Prolonged administration of oral phenylbutazone and firocoxib in horses has no impact on selected cytokine and growth factor concentrations in platelet-rich plasma and autologous protein solution.

OBJECTIVE: To determine the effects of prolonged administration of the oral NSAIDs phenylbutazone and firocoxib on concentrations of cytokines and growth factors in platelet-rich plasma (PRP) and autologous protein solution (APS). ANIMALS: 6 adult University owned horses. METHODS: Horses were randomized to receive phenylbutazone (1 g, orally, q 12 h) or firocoxib (57 mg, orally, q 24 h) for 6 days. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before the administration of NSAIDs and at 7 days (1 day following cessation of NSAIDs). Horses underwent a two-week washout period, during which blood was obtained at 14 days and 21 days. The protocol was repeated with a crossover design. PRP and APS were analyzed for concentrations of platelets, leukocytes, and several cytokines (IL-1ß, IL-10, IL-6, IL-8, and tumor necrosis factor-α) and growth factors (PDGF, FGF-2, and TGF-ß1) using immunoassays. Plasma was evaluated for drug concentrations. RESULTS: No significant differences existed in concentrations of growth factors and cytokines before or after prolonged administration of NSAIDs. There were significant differences in concentrations of leukocytes and platelets in PRP compared to APS, with higher concentrations of leukocytes at the day 7 time point (T) in APS (phenylbutazone) and in concentrations of platelets in APS at T0 (firocoxib) and in APS at T7 (phenylbutazone). CLINICAL RELEVANCE: Veterinarians can recommend the administration of these oral NSAIDs prior to obtaining blood for PRP and APS provided a single-day washout period is instituted.

Effect of video angle on detection of induced front limb lameness in horses.

BACKGROUND: Lameness examinations are commonly performed in equine medicine. Advancements in digital technology have increased the use of video recordings for lameness assessment, however, standardization of ideal video angle is not available yielding videos of poor diagnostic quality. The objective of this study was to evaluate the effect of video angle on the subjective assessment of front limb lameness. A randomized, blinded, crossover study was performed. Six horses with and without mechanically induced forelimb solar pain were recorded using 9 video angles including horses trotting directly away and towards the video camera, horses trotting away and towards a video camera placed to the left and right side of midline, and horses trotting in a circle with the video camera placed on the inside and outside of the circle. Videos were randomized and assessed by three expert equine veterinarians using a 0-5 point scoring system. Objective lameness parameters were collected using a body-mounted inertial sensor system (Lameness Locator®, Equinosis LLC). Interobserver agreement for subjective lameness scores and ease of grading scores were determined. RESULTS: Induction of lameness was successful in all horses. There was excellent agreement between objective lameness parameters and subjective lameness scores (AUC of the ROC = 0.87). For horses in the "lame" trials, interobserver agreement was moderate for video angle 2 when degree of lameness was considered and perfect for video angle 2 and 9 when lameness was considered as a binary outcome. All other angles had no to fair agreement. For horses in the "sound" trials, interobserver agreement was perfect for video angle 5. All other video angles had slight to moderate agreement. CONCLUSIONS: When video assessment of forelimb lameness is required, a video of the horse trotting directly towards the video camera at a minimum is recommended. Other video angles may provide supportive information regarding lameness characteristics.

Single-dose nonsteroidal anti-inflammatory drugs in horses have no impact on concentrations of cytokines or growth factors in autologous protein solution and platelet-rich plasma.

OBJECTIVE: To determine the effects of a single dose of the NSAIDs phenylbutazone, firocoxib, flunixin meglumine, and ketoprofen on concentrations of growth factors and cytokines in autologous protein solution (APS) and platelet-rich plasma (PRP). ANIMALS: 6 adult university-owned horses. METHODS: For the first phase, 6 horses were randomized to receive ketoprofen (1,000 mg) or flunixin meglumine (500 mg) IV. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before and 6 hours after administration of NSAIDs. Horses underwent a 2-week washout period, after which the protocol was repeated using a crossover design. For the second phase, following at least a 2-week washout period, the study protocol was repeated with phenylbutazone (1 g) or firocoxib (57 mg) administered orally. Plasma was collected 6 hours after administration for evaluation of drug concentrations, and APS and PRP were analyzed for concentrations of drug, platelets, leukocytes, and several growth factors and cytokines (PDGF, fibroblast growth factor, TGF-ß1, IL-1ß, IL-10, IL-6, IL-8, and tumor necrosis factor-α) before and 6 hours after administration of NSAIDs using immunoassays. RESULTS: There were no significant differences in concentrations of cytokines or growth factors before or after administration of any NSAID. There were significant differences in concentrations of leukocytes and platelets based on both product and time. NSAID concentrations in plasma were not significantly different from concentrations in APS and PRP. CLINICAL RELEVANCE: These results help guide clinicians on the appropriate use of these NSAIDs in conjunction with the processing of APS and PRP, which is unlikely to significantly alter the final product after single-dose administration.

