Correlation, agreement and concordance of cardiac output estimated by transthoracic ultrasound and transesophageal Doppler with pulmonary artery thermodilution in anesthetized cats.

OBJECTIVE: To characterize the correlation, agreement and concordance of cardiac output (CO) measured with transthoracic ultrasound and the correlation and concordance of aortic blood flow (ABF) minute distance (MD) measured by transesophageal Doppler with CO measured by pulmonary artery thermodilution (PATD) in cats. STUDY DESIGN: Experimental study. ANIMALS: A group of six healthy male neutered cats, aged 2-8 years and weighing 5.3 ± 0.3 kg. METHODS: Cats were anesthetized with isoflurane in oxygen. CO was measured by PATD (COPATD) and transthoracic echocardiography (COECHO). ABF MD was measured using an esophageal Doppler flow probe aligned with descending ABF. All measurements were made under three conditions: dexmedetomidine (20 µg kg-1) intravenously; atipamezole (200 µg kg-1) intramuscularly and atropine (20 µg kg-1) intravenously as needed to achieve a minimum heart rate of 140 beats minute-1; and dopamine (20 µg kg-1 minute-1) intravenously in that order. Correlation between COPATD and COECHO, and COPATD and Doppler MD was evaluated using repeated measures correlation. Agreement between COPATD and COECHO was evaluated using Bland-Altman method. Differences between consecutive pairs of CO measurements were calculated for concordance analysis. RESULTS: Correlation between COPATD and COECHO and between COPATD and MD was significant (p < 0.001), with correlation coefficients greater than 0.92. A bias of > 27% and upper limits of agreement of 66% were found between COPATD and COECHO. Concordance rate with COPATD was 76-80% for COECHO and 72% for MD. CONCLUSIONS AND CLINICAL RELEVANCE: Echocardiographic methods for the measurement of CO showed poor agreement and concordance with PATD. MD showed poor concordance with PATD. As such, these methods cannot be used as an alternative to PATD nor can they appropriately track changes in CO in anesthetized cats.

Sensitive Blood-Based Detection of HIV-1 and Mycobacterium tuberculosis Peptides for Disease Diagnosis by Immuno-Affinity Liquid Chromatography-Tandem Mass Spectrometry: A Method Development and Proof-of-Concept Study.

BACKGROUND: Novel approaches that allow early diagnosis and treatment monitoring of both human immunodeficiency virus-1 (HIV-1) and tuberculosis disease (TB) are essential to improve patient outcomes. METHODS: We developed and validated an immuno-affinity liquid chromatography-tandem mass spectrometry (ILM) assay that simultaneously quantifies single peptides derived from HIV-1 p24 and Mycobacterium tuberculosis (Mtb) 10-kDa culture filtrate protein (CFP10) in trypsin-digested serum derived from cryopreserved serum archives of cohorts of adults and children with/without HIV and TB. RESULTS: ILM p24 and CFP10 results demonstrated good intra-laboratory precision and accuracy, with recovery values of 96.7% to 104.6% and 88.2% to 111.0%, total within-laboratory precision (CV) values of 5.68% to 13.25% and 10.36% to 14.92%, and good linearity (r2 > 0.99) from 1.0 to 256.0 pmol/L and 0.016 to 16.000 pmol/L, respectively. In cohorts of adults (n = 34) and children (n = 17) with HIV and/or TB, ILM detected p24 and CFP10 demonstrated 85.7% to 88.9% and 88.9% to 100.0% diagnostic sensitivity for HIV-1 and TB, with 100% specificity for both, and detected HIV-1 infection earlier than 3 commercial p24 antigen/antibody immunoassays. Finally, p24 and CFP10 values measured in longitudinal serum samples from children with HIV-1 and TB distinguished individuals who responded to TB treatment from those who failed to respond or were untreated, and who developed TB immune reconstitution inflammatory syndrome. CONCLUSIONS: Simultaneous ILM evaluation of p24 and CFP10 results may allow for early TB and HIV detection and provide valuable information on treatment response to facilitate integration of TB and HIV diagnosis and management.

Sex-specific differences and predictors of echocardiographic measures of diastolic dysfunction in rhesus macaques (Macaca mulatta).

