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1.
Transl Psychiatry ; 14(1): 234, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830866

ABSTRACT

Prior regional Cerebral Blood Flow (rCBF) studies in Major Depressive Disorder (MDD) have been limited by small, highly selective, non-representative samples that have yielded variable and poorly replicated findings. The aim of this study was to compare rCBF measures in a large, more representative community sample of adults with MDD and healthy control participants. This is a cross-sectional, retrospective multi-site cohort study in which clinical data from 338 patients 18-65 years of age with a primary diagnosis of MDD were retrieved from a central database for 8 privately owned, private-pay outpatient psychiatric centers across the United States. Two 99mTc-HMPAO SPECT brain scans, one at rest and one during performance of a continuous performance task, were acquired as a routine component of their initial clinical evaluation. In total, 103 healthy controls, 18-65 years old and recruited from the community were also assessed and scanned. Depressed patients had significantly higher rCBF in frontal, anterior cingulate, and association cortices, and in basal ganglia, thalamus, and cerebellum, after accounting for significantly higher overall CBF. Depression severity associated positively with rCBF in the basal ganglia, hippocampus, cerebellum, and posterior white matter. Elevated rCBF was especially prominent in women and older patients. Elevated rCBF likely represents pathogenic hypermetabolism in MDD, with its magnitude in direct proportion to depression severity. It is brain-wide, with disproportionate increases in cortical and subcortical attentional networks. Hypermetabolism may be a reasonable target for novel therapeutics in MDD.


Subject(s)
Brain , Cerebrovascular Circulation , Depressive Disorder, Major , Technetium Tc 99m Exametazime , Tomography, Emission-Computed, Single-Photon , Humans , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/physiopathology , Adult , Female , Male , Middle Aged , Cerebrovascular Circulation/physiology , Cross-Sectional Studies , Young Adult , Retrospective Studies , Adolescent , Brain/diagnostic imaging , Brain/physiopathology , Brain/blood supply , Aged , Radiopharmaceuticals
2.
Am J Perinatol ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698596

ABSTRACT

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth. Infants with BPD are at increased risk for pulmonary hypertension (PH). Cardiac catheterization is the gold standard for diagnosing PH, but cardiac catheterization is challenging to perform in small, sick, premature infants. The utility of echocardiography for diagnosing PH and predicting outcomes in extremely premature infants has not been clearly defined. Therefore, we sought to use predefined criteria to diagnose PH by echocardiogram and relate PH severity to mortality in extremely premature infants with BPD. STUDY DESIGN: Echocardiograms from 46 infants born ≤28 weeks' postmenstrual age with a diagnosis of BPD were assessed for PH by three pediatric cardiologists using predefined criteria, and survival times among categories of PH patients were compared. A total of 458 echocardiograms were reviewed, and 15 (33%) patients were found to have at least moderate PH. Patients with at least moderate PH had similar demographic characteristics to those with no/mild PH. RESULTS: Ninety percent of infants without moderate to severe PH survived to hospital discharge, compared with 67% of infants with at least moderate PH (p = 0.048). Patients with severe PH had decreased survival to hospital discharge (38%) compared with moderate (100%) and no/mild PH (90%) groups. Kaplan-Meier survival curves also differed among PH severity groups (Wilcoxon p < 0.001). CONCLUSION: Using predefined criteria for PH, premature infants with BPD can be stratified into PH severity categories. Patients diagnosed with severe PH by echocardiogram have significantly reduced survival. KEY POINTS: · A composite score definition of PH by echocardiogram showed high inter- and intrarater reliability.. · Infants with severe PH by echocardiogram had decreased survival rates.. · Early diagnosis of PH by echocardiogram dictates treatment which may improve outcomes..