Prospective, longitudinal assessment of subchondral bone morphology and pathology using standing, cone-beam computed tomography in fetlock joints of 2-year-old Thoroughbred racehorses in their first year of training.

BACKGROUND: Catastrophic injuries of the fetlock joints occur in Thoroughbred racehorses and are preceded by stress-induced bone injury. Early detection of subchondral bone injury is essential to prevent irreversible damage or bone failure. OBJECTIVES: To investigate the use of standing, robotic cone-beam computed tomography (CBCT) for assessing longitudinal changes in subchondral bone morphology and pathology of the fetlock joints associated with race training in young Thoroughbreds. STUDY DESIGN: Observational cohort study. METHODS: Forty-one 2-year-old Thoroughbred racehorses were recruited prior to the start of race training. Standing CBCT and radiographs of all 4 metacarpo-/metatarsophalangeal (MCP/MTP) joints were obtained at 0, 6 and 12 months. Hyperdensity, as an estimate of subchondral bone sclerosis, was measured in the distal third metacarpal (MC3)/metatarsal (MT3) bone and proximal phalanx (P1) at each time point on computed tomography. CBCTs were examined for subchondral bone pathology consisting of areas of hypodensity within regions of hyperdensity. RESULTS: Subchondral bone sclerosis increased significantly over time in the medial and lateral MC3/MT3 condyles and in the medial and lateral parasagittal grooves of MC3/MT3. The presence of subchondral bone pathology increased significantly over time in the medial and lateral palmar condyles of MC3/MT3, the lateral parasagittal groove, the medial dorsal condyle and the medial and lateral ridges of P1. MAIN LIMITATIONS: There was attrition of horses due to relocation, change in ownership, and retirement from racing. Husbandry, training regimens and racing schedules were not controlled for in the study. CONCLUSIONS: Standing CBCT is an efficient and effective screening tool for assessing subchondral bone morphology and identifying pathology of the fetlock joint in young Thoroughbred racehorses. CBCT may facilitate early detection of bone pathology allowing for timely intervention and prevention of more serious injuries.

Chiropractic effects on stride parameters and heart rate during exercise in sport horses.

BACKGROUND: Equine veterinarians performing chiropractic treatments are frequently asked to evaluate and treat sound horses to improve their performance and address pain associated with the axial skeleton. Studies describing the effects and mechanisms of chiropractic treatments in horses without overt lameness are scarce. OBJECTIVES: This study aimed to evaluate the effect of chiropractic treatments on stride rate, length, symmetry, heart rate and rider-perceived quality of the ridden work in sport horses. STUDY DESIGN: A blind randomised controlled trial with crossover design. METHODS: Thirty-eight horses ridden in the hunter-jumper discipline were enrolled. Exercise tests were recorded before and after chiropractic or sham treatment while horses were wearing a fitness tracker. Stride length, rate and symmetry, heart rate and the perceived quality of the ridden work were compared. RESULTS: There was a difference in the qualitative assessment of the ridden work by riders between treatments (odds ratio 33.8, 95% CI [4.68, 458.71], p < 0.01). Stride length, rate, symmetry and heart rate were not different between treatments. MAIN LIMITATIONS: The quantitative outcomes measured may not be sensitive enough to detect changes that improve the ridden work. Terrain, weather and rider were not standard across horses making small changes difficult to detect. CONCLUSIONS: Riders participating in a blind randomised controlled trial perceived a positive effect of chiropractic treatments on the quality of the ridden work. There were no differences in stride length, stride rate, stride symmetry or heart rate. The mechanisms, indications and potential benefits of chiropractic treatments in horses need further study.