BACKGROUND: Diastolic dysfunction in humans is an age-related process with an overrepresentation in women. In rhesus macaques (Macaca mulatta), the incidence and predictors of diastolic dysfunction have yet to be reported. METHODS: Data from routine echocardiographic evaluations on clinically healthy rhesus macaques was obtained and used for univariate, bivariate, hypothesis testing, and linear regression statistical analyses interrogating differences and predictors of diastolic function. RESULTS: Rhesus macaques fully recapitulate previously reported human hemodynamic studies. Female monkeys display impaired diastology and are at an increased risk for developing diastolic dysfunction. Age, sex, and proxies of exercise activity are confirmed predictors for measures of diastolic dysfunction, regardless of specific pathogen-free status. CONCLUSIONS: Rhesus macaques share common sex- and age-related echocardiographic findings as humans, therefore, serve as a valuable translational nonhuman primate model for future studies of diastolic dysfunction. These findings confirm the importance of sex- and age-matching within future rhesus macaque cardiovascular research.

Risks of adverse perinatal outcomes in relation to maternal depressive symptoms: A prospective cohort study in Kenya.

BACKGROUND: Evidence gaps remain regarding the influence of prenatal psychosocial factors on adverse pregnancy outcomes. OBJECTIVE: The objective of this study is to evaluate relationships between psychosocial factors and adverse perinatal outcomes among Kenyan women. METHODS: We analysed data from a prospective cohort study enrolling HIV-negative women in pregnancy (NCT03070600) in 20 antenatal clinics in Western Kenya. Study nurses assessed depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CESD-10), social support using the Medical Outcomes Survey scale (MOS-SSS), intimate partner violence (IPV) with the Hurt, Insult, Threaten, Scream scale (HITS), and pregnancy outcomes at 6 weeks postpartum. Cox proportional hazards models were used to evaluate relationships between depressive symptoms (moderate-to-severe [MSD, CESD-10 ≥10] and mild-to-severe [Mild-SD, CESD-10 ≥5]), low social support (MOS-SSS <72), and IPV (HITS ≥10) with adverse perinatal outcomes of pregnancy loss, stillbirth, preterm birth (PTB), small for gestational age, and neonatal mortality. We also estimated the population attributable risk. RESULTS: Among 4153 women, 23.9% (n = 994) had MSD, 54.7% (n = 2273) mild-SD, 37.3% (n = 1550) low social support, and 7.8% (n = 323) experienced IPV. Pregnancy loss was 5-fold higher among women with MSD (adjusted hazard ratio [HR] 5.04, 95% confidence interval [CI] 2.44, 10.42); 37.4% of losses were attributable to MSD. Mild-SD was associated with PTB (HR 1.39, 95% CI 1.03, 1.87). Stillbirth risk more than doubled among women reporting low social support (HR 2.37, 95% CI 1.14, 4.94). CONCLUSIONS: Adverse perinatal outcomes were common and associated with prenatal depressive symptoms and low social support in this large cohort of Kenyan mother-infant pairs.

Pharmacokinetics of a single dose of Aficamten (CK-274) on cardiac contractility in a A31P MYBPC3 hypertrophic cardiomyopathy cat model.

Hypertrophic cardiomyopathy (HCM) is the most prevalent cardiac disease in cats and lacks efficacious preclinical pharmacologic intervention, prompting investigation of novel therapies. Genetic mutations encoding sarcomeric proteins are implicated in the development of HCM and small molecule myosin inhibitors are an emerging class of therapeutics designed to target the interaction of actin and myosin to alleviate the detrimental effects of inappropriate contractile protein interactions. The purpose of this study was to characterize the pharmacodynamic effects of a single oral dose of the novel cardiac myosin inhibitor aficamten (CK-274) on cardiac function in purpose bred cats with naturally occurring A31P MYBPC3 mutation and a clinical diagnosis of HCM with left ventricular outflow tract obstruction (LVOTO). Five purpose bred cats were treated with aficamten (2 mg/kg) or vehicle and echocardiographic evaluations were performed at 0, 6, 24, and 48 h post-dosing. High dose aficamten (2 mg/kg) reduced left ventricular fractional shortening (LVFS%) by increasing the LV systolic internal dimension (LVIDs) and reduced isovolumic relaxation time (IVRT) compared with baseline without significant adverse effects. The marked reduction in systolic function and reduced IVRT coupled with an increased heart rate in treated cats, suggest a lower dose may be optimal. Further studies to determine optimal dosing of aficamten are indicated.