3.
J Am Heart Assoc ; 13(11): e033937, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38780186

ABSTRACT

BACKGROUND: Socioeconomic factors may lead to a disproportionate impact on health care usage and death among individuals with congenital heart defects (CHD) by race, ethnicity, and socioeconomic factors. How neighborhood poverty affects racial and ethnic disparities in health care usage and death among individuals with CHD across the life span is not well described. METHODS AND RESULTS: Individuals aged 1 to 64 years, with at least 1 CHD-related International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code were identified from health care encounters between January 1, 2011, and December 31, 2013, from 4 US sites. Residence was classified into lower- or higher-poverty neighborhoods on the basis of zip code tabulation area from the 2014 American Community Survey 5-year estimates. Multivariable logistic regression models, adjusting for site, sex, CHD anatomic severity, and insurance-evaluated associations between race and ethnicity, and health care usage and death, stratified by neighborhood poverty. Of 31 542 individuals, 22.2% were non-Hispanic Black and 17.0% Hispanic. In high-poverty neighborhoods, non-Hispanic Black (44.4%) and Hispanic (47.7%) individuals, respectively, were more likely to be hospitalized (adjusted odds ratio [aOR], 1.2 [95% CI, 1.1-1.3]; and aOR, 1.3 [95% CI, 1.2-1.5]) and have emergency department visits (aOR, 1.3 [95% CI, 1.2-1.5] and aOR, 1.8 [95% CI, 1.5-2.0]) compared with non-Hispanic White individuals. In high poverty neighborhoods, non-Hispanic Black individuals with CHD had 1.7 times the odds of death compared with non-Hispanic White individuals in high-poverty neighborhoods (95% CI, 1.1-2.7). Racial and ethnic disparities in health care usage were similar in low-poverty neighborhoods, but disparities in death were attenuated (aOR for non-Hispanic Black, 1.2 [95% CI=0.9-1.7]). CONCLUSIONS: Racial and ethnic disparities in health care usage were found among individuals with CHD in low- and high-poverty neighborhoods, but mortality disparities were larger in high-poverty neighborhoods. Understanding individual- and community-level social determinants of health, including access to health care, may help address racial and ethnic inequities in health care usage and death among individuals with CHD.


Subject(s)
Healthcare Disparities , Heart Defects, Congenital , Humans , Heart Defects, Congenital/ethnology , Heart Defects, Congenital/mortality , Heart Defects, Congenital/therapy , Male , Female , United States/epidemiology , Child, Preschool , Adolescent , Adult , Infant , Middle Aged , Young Adult , Healthcare Disparities/ethnology , Healthcare Disparities/statistics & numerical data , Child , Poverty/statistics & numerical data , Patient Acceptance of Health Care/ethnology , Patient Acceptance of Health Care/statistics & numerical data , Black or African American/statistics & numerical data , Ethnicity/statistics & numerical data , Neighborhood Characteristics , Hispanic or Latino/statistics & numerical data , Residence Characteristics/statistics & numerical data , White People/statistics & numerical data
4.
Curr Oncol Rep ; 26(5): 496-503, 2024 05.
Article in English | MEDLINE | ID: mdl-38602581

ABSTRACT

PURPOSE OF REVIEW: To summarize and evaluate the literature on treatment approaches for oligometastatic and locally recurrent urothelial cancer. RECENT FINDINGS: There is no clear definition for oligometastatic urothelial cancers due to limited data. Studies focusing on oligometastatic and locally recurrent urothelial cancer have been primarily retrospective. Treatment options include local therapy with surgery or radiation, and generalized systemic therapy such as chemotherapy or immunotherapy. Oligometastatic and locally recurrent urothelial cancers remain challenging to manage, and treatment requires an interdisciplinary approach. Systemic therapy is nearly always a component of current care in the form of chemotherapy, but the role of immunotherapy has not been explored. Consideration of surgical and radiation options may improve outcomes, and no studies have compared directly between the two localized treatment options. The development of new prognostic and predictive biomarkers may also enhance the treatment landscape in the future.


Subject(s)
Neoplasm Recurrence, Local , Urinary Bladder Neoplasms , Humans , Neoplasm Recurrence, Local/therapy , Neoplasm Recurrence, Local/pathology , Urinary Bladder Neoplasms/therapy , Urinary Bladder Neoplasms/pathology , Carcinoma, Transitional Cell/therapy , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/secondary , Neoplasm Metastasis , Immunotherapy , Combined Modality Therapy , Urologic Neoplasms/pathology , Urologic Neoplasms/therapy , Prognosis
5.
Ophthalmology ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38678469

