Glycine supplementation can partially restore oxidative stress-associated glutathione deficiency in ageing cats.

Intracellular levels of glutathione, the major mammalian antioxidant, are reported to decline with age in several species. To understand whether ageing affects circulating glutathione levels in cats, blood was sampled from two age groups, < 3 years and > 9 years. Further, to determine whether dietary supplementation with glutathione precursor glycine (GLY) affects glutathione concentrations in senior cats (> 8 years), a series of free GLY inclusion level dry diets were fed. Subsequently, a 16-week GLY feeding study was conducted in senior cats (> 7 years), measuring glutathione, and markers of oxidative stress. Whole blood and erythrocyte total, oxidised and reduced glutathione levels were significantly decreased in senior cats, compared with their younger counterparts (P ≤ 0·02). The inclusion level study identified 1·5 % free GLY for the subsequent dry diet feeding study. Significant increases in erythrocyte total and reduced glutathione were observed between senior cats fed supplemented and control diets at 4 weeks (P ≤ 0·03; maximum difference of 1·23 µM). Oxidative stress markers were also significantly different between groups at 8 (P = 0·004; difference of 0·68 nG/ml in 8-hydroxy-2'-deoxyguanosine) and 12 weeks (P ≤ 0·049; maximum difference of 0·62 nG/mG Cr in F2-isoprostane PGF2α). Senior cats have lower circulating glutathione levels compared with younger cats. Feeding senior cats a complete and balanced dry diet supplemented with 1·5 % free GLY for 12 weeks elevated initial erythrocyte glutathione and altered markers of oxidative stress. Dietary supplementation with free GLY provides a potential opportunity to restore age-associated reduction in glutathione in cats.

The MARS PETCARE BIOBANK protocol: establishing a longitudinal study of health and disease in dogs and cats.

BACKGROUND: The veterinary care of cats and dogs is increasingly embracing innovations first applied to human health, including an increased emphasis on preventative care and precision medicine. Large scale human population biobanks have advanced research in these areas; however, few have been established in veterinary medicine. The MARS PETCARE BIOBANK™ (MPB) is a prospective study that aims to build a longitudinal bank of biological samples, with paired medical and lifestyle data, from 20,000 initially healthy cats and dogs (10,000 / species), recruited through veterinary hospitals over a ten-year period. Here, we describe the MPB protocol and discuss its potential as a platform to increase understanding of why and how diseases develop and how to advance personalised veterinary healthcare. METHODS: At regular intervals, extensive diet, health and lifestyle information, electronic medical records, clinicopathology and activity data are collected, genotypes, whole genome sequences and faecal metagenomes analysed, and blood, plasma, serum, and faecal samples stored for future research. DISCUSSION: Proposed areas for research include the early detection and progression of age-related disease, risk factors for common conditions, the influence of the microbiome on health and disease and, through genome wide association studies, the identification of candidate loci for disease associated genetic variants. Genomic data will be open access and research proposals for access to data and samples will be considered. Over the coming years, the MPB will provide the longitudinal data and systematically collected biological samples required to generate important insights into companion animal health, identifying biomarkers of disease, supporting earlier identification of risk, and enabling individually tailored interventions to manage disease.

Quality assessment of polymer materials for human model eye development.

PURPOSE: We developed model eyes using six polymer materials to determine which materials were most appropriate in simulating real human sclera and extraocular muscle (EOM). METHODS: Five three-dimensional (3-D) printed polymers (FlexFill, PolyFlex, PCTPE, Soft PLA, and NinjaFlex) and one silicone material were systematically tested by board-certified ophthalmologists and senior ophthalmology residents. Material testing included scleral passes with 6-0 Vicryl sutures through each eye model. Participants completed a survey designed to collect demographic data, subjective assessment of each material's accuracy in simulating real human sclera and EOM, and a ranking for each polymer material to identify which would be most suitable for an ophthalmic surgery training tool. The Wilcoxon signed-rank test was conducted to determine if there was a statistically significant difference in the distribution of ranks between the polymer materials. RESULTS: The distribution of ranks for silicone material's "sclera" and "EOM" components were statistically significantly higher than that of all other polymer materials (all p < 0.05). Silicone material received the highest rank for both "sclera" and "EOM" components. Survey results indicated that the silicone material effectively simulated real human tissue. CONCLUSION: Silicone model eyes performed better than 3-D printed polymers as an educational tool for incorporation into a microsurgical training curriculum. Silicone models provide a low-cost teaching tool that allows for independent practice of microsurgical techniques without requiring a wet-laboratory facility.