Effectiveness of Human Papillomavirus (HPV) Vaccination Against Penile HPV Infection in Men Who Have Sex With Men and Transgender Women.

BACKGROUND: In the United States, human papillomavirus (HPV) vaccination has been recommended since 2011 for boys aged 11-12 years, with catch-up vaccination recommended through age 26 years for previously unvaccinated men who have sex with men (MSM). METHODS: During 2016-2018, a cross-sectional study enrolled MSM and transgender women aged 18-26 years in Seattle, Washington. Participants submitted self-collected penile swab specimens for HPV genotyping. HPV vaccination history was self-reported. We compared HPV prevalence among vaccinated participants with that in participants with no or unknown vaccination history, using log-binomial regression to estimate adjusted prevalence ratios and confidence intervals. RESULTS: Among 687 participants, 348 (50.7%) self-reported ever receiving ≥1 HPV vaccine dose; the median age at first HPV vaccination was 21 years, and the median age at first sex, 17 years. Overall, the prevalence of penile quadrivalent HPV vaccine (4vHPV)-type HPV was similar in vaccinated participants (12.1%) and participants with no or unknown vaccination (15.6%) (adjusted prevalence ratio, 0.69 [95% confidence interval, .47-1.01]). However, the prevalence was significantly lower in participants vaccinated at age ≤18 years than in those with no of unknown vaccination (0.15 [.04-.62]), corresponding to a vaccine effectiveness of 85% against 4vHPV-type HPV. CONCLUSIONS: Results suggest that HPV vaccination is effective in preventing penile HPV infections in young MSM when administered at age ≤18 years.

Optimizing pain management following kidney stone surgery: can we avoid narcotics?

INTRODUCTION: Opioids are often used to manage postoperative pain. Non-narcotic alternatives have increasingly been used to reduce opioid usage. We conducted an open-label randomized non-inferiority clinical trial to compare non-opioid to opioid therapy for pain management after nephrolithiasis surgery. METHODS: Patients undergoing elective ureteroscopy or percutaneous nephrolithotomy between July 2018 and May 2021 were randomized to receive ketorolac (non-opioid) or oxycodone-acetaminophen (opioid). Each patient was surveyed one week postoperatively to assess pain outcomes. Patient demographics, surgical variables, number of pills used, constipation, and adverse events were also assessed. We evaluated whether non-opioid analgesia was non-inferior to opioid analgesia for postoperative pain, assuming a non-inferiority margin of 1.3 in pain score between groups. RESULTS: Analyses were based on 90 patients with postoperative pain data: 44 in the ketorolac group and 46 in the oxycodone-acetaminophen group. The groups were similar regarding demographics, type of surgery, ureteral stent placement, and stone burden. Non-inferiority of non-opioids compared to opioids was demonstrated for all outcomes. At follow-up, the average pain scores were 3.20 ± 1.94 (SD) in the non-opioid group and 4.17 ± 1.84 in the opioid group (difference = - 0.96; 95% CI: - 1.76, - 0.17, p = 0.018). The mean proportions of unused pills were similar between groups (p = 0.47) as were rates of constipation (p = 0.32). CONCLUSIONS: Non-opioid analgesia was non-inferior to opioid analgesia in pain management after kidney stone surgery. This trial contributes to the evidence that non-opioid analgesics should be considered an effective option for pain management following non-invasive urologic procedures.

Social Support and Linkage to HIV Care Following Routine HIV Testing in a Ugandan Refugee Settlement.