HISTORIAL: A los veterinarios de equinos que realizan tratamientos quiroprácticos, se les pide frecuentemente evaluar y tratar caballos que están sanos para mejorar su desempeño y tratar el dolor asociado con el esqueleto axial. Estudios que describen los efectos y mecanismos de los tratamientos quiropráctico en caballos sin cojeras aparentes, son pocos. OBJETIVOS: Este estudio tiene por objetivo evaluar el efecto de los tratamientos quiroprácticos sobre frecuencia, largo y simetría de la zancada, la frecuencia cardiaca y la calidad del trabajo montado percibida por el jinete en caballos de deporte. DISEÑO DEL ESTUDIO: Prueba aleatoria cegada controlada con diseño cruzado. MÉTODOS: Se enrolaron 38 caballos montados en la disciplina de caza-salto. Pruebas de ejercicio fueron anotadas antes y después de tratamientos quiropráctico reales o simulados mientras los caballos llevaban un monitor físico. Se compararon el largo, frecuencia y simetría de la zancada, frecuencia cardiaca y calidad del trabajo montado percibida por el jinete. RESULTADOS: Se encontró una diferencia en la evaluación cualitativa del trabajo montado por los jinetes entre los tratamientos (odds ratio 33.8, 95% CI [4.68, 458.71], p < 0.01). Largo, frecuencia y simetría de zancada y frecuencia cardiacas no difirieron entre tratamientos. LIMITACIONES PRINCIPALES: Los resultados cuantitativos medidos, pueden no ser lo suficientemente sensibles para detectar cambios que mejoran el trabajo montado. El terreno, tiempo y jinete no fueron estandarizados a través de los caballos, lo que hizo que cambios pequeños fuesen difíciles de detectar. CONCLUSIONES: Los jinetes que participaron en una prueba aleatoria cegada controlada, percibieron un efecto positivo de los tratamientos quiroprácticos sobre la calidad del trabajo montado. No hubo diferencia en largo de zancada, frecuencia de zancada, simetría de zancada o frecuencia cardiaca. Los mecanismos, indicaciones y beneficios potenciales de los tratamientos quiroprácticos en caballos necesitan ser estudiados mas.

Clinical and histopathological features in horses with neuroaxonal degeneration: 100 cases (2017-2021).

BACKGROUND: Adult horses with proprioceptive ataxia and behavior changes that have histologic lesions consistent with neurodegenerative disease have been increasingly recognized. HYPOTHESIS/OBJECTIVES: Describe the history, clinical findings and histopathologic features of horses presented to a referral institution with neuroaxonal degeneration. ANIMALS: One hundred horses with a necropsy diagnosis of neuroaxonal degeneration compatible with neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM). METHODS: Retrospective study of horses presented to the University of Pennsylvania, New Bolton Center, between 2017 and 2021 with a necropsy diagnosis of eNAD/EDM. RESULTS: Affected horses had a median age of 8 years (range, 1-22), and the majority were Warmbloods (72). Sixty-eight horses had behavioral changes, and all 100 had proprioceptive ataxia (median grade, 2/5). Fifty-seven horses had abnormal findings on cervical vertebral radiographs, and 14 had myelographic findings consistent with compressive myelopathy. No antemortem diagnostic test results were consistently associated with necropsy diagnosis of neurodegenerative disease. All 100 horses had degenerative lesions characteristic of eNAD in the brainstem gray matter, and 24 had concurrent degenerative features of EDM in the spinal cord white matter. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical and histopathologic findings in this large group of horses with neurodegenerative disease were most consistent with eNAD/EDM, but with a different signalment and clinical presentation from earlier descriptions. The increasing occurrence of neurodegenerative disease in horses and the safety risk posed emphasize the importance of focused research in affected horses.

Establishing and sustaining an acute care for elders unit: An incremental journey to success.

