Clinical Outcomes of a Newly Instituted Hospital at Home Program During the COVID19 Pandemic.

Context: The COVID19 pandemic stressed U.S. health systems beyond their capacity and created worsening clinical outcomes. Hospital a Home (HaH) programs were utilized infrequently prior to pandemic. The Acute Care at Home Waiver was introduced in 2020 to facilitate the creation of HaH programs with a goal of promoting treatment in the home setting. A potential alternative approach to creating rapid inpatient level health system capacity is providing hospital-level care at home to substitute for inpatient hospitalization. The overall impact on clinical outcomes of a HaH program in patients with COVID19 is not well understood. Objective: To compare clinical outcomes of a HaH program versus usual hospital care for patients admitted for COVID19. Study Design: Matched case-control retrospective chart review. Setting or Dataset: Academic medical center. Population studied: Patients admitted with COVID19 and subsequently enrolled into the HaH program from February 1, 2021 to January 31, 2022. Patients aged <18 were excluded from consideration for enrollment. A case-control sample was matched on age, gender, and severity of illness. A total of 200 patients (100 HaH and 100 control) were included for analysis. Outcome Measures: Primary outcome: 30-day readmissions, Secondary outcomes: Inpatient length of stay (iLOS) defined as length of stay in the physical hospital, total length of stay (tLOS) (sum of iLOS and HaH program days), time to readmission, and 30-day emergency department visits. Results: Analysis included 200 patents. The mean age was 50.4. The sample was 55% female. 48.5% were black, 43.5% were white, and 8% were other races. Compared with usual care patients, HaH patients had no difference in 30-day readmissions (11% vs. 14%, p=0.648), mean days to readmission (9.0 vs. 11.8, p=0.201), or return ED visits (17% vs. 20%, p=0.701). Inpatient LOS (5.7 vs. 9.4 days, p=0.005) was shorter in the HaH group. Total LOS (13.0 vs. 9.4 days, p<0. 001) was longer in the HaH group. Conclusions: The HaH program was associated with no difference in readmissions, time to readmission, or return ED visits compared to usual hospital care. HaH programs were associated with shorter inpatient length of stays, but longer total length of stays. In surge times, HaH programs could potentially reduce iLOS and increase bed capacity. Future studies should look to evaluate the economic impact of HaH programs and investigate the drivers of the increased tLOS.

Horse and Cattle-Related Trauma: A Retrospective Review of Injuries and Management in a Regional Queensland Hospital.

BACKGROUND: Horse and cattle-related trauma is a common presentation to regional hospitals in Australia. We review local incidence and patterns of injuries relating to horse and cattle trauma over a three-year period at the Toowoomba Base Hospital within the Darling Downs region in Queensland, an area rich in cattle farming and equestrian recreation. METHODS: We conducted a single-centre retrospective cohort study. The inclusion criteria were all patients presenting with injuries following cattle or horse-related incidents between January 2018 and April 2021. Primary outcomes were the mechanism of trauma, confirmed injuries, and the need for admission, operative intervention, or inter-hospital transfer. RESULTS: A total of 1002 individuals (55% female; mean age 34 years; median Injury Severity Score (ISS) 2) were identified during the study period. Presentations relating to horses (81%) were more frequent than cattle (19%). The most common mechanism of injury was "falling" for horse incidents (68%) and "trampling" for cattle incidents (40%). Horse incidents often resulted in soft tissue injury (55%), upper limb fracture (19%), or lower limb fracture (9%). Cattle incidents often resulted in soft tissue injury (57%), upper limb fracture (15%), and rib fracture (15%). Overall, 14% required admission, 13% required operative intervention, and 1% required inter-hospital transfer. CONCLUSIONS: This local series demonstrates a high volume of cattle and horse-related trauma in our region. Whilst most patients are managed locally without operative intervention, the high frequency of injuries observed necessitates further development of preventative measures and safety advocacy.