ABSTRACT

PURPOSE: To review the published literature on the safety and outcomes of keratolimbal allograft (KLAL) transplantation and living-related conjunctival limbal allograft (lr-CLAL) transplantation for bilateral severe/total limbal stem cell deficiency (LSCD). METHODS: Literature searches were last conducted in the PubMed database in February 2023 and were limited to the English language. They yielded 523 citations; 76 were reviewed in full text, and 21 met the inclusion criteria. Two studies were rated level II, and the remaining 19 studies were rated level III. There were no level I studies. RESULTS: After KLAL surgery, best-corrected visual acuity (BCVA) improved in 42% to 92% of eyes at final follow-up (range, 12-95 months). The BCVA was unchanged in 17% to 39% of eyes and decreased in 8% to 29% of eyes. Two of 14 studies that evaluated the results of KLAL reported a notable decline in visual acuity over time postoperatively. Survival of KLAL was variable, ranging from 21% to 90% at last follow-up (range, 12-95 months) and decreased over time. For patients undergoing lr-CLAL surgery, BCVA improved in 31% to 100% of eyes at final follow-up (range, 16-49 months). Of the 9 studies evaluating lr-CLAL, 4 reported BCVA unchanged in 30% to 39% of patients, and 3 reported a decline in BCVA in 8% to 10% of patients. The survival rate of lr-CLAL ranged from 50% to 100% at final follow-up (range, 16-49 months). The most common complications were postoperative elevation of intraocular pressure, persistent epithelial defects, and acute allograft immune rejections. CONCLUSIONS: Given limited options for patients with bilateral LSCD, both KLAL and lr-CLAL are viable choices that may provide improvement of vision and ocular surface findings. The studies trend toward a lower rejection rate and graft failure with lr-CLAL. However, the level and duration of immunosuppression vary widely between the studies and may impact allograft rejections and long-term graft survival. Complications related to immunosuppression are minimal. Repeat surgery may be needed to maintain a viable ocular surface. Reasonable long-term success can be achieved with both KLAL and lr-CLAL with appropriate systemic immunosuppression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

6.
Am J Med Genet A ; : e63616, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38551204

ABSTRACT

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder characterized by progressive osteolysis involving the carpal and tarsal bones, and often associated with nephropathy. It is caused by heterozygous mutation in the MAF bZIP transcription factor B (MAFB) gene. Heterogeneous clinical manifestation and wide spectrum of disease severity have been observed in patients with MCTO. Here, we report a case of a male patient who presented with kidney failure in childhood with progressive disabling skeletal deformity. He was diagnosed with MCTO at 31-years-old, where a de novo pathogenic heterozygous variant in NM_005461.5:c.212C>A: p.(Pro71His) of the MAFB gene was identified. While there has been little data on the long-term prognosis and life expectancy of this disease, this case report sheds light on the debilitating disease course with multiple significant morbidities of a patient with MCTO throughout his lifetime of 33 years.

7.
NPJ Digit Med ; 7(1): 70, 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38493216

ABSTRACT

Daily routines, including in-person school and extracurricular activities, are important for maintaining healthy physical activity and sleep habits in children. The COVID-19 pandemic significantly disrupted daily routines as in-person school and activities closed to prevent spread of SARS-CoV-2. We aimed to examine and assess differences in objectively measured physical activity levels and sleep patterns from wearable sensors in children with obesity before, during, and after a period of school and extracurricular activity closures associated with the COVID-19 pandemic. We compared average step count and sleep patterns (using the Mann-Whitney U Test) before and during the pandemic-associated school closures by using data from activity tracker wristbands (Garmin VivoFit 3). Data were collected from 94 children (aged 5-17) with obesity, who were enrolled in a randomized controlled trial testing a community-based lifestyle intervention for a duration of 12-months. During the period that in-person school and extracurricular activities were closed due to the COVID-19 pandemic, children with obesity experienced objectively-measured decreases in physical activity, and sleep duration. From March 15, 2020 to March 31, 2021, corresponding with local school closures, average daily step count decreased by 1655 steps. Sleep onset and wake time were delayed by about an hour and 45 min, respectively, while sleep duration decreased by over 12 min as compared with the pre-closure period. Step counts increased with the resumption of in-person activities. These findings provide objective evidence for parents, clinicians, and public health professionals on the importance of in-person daily activities and routines on health behaviors, particularly for children with pre-existing obesity. Trial Registration: Clinical trial registration: NCT03339440.