Repeatability and reliability of semi-automated anterior segment-optical coherence tomography imaging compared to manual analysis in normal and keratoconus eyes.

PURPOSE: To assess the repeatability and reliability of semi-automated EyeMark Python program measurements compared to manual ImageJ image processing of anterior segment-optical coherence tomography (AS-OCT) structures in healthy and keratoconus eyes. METHODS: Heidelberg AS-OCT was used to image 25 eyes from 14 healthy subjects and 25 eyes from 15 subjects with keratoconus between the ages of 20 and 80 years, collected prospectively, in this observational case-control study. Visual axis scan containing vertical fixation light beam was selected from the 15-line AS-OCT scan raster. Central corneal thickness (CCT), anterior corneal radius of curvature (ACRC), posterior corneal radius of curvature (PCRC), and truncated anterior vault (TAV) were measured using ImageJ software and the EyeMark Python program. MedCalc and R were used to calculate the intraclass correlation coefficient (ICC) and generate Bland-Altman plots (BAP). RESULTS: When comparing the measurements of CCT, ACRC, PCRC, and TAV between manual ImageJ analysis and the EyeMark Python program, ICC values were consistently greater than 0.9, indicating excellent agreement. BAPs comparing the ImageJ and Python measurements of anterior segment structures show no systematic proportional bias and the average differences were near zero and within 95% of the limits of agreement. CONCLUSIONS: Semi-automated tools may provide the necessary efficiency for point-of-care quantitative corneal analysis of raw AS-OCT images. The semi-automated EyeMark Python program offers a repeatable and reliable tool compared to manual ImageJ analysis for measuring anterior segment structures from AS-OCT images among individuals with keratoconus.

Dietary calcium to phosphorus ratio affects postprandial phosphorus concentrations in feline plasma.

The impact of dietary phosphorus on chronic renal disease in cats, humans and other species is receiving increasing attention. As Ca and P metabolism are linked, the ratio of Ca:P is an important factor for consideration when formulating diets for cats and other animals. Here, we describe a fully randomised crossover study including twenty-four healthy, neutered adult cats, investigating postprandial responses in plasma P, ionised Ca and parathyroid hormone (PTH) following one meal (50 % of individual metabolic energy requirement) of each of six experimental diets. Diets were formulated to provide P at either 0·75 or 1·5 g/1000 kcal (4184 kJ) from the soluble phosphorus salt sodium tripolyphosphate (STPP, Na5P3O10), variable levels of organic Ca and P sources, and an intended total Ca:P of about 1·0, 1·5 or 2·0. For each experimental diet, baseline fasted blood samples were collected prior to the meal, and serial blood samples collected hourly for 6 h thereafter. For all diets, a significant increase from baseline was observed at 120 min in plasma PTH (P < 0·001). The diet containing the highest STPP inclusion level and lowest Ca:P induced the highest peaks in postprandial plasma P and PTH levels (1·8 mmol/l and 27·2 pg/ml, respectively), and the longest duration of concentrations raised above baseline were observed at 3 h for P and 6 h for PTH. Data indicate that Ca:P modulates postprandial plasma P and PTH. Therefore, when formulating diets containing soluble P salts for cats, increasing the Ca:P ratio should be considered.

Corneal Structural Changes in Congenital Glaucoma.

OBJECTIVE: To identify corneal structure differences on quantitative high-frequency ultrasound biomicroscopy (UBM) among subjects with congenital glaucoma compared with controls. METHODS: This prospective case-control study evaluated 180 UBM images from 44 eyes of 30 subjects (18 control and 12 glaucoma, mean age 5.2±8.0 years, range 0.2-25.8 years) enrolled in the Pediatric Anterior Segment Imaging and Innovation Study (PASIIS). ImageJ was used to quantify a comprehensive set of corneal structures according to 21 quantitative parameters. Statistical analysis compared corneal measurements in glaucoma subtypes and age-matched controls with significance testing and mixed effects models. RESULTS: Significant differences between congenital glaucoma cases and controls were identified in 16 of 21 measured parameters including angle-to-angle, central and peripheral corneal thicknesses, scleral integrated pixel density, anterior corneal radius of curvature, and posterior corneal radius of curvature. Eight parameters differed significantly between primary congenital glaucoma and glaucoma following congenital cataract surgery. CONCLUSION: Multiple measurable corneal structural differences exist between congenital glaucoma and control eyes, and between primary and secondary congenital glaucoma, including but not limited to corneal width and thickness. The structural differences can be quantified from UBM image analysis. Further studies are needed to determine whether corneal features associated with glaucoma can be used to diagnose or monitor progression of congenital glaucoma.