Implementation of a Telemedicine Student Clinical Experience.

Background: As part of a curricular change, an academic medical center implemented a medical student telemedicine clinical experience for first-year medical students in October 2020. This research is a process evaluation of the implementation of a preclerkship medical student telemedicine clinical experience. Methods: Patients with two or more chronic diseases were recruited from affiliated primary care practices. We monitored the recruitment and retainment of patients throughout the curriculum. We used surveys to evaluate patient, student, and primary care overall experience with the program. We tracked referrals to higher levels of care and assessed skills students' felt they practice with each encounter. We followed progression of notes through chart review as the year progressed. Results: Of the 408 patients contacted, 150 agreed to participate in this program (36%). Of 1,053 scheduled visits, 686 (65%) were successfully completed. Seventy-five percent of patients were seen two or more times. Nearly 70% of surveyed patients felt that the clinical experience enhanced their communication with their primary care provider, and nearly 90% stated that students were "somewhat" or "extremely" professional. The majority (97%) of students reported an "excellent" or "good" view of the medical student telemedicine clinical experience. Qualitative measures of student performance, such as note writing, showed improvement over the course of the curriculum. Conclusions: Our data suggest that patients, students, and primary care providers were widely accepting of the curriculum, patients were successfully recruited and retained, and students successfully practiced key clinical skills on a telemedicine platform.

Choledocholithiasis: A Review of Management and Outcomes in a Regional Setting.

Background Choledocholithiasis is a common surgical presentation with an incidence of 8% to 16% in symptomatic cholelithiasis. Treatment often requires a multi-stage approach via endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic cholecystectomy (LC), which can prolong the length of stay (LoS) and expose patients to unnecessary risks. A single-stage procedure, such as LC with common bile duct exploration (CBDE), is a safe and effective option that may decrease LoS. This study compares patient outcomes and management in a regional center and aims to identify factors that predict the presence of confirmed choledocholithiasis. Methods A retrospective cross-sectional analysis was performed on all patients admitted to Toowoomba Hospital for management of diagnosed or suspected choledocholithiasis from January 2021 to March 2023. Patient demographics, ERCP findings, and operative data were collated. Results A total of 195 patients were identified, including 136 patients undergoing multi-stage management, 34 patients who had an ERCP alone, and 25 patients who underwent single-stage management. Single-stage procedures had an 80% success rate with an average LoS of 3.6 days. Multi-stage procedures had an average LoS of 8.1 days and an ERCP success rate of 93%. Complication rates between ERCP (11.7%) and LC with CBDE (9.7%) were comparable. Time to index ERCP and serum bilirubin level were found to be significantly lower in those with positive index ERCP findings compared to those without. Conclusion Single-stage procedures are a safe way to manage choledocholithiasis and are associated with a reduced LoS when compared to multi-stage management, with comparable efficacy and morbidity rates.

Rapid initiation of nasal saline irrigation to reduce severity in high-risk COVID+ outpatients.

