TMZ.

Maximum tumor resection improves overall survival (OS) in patients with glioblastoma. The extent of resection (EOR) is historically dichotomized. The RANO resect group recently proposed criteria for volumetry-based EOR assessment in patients that were treated according to Stupp´s protocol. The purpose of this study was (1) to investigate the prognostic value of EOR in patients receiving combined chemotherapy with lomustine (CCNU)/temozolomide (TMZ), and (2) to analyse the prognostic performance of binary EOR assessment compared to volumetric assessment. 78 patients with newly diagnosed MGMT-methylated GBM undergoing tumor resection followed by radiochemotherapy with CCNU/TMZ were included in this study. Residual contrast-enhancing (CE) tumor volume after the first resection was measured and its influence on OS and PFS was analysed using uni- and multivariable Cox regression analysis as well as two-sided log rank test. Patients were divided into RTV ≤1 cm³, >1 cm³ - ≤5 cm³ and >5 cm³ following the proposed criteria of the RANO resect group. Prolonged OS was associated with age <60 years, low RTV, and gross total resection (GTR). Residual tumor volume (RTV) had a superior prognostic value compared to binary EOR assessment. Patients with total or near total resection of CE tumor (≤1 cm³ RTV) showed prolonged OS (median 54.4 months, 95% CI 46.94-not reached), with a 5-year survival rate of 49%. Low RTV is associated with increased survival in glioblastoma patients undergoing radiochemotherapy with CCNU/TMZ. This study demonstrates the applicability of the recently proposed RANO resect criteria in this subgroup of patients.

Comparing the nutritional value and prices of meat and milk substitutes with their animal-based benchmarks across six European countries

Since overconsumption of animal-sourced foods is directly linked to multiple environmental and health issues, a dietary shift is imperative. One approach to facilitate this change is the production of substitutes for animal-sourced foods based on plant-based or novel ingredients. However, to be a valid alternative, substitute products must match animal-sourced foods regarding their nutritional value while being price competitive. To understand where substitutes currently stand in that regard, this study presents a novel dataset containing the prices, main ingredients, and nutritional composition of almost 2600 substitute products as well as prices of approximately 7500 conventional products sold in major supermarket chains in France, Germany, Italy, the Netherlands, Spain, and the United Kingdom.Although comparative analyses (non-parametric two-sided Wilcoxon rank-sum tests at a 5 % significance level) of the results indicate that the meat substitutes generally contain a higher level of dietary fiber with lower saturated fats, these meat substitutes often also have lower protein quality and higher salt and sugar levels than the conventional products. On average, meat substitutes were found to be 24 to 115 % more expensive compared to conventional meat, except for the German samples where price parity has been reached. Among milk substitutes, only soy-based products have favorable macronutrient profiles. The average price premium charged for milk substitutes compared to cows’ milk is 35 to 58 %. In general, fortification rates of substitutes should be increased to ensure sufficient supplies of micronutrients, particularly among meat substitutes where fortification rates are below 20% except for the Netherlands. Following these results, certain individual products already provide high nutritional value at low costs. However, further improvements are required for substitutes to become a compelling alternative at each scale.

Testing mean and variance by e-processes

Abstract We address the problem of testing conditional mean and conditional variance for nonstationary data. We build e-values and p-values for four types of non-parametric composite hypotheses with specified mean and variance as well as other conditions on the shape of the data-generating distribution. These shape conditions include symmetry, unimodality, and their 15 combination. Using the obtained e-values and p-values, we construct tests via e-processes, also known as testing by betting, as well as some tests based on combining p-values for comparison. Although we mainly focus on one-sided tests, the two-sided test for the mean is also studied. Simulation and empirical studies are conducted under a few settings, and they illustrate features of the methods based on e-processes.

Detection of ethanol, cannabinoids, benzodiazepines, and opioids in older adults evaluated for serious injuries from falls

Background In 2020, there were 36.7 million reported falls among older adults (65+) in the United States. Ethanol and other sedating substances may increase fall risk among older adults due to their effect on cognitive and physical function. We estimate the prevalence of these substances in blood specimens of older adults presenting with a fall injury at selected trauma centers. Methods The initial study collected blood specimens from May 2020 through July 2021 from adults undergoing a trauma team evaluation at selected United States Level 1 trauma centers. We limited our study to older adults evaluated after a fall (n = 1,365) and selected a random sample (n = 300) based on age, sex, and trauma-center quotas. Medical health records and blood specimens obtained at trauma center presentation were analyzed. We estimated the prevalence of ethanol, benzodiazepines, cannabinoids, and opioids in the blood specimens. Two-sample tests of binomial proportions and Chi-square two-tailed tests were used to compare prevalence estimates of substances by demographic characteristics. Results At least one substance was detected among 31.3% of samples analyzed. Prevalences of specific substances detected were 9.3% (95% CI: 6.0–12.6%) for benzodiazepines, 4.3% (95% CI: 2.0–6.7%) for cannabinoids, 8.0% (95% CI: 5.2–11.7%) for ethanol, and 15.0% (95% CI: 10.9–19.1%) for opioids. There were 18 deaths (6%; 95% CI: 3.6–9.3%). One-third of decedents had at least one substance detected in their blood. Discussion Opioids were the most frequently detected substance, followed by benzodiazepines, ethanol, and cannabinoids. Substance use prevalence was not uniform across demographics, with differences observed by sex and age. Conclusions This study provides insight into the frequency of the presence of substances that may contribute to fall risk and serious injury among older adults. Screening older adults for substances that impair cognitive and physical function can enhance clinical fall prevention efforts.