Towards establishing no observed adverse effect levels (NOAEL) for different sources of dietary phosphorus in feline adult diets: results from a 7-month feeding study.

High dietary phosphorus (P), particularly soluble salts, may contribute to chronic kidney disease development in cats. The aim of the present study was to assess the safety of P supplied at 1 g/1000 kcal (4184kJ) from a highly soluble P salt in P-rich dry format feline diets. Seventy-five healthy adult cats (n 25/group) were fed either a low P control (1·4 g/1000 kcal [4184kJ]; Ca:P ratio 0·97) or one of two test diets with 4 g/1000 kcal (4184 kJ); Ca:P 1·04 or 5 g/1000 kcal (4184kJ); Ca:P 1·27, both incorporating 1 g/1000 kcal (4184 kJ) sodium tripolyphosphate (STPP) - for a period of 30 weeks in a randomised parallel-group study. Health markers in blood and urine, glomerular filtration rate, renal ultrasound and bone density were assessed at baseline and at regular time points. At the end of the test period, responses following transition to a commercial diet (total P - 2·34 g/1000 kcal [4184kJ], Ca:P 1·3) for a 4-week washout period were also assessed. No adverse effects on general, kidney or bone (skeletal) function and health were observed. P and Ca balance, some serum biochemistry parameters and regulatory hormones were increased in cats fed test diets from week 2 onwards (P ≤ 0·05). Data from the washout period suggest that increased serum creatinine and urea values observed in the two test diet groups were influenced by dietary differences during the test period, and not indicative of changes in renal function. The present data suggest no observed adverse effect level for feline diets containing 1 g P/1000 kcal (4184 kJ) from STPP and total P level of up to 5 g/1000 kcal (4184 kJ) when fed for 30 weeks.

Inter-rater Reliability and Repeatability of Manual Anterior Segment Optical Coherence Tomography Image Grading in Keratoconus.

OBJECTIVES: To determine the repeatability of corneal measurements from anterior segment optical coherence tomography (AS-OCT) images using ImageJ software in healthy eyes compared with eyes with keratoconus. METHODS: Anterior segment OCT images of 25 eyes from 14 healthy subjects and 25 eyes from 15 subjects with keratoconus between the ages of 20 and 80 years were evaluated. Two trained observers used ImageJ to measure the central corneal cross-sectional area and anterior and posterior corneal arc lengths. MedCalc statistical software was used to generate the intraclass correlation coefficient (ICC) and Bland-Altman plots (BAPs) for observer measurements. RESULTS: Observer measurements of the central corneal cross-sectional area and anterior and posterior corneal arc lengths yielded an ICC >0.7. The ICC comparing the 3 parameters ranged from 0.75 to 0.84 for the control and 0.96 to 0.98 for the keratoconus group. No systematic proportional bias was detected by the BAPs. There were minimal differences between the 2 observer's measurements, with a mean of the difference of 0.3 mm2, 0 mm, and 0 mm, for the 3 measurements, respectively. CONCLUSIONS: This study suggests that ImageJ software is a repeatable and reliable tool in the analysis of corneal parameters from AS-OCT images among patients with keratoconus and may be applicable to AS-OCT imaging protocol development, an area of active keratoconus research.

Novel Homozygous Missense Variant in GJA3 Connexin Domain Causing Congenital Nuclear and Cortical Cataracts.