OBJECTIVE: To determine whether initiating saline nasal irrigation after COVID-19 diagnosis reduces hospitalization and death in high-risk outpatients compared with observational controls, and if irrigant composition impacts severity. METHODS: Participants 55 and older were enrolled within 24 hours of a + PCR COVID-19 test between September 24 and December 21, 2020. Among 826 screened, 79 participants were enrolled and randomly assigned to add 2.5 mL povidone-iodine 10% or 2.5 mL sodium bicarbonate to 240 mL of isotonic nasal irrigation twice daily for 14 days. The primary outcome was hospitalization or death from COVID-19 within 28 days of enrollment by daily self-report confirmed with phone calls and hospital records, compared to the CDC Surveillance Dataset covering the same time. Secondary outcomes compared symptom resolution by irrigant additive. RESULTS: Seventy-nine high-risk participants were enrolled (mean [SD] age, 64 [8] years; 36 [46%] women; 71% Non-Hispanic White), with mean BMI 30.3. Analyzed by intention-to-treat, by day 28, COVID-19 symptoms resulted in one ED visit and no hospitalizations in 42 irrigating with alkalinization, one hospitalization of 37 in the povidone-iodine group, (1.27%) and no deaths. Of nearly three million CDC cases, 9.47% were known to be hospitalized, with an additional 1.5% mortality in those without hospitalization data. Age, sex, and percentage with pre-existing conditions did not significantly differ by exact binomial test from the CDC dataset, while reported race and hospitalization rate did. The total risk of hospitalization or death (11%) was 8.57 times that of enrolled nasal irrigation participants (SE = 2.74; P = .006). Sixty-two participants completed daily surveys (78%), averaging 1.8 irrigations/day. Eleven reported irrigation-related complaints and four discontinued use. Symptom resolution was more likely for those reporting twice daily irrigation (X2 = 8.728, P = .0031) regardless of additive. CONCLUSION: SARS-CoV-2+ participants initiating nasal irrigation were over 8 times less likely to be hospitalized than the national rate.

Dairying, diseases and the evolution of lactase persistence in Europe.

In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years1. Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions2,3. Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectories than uniform selection since the Neolithic period. In the UK Biobank4,5 cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation-proxies for these drivers-provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.

Dual endothelin receptor antagonism increases resting energy expenditure in people with increased adiposity.

Increased adiposity is associated with dysregulation of the endothelin system, both of which increase the risk of cardiovascular disease (CVD). Preclinical data indicate that endothelin dysregulation also reduces resting energy expenditure (REE). The objective was to test the hypothesis that endothelin receptor antagonism will increase REE in people with obesity compared with healthy weight individuals. Using a double blind, placebo-controlled, crossover design, 32 participants [healthy weight (HW): n = 16, BMI: 21.3 ± 2.8 kg/m2, age: 26 ± 7 yr and overweight/obese (OB): n = 16, BMI: 33.5 ± 9.5 kg/m2, age: 31 ± 6 yr] were randomized to receive either 125 mg of bosentan (ETA/B antagonism) or placebo twice per day for 3 days. Breath-by-breath gas exchange data were collected and REE was assessed by indirect calorimetry. Venous blood samples were analyzed for concentrations of endothelin-1 (ET-1). Treatment with bosentan increased plasma ET-1 in both OB and HW groups. Within the OB group, the changes in absolute REE (PLA: -77.6 ± 127.6 vs. BOS: 72.2 ± 146.6 kcal/day; P = 0.046). The change in REE was not different following either treatment in the HW group. Overall, absolute plasma concentrations of ET-1 following treatment with bosentan were significantly associated with kcal/day of fat (r = 0.488, P = 0.005), percentage of fat utilization (r = 0.415, P = 0.020), and inversely associated with the percentage of carbohydrates (r = -0.419, P = 0.019), and respiratory exchange ratio (r = -0.407, P = 0.023). Taken together, these results suggest that modulation of the endothelin system may represent a novel therapeutic approach to increase both resting metabolism and caloric expenditure, and reduce CVD risk in people with increased adiposity.NEW & NOTEWORTHY Findings from our current translational investigation demonstrate that dual endothelin A/B receptor antagonism increases total REE in overweight/obese individuals. These results suggest that modulation of the endothelin system may represent a novel therapeutic target to increase both resting metabolism and caloric expenditure, enhance weight loss, and reduce CVD risk in seemingly healthy individuals with elevated adiposity.

A robust mean and variance test with application to high-dimensional phenotypes.