We aimed to identify factors associated with linkage to care for individuals newly diagnosed with HIV in a refugee settlement. This study was conducted from October 2018 through January 2020 in Nakivale Refugee Settlement in Uganda. We conducted a cross-sectional survey among individuals accessing routine HIV testing services. The survey included questions on demographic factors, physical and mental health conditions, social support, and HIV-related stigma. We collected GPS coordinates of the homes of individuals newly diagnosed with HIV. Associations with linkage to care were assessed using bivariate and multivariable analyses. Linkage to care was defined as clinic attendance within 90 days of a positive HIV test, not including the day of testing. Network analysis was used to estimate the travel distance between participants' homes and HIV clinic and to spatially characterize participants living with HIV and their levels of social support. Of 219 participants diagnosed with HIV (out of 5,568 participants screened), 74.4% linked to HIV care. Those who reported higher social support had higher odds of linking to care compared with those who reported lower social support. On spatial analysis, lower levels of social support were most prevalent in Nakivale Refugee Settlement itself, with more robust social support southeast and west of the study area. Social support is a salient correlate of linkage to care for individuals living in refugee settlements and could be the focus of an intervention for improving uptake of HIV care services.

The TNNT2:c.95-108G>A variant is common in Maine Coons and shows no association with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common and potentially fatal heart disease in many cat breeds. An intronic variant in TNNT2, c.95-108G>A, was recently reported as the cause of HCM in the Maine Coon. The aim of this study was to determine this variant's allele frequency in different populations and its possible association with HCM. Based on 160 Maine Coon samples collected in Belgium, Italy, Sweden and the USA, the variant's allele frequency was estimated to be 0.32. Analysis of the 99 Lives feline whole genome sequencing database showed that the TNNT2 variant also occurs in other breeds, as well as mixed-breed cats. Comparison of 31 affected and 58 healthy cats did not reveal significantly increased odds for HCM in homozygotes. Based on the combined evidence and in agreement with the standards and guidelines for the interpretation of sequence variants, this variant is currently classified as a variant of unknown significance and should not be used for breeding decisions regarding HCM.

Closure of a patent ductus arteriosus in a 2-week-old llama cria using an Amplatz canine duct occluder.

A two-week-old female llama cria was brought to the UC Davis Large Animal Hospital for evaluation of a cardiac murmur and suspected syncopal episodes. A grade IV/VI left basilar continuous murmur was present on cardiac auscultation. Echocardiography revealed a left-to-right shunting patent ductus arteriosus (PDA), mild left ventricular enlargement, scant pericardial effusion, and a suspected persistent left cranial vena cava. The PDA was successfully closed with an Amplatz canine duct occluder. Mild mitral regurgitation was present on echocardiography performed 7 d following PDA occlusion. No syncopal episodes were observed in hospital prior to or following PDA occlusion. At approximately 1 mo following PDA closure, a grade I/VI left apical systolic murmur was present and the cria's body condition was improved. Key clinical message: Patent ductus arteriosus closure is achievable in New World camelids using interventional cardiology which provides a minimally invasive treatment option for valuable or companion animals. Since interventional cardiac catheterization is commonly performed in small animal species, veterinary cardiologists are well-equipped to apply these skills to camelids.

Fermeture d'un canal artériel persistant chez un lama cria âgé de 2 semaines à l'aide d'un obturateur de conduit canin Amplatz. Une femelle lama cria âgée de deux semaines a été amenée à l'UC Davis Large Animal Hospital pour l'évaluation d'un souffle cardiaque et d'épisodes syncopaux suspectés. Un souffle continu basilaire gauche de grade IV/VI était présent à l'auscultation cardiaque. L'échocardiographie a révélé une persistance du canal artériel avec perméabilité de gauche à droite (PDA), une légère hypertrophie ventriculaire gauche, un léger épanchement péricardique et une suspicion de veine cave crâniale gauche persistante. Le PDA a été fermé avec succès avec un obturateur de conduit canin Amplatz. Une régurgitation mitrale légère était présente sur l'échocardiographie réalisée 7 jours après l'occlusion du PDA. Aucun épisode de syncope n'a été observé à l'hôpital avant ou après l'occlusion du PDA. Environ 1 mois après la fermeture du PDA, un souffle systolique apical gauche de grade I/VI était présent et l'état corporel du cria s'était amélioré.Message clinique clé :La fermeture brevetée du canal artériel est réalisable chez les camélidés du Nouveau Monde en utilisant la cardiologie interventionnelle qui offre une option de traitement peu invasive pour les animaux de valeur ou de compagnie. Étant donné que le cathétérisme cardiaque interventionnel est couramment pratiqué chez les petites espèces animales, les cardiologues vétérinaires sont bien équipés pour appliquer ces compétences aux camélidés.(Traduit par Dr Serge Messier).