8.
Pediatr Cardiol ; 45(5): 976-985, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38485760

ABSTRACT

Adults with congenital heart disease (CHD) benefit from cardiology follow-up at recommended intervals of ≤ 2 years. However, benefit for children is less clear given limited studies and unclear current guidelines. We hypothesize there are identifiable risks for gaps in cardiology follow-up in children with CHD and that gaps in follow-up are associated with differences in healthcare utilization. Our cohort included children < 10 years old with CHD and a healthcare encounter from 2008 to 2013 at one of four North Carolina (NC) hospitals. We assessed associations between cardiology follow-up and demographics, lesion severity, healthcare access, and educational isolation (EI). We compared healthcare utilization based on follow-up. Overall, 60.4% of 6,969 children received cardiology follow-up within 2 years of initial encounter, including 53.1%, 58.1%, and 79.0% of those with valve, shunt, and severe lesions, respectively. Factors associated with gaps in care included increased drive time to a cardiology clinic (Hazard Ratio (HR) 0.92/15-min increase), EI (HR 0.94/0.2-unit increase), lesion severity (HR 0.48 for shunt/valve vs severe), and older age (HR 0.95/month if < 1 year old and 0.94/year if > 1 year old; p < 0.05). Children with a care gap subsequently had more emergency department (ED) visits (Rate Ratio (RR) 1.59) and fewer inpatient encounters and procedures (RR 0.51, 0.35; p < 0.05). We found novel factors associated with gaps in care for cardiology follow-up in children with CHD and altered health care utilization with a gap. Our findings demonstrate a need to mitigate healthcare barriers and generate clear cardiology follow-up guidelines for children with CHD.


Subject(s)
Heart Defects, Congenital , Humans , Heart Defects, Congenital/therapy , Male , Female , Child, Preschool , Risk Factors , Infant , Child , North Carolina/epidemiology , Health Services Accessibility , Retrospective Studies , Patient Acceptance of Health Care/statistics & numerical data , Infant, Newborn , Follow-Up Studies
9.
Sci Rep ; 14(1): 6238, 2024 03 14.
Article in English | MEDLINE | ID: mdl-38485975

ABSTRACT

This study evaluated the tolerability and efficacy of the topical rho-kinase inhibitor netarsudil for canine primary corneal endothelial degeneration (PCED). Twenty-six eyes of 21 client-owned dogs with PCED were enrolled in a prospective, randomized, vehicle control clinical trial and received topical netarsudil 0.02% (Rhopressa®) or vehicle control twice daily (BID) for the first 4 months. Then, all patients received netarsudil for the next 4 or 8 months. Complete ophthalmic examination, ultrasonic pachymetry, Fourier-domain optical coherence tomography, and in vivo confocal microscopy were performed at baseline and 1, 2, 4, 6, 8 and 12 months. Effect of netarsudil on central corneal thickness (CCT), percentage of cornea with edema, and endothelial cell density (ECD) were evaluated by repeated measures ANOVA. Kaplan-Meier curves and log-rank test were used to compare corneal edema and clinical progression of eyes in netarsudil versus vehicle control groups. All dogs developed conjunctival hyperemia in at least one eye while receiving netarsudil. Unilateral transient reticulated intraepithelial bullae and stromal hemorrhage were observed respectively in 2 dogs in the netarsudil group. Two dogs showed persistently decreased tear production while receiving netarsudil, requiring topical immunomodulatory treatment. No significant differences in CCT, ECD, corneal edema or clinical progression were observed between netarsudil or vehicle treated eyes. When comparing efficacy of topical netarsudil BID and topical ripasudil 0.4% administered four times daily from our previous study, dogs receiving ripasudil had significantly less progression than those receiving netarsudil.


Subject(s)
Benzoates , Corneal Dystrophies, Hereditary , Corneal Edema , Isoquinolines , Sulfonamides , beta-Alanine , Animals , Dogs , beta-Alanine/analogs & derivatives , Corneal Edema/drug therapy , Disease Progression , Ophthalmic Solutions/therapeutic use , Prospective Studies
10.
Cell Rep ; 43(4): 113973, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38507406

ABSTRACT

We identified and validated a collection of circular RNAs (circRNAs) in Drosophila melanogaster. We show that depletion of the pro-viral circRNA circATP8B(2), but not its linear siblings, compromises viral infection both in cultured Drosophila cells and in vivo. In addition, circATP8B(2) is enriched in the fly gut, and gut-specific depletion of circATP8B(2) attenuates viral replication in an oral infection model. Furthermore, circATP8B(2) depletion results in increased levels of reactive oxygen species (ROS) and enhanced expression of dual oxidase (Duox), which produces ROS. Genetic and pharmacological manipulations of circATP8B(2)-depleted flies that reduce ROS levels rescue the viral replication defects elicited by circATP8B(2) depletion. Mechanistically, circATP8B(2) associates with Duox, and circATP8B(2)-Duox interaction is crucial for circATP8B(2)-mediated modulation of Duox activity. In addition, Gαq, a G protein subunit required for optimal Duox activity, acts downstream of circATP8B(2). We conclude that circATP8B(2) regulates antiviral defense by modulating Duox expression and Duox-dependent ROS production.