Acute Care for Elders (ACE) units reduce hospital-associated delirium, functional decline, and lengths of stay. However, establishing and sustaining such units have proven difficult. There are only 43 ACE units among the >3500 hospitals in the United States. This study describes an iterative quality improvement process, which allowed us to establish and sustain an ACE unit care model in a modern academic hospital. This continuous process was centered on implementing the key principles of the ACE unit model of care: patient-centered care assessments, medical care review, specialized prepared environment, early mobilization, physical therapy, and early planning for discharge to home. Quality of care and patient outcomes data for older adults admitted to our ACE unit includes mortality index (observed/expected) consistently <1 (FY22 = 0.86), 30-day readmission rate of <10% (FY22 9.31%), and length of stay index of ~1 (FY22 1.07). We describe how work on our ACE unit has led to hospital-wide initiatives, including dementia-friendly hospital certification. Our hope is that others can use this process to enhance the dissemination of the ACE unit model of care.

Interobserver agreement of lateral and oblique radiography and standing cone beam CT of the caudal cervical articular process joints of horses.

Caudal cervical articular process joint osteoarthritis (CAPJ OA) leads to career-altering clinical signs in the horse. Oblique radiographs and standing cone beam computed tomography (CBCT) facilitate the assessment of this area, however, the variability of interpretation of these images is currently unknown. This retrospective, secondary analysis, methods comparison study investigated interobserver agreement between clinicians and modality in grades of CAPJ OA on lateral and oblique radiographs and CBCT. We hypothesized that agreement between clinicians' grades of CAPJ OA would be lowest for oblique radiographs and highest for CBCT, and agreement between grades of CAPJ OA would be low for all pairs of modalities. Horses underwent lateral and oblique radiography and CBCT of the CAPJs of C5-C6 and C6-C7. Radiographs and CBCT images were graded retrospectively by four blinded clinicians using 3-point scales. Cohen's kappa analysis was used to evaluate interobserver agreement between grades of CAPJ OA, and agreement between grades of CAPJ OA between different modalities was explored using kappa-weighted analysis. Agreement between clinicians' grades of CAPJ OA was moderate for lateral radiographs (0.49), and fair for oblique radiographs (0.23) and CBCT (0.36). For all modalities, agreement was slight to fair between clinicians for CAPJs with grade 1 (normal, 0.21-0.32) or 2 (mild, 0.13-0.36) CAPJ OA, and moderate to substantial for grade 3 (moderate to severe, 0.45-0.77) CAPJ OA. Agreement between grades of CAPJ OA was fair for all pairs of modalities. This study provides important information regarding the inconsistency of interpretation of mild CAPJ OA on radiographs and CBCT amongst clinicians.

Onchocerca sp. in an imported Zangersheide gelding causing suspensory ligament desmitis.

A 5-year-old imported Zangersheide gelding was evaluated for SC swellings over both forelimbs and lameness localized to the distal metacarpus. Ultrasound examination of the SC masses was compatible with verminous granulomas. Linear hyperechoic foci were present within the suspensory ligament branches of both forelimbs, suggestive of ligamentous parasitic infiltrates. A diagnosis of onchocerciasis was confirmed on biopsy of a SC mass. The gelding was treated with ivermectin and a tapering course of PO dexamethasone but was eventually euthanized. Necropsy confirmed the presence of SC eosinophilic granulomas and degenerative suspensory ligament desmitis, both with intralesional nematodes. Given the location and appearance of the nematode, a diagnosis of Onchocerca sp., most likely O. reticulata, was made. Onchocerciasis should be included as a differential diagnosis for multifocal suspensory ligament desmitis with these sonographic characteristics when paired with SC masses in imported European Warmbloods.

Emotional Well-Being of Pediatric Brain Tumor Survivors and Comparison Peers: Perspectives From Children and Their Parents.

OBJECTIVE: The aim of this study was to examine the emotional well-being of pediatric brain tumor survivors (PBTS) from the perspective of children's self-reports and parents' reports relative to matched comparison peers (COMP) and their parents. It was hypothesized that PBTS would self-report more depression symptoms, loneliness, and lower self-concept than COMP. We also hypothesized that mothers and fathers of PBTS would report more internalizing symptoms and lower total competence for their children. Age and sex effects were examined in exploratory analyses. METHODS: Families of 187 PBTS and 186 COMP participated across 5 sites. Eligible children in the PBTS group were 8-15 years of age and 1-5 years post-treatment for a primary intracranial tumor without progressive disease. COMP were classmates matched for sex, race, and age. RESULTS: PBTS self-reported lower scholastic, athletic, and social competence, but not more depression, loneliness, or lower global self-worth than COMP. Parents of PBTS reported more internalizing symptoms and lower total competence than parents of COMP. With few exceptions, group differences did not vary as a function of child age and sex. CONCLUSION: PBTS reported diminished self-concept in scholastic, athletic, and social domains, while their parents reported broader challenges with internalizing symptoms and total competence. Discrepancies between self-report and parent report require further study to inform targeted interventions for PBTS. Screening survivors for emotional challenges in follow-up clinic or in school setting may help with the allocation of psychosocial support and services for PBTS and their families.