Most studies of continuous health-related outcomes examine differences in mean levels (location) of the outcome by exposure. However, identifying effects on the variability (scale) of an outcome, and combining tests of mean and variability (location-and-scale), could provide additional insights into biological mechanisms. A joint test could improve power for studies of high-dimensional phenotypes, such as epigenome-wide association studies of DNA methylation at CpG sites. One possible cause of heterogeneity of variance is a variable interacting with exposure in its effect on outcome, so a joint test of mean and variability could help in the identification of effect modifiers. Here, we review a scale test, based on the Brown-Forsythe test, for analysing variability of a continuous outcome with respect to both categorical and continuous exposures, and develop a novel joint location-and-scale score (JLSsc) test. These tests were compared to alternatives in simulations and used to test associations of mean and variability of DNA methylation with gender and gestational age using data from the Accessible Resource for Integrated Epigenomics Studies (ARIES). In simulations, the Brown-Forsythe and JLSsc tests retained correct type I error rates when the outcome was not normally distributed in contrast to the other approaches tested which all had inflated type I error rates. These tests also identified > 7500 CpG sites for which either mean or variability in cord blood methylation differed according to gender or gestational age. The Brown-Forsythe test and JLSsc are robust tests that can be used to detect associations not solely driven by a mean effect.

Electronic Health Record-Embedded Individualized Pain Plans for Emergency Department Treatment of Vaso-occlusive Episodes in Adults With Sickle Cell Disease: Protocol for a Preimplementation and Postimplementation Study.

BACKGROUND: Individuals living with sickle cell disease often require aggressive treatment of pain associated with vaso-occlusive episodes in the emergency department. Frequently, pain relief is poor. The 2014 National Heart, Lung, and Blood Institute evidence-based guidelines recommended an individualized treatment and monitoring protocol to improve pain management of vaso-occlusive episodes. OBJECTIVE: This study will implement an electronic health record-embedded individualized pain plan with provider and patient access in the emergency departments of 8 US academic centers to improve pain treatment for adult patients with sickle cell disease. This study will assess the overall effects of electronic health record-embedded individualized pain plans on improving patient and provider outcomes associated with pain treatment in the emergency department setting and explore barriers and facilitators to the implementation process. METHODS: A preimplementation and postimplementation study is being conducted by all 8 sites that are members of the National Heart, Lung, and Blood Institute-funded Sickle Cell Disease Implementation Consortium. Adults with sickle cell disease aged 18 to 45 years who had a visit to a participating emergency department for vaso-occlusive episodes within 90 days prior to enrollment will be eligible for inclusion. Patients will be enrolled in the clinic or remotely. The target analytical sample size of this study is 160 patient participants (20 per site) who have had an emergency department visit for vaso-occlusive episode treatment at participating emergency departments during the study period. Each site is expected to enroll approximately 40 participants to reach the analytical sample size. The electronic health record-embedded individualized pain plans will be written by the patient's sickle cell disease provider, and sites will work with the local informatics team to identify the best method to build the electronic health record-embedded individualized pain plan with patient and provider access. Each site will adopt required patient and provider implementation strategies and can choose to adopt optional strategies to improve the uptake and sustainability of the intervention. The study is informed by the Technology Acceptance Model 2 and the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. Provider and patient baseline survey, follow-up survey within 96 hours of an emergency department vaso-occlusive episode visit, and selected qualitative interviews within 2 weeks of an emergency department visit will be performed to assess the primary outcome, patient-perceived quality of emergency department pain treatment, and additional implementation and intervention outcomes. Electronic health record data will be used to analyze individualized pain plan adherence and additional secondary outcomes, such as hospital admission and readmission rates. RESULTS: The study is currently enrolling study participants. The active implementation period is 18 months. CONCLUSIONS: This study proposes a structured, framework-informed approach to implement electronic health record-embedded individualized pain plans with both patient and provider access in routine emergency department practice. The results of the study will inform the implementation of electronic health record-embedded individualized pain plans at a larger scale outside of Sickle Cell Disease Implementation Consortium centers. TRIAL REGISTRATION: ClinicalTrials.gov NCT04584528; https://clinicaltrials.gov/ct2/show/NCT04584528. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24818.

The variant call format provides efficient and robust storage of GWAS summary statistics.