Subject(s)
Drosophila Proteins , Drosophila melanogaster , RNA, Circular , Reactive Oxygen Species , Animals , Reactive Oxygen Species/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Drosophila melanogaster/immunology , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Virus Replication , RNA/metabolism , RNA/genetics , NADPH Oxidases/metabolism , NADPH Oxidases/genetics , Dual Oxidases/metabolism , Dual Oxidases/genetics
12.
Contemp Clin Trials Commun ; 38: 101257, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38298917

ABSTRACT

Background: Registry-based trials have the potential to reduce randomized clinical trial (RCT) costs. However, observed cost differences also may be achieved through pragmatic trial designs. A systematic comparison of trial costs across different designs has not been previously performed. Methods: We conducted a study to compare the current Steroids to Reduce Systemic inflammation after infant heart surgery (STRESS) registry-based RCT vs. two established designs: pragmatic RCT and explanatory RCT. The primary outcome was total RCT design costs. Secondary outcomes included: RCT duration and personnel hours. Costs were estimated using the Duke Clinical Research Institute's pricing model. Results: The Registry-Based RCT estimated duration was 31.9 weeks greater than the other designs (259.5 vs. 227.6 weeks). This delay was caused by the Registry-Based design's periodic data harvesting that delayed site closing and statistical reporting. Total personnel hours were greatest for the Explanatory design followed by the Pragmatic design and the Registry-Based design (52,488 vs 29,763 vs. 24,480 h, respectively). Total costs were greatest for the Explanatory design followed by the Pragmatic design and the Registry-Based design ($10,140,263 vs. $4,164,863 vs. $3,268,504, respectively). Thus, Registry-Based total costs were 32 % of the Explanatory and 78 % of the Pragmatic design. Conclusion: Total costs for the STRESS RCT with a registry-based design were less than those for a pragmatic design and much less than an explanatory design. Cost savings reflect design elements and leveraging of registry resources to improve cost efficiency, but delays to trial completion should be considered.

13.
J Surg Educ ; 81(4): 486-494, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38388311

ABSTRACT

OBJECTIVES: The objective of this study was to evaluate the psychological impact of the COVID-19 pandemic on surgical residents. DESIGN: An online survey was distributed evaluating multiple domains: demographics, health and socioeconomic factors, clinical experience, educational experience, and psychological outcomes. The Mayo Clinic Resident Well-Being Index (RWBI) was used as a validated measure of resident mental health. SETTING AND PARTICIPANTS: Surgical residents from University of British Columbia's surgical residency programs. RESULTS: A total of 31/86 surgical residents responded to the survey. Of which, 57% and 46% reported feeling burned out or depressed, respectively. Residents who were concerned about personal protective equipment supply and who lived with family members with comorbidities had a higher risk of depression (p = 0.03, p = 0.04). The median Mayo Clinic Resident Well-Being Index was 2.5, higher than the median of 2 observed in the United States national survey of residents. CONCLUSIONS: The pandemic had a considerable negative impact on the psychological well-being of surgical residents.


Subject(s)
Burnout, Professional , COVID-19 , Internship and Residency , Humans , United States , COVID-19/epidemiology , Pandemics , Canada , Surveys and Questionnaires , Burnout, Professional/epidemiology
14.
J Clin Transl Sci ; 8(1): e4, 2024.
Article in English | MEDLINE | ID: mdl-38384905

ABSTRACT

Introduction: The institutions (i.e., hubs) making up the National Institutes of Health (NIH)-funded network of Clinical and Translational Science Awards (CTSAs) share a mission to turn observations into interventions to improve public health. Recently, the focus of the CTSAs has turned increasingly from translational research (TR) to translational science (TS). The current NIH Funding Opportunity Announcement (PAR-21-293) for CTSAs stipulates that pilot studies funded through the CTSAs must be "focused on understanding a scientific or operational principle underlying a step of the translational process with the goal of developing generalizable solutions to accelerate translational research." This new directive places Pilot Program administrators in the position of arbiters with the task of distinguishing between TR and TS projects. The purpose of this study was to explore the utility of a set of TS principles set forth by NCATS for distinguishing between TR and TS. Methods: Twelve CTSA hubs collaborated to generate a list of Translational Science Principles questions. Twenty-nine Pilot Program administrators used these questions to evaluate 26 CTSA-funded pilot studies. Results: Factor analysis yielded three factors: Generalizability/Efficiency, Disruptive Innovation, and Team Science. The Generalizability/Efficiency factor explained the largest amount of variance in the questions and was significantly able to distinguish between projects that were verified as TS or TR (t = 6.92, p < .001) by an expert panel. Conclusions: The seven questions in this factor may be useful for informing deliberations regarding whether a study addresses a question that aligns with NCATS' vision of TS.