Microstate analysis in infancy.

BACKGROUND: Microstate analysis is an emerging method for investigating global brain connections using electroencephalography (EEG). Microstates have been colloquially referred to as the "atom of thought," meaning that from these underlying networks comes coordinated neural processing and cognition. The present study examined microstates at 6-, 8-, and 10-months of age. It was hypothesized that infants would demonstrate distinct microstates comparable to those identified in adults that also parallel resting-state networks using fMRI. An additional exploratory aim was to examine the relationship between microstates and temperament, assessed via parent reports, to further demonstrate microstate analysis as a viable tool for examining the relationship between neural networks, cognitive processes as well as emotional expression embodied in temperament attributes. METHODS: The microstates analysis was performed with infant EEG data when the infant was either 6- (n = 12), 8- (n = 16), or 10-months (n = 6) old. The resting-state task involved watching a 1-minute video segment of Baby Einstein while listening to the accompanying music. Parents completed the IBQ-R to assess infant temperament. RESULTS: Four microstate topographies were extracted. Microstate 1 had an isolated posterior activation; Microstate 2 had a symmetric occipital to prefrontal orientation; Microstate 3 had a left occipital to right frontal orientation; and Microstate 4 had a right occipital to left frontal orientation. At 10-months old, Microstate 3, thought to reflect auditory/language processing, became activated more often, for longer periods of time, covering significantly more time across the task and was more likely to be transitioned into. This finding is interpreted as consistent with language acquisition and phonological processing that emerges around 10-months. Microstate topographies and parameters were also correlated with differing temperament broadband and narrowband scales on the IBQ-R. CONCLUSION: Three microstates emerged that appear comparable to underlying networks identified in adult and infant microstate literature and fMRI studies. Each of the temperament domains was related to specific microstates and their parameters. These networks also correspond with auditory and visual processing as well as the default mode network found in prior research and can lead to new investigations examining differences across stimulus presentations to further explain how infants begin to recognize, respond to, and engage with the world around them.

The Mental and Physical Health Impacts of Overturning Roe v Wade.

ABSTRACT: The overturning of Roe v Wade has resulted in the loss of reproductive rights for millions of women in the United States. It has also put these women at risk of severe mental and physical health consequences. When legal abortions are restricted, there is a rise in illegal abortion with the risk of hemorrhage, infection, infertility, and death. There are many more risks of carrying a pregnancy to term than health or psychological risks of a legal abortion. Women who have a miscarriage risk having to prove they did not abort. In cases of medical emergencies, doctors may be restricted from performing life-saving abortions for fear of penalties. Women or children who have been victims of rape or incest will have to either have an illegal abortion or carry an unwanted pregnancy to term. In states that allow an abortion in cases of severe risk to a mother's health, panels of internists and psychiatrist may, again, be charged with deciding whether her risks are valid. Women's physical and mental health will suffer.

Links between television exposure and toddler dysregulation: Does culture matter?

Television exposure in early childhood has increased, with concerns raised regarding adverse effects on social-emotional development, and emerging self-regulation in particular. The present study addressed television exposure (i.e., amount of time watching TV) and its associations with toddler behavioral/emotional dysregulation, examining potential differences across 14 cultures. The sample consisted of an average of 60 toddlers from each of the 14 countries from the Joint Effort Toddler Temperament Consortium (JETTC; Gartstein & Putnam, 2018). Analyses were conducted relying on the multi-level modeling framework (MLM), accounting for between- and within-culture variability, and examining the extent to which TV exposure contributions were universal vs. variable across sites. Effects of time watching TV were evaluated in relation to temperament reactivity and regulation, as well as measures of emotional reactivity, attention difficulties, and aggression. Results indicated that more time spent watching TV was associated with higher ratings on Negative Emotionality, emotional reactivity, aggression, and attention problems, as well as lower levels of soothability. However, links between TV exposure and both attention problems and soothability varied significantly between cultures. Taken together, results demonstrate that increased time spent watching television was generally associated with dysregulation, although effects were not consistently uniform, but rather varied as a function of culturally-dependent contextual factors.