GWAS summary statistics are fundamental for a variety of research applications yet no common storage format has been widely adopted. Existing tabular formats ambiguously or incompletely store information about genetic variants and associations, lack essential metadata and are typically not indexed yielding poor query performance and increasing the possibility of errors in data interpretation and post-GWAS analyses. To address these issues, we adapted the variant call format to store GWAS summary statistics (GWAS-VCF) and developed open-source tools to use this format in downstream analyses. We provide open access to over 10,000 complete GWAS summary datasets converted to this format ( https://gwas.mrcieu.ac.uk ).

Acute severe cholecystitis with empyema presenting as a gallbladder mass, jaundice and Mirizzi Syndrome: A case report.

INTRODUCTION: Acute severe cholecystitis with empyema presenting as a gallbladder mass, jaundice and Mirizzi Syndrome (MS) is a complex surgical problem both diagnostically and in terms of management as it mimics both xanthogranulomatous cholecystitis (XGC) and gallbladder carcinoma. PRESENTATION OF CASE: A 48-year-old gentleman was referred to us with biliary colic and weight loss with ultrasound findings of gallstones. At subsequent follow-up he became deeply jaundiced with deranged liver function and a CT showing a gallbladder mass and dilated biliary tree. Follow-up MRCP suggested XGC and concomitant MS, but a malignant process could not be excluded. Pre-operative fine needle aspiration cytology (FNAC) at the time of percutaneous biliary drainage for his jaundice demonstrated XGC with no evidence of malignancy. Given the dense inflammation and a tense empyema at laparoscopy, he underwent a subtotal fenestrating cholecystectomy. The final histopathological diagnosis was acute cholecystitis. DISCUSSION: Our patient likely had unrecognised acute cholecystitis which progressed to a complex mass with empyema and type I Mirizzi Syndrome, ultimately resulting in severe obstructive jaundice mimicking gallbladder carcinoma. Given that a laparoscopic total cholecystectomy is dangerous in these cases of severe inflammation, a laparoscopic subtotal cholecystectomy has been shown to be a safe alternative to more invasive strategies and was successfully utilised in our patient. CONCLUSION: Acute severe cholecystitis with empyema presenting as a gallbladder mass, jaundice and Mirizzi Syndrome is a rare manifestation that requires adequate pre-operative work-up to exclude malignancy. Subtotal fenestrating cholecystectomy is a safe and effective alternative to open surgery in these cases of complex inflammation.

Outcomes of an Emergency Department Observation Unit-Based Pathway for the Treatment of Uncomplicated Vaso-occlusive Events in Sickle Cell Disease.

STUDY OBJECTIVE: This was a prospective, pre-post, 13-year observational study documenting the multiyear implementation of an observation unit sickle cell pathway for patients with uncomplicated vaso-occlusive events. METHODS: The sickle cell pathway begins with rapid triage to identify patients with uncomplicated vaso-occlusive events for immediate transfer to the observation unit and initiation of patient-controlled analgesia followed by repeated evaluations of pain and identification of other complications. Data were abstracted from the electronic medical record or observation unit database. The sickle cell pathway was initiated in April 2006. Major revisions of it were carried out in June 2009 (physician evaluation occurs in sickle cell pathway and only patient-controlled analgesia administration of medications) and October 2010 (multidisciplinary management and individual dosing). RESULTS: Annual ED visits ranged between 287 and 528. The preimplementation hospital admission rate was 33% (123/368), 3-day return rate 16% (60/368), and 30-day return rate 67% (248/368). Refinements to the sickle cell pathway have resulted in a decrease in admission rate to 20% (258/1276); 3-day return rate, to 3.6% (46/1,276); and 30-day return rate, to 41% (525/1,276) for the past 3 years. CONCLUSION: The use of a sickle cell pathway for the treatment of uncomplicated vaso-occlusive events has been effective in providing rapid treatment and reducing hospital admissions. However, it was not only the intervention and its refinement that made the sickle cell pathway successful. With the Consolidated Framework for Implementation Research, it was discerned that outer setting factors of organizational commitment to the care of patients with SCD, inner setting factors of learning climate and leadership engagement, individuals, and process contributed to the success of the sickle cell pathway.