Evaluation of a Fluoroscopic Angiography Protocol in Hispaniolan Amazon Parrots (Amazona ventralis).

Fluoroscopic angiography evaluates the heart and vascular tree in real time and can be recorded for further diagnostic analysis and measurements. Although reports have been published of the use of fluoroscopic angiography in birds, this technique has not been evaluated in any avian species. The purpose of this study was to evaluate a fluoroscopic angiography protocol in 12 adult Hispaniolan Amazon parrots (Amazona ventralis). Under general anesthesia, the birds were positioned in right lateral (LAT) recumbency on a fluoroscopy table. A bolus of nonionic iodinated contrast agent was injected through a catheter inserted into the basilic or medial metatarsal vein during video acquisition. The same bolus was repeated to obtain the ventrodorsal (VD) view with the bird placed in dorsal recumbency. Eleven studies were performed. A total of 19 (10 VD, 9 LAT) continuous, real-time, fluoroscopic angiograms were successfully captured. The brachiocephalic trunk, aorta, pulmonary arteries, pulmonary veins, and caudal vena cava were visualized, and selected intraluminal measurements collected. The intraobserver and interobserver variability for 3 observers was calculated. Intraobserver agreement was found to be near perfect (intraclass correlation coefficient ≥0.95), whereas interobserver agreement was moderate to substantial (intraclass correlation coefficient ≥0.52). Coefficients of variation were excellent (VD 0.99, LAT 0.99) for intraobserver assessments and moderate (VD 0.72, LAT 0.52) for interobserver assessments. For the interobserver assessments, the VD projection measurements performed better than the LAT measurements. These results suggest that although there was some variation between different observers, relatively consistent vascular measurements could be obtained. The described fluoroscopic angiography protocol is a repeatable and reliable technique that could be useful for the diagnosis and monitoring of cardiovascular diseases in birds.

Understanding the Role of Emerging Vitamin D Biomarkers on Short-term Persistence of High-Risk Human Papillomavirus Infection Among Mid-Adult Women.

BACKGROUND: Associations between vitamin D biomarkers and persistent high-risk human papillomavirus (hrHPV) detection have not been evaluated. METHODS: 2011-2012 stored sera from 72 women aged 30-50 years with prevalent hrHPV (n = 116 type-specific infections) were tested for 5 vitamin D biomarkers: 25(OH)D and 4 emerging biomarkers, 1,25(OH)2D; 24,25(OH)2D; free vitamin D; and vitamin D binding protein (DBP). The hrHPV detection patterns (persistent vs transient/sporadic) were determined using cervicovaginal swabs collected monthly for 6 months. Associations between vitamin D and short-term type-specific hrHPV persistence were estimated using logistic regression. Our primary exposure was continuous 25(OH)D, with additional biomarkers evaluated as secondary exposures. Primary models were adjusted for age, race, body mass index, education, contraceptives, smoking, season, and calcium/phosphate levels. Sensitivity analyses were restricted from 19 hrHPV types to 14 used in cervical cancer screening. RESULTS: In primary analyses, nonsignificant positive associations with hrHPV persistence were observed for measures of 25(OH)D and 24,25(OH)2D. Associations were stronger and significant when restricting to 14 hrHPV types (25(OH)D per 10 ng/mL increase: adjusted odds ratio [aOR], 1.82 [95% confidence interval {CI}, 1.15-2.88] and aOR, 4.19 [95% CI, 1.18-14.88] DBP-adjusted; 25(OH)D ≥30 vs <30 ng/mL: aOR, 8.85 [95% CI, 2.69-29.06]; 24,25(OH)2D: aOR, 1.85 [95% CI, 1.18-2.88]). 1,25(OH)2D was unassociated with persistence. CONCLUSIONS: Serum vitamin D measured by multiple biomarkers showed positive associations with short-term hrHPV persistence that were significant only when restricting to 14 clinically relevant hrHPV types.