Congenital cataracts (CC) are responsible for approximately one-tenth of childhood blindness cases globally. Here, we report an African American family with a recessively inherited form of CC. The proband demonstrated decreased visual acuity and bilateral cataracts, with nuclear and cortical cataracts in the right and left eye, respectively. Exome sequencing revealed a novel homozygous variant (c.563A > G; p.(Asn188Ser)) in GJA3, which was predicted to be pathogenic by structural analysis. Dominantly inherited variants in GJA3 are known to cause numerous types of cataracts in various populations. Our study represents the second case of recessive GJA3 allele, and the first report in African Americans. These results validate GJA3 as a bona fide gene for recessively inherited CC in humans.

Acute Stroke Presentation, Care, and Outcomes in Community Hospitals in Northern California During the COVID-19 Pandemic.

BACKGROUND AND PURPOSE: Shelter-in-place (SIP) orders implemented to mitigate severe acute respiratory syndrome coronavirus 2 spread may inadvertently discourage patient care-seeking behavior for critical conditions like acute ischemic stroke. We aimed to compare temporal trends in volume of acute stroke alerts, patient characteristics, telestroke care, and short-term outcomes pre- and post-SIP orders. METHODS: We conducted a cohort study in 21 stroke centers of an integrated healthcare system serving 4.4+ million members across Northern California. We included adult patients who presented with suspected acute stroke and were evaluated by telestroke between January 1, 2019, and May 9, 2020. SIP orders announced the week of March 15, 2020, created pre (January 1, 2019, to March 14, 2020) and post (March 15, 2020, to May 9, 2020) cohort for comparison. Main outcomes were stroke alert volumes and inpatient mortality for stroke. RESULTS: Stroke alert weekly volume post-SIP (mean, 98 [95% CI, 92-104]) decreased significantly compared with pre-SIP (mean, 132 [95% CI, 130-136]; P<0.001). Stroke discharges also dropped, in concordance with acute stroke alerts decrease. In total, 9120 patients were included: 8337 in pre- and 783 in post-SIP cohorts. There were no differences in patient demographics. Compared with pre-SIP, post-SIP patients had higher National Institutes of Health Stroke Scale scores (P=0.003), lower comorbidity score (P<0.001), and arrived more often by ambulance (P<0.001). Post-SIP, more patients had large vessel occlusions (P=0.03), and there were fewer stroke mimics (P=0.001). Discharge outcomes were similar for post-SIP and pre-SIP cohorts. CONCLUSIONS: In this cohort study, regional stroke alert and ischemic stroke discharge volumes decreased significantly in the early COVID-19 pandemic. Compared with pre-SIP, the post-SIP population showed no significant demographic differences but had lower comorbidity scores, more severe strokes, and more large vessel occlusions. The inpatient mortality was similar in both cohorts. Further studies are needed to understand the causes and implications of care avoidance to patients and healthcare systems.

Gestational Age and Risk of Mortality in Term-Born Critically Ill Neonates Admitted to PICUs in Australia and New Zealand.

OBJECTIVES: Gestational age at birth is declining, probably because more deliveries are being induced. Gestational age is an important modifiable risk factor for neonatal mortality and morbidity. We aimed to investigate the association between gestational age and mortality in hospital for term-born neonates (≥ 37 wk') admitted to PICUs in Australia and New Zealand. DESIGN: Observational multicenter cohort study. SETTING: PICUs in Australia and New Zealand. PATIENTS: Term-born neonates (≥ 37 wk) admitted to PICUs. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS:: We studied 5,073 infants born with a gestational age greater than or equal to 37 weeks and were less than 28 days old when admitted to a PICU in Australia or New Zealand between 2007 and 2016. The association between gestational age and mortality was estimated using a multivariable logistic regression model, adjusting for age, sex, indigenous status, Pediatric Index of Mortality version 2, and site. The median gestational age was 39.1 weeks (interquartile range, 38.2-40 wk) and mortality in hospital was 6.6%. Risk of mortality declined log-linearly with gestational age. The adjusted analysis showed a 20% (95% CI, 11-28%) relative reduction in mortality for each extra week of gestation beyond 37 weeks. The effect of gestation was stronger among those who received extracorporeal life support: each extra week of gestation was associated with a 44% (95% CI, 25-57%) relative reduction in mortality. Longer gestation was also associated with reduced length of stay in hospital: each week increase in gestation, the average length of stay decreased by 4% (95% CI, 2-6%). CONCLUSIONS: Among neonates born at "term" who are admitted to a PICU, increasing gestational age at birth is associated with a substantial reduction in the risk of dying in hospital. The maturational influence on outcome was more strongly noted in the sickest neonates, such as those requiring extracorporeal life support. This information is important in view of the increasing proportion of planned births in both high- and low-/middle-income countries.