Correction: Blood RNA analysis can increase clinical diagnostic rate and resolve variants of uncertain significance.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Blood RNA analysis can increase clinical diagnostic rate and resolve variants of uncertain significance.

PURPOSE: Diagnosis of genetic disorders is hampered by large numbers of variants of uncertain significance (VUSs) identified through next-generation sequencing. Many such variants may disrupt normal RNA splicing. We examined effects on splicing of a large cohort of clinically identified variants and compared performance of bioinformatic splicing prediction tools commonly used in diagnostic laboratories. METHODS: Two hundred fifty-seven variants (coding and noncoding) were referred for analysis across three laboratories. Blood RNA samples underwent targeted reverse transcription polymerase chain reaction (RT-PCR) analysis with Sanger sequencing of PCR products and agarose gel electrophoresis. Seventeen samples also underwent transcriptome-wide RNA sequencing with targeted splicing analysis based on Sashimi plot visualization. Bioinformatic splicing predictions were obtained using Alamut, HSF 3.1, and SpliceAI software. RESULTS: Eighty-five variants (33%) were associated with abnormal splicing. The most frequent abnormality was upstream exon skipping (39/85 variants), which was most often associated with splice donor region variants. SpliceAI had greatest accuracy in predicting splicing abnormalities (0.91) and outperformed other tools in sensitivity and specificity. CONCLUSION: Splicing analysis of blood RNA identifies diagnostically important splicing abnormalities and clarifies functional effects of a significant proportion of VUSs. Bioinformatic predictions are improving but still make significant errors. RNA analysis should therefore be routinely considered in genetic disease diagnostics.

Structural core of the executive control network: A high angular resolution diffusion MRI study.

Executive function (EF) is a set of cognitive capabilities considered essential for successful daily living, and is negatively affected by ageing and neurodegenerative conditions. Underpinning EF performance are functional nodes in the executive control network (ECN), while the structural connectivity underlying this network is not well understood. In this paper, we evaluated the structural white matter tracts that interconnect the ECN and investigated their relationship to the EF performance. Using high-angular resolution diffusion MRI data, we performed tractography analysis of structural connectivity in a cognitively normal cohort (n = 140), specifically targeting the connectivity between ECN nodes. Our data revealed the presence of a strongly-connected "structural core" of the ECN comprising three components: interhemispheric frontal connections, a fronto-parietal subnetwork and fronto-striatal connections between right dorsolateral prefrontal cortex and right caudate. These pathways were strongly correlated with EF performance (p = .003). Post-hoc analysis of subregions within the significant ECN connections showed that these effects were driven by a highly specific subset of interconnected cortical regions. The structural core subnetwork of the functional ECN may be an important feature crucial to a better future understanding of human cognition and behaviour.

Increased Intracranial Pressure Damages Optic Nerve Structural Support.

Optic nerve sheath diameter (ONSD) is used clinically as a noninvasive measure for elevated intracranial pressure (ICP). This study had two purposes: to investigate the immediate effects optic nerve sheath (ONS) dilation post-ICP increase on trabecular fibers connecting the optic nerve to the ONS and to document any changes in these fibers 30 days post-increased ICP. In a swine model, ICP was increased by inflating a Foley catheter balloon in the epidural space. Three control pigs received the catheter insertion without inflation (no increase in ICP) and four experimental pigs received the catheter with inflation (increased ICP). The control and two randomly selected pigs with increased ICP were euthanized immediately after the procedure. The two other pigs were euthanized 30 days post-catheter inflation. For all pigs, the ONS was removed and imaged using a scanning electron microscope, calculating percent porosity values. Porosity values for the experimental groups (Immediately measured [IM] µ = 0.5749; Delayed measured [DM] µ = 0.5714) were larger than the control group (µ = 0.4336) and statistically significant (IM vs. Control, p = 0.0018; DM vs. Control, p = 0.0092). There was no significant difference (p = 0.9485) in porosity of the DM group when compared with the IM group. This study demonstrated that the trabecular fibers immediately post-increased ICP (ONS dilation) were more porous than the control and remained statistically different (more porous) after 30 days. These results suggest a structural change that occurs in the ONS with elevations in ICP.