Evaluation of automated pediatric sleep stage classification using U-Sleep: a convolutional neural network.

U-Sleep is a publicly available automated sleep stager, but has not been independently validated using pediatric data. We aimed to a) test the hypothesis that U-Sleep performance is equivalent to trained humans, using a concordance dataset of 50 pediatric polysomnogram excerpts scored by multiple trained scorers, and b) identify clinical and demographic characteristics that impact U-Sleep accuracy, using a clinical dataset of 3114 polysomnograms from a tertiary center. Agreement between U-Sleep and 'gold' 30-second epoch sleep staging was determined across both datasets. Utilizing the concordance dataset, the hypothesis of equivalence between human scorers and U-Sleep was tested using a Wilcoxon two one-sided test (TOST). Multivariable regression and generalized additive modelling were used on the clinical dataset to estimate the effects of age, comorbidities and polysomnographic findings on U-Sleep performance. The median (interquartile range) Cohen's kappa agreement of U-Sleep and individual trained humans relative to "gold" scoring for 5-stage sleep staging in the concordance dataset were similar, kappa=0.79 (0.19) vs 0.78 (0.13) respectively, and satisfied statistical equivalence (TOST p < 0.01). Median (interquartile range) kappa agreement between U-Sleep 2.0 and clinical sleep-staging was kappa=0.69 (0.22). Modelling indicated lower performance for children < 2 years, those with medical comorbidities possibly altering sleep electroencephalography (kappa reduction=0.07-0.15) and those with decreased sleep efficiency or sleep-disordered breathing (kappa reduction=0.1). While U-Sleep algorithms showed statistically equivalent performance to trained scorers, accuracy was lower in children < 2 years and those with sleep-disordered breathing or comorbidities affecting electroencephalography. U-Sleep is suitable for pediatric clinical utilization provided automated staging is followed by expert clinician review.

DCE-MRI of the liver with sub-second temporal resolution using GRASP-Pro with navi-stack-of-stars sampling.

Respiratory motion-induced image blurring and artifacts can compromise image quality in dynamic contrast-enhanced MRI (DCE-MRI) of the liver. Despite remarkable advances in respiratory motion detection and compensation in past years, these techniques have not yet seen widespread clinical adoption. The accuracy of image-based motion detection can be especially compromised in the presence of contrast enhancement and/or in situations involving deep and/or irregular breathing patterns. This work proposes a framework that combines GRASP-Pro (Golden-angle RAdial Sparse Parallel MRI with imProved performance) MRI with a new radial sampling scheme called navi-stack-of-stars for free-breathing DCE-MRI of the liver without the need for explicit respiratory motion compensation. A prototype 3D golden-angle radial sequence with a navi-stack-of-stars sampling scheme that intermittently acquires a 2D navigator was implemented. Free-breathing DCE-MRI of the liver was conducted in 24 subjects at 3T including 17 volunteers and 7 patients. GRASP-Pro reconstruction was performed with a temporal resolution of 0.34-0.45 s per volume, whereas standard GRASP reconstruction was performed with a temporal resolution of 15 s per volume. Motion compensation was not performed in all image reconstruction tasks. Liver images in different contrast phases from both GRASP and GRASP-Pro reconstructions were visually scored by two experienced abdominal radiologists for comparison. The nonparametric paired two-tailed Wilcoxon signed-rank test was used to compare image quality scores, and the Cohen's kappa coefficient was calculated to evaluate the inter-reader agreement. GRASP-Pro MRI with sub-second temporal resolution consistently received significantly higher image quality scores (P < 0.05) than standard GRASP MRI throughout all contrast enhancement phases and across all assessment categories. There was a substantial inter-reader agreement for all assessment categories (ranging from 0.67 to 0.89). The proposed technique using GRASP-Pro reconstruction with navi-stack-of-stars sampling holds great promise for free-breathing DCE-MRI of the liver without respiratory motion compensation.