15.
R I Med J (2013) ; 107(1): 12-14, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38166068

ABSTRACT

Spontaneous community-acquired meningitis caused by E. coli is rare in the adult population. It is associated with a high risk of morbidity and mortality. We describe a case of a 72-year-old woman who presented with altered mental status and neck stiffness and was found to have E. coli meningitis. Urine cultures grew E. coli, representing a likely source. The E. coli strain was identified as sequence type 73 (E. coli ST73). Her symptoms and laboratory values improved following antibiotic initiation, and she was discharged from the hospital to a rehabilitation facility.


Subject(s)
Escherichia coli Infections , Meningitis, Escherichia coli , Meningitis , Aged , Female , Humans , Anti-Bacterial Agents/therapeutic use , Escherichia coli , Escherichia coli Infections/diagnosis , Escherichia coli Infections/drug therapy , Meningitis/diagnosis , Meningitis/drug therapy , Meningitis/etiology , Meningitis, Escherichia coli/diagnosis , Meningitis, Escherichia coli/complications , Meningitis, Escherichia coli/drug therapy
16.
BMJ Open Ophthalmol ; 9(1)2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38286566

ABSTRACT

BACKGROUND: It remains uncertain which endothelial keratoplasty (EK) technique yields the best outcomes while maintaining safety, particularly in eyes with coexisting ocular conditions. Moreover, the impact of endothelial cell loss (ECL) on long-term graft survival requires further investigation. Adjuvant ripasudil, a rho kinase inhibitor, may address the challenge of ECL in corneal transplantation. This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1), a multicentre, outcome-masked, randomised, placebo-controlled, four-arm clinical trial. METHODS: A total of 160 eligible patients with endothelial dysfunction will be enrolled from five participating sites in the USA. The patients will be randomly assigned in a 2×2 factorial design to one of the following treatment groups: group 1-ultrathin Descemet stripping endothelial keratoplasty (UT-DSAEK) plus topical ripasudil 0.4%; group 2-UT-DSAEK plus topical placebo; group 3-Descemet membrane endothelial keratoplasty (DMEK) plus topical ripasudil 0.4% and group 4-DMEK plus topical placebo. Primary outcomes include the best spectacle-corrected visual acuity at 12 months and ECL at 12 months. Secondary outcomes include visual acuity at different time points, vision-related quality of life, endothelial cell morphology and cost-effectiveness. RESULTS: The study outcomes will be analysed using mixed effects linear regression models, taking into account the treatment arms and relevant covariates. Adverse events, including rebubble procedures, graft failure and graft rejection, will be documented and analysed using appropriate statistical methods. CONCLUSION: DETECT I aims to provide evidence on the comparative effectiveness of UT-DSAEK and DMEK, as well as the potential benefits of adjuvant topical ripasudil in reducing ECL. The results of this trial will contribute to optimising corneal transplantation techniques and improving long-term graft survival, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation. ETHICS AND DISSEMINATION: A data and safety monitoring committee (DSMC) has been empaneled by the NEI.All study protocols will be subject to review and approval by WCG IRB as the single IRB of record.This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request.


Subject(s)
Descemet Stripping Endothelial Keratoplasty , Fuchs' Endothelial Dystrophy , Isoquinolines , Sulfonamides , Humans , Fuchs' Endothelial Dystrophy/surgery , Descemet Membrane , rho-Associated Kinases , Quality of Life , Descemet Stripping Endothelial Keratoplasty/adverse effects , Endothelium, Corneal , Endothelial Cells , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
17.
Brain Struct Funct ; 229(2): 323-348, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38170266