Profound and reproducible patterns of reduced regional gray matter characterize major depressive disorder.

Reduced gray matter (GM) volume may represent a hallmark of major depressive disorder (MDD) neuropathology, typified by wide-ranging distribution of structural alteration. In the study, we aimed to replicate and extend our previous finding of profound and widespread GM loss in MDD, and evaluate the diagnostic accuracy of a structural biomarker derived from GM volume in an interconnected pattern across the brain. In a sub-study of the International Study to Predict Optimized Treatment in Depression (iSPOT-D), two cohorts of clinically defined MDD participants "Test" (n = 98) and "Replication" (n = 131) were assessed alongside healthy controls (n = 66). Using 3T MRI T1-weighted volumes, GM volume differences were evaluated using voxel-based morphometry. Sensitivity, specificity, and area under the receiver operating characteristic curve were used to evaluate an MDD diagnostic biomarker based on a precise spatial pattern of GM loss constructed using principal component analysis. We demonstrated a highly conserved symmetric widespread pattern of reduced GM volume in MDD, replicating our previous findings. Three bilateral dominant clusters were observed: Cluster 1: midline/cingulate (GM reduction: Test: 6.4%, Replication: 5.3%), Cluster 2: medial temporal lobe (GM reduction: Test: 8.2%, Replication: 11.9%), Cluster 3: prefrontal cortex (GM reduction: Test: 12.1%, Replication: 23.2%). We developed a biomarker reflecting the global pattern of GM reduction, achieving good diagnostic classification performance (AUC: Test = 0.75, Replication = 0.84). This study establishes that a highly specific pattern of reduced GM volume is a feature of MDD, suggestive of a structural basis for this disease. We introduce and validate a novel diagnostic biomarker based on this pattern.

The Use of the Abdominal Aortic and Junctional Tourniquet Versus Combat Gauze in a Porcine Hemicorporectomy Model.

BACKGROUND: Junctional hemorrhage is a potentially preventable cause of death. The Abdominal Aortic and Junctional Tourniquet (AAJT) compresses major vascular structures and arrests blood flow in exsanguinating hemorrhage. In a human model, the AAJT was effective in stopping blood flow in the femoral arteries via compression of the distal aorta. This study compares the ability of AAJT and Combat Gauze (CG) to stop hemorrhagic bleeding from a hemicorporectomy in a swine model. METHOD: Six anesthetized swine were used. Carotid arterial catheters were placed for continuous mean arterial pressure (MAP) readings. A hemicorporectomy was accomplished with a blade lever device by cutting the animal through both femoral heads transecting the proximal iliac arteries and veins. Hemorrhage control was attempted with the AAJT and regular Kerlix gauze or CG packing and direct pressure followed by Kerlix gauze placed over the CG. The primary outcome measure was survival at 60 minutes. RESULTS: The 60-minute survival was 100% for the AAJT and 0% for the CG group. During the 60-minute monitoring period, only one CG animal achieved hemostasis. For the AAJT group, the mean time to hemostasis was 30 seconds. Initial MAP was higher in the AAJT group (mean, 87mmHg) than the CG group (mean, 70mmHg). The mean 60-minute MAP was 73mmHg for the AAJT group. Mean blood loss at 5 minutes and mean total blood loss were greater in the CG group than in the AAJT group. CONCLUSION: AAJT is superior to CG in controlling hemorrhage in a junctional wound in a swine model.