Acute pharmacodynamic effects of pimobendan in client-owned cats with subclinical hypertrophic cardiomyopathy.

BACKGROUND: Prior studies have suggested that pimobendan is associated with several positive effects in cats, including improved survival in cats with congestive heart failure and improved left atrial function in research colony cats with hypertrophic cardiomyopathy (HCM) and normal cats. However, there is still a paucity of pharmacodynamic data refuting or supporting the use of pimobendan in a clinical cat population. This clinical trial aimed to evaluate the pharmacodynamic effects and tolerability of a single dose of pimobendan in cats with HCM. Echocardiograms and Doppler-derived systolic blood pressures were performed in 21 client-owned cats with subclinical HCM at baseline and 90-min after oral administration of 1.25 mg of pimobendan (Vetmedin). Seven additional cats were evaluated post-placebo administration to account for intra-day variability. RESULTS: Heart rate, systolic blood pressure, and murmur grade were not significantly different between baseline and post-pimobendan evaluations. Left auricular blood flow velocity, left atrial size, and left ventricular fractional shortening were not significantly different between baseline and post-pimobendan evaluations. Mean (± standard deviation) tissue Doppler peak systolic velocity of the mitral annulus was significantly higher following pimobendan (7.4 cm/s ± 1.5 vs 8.5 ± 1.6; p = 0.02). Median (min, max) left-ventricular outflow tract maximum velocity was significantly higher following pimobendan [1.9 m/sec (1.5, 3.4) vs 2.6 m/sec (2.0, 4.0); p = 0.01]. Mean right-ventricular outflow tract maximum velocity was also significantly higher following pimobendan (1.5 m/s ± 0.51 vs 2.0 ± 0.53; p = 0.004). Mean left atrial fractional shortening was significantly higher following pimobendan (28% ± 6 vs 32% ± 7; p = 0.02). No adverse events were observed following pimobendan administration. Right ventricular outflow tract velocity was significantly higher following placebo in control cats (1.02 ± 0.21 versus 1.31 ± 0.31; p = 0.01). No other significant differences were detected. CONCLUSIONS: In client-owned cats with HCM, pimobendan acutely increased left atrial function and mildly increased left ventricular systolic function. Left ventricular outflow tract velocity was increased after pimobendan. Pimobendan was well tolerated in the acute setting in cats with HCM. The findings of this prospective, acute-dosing study confirm previous findings in research animals and retrospective analyses and suggest that chronic dosing studies are safe and warranted.

Whole genome variant association across 100 dogs identifies a frame shift mutation in DISHEVELLED 2 which contributes to Robinow-like syndrome in Bulldogs and related screw tail dog breeds.

Domestic dog breeds exhibit remarkable morphological variations that result from centuries of artificial selection and breeding. Identifying the genetic changes that contribute to these variations could provide critical insights into the molecular basis of tissue and organismal morphogenesis. Bulldogs, French Bulldogs and Boston Terriers share many morphological and disease-predisposition traits, including brachycephalic skull morphology, widely set eyes and short stature. Unlike other brachycephalic dogs, these breeds also exhibit vertebral malformations that result in a truncated, kinked tail (screw tail). Whole genome sequencing of 100 dogs from 21 breeds identified 12.4 million bi-allelic variants that met inclusion criteria. Whole Genome Association of these variants with the breed defining phenotype of screw tail was performed using 10 cases and 84 controls and identified a frameshift mutation in the WNT pathway gene DISHEVELLED 2 (DVL2) (Chr5: 32195043_32195044del, p = 4.37 X 10-37) as the most strongly associated variant in the canine genome. This DVL2 variant was fixed in Bulldogs and French Bulldogs and had a high allele frequency (0.94) in Boston Terriers. The DVL2 variant segregated with thoracic and caudal vertebral column malformations in a recessive manner with incomplete and variable penetrance for thoracic vertebral malformations between different breeds. Importantly, analogous frameshift mutations in the human DVL1 and DVL3 genes cause Robinow syndrome, a congenital disorder characterized by similar craniofacial, limb and vertebral malformations. Analysis of the canine DVL2 variant protein showed that its ability to undergo WNT-induced phosphorylation is reduced, suggesting that altered WNT signaling may contribute to the Robinow-like syndrome in the screwtail breeds.

Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial.

BACKGROUND: Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel. METHODS: In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128. FINDINGS: Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment. INTERPRETATION: Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients. FUNDING: UroGen Pharma.

Associations between Socioeconomic Status and Urge Urinary Incontinence: An Analysis of NHANES 2005 to 2016.

PURPOSE: Urge urinary incontinence significantly impacts quality of life. We investigated the association between urge urinary incontinence and socioeconomic status in a nationally representative adult population. MATERIALS AND METHODS: We analyzed the 2005 to 2016 NHANES (National Health and Nutrition Examination Survey), a United States population based, cross-sectional study. Urge urinary incontinence was determined by self-report of leaking urine before reaching the toilet. Socioeconomic status was represented by the poverty income ratio, which reflects the family income relative to poverty thresholds specific to that year and household size. Survey weighted logistic regression models were used to analyze the relationship between socioeconomic status and the poverty income ratio. Multiplicative terms were applied to test for interaction in prespecified subgroups of interest. RESULTS: A total of 25,553 participants were included in the final analysis, representing 180 million people in the United States. Of the participants 19.4% reported any urge urinary incontinence, 4.2% reported weekly urge urinary incontinence and 1.6% reported daily urge urinary incontinence. In the fully adjusted multivariable models those with a poverty income ratio less than 2.00 showed significantly higher odds of any urge urinary incontinence compared to the group with a poverty income ratio of 2.00 or greater (OR 1.17, 95% CI 1.05-1.30, p=0.003). There was increasing strength of association for weekly and daily urge urinary incontinence (OR 1.31, 95% CI 1.12-1.55, p <0.001, and OR 1.60, 95% CI 1.23-2.09, p=0.001, respectively). Individual interaction analyses revealed no significant effect of female gender, age greater than 50 years, body mass index 30 kg/m2 or greater, or less than a high school education on the association of urge urinary incontinence with the poverty income ratio. CONCLUSIONS: This study revealed a significant association between urge urinary incontinence and socioeconomic status after meaningful adjustment for covariates. Health care interventions targeting low socioeconomic status individuals with urge urinary incontinence are needed to address this disparity.

Newly diagnosed HIV positive children: a unique index case to improve HIV diagnosis and linkage to care of parents.

Newly diagnosed HIV positive children may be unique index cases to identify undiagnosed parents. Data was used from the Pediatric Urgent Start of HAART (NCT02063880) trial, which enrolled hospitalized, ART-naïve, HIV positive children ages 0-12 years in Kenya. Exact McNemar's tests were used to compare proportions of mothers and fathers tested for HIV, linked to care, and on ART at baseline and 6 months. This analysis included 87 newly diagnosed children with HIV who completed 6 months of follow-up. Among 83 children with living mothers, there were improvements in maternal linkage to care and treatment comparing baseline to 6 months (36% vs. 78%; p < 0.0001 and 22% vs. 52%; p < 0.0001). Among 80 children with living fathers, there were increases from baseline to 6 months in the number of fathers who knew the child's HIV status (34% vs. 78%; p < 0.0001), fathers ever tested for HIV (43% vs. 65%; p < 0.0001), fathers ever tested HIV positive (21% vs. 43%; p < 0.0001), fathers ever linked to care (15% vs. 35%; p < 0.0001), and fathers ever initiated on ART (11% vs. 23%; p = 0.0039). Newly diagnosed HIV positive children can be important index cases to identify parents with undiagnosed HIV or poor engagement in care.

Sexual Behavior Patterns and Condom Use in Newly Sexually Active Female University Students.