ABSTRACT

Anorexia nervosa (AN) is a mental illness with high rates of mortality and relapse, and no approved pharmacotherapy. Using the activity-based anorexia (ABA) model of AN, we previously showed that a single sub-anesthetic intraperitoneal injection of ketamine (30 mg/kg-KET, but not 3 mg/kg-KET), has an immediate and long-lasting effect of reducing anorexia-like behavior among adolescent female mice. We also showed previously that excitatory outflow from medial prefrontal cortex (mPFC) engages hunger-evoked hyperactivity, leading to the ABA condition of severe weight loss. Ketamine is known to target GluN2B-containing NMDARs (NR2B). Might synaptic plasticity involving NR2B in mPFC contribute to ketamine's ameliorative effects? We addressed this question through electron microscopic immunocytochemical quantification of GluN2B at excitatory synapses of pyramidal neurons (PN) and GABAergic interneurons (IN) in mPFC layer 1 of animals that underwent recovery from a second ABA induction (ABA2), 22 days after ketamine injection during the first ABA induction. The 30 mg/kg-KET evoked synaptic plasticity that differed for PN and IN, with changes revolving the cytoplasmic reserve pool of NR2B more than the postsynaptic membrane pool. Those individuals that suppressed hunger-evoked wheel running the most and increased food consumption during recovery from ABA2 the most showed the greatest increase of NR2B at PN and IN excitatory synapses. We hypothesize that 30 mg/kg-KET promotes long-lasting changes in the reserve cytoplasmic pool of NR2B that enables activity-dependent rapid strengthening of mPFC circuits underlying the more adaptive behavior of suppressed running and enhanced food consumption, in turn supporting better weight restoration.


Subject(s)
Ketamine , Mice , Animals , Female , Ketamine/pharmacology , Anorexia/drug therapy , Receptors, N-Methyl-D-Aspartate/metabolism , Motor Activity/physiology , Pyramidal Cells/metabolism , Interneurons/metabolism , Prefrontal Cortex/metabolism
18.
Rheumatology (Oxford) ; 63(4): 953-961, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-37632777

ABSTRACT

OBJECTIVES: There is little data on renal relapse in childhood-onset LN (cLN). We investigate the incidence, predictive factors and outcomes related to renal relapse. METHODS: We conducted a retrospective cohort study of all cLN diagnosed at ≤18 years between 2001-2021 to investigate the incidence and outcomes related to renal relapse. RESULTS: Ninety-five Chinese cLN patients (91% proliferative LN) were included. Induction immunosuppression was prednisolone and CYC [n = 36 (38%)] or MMF [n = 33 (35%)]. Maintenance immunosuppression was prednisolone and MMF [n = 53 (54%)] or AZA [n = 29 (31%)]. The rates of complete remission/partial remission (CR/PR) at 12 months were 78.9%/7.4%. Seventy renal relapses occurred in 39 patients over a follow-up of 10.2 years (s.d. 5.9) (0.07 episode/patient-year). Relapse-free survival was 94.7, 86.0, 80.1, 71.2, 68.3, 50.3 and 44.5% at 1, 2, 3, 4, 5, 10 and 20 years, respectively. Multivariate analysis showed that LN diagnosis <13.1 years [adjusted hazard ratio (HRadj) 2.59 995% CI 1.27, 5.29), P = 0.01], AZA maintenance [HRadj 2.20 (95% CI 1.01, 4.79), P = 0.05], PR [HRadj 3.9 (95% CI 1.03, 9.19), P = 0.01] and non-remission [HRadj 3.08 (95% CI 1.35, 11.3), P = 0.04] at 12 months were predictive of renal relapse. Renal relapse was significantly associated with advanced chronic kidney disease (stages 3-5) and end-stage kidney disease (17.9% vs 1.8%, P < 0.01). Furthermore, patients with renal relapse showed an increased incidence of infections (30.8% vs 10.7%, P = 0.02), osteopenia (38.5% vs 17.9%, P = 0.04) and hypertension (30.8% vs 7.1%, P < 0.01). CONCLUSION: Renal relapse is common among cLN, especially among young patients, and is associated with an increased incidence of morbidity and mortality. Attaining CR and the use of MMF appear to decrease the incidence of renal relapse.