Inflammatory cytokines in horses with cervical articular process joint osteoarthritis on standing cone beam computed tomography.

BACKGROUND: Standing cone beam computed tomography (CT) provides cross-sectional imaging of the caudal cervical articular process joints (CAPJs) in the sedated horse, though the clinical implications of osteoarthritis (OA) identified on CT in this location are unknown. Increases in concentrations of intra-synovial cytokines could lend support to the clinical significance of CAPJ OA identified on this imaging modality. OBJECTIVES: Investigate the presence and concentration of intra-synovial inflammatory cytokines in CAPJs with and without standing cone beam CT evidence of OA using an equine specific multiplex assay. STUDY DESIGN: Prospective clinical study. METHODS: Standing cone beam CT of C5-6 and C6-7 was performed on horses with CAPJ OA and control horses. Synovial fluid samples of the CAPJs of C5-6 and C6-7 were obtained bilaterally using ultrasound guidance and analysed for concentrations of IFN-γ, IL-1ß, IL-6, IL-10, IL-17 and TNFα with the Milliplex® multi-analyte profiling kit. CT Images were retrospectively graded using a novel grading scheme. Significant differences between concentrations of inflammatory cytokines between joints with different categories of osteoarthritis severity were explored using a Wilcoxon rank-sum test or Kruskal-Wallis test. RESULTS: Concentrations of intra-synovial cytokines were higher in joints with moderate to severe OA when compared to joints with no or mild OA, with differences in concentrations of IL-17 reaching statistical significance (P = .007). MAIN LIMITATIONS: Limitations include discrepancy in number, age, and breed between control and OA populations, use of a novel grading scheme, and lack of a histologic gold-standard to confirm the presence and severity of CAPJ OA. CONCLUSIONS: Differences in inflammatory cytokines between caudal CAPJs with and without evidence of moderate to severe osteoarthritis on standing cone beam CT exist. This finding lends support to the clinical relevance of a diagnosis of moderate to severe CAPJ OA in the caudal cervical vertebral column as identified with this imaging modality.

Long-term outcome and effect of diagnostic analgesia in horses undergoing interspinous ligament desmotomy for overriding dorsal spinous processes.

OBJECTIVE: To report the long-term outcome of horses treated with interspinous ligament desmotomy (ISLD) for pain associated with overriding dorsal spinous processes (ORDSP) and determine the influence of preoperative diagnostic analgesia on long-term outcome. STUDY DESIGN: Retrospective study. ANIMALS: Eighteen horses. METHODS: Data were collected from horses presenting for ISLD to the University of Pennsylvania New Bolton Center between January 2013 and May 2018. Follow-up of ≥3 months postsurgically was obtained from the owner, trainer, or referring veterinarian. Long-term improvement was compared between horses that improved with diagnostic analgesia presurgically and horses that did not undergo diagnostic analgesia presurgically by using a χ2 test. Univariate logistic regression was used to test associations between long-term improvement and independent variables. RESULTS: Clinical signs had improved in 13 of 18 horses at long-term follow-up (median, 14.5 months; range, 3-57). Clinical signs improved in nine of 10 horses responding to diagnostic analgesia but only in four of eight horses that did not undergo diagnostic analgesia (χ2 [1], N = 18) = 3.55; P = .06). Although the likelihood of long-term improvement increased with prior diagnostic analgesia (odds ratio = 6.3; 95% confidence interval = 0.73, 55.0; P = .09), it did not reach statistical significance. CONCLUSION: A higher proportion of horses experienced long-term improvement in clinical signs after ISLD when horses responding to preoperative diagnostic analgesia were compared with horses that were not tested. CLINICAL SIGNIFICANCE: This study provides some evidence to support the use of diagnostic analgesia in conjunction with clinical examination for identification of clinically relevant ORDSP.