The Effect of Imputation of PaO2/FIO2 From SpO2/FIO2 on the Performance of the Pediatric Index of Mortality 3.

OBJECTIVES: To investigate if the performance of Pediatric Index of Mortality 3 is improved by including imputed values for the PaO2/FIO2 ratio where measurements of PaO2 or FIO2 are missing. DESIGN: A prospective observational study. SETTING: A bi-national pediatric intensive care registry. PATIENTS: The records of 37,983 admissions of children less than 16 years old admitted to 19 ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Seven published equations describing an association between PaO2/FIO2 and oxygen saturation measured by pulse oximetry (SpO2)/FIO2 were used to derive an alternative variable d100 × FIO2/PaO2 for the Pediatric Index of Mortality 3 variable 100 × FIO2/PaO2. Six equations exclude SpO2/FIO2 values if SpO2 is greater than 96-98%. 100 × FIO2/PaO2 was missing in 72% of patient records primarily due to missing PaO2, d100 × FIO2/PaO2 was missing in 71% of patient records if values of SpO2greater than 97% were excluded or in 17% of patient records if all measurements of SpO2 were included. Univariable analysis supported the inclusion of SpO2 values greater than 97%. Compared to the standard Pediatric Index of Mortality 3 model, two alternative models imputing 100 × FIO2/PaO2 from d100 × FIO2/PaO2 only if 100 × FIO2/PaO2 was missing, or using d100 × FIO2/PaO2 values exclusively, resulted in a small but statistically significant improvements in discrimination of Pediatric Index of Mortality 3 (area under the receiver operator curve 0.9068 [0. 8965-0. 9171]; 0.9083 [0.8981-0.9184]; 0.9087 [0.8987-0.9188], respectively). CONCLUSIONS: Imputation of the PaO2/FIO2 ratio in cases where arterial sampling was not performed resulted in a large reduction in the rate of missing data if all values of SpO2 were included. The imputation technique improved the discrimination of Pediatric Index of Mortality 3; however, the magnitude of the increment in overall model performance was small. A possible benefit of the approach is reducing the potential for bias resulting from variation in practice for invasive monitoring of oxygenation.

Comparative Effectiveness of 2 Diabetes Prevention Lifestyle Programs in the Workplace: The City and County of San Francisco Diabetes Prevention Trial.

INTRODUCTION: Data on the comparative effectiveness of Diabetes Prevention Programs (DPPs) in the workplace are limited. METHODS: Between September 2015 and July 2016, employees of the City and County of San Francisco who were at risk for type 2 diabetes (N = 158) were randomly assigned to one of 2 DPP-derived programs recognized by the Centers for Disease Control and Prevention: an in-person YMCA-DPP (n = 78) or an online virtual lifestyle management DPP (VLM-DPP) offered through Canary Health (n = 80). The primary outcome was change in body weight assessed at 6 and 12 months. Follow-up ended in August 2017. RESULTS: Both the YMCA-DPP and VLM-DPP yielded a significant reduction in percentage body weight at 6 months. For the YMCA-DPP, mean percentage change at 6 months was -2.70% (95% confidence interval [CI], -3.91% to -1.48%) and at 12 months was -2.46% (95% CI, -4.24% to -0.68%). For the VLM-DPP, mean percentage change at 6 months was -2.41% (95% CI, -4.07% to -0.77%) and at 12 months was -1.59% (95% CI, -3.51% to 0.33%). The mean between-condition difference at 6 months was -0.25% (95% CI, -2.04% to 1.55%) and at 12 months was -0.84% (95% CI, -3.03% to 1.34%). No significant differences were observed between conditions. The YMCA-DPP had a slightly higher reduction in waist circumference than VLM-DDP at 6 months (mean between-condition difference -2.00 cm [95% CI, -4.24 to 0.25 cm]). Participant engagement, expressed as mean number of completed core program sessions, was significantly higher for the YMCA-DPP than the VLM-DPP. Participants of the YMCA-DPP completed an average of 10.2 sessions (95% CI, 9.0 to 11.4), and participants of the VLM-DPP completed an average of 5.9 sessions (95% CI, 4.7 to 7.1). The adjusted mean between-condition difference was 4.2 sessions (95% CI, 2.54 to 5.99). CONCLUSION: Both the YMCA-DPP and VLM-DPP yielded weight loss at 6 months, which was maintained at 12 months in the YMCA-DPP. The workplace may be an effective setting to offer DPPs.