Our objective was to describe sexual behavior patterns and condom use in newly sexually active female university students. We conducted a 4-year retrospective cohort study (2000-2007) of university women enrolled close to sexual debut (N = 250). Participants reported daily information on intercourse, condom use, and partner/partnership characteristics into Web-based biweekly sexual behavior diaries. We calculated intercourse frequency, proportion of condom-protected events, and incidence of new partner acquisition. We used logistic regression to examine factors associated with condom use at sexual debut; Kaplan-Meier methods to describe cumulative incidence of condom non-use after use at debut; and Cox proportional hazards ratios to examine factors associated with condom non-use. A total of 188 women had at least one male sex partner prior to enrollment or during follow-up. One-third (34.1%) of 27,736 intercourse events were condom-protected. Older age (20+ vs. < 20 years) and use of hormonal birth control were associated with lower likelihood of condom use at sexual debut (adjusted odds ratio [aOR] 0.41, 95% CI 0.17-0.97 and aOR 0.32, 95% CI 0.10-1.03, respectively). Women who reported partners with previous sex partners were less likely to discontinue using condoms after debut (hazard ratio = 0.35, 0.16-0.77) than those reporting partners without previous partners. In college-aged women, older age and hormonal contraceptive use were each inversely associated with condom use at first intercourse. Women with sexually experienced partners were more likely to continue using condoms. Continued efforts are necessary to promote condom use among college-aged women.

Echocardiographic reference intervals with allometric scaling of 823 clinically healthy rhesus macaques (Macaca mulatta).

BACKGROUND: Echocardiography is commonly used for assessing cardiac structure and function in various species including non-human primates. A few previous studies reported normal echocardiographic reference intervals of clinically healthy rhesus macaques under sedation. However, these studies were under-powered, and the techniques were not standardized. In addition, body weight, age, and sex matched reference intervals should be established as echocardiographic measurements are commonly influenced by these variables. The purpose of this study was to establish reference intervals for complete echocardiographic parameters based on a large cohort of clinically healthy rhesus macaques with wide ranges of weight and age distributions using allometric scaling. RESULTS: A total of 823 rhesus macaques (ages 6 months to 31 years old; body weights 1.4 to 22.6 kg) were enrolled. Of these rhesus macaques, 421 were males and 402 were females. They were assessed with a complete echocardiographic examination including structural and functional evaluation under sedation with ketamine hydrochloride. The reference intervals of the key echocardiographic parameters were indexed to weight, age, and sex by calculating the coefficients of the allometric eq. Y = aMb. On correlation matrix, body weight, age, sex, and heart rate were significantly correlated with various echocardiographic parameters and some of the parameters were strongly correlated with body weight and age. Multiple regression analysis revealed that heart rate and body weight statistically significantly predicted several echocardiographic parameters. Valve regurgitation including tricuspid, aortic, pulmonic, and mitral regurgitations without other cardiac structural and functional abnormalities are common in clinically healthy rhesus macaques under ketamine sedation. CONCLUSIONS: In this study, the reference intervals of echocardiographic parameters were established by performing complete echocardiographic examinations on a large number of clinical healthy rhesus macaques. In addition, allometric scaling was performed based on their weight, and further indexed to age and sex. These allometrically scaled reference intervals can be used to accurately evaluate echocardiographic data in rhesus macaques and diagnose structural and functional evidence of cardiac disease.

Lamotrigine Toxicosis Treated with Intravenous Lipid Emulsion Therapy in a Dog.

A female spayed dachshund/mixed-breed dog was evaluated following ingestion of lamotrigine tablets with subsequent rapid onset of vomiting, diarrhea, and generalized tremoring. On initial examination, the dog was moderately obtunded and nonambulatory with intermittent myoclonus and hyperesthesia. Electrocardiogram revealed sinus tachycardia with prolongation of the QT interval. Intravenous lipid emulsion (ILE) infusion was initiated, with reduction in tremoring and improved patient mentation being noted after ∼20 min of therapy. An elevated cardiac troponin I value measured at 1.02 ng/mL the day after presentation. Serum toxicological assay revealed marked reduction in serum lamotrigine levels following ILE and continued reduction during hospitalization. The dog's clinical signs resolved, corrected QT interval returned to normal, and the patient was discharged 38 hr after presentation. Individual cases of lamotrigine toxicosis have not been fully reported in veterinary literature. This case report documents the rapid onset of clinical signs including neurologic dysfunction, cardiac arrhythmias, and transient corrected QT prolongation. Serial serum concentrations of lamotrigine showed a rapid reduction with ILE therapy and corresponded with clinical recovery, suggesting efficacy of ILE treatment in this case.