Auditory EEG Biomarkers in Fragile X Syndrome: Clinical Relevance.

Sensory hypersensitivities are common and distressing features of Fragile X Syndrome (FXS). While there are many drug interventions that reduce behavioral deficits in Fmr1 mice and efforts to translate these preclinical breakthroughs into clinical trials for FXS, evidence-based clinical interventions are almost non-existent potentially due to lack of valid neural biomarkers. Local circuit function in sensory networks is dependent on the dynamic balance of activity in inhibitory/excitatory synapses. Studies are needed to examine the association of electrophysiological alterations in neural systems with sensory and other clinical features of FXS to establish their clinical relevance. Adolescents and adults with FXS (n = 38, Mean age = 25.5, std = 10.1; 13 females) and age matched typically developing controls (n = 40, Mean age = 27.7, std = 12.1; 17 females) completed auditory chirp and auditory habituation tasks while undergoing dense array electroencephalography (EEG). Amplitude, latency, and percent change (habituation) in N1 and P2 event-related potential (ERP) components were characterized for the habituation task; time-frequency calculations using Morlet wavelets characterized phase-locking and single trial power for the habituation and chirp tasks. FXS patients showed increased amplitude but some evidence for reduced habituation of the N1 ERP, and reduced phase-locking in the low and high gamma frequency range and increased low gamma power to the chirp stimulus. FXS showed increased theta power in both tasks. While the habituation finding was weaker than previously found, the remaining findings replicate our previous work in a new sample of patients with FXS. Females showed less deficit in the chirp task but not the habituation task. Abnormal increases in gamma power were related to more severe behavioral and psychiatric features as well as reductions in neurocognitive abilities. Replicating electrophysiological deficits in a new group of patients using different EEG equipment at a new data collection site with differing levels of environmental noise that were robust to data processing techniques utilizing multiple researchers, indicates a potential for scalability to multi-site clinical trials. Given the robust replicability, relevance to clinical measures, and preclinical evidence for sensitivity of these EEG measures to pharmacological intervention, the observed abnormalities may provide novel translational markers of target engagement and potentially outcome measures in large-scale studies evaluating new treatments targeting neural hyperexcitability in FXS.

Food Insecurity Is Associated With Poorer Glycemic Control in Patients Receiving Free Versus Fee-Based Care.

IN BRIEF This study examined differences in household food security (HFS), household adult food security (HAFS), and indicators of diabetes management between clients using free and fee-for-service clinics for diabetes care and management. The study's 166 participants (free clinic, n = 41; fee-for-service clinic, n =125) had a mean age of 53 ± 16 years and were primarily Caucasian (n = 147 [91.9%]). Both HFS (P <0.001) and HAFS (P <0.001) differed between the clinic groups, as did A1C (free clinic 8.7 ± 1.7%; fee-for-service 7.8 ± 1.6%; P = 0.005). A1C increased as HFS (r = 0.293, P <0.001) and HAFS (r = 0.288, P = 0.001) worsened.

Use of natural language processing in electronic medical records to identify pregnant women with suicidal behavior: towards a solution to the complex classification problem.

We developed algorithms to identify pregnant women with suicidal behavior using information extracted from clinical notes by natural language processing (NLP) in electronic medical records. Using both codified data and NLP applied to unstructured clinical notes, we first screened pregnant women in Partners HealthCare for suicidal behavior. Psychiatrists manually reviewed clinical charts to identify relevant features for suicidal behavior and to obtain gold-standard labels. Using the adaptive elastic net, we developed algorithms to classify suicidal behavior. We then validated algorithms in an independent validation dataset. From 275,843 women with codes related to pregnancy or delivery, 9331 women screened positive for suicidal behavior by either codified data (N = 196) or NLP (N = 9,145). Using expert-curated features, our algorithm achieved an area under the curve of 0.83. By setting a positive predictive value comparable to that of diagnostic codes related to suicidal behavior (0.71), we obtained a sensitivity of 0.34, specificity of 0.96, and negative predictive value of 0.83. The algorithm identified 1423 pregnant women with suicidal behavior among 9331 women screened positive. Mining unstructured clinical notes using NLP resulted in a 11-fold increase in the number of pregnant women identified with suicidal behavior, as compared to solely reliance on diagnostic codes.