Effects of the long-term feeding of diets enriched with inorganic phosphorus on the adult feline kidney and phosphorus metabolism.

Renal disease has a high incidence in cats, and some evidence implicates dietary P as well. To investigate this further, two studies in healthy adult cats were conducted. Study 1 (36 weeks) included forty-eight cats, stratified to control or test diets providing 1·2 or 4·8 g/1000 kcal (4184 kJ) P (0 or approximately 3·6 g/1000 kcal (4184 kJ) inorganic P, Ca:P 1·2, 0·6). Study 2 (29 weeks) included fifty cats, stratified to control or test diets, providing 1·3 or 3·6 g/1000 kcal (4184 kJ) P (0 or approximately 1·5 g/1000 kcal (4184 kJ) inorganic P, Ca:P 1·2, 0·9). Health markers, glomerular filtration rate (GFR) and mineral balance were measured regularly, with abdominal ultrasound. Study 1 was halted after 4 weeks as the test group GFR reduced by 0·4 (95 % CI 0·3, 0·5) ml/min per kg, and ultrasound revealed changes in renal echogenicity. In study 2, at week 28, no change in mean GFR was observed (P >0·05); however, altered renal echogenicity was detected in 36 % of test cats. In agreement with previous studies, feeding a diet with Ca:P <1·0, a high total and inorganic P inclusion resulted in loss of renal function and changes in echogenicity suggestive of renal pathology. Feeding a diet containing lower total and inorganic P with Ca:P close to 1·0 led to more subtle structural changes in a third of test cats; however, nephrolithiasis occurred in both diet groups, complicating data interpretation. We conclude that the no observed adverse effects level for total dietary P in adult cats is lower than 3·6 g/1000 kcal (4184 kJ), however the effect of inorganic P sources and Ca:P require further investigation.

Acute direct traumatic optic neuropathy treated with steroids, minocycline and hyperbaric oxygen: a case report.

We describe the emergency management of a man who experienced acute vision loss diagnosed as direct traumatic optic neuropathy (TON) in his right eye (no light perception) after falling from a height. TON is caused by a high-impact mechanism of injury. Clinical findings include acute vision loss, which is typically immediate, afferent pupillary defect, decreased color vision, and visual field defects. Treatment is controversial because of the lack of strong evidence supporting intervention over observation. In this case report, our treatment strategy comprised immediate hyperbaric oxygen (HBO2) and daily high doses of a steroid. On the second day, minocycline was added to the treatment regimen for its neuroprotective effects. The patient was discharged after receiving six HBO2 treatments and six days of intravenous solumedrol transitioned to oral prednisone. After the third HBO2 treatment, his vision improved to 20/100; after the fourth treatment, it was 20/40 and plateaued. At the time of discharge, it was 20/40. At two-month follow-up, his corrected visual acuity was 20/60+2 in the affected eye. Immediate HBO2 for ischemic and mechanical injury to the optic nerve following trauma is a therapeutic option.

Anterior segment ultrasound biomicroscopy image analysis using ImageJ software: Intra-observer repeatability and inter-observer agreement.