Subject(s)
Lupus Nephritis , Child , Humans , Adolescent , Lupus Nephritis/drug therapy , Lupus Nephritis/epidemiology , Lupus Nephritis/diagnosis , Immunosuppressive Agents/therapeutic use , Azathioprine/therapeutic use , Retrospective Studies , Mycophenolic Acid , Treatment Outcome , Prednisolone/therapeutic use , Recurrence , Cyclophosphamide , Remission Induction
19.
J Obstet Gynaecol Can ; 46(3): 102268, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37944817

ABSTRACT

OBJECTIVES: This was the first urogynaecology specialty nurse teleconsultation offered by a public hospital during COVID-19 for learning pelvic floor exercises. This study assessed patients' perception, acceptance, and satisfaction using 2 validated questionnaires. METHODS: In total, 25 patients with stress urinary incontinence attended the teleconsultation via videoconferencing in April 2022, and completed the Telemedicine Perception Questionnaire (TMPQ) and Telemedicine Satisfaction Questionnaire (TSQ). The TMPQ was a 17-item, 5-point Likert scale questionnaire for assessing the acceptability of telemedicine. The TSQ was a 14-item, 5-point Likert scale questionnaire for assessing satisfaction with teleconsultation. The higher the score, the greater the acceptance and satisfaction. Information on demographics, symptom severity by Urogenital Distress Inventory-6 and Incontinence Impact Questionnaire-7, internet access, and transport arrangements were included. RESULTS: Participants had a mean age of 54.6 ± 7.37 years. Their mean Urogenital Distress Inventory-6 score was 40.60/100 (SD = 17.83) and Impact Questionnaire-7 was 27.90/100 (SD = 19.83). Pre-teleconsultation mean TMPQ score was 59.16 ± 5.78/85. Post-teleconsultation mean score was 64.92 ± 5.21/85, which was 3.64 higher (t = 3.642, df = 24, P = 0.001), indicating a significant increase in positive perception and acceptability. There were fewer concerns with the usage (P = 0.017) and reliability (P = 0.003) of technology, while there was increased agreement that teleconsultation is cost-saving for the health care system (P = 0.003) and offers easier access to health care providers (P = 0.006) after the teleconsultation. Mean TSQ score was 59.85 ± 9.46/70. CONCLUSION: Our pilot study demonstrated positive perception, high acceptability, and satisfaction from patients' first teleconsultation experience. Further multi-centre studies with the inclusion of a control group would help in understanding patients' needs and for service planning.


Subject(s)
COVID-19 , Remote Consultation , Telemedicine , Urinary Incontinence, Stress , Humans , Middle Aged , Urinary Incontinence, Stress/therapy , Pelvic Floor , Pilot Projects , Reproducibility of Results , Patient Satisfaction
20.
Ophthalmology ; 131(1): 107-121, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37855776

ABSTRACT

PURPOSE: To review the published literature on the diagnostic capabilities of the newest generation of corneal imaging devices for the identification of keratoconus. METHODS: Corneal imaging devices studied included tomographic platforms (Scheimpflug photography, OCT) and functional biomechanical devices (imaging an air impulse on the cornea). A literature search in the PubMed database for English language studies was last conducted in February 2023. The search yielded 469 citations, which were reviewed in abstract form. Of these, 147 were relevant to the assessment objectives and underwent full-text review. Forty-five articles met the criteria for inclusion and were assigned a level of evidence rating by the panel methodologist. Twenty-six articles were rated level II, and 19 articles were rated level III. There were no level I evidence studies of corneal imaging for the diagnosis of keratoconus found in the literature. To provide a common cross-study outcome measure, diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were extracted. (A perfect diagnostic test that identifies all cases properly has an AUC of 1.0.) RESULTS: For the detection of keratoconus, sensitivities for all devices and parameters (e.g., anterior or posterior corneal curvature, corneal thickness) ranged from 65% to 100%. The majority of studies and parameters had sensitivities greater than 90%. The AUCs ranged from 0.82 to 1.00, with the majority greater than 0.90. Combined indices that integrated multiple parameters had an AUC in the mid-0.90 range. Keratoconus suspect detection performance was lower with AUCs ranging from 0.66 to 0.99, but most devices and parameters had sensitivities less than 90%. CONCLUSIONS: Modern corneal imaging devices provide improved characterization of the cornea and are accurate in detecting keratoconus with high AUCs ranging from 0.82 to 1.00. The detection of keratoconus suspects is less accurate with AUCs ranging from 0.66 to 0.99. Parameters based on single anatomic locations had a wide range of AUCs. Studies with combined indices using more data and parameters consistently reported high AUCs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Subject(s)
Keratoconus , Ophthalmology , Humans , Cornea/diagnostic imaging , Corneal Pachymetry/methods , Corneal Topography/methods , Keratoconus/diagnostic imaging , ROC Curve , Tomography
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