PURPOSE: In this novel study, we demonstrate a standardized imaging and measurement protocol of anterior segment (AS) structures with reliability analysis using ultrasound biomicroscopy (UBM) and ImageJ software. METHODS: Ten pediatric and young adult patients undergoing examination under anesthesia for AS pathology were imaged using UBM. Four trained observers analyzed 20 images using ImageJ. Forty-five structural parameters were measured. Those that relied on the trabecular-iris angle (TIA) as a reference landmark were labeled TIA-dependent (TD) and all others were labeled non-TIA dependent (NTD). Intra-observer repeatability (IOR) and inter-observer agreement (IOA) of measurements were determined using coefficient of variation (CV) and intra-class correlation (ICC) followed by assessment of Bland-Altman plots (BAP) for each pair of observers, respectively. RESULTS: For NTD parameters, non-ciliary body (CB) related measurements showed CV range 0.60-16.22% and ICC range 0.84-0.89, whereas CB-related parameters showed CV range 2.86-23.40% and ICC range 0.29-0.92. For TD parameters, parameters < 2 degrees removed from reference showed CV range 0.02-5.40% and ICC range 0.89-1.00, whereas parameters > 1 degree removed showed CV range 0.63-27.44% and ICC range 0.22-1.00. No systematic proportional bias was detected by BAPs. CONCLUSIONS: Preplaced landmarks yielded good IOR and IOA in quantitative assessment of AS structures that were NTD and non-CB-related or less removed from the reference. CB-related NTD measurements varied greatly in IOR and IOA, indicating protocol modifications or CB qualitative assessments needed to improve accuracy. Variability in TD measurements increased the further removed from the reference, which supports implementation of a reliable reference landmark to minimize variation.

Impact of dietary macronutrient profile on feline body weight is not consistent with the protein leverage hypothesis.

The protein leverage hypothesis proposes that the need to prioritise protein intake drives excess energy intake (EI) when the dietary ratio of protein to fat and carbohydrate is reduced. We hypothesised that cats may become prone to overconsuming energy content when moderate protein diets were offered, and considered the potential influence of fat and carbohydrate on intake. To determine the effect of dietary protein and macronutrient profile (MNP) on EI, weight and body composition, cats (1-4 years) were offered food in excess of energy requirements (ER). A total of six diets were formulated, containing moderate (approximately 7 % w/w; approximately 22 % metabolisable energy (ME)) or high (approximately 10 % w/w; approximately 46 % ME) protein and varying levels of carbohydrate and fat. For 4 weeks, 120 cats were offered 100 % of their individual ER of a diet at the MNP selected by adult cats (50:40:10 protein energy ratio:fat energy ratio:carbohydrate energy ratio). EI, body weight (BW), body composition, activity and palatability were measured. Subsequently, cats were offered one of the six diets at 200 % of their individual ER for 4 weeks when measurements were repeated. Cats offered excess high protein diets had higher EI (kJ/kg) throughout, but at 4 weeks BW was not significantly different to baseline. Cats offered excess moderate protein diets reduced EI and gradually lost weight (average loss of 0·358 (99 % CI 0·388, 0·328) kg), irrespective of fat:carbohydrate and initial palatability. The data do not support the protein leverage hypothesis. Furthermore, cats were able to adapt intake of a wet diet with high protein in an overfeeding environment within 28 d.

Burden of disease and change in practice in critically ill infants with bronchiolitis.

Bronchiolitis represents the most common cause of non-elective admission to paediatric intensive care units (ICUs).We assessed changes in admission rate, respiratory support, and outcomes of infants <24 months with bronchiolitis admitted to ICU between 2002 and 2014 in Australia and New Zealand.During the study period, bronchiolitis was responsible for 9628 (27.6%) of 34 829 non-elective ICU admissions. The estimated population-based ICU admission rate due to bronchiolitis increased by 11.76 per 100 000 each year (95% CI 8.11-15.41). The proportion of bronchiolitis patients requiring intubation decreased from 36.8% in 2002, to 10.8% in 2014 (adjusted OR 0.35, 95% CI 0.27-0.46), whilst a dramatic increase in high-flow nasal cannula therapy use to 72.6% was observed (p<0.001). We observed considerable variability in practice between units, with six-fold differences in risk-adjusted intubation rates that were not explained by ICU type, size, or major patient factors. Annual direct hospitalisation costs due to severe bronchiolitis increased to over USD30 million in 2014.We observed an increasing healthcare burden due to severe bronchiolitis, with a major change in practice in the management from invasive to non-invasive support that suggests thresholds to admittance of bronchiolitis patients to ICU have changed. Future studies should assess strategies for management of bronchiolitis outside ICUs.

The burden of invasive infections in critically ill Indigenous children in Australia.

OBJECTIVES: To describe the incidence and mortality of invasive infections in Indigenous children admitted to paediatric and general intensive care units (ICUs) in Australia. DESIGN: Retrospective multi-centre cohort study of Australian and New Zealand Paediatric Intensive Care Registry data. PARTICIPANTS: All children under 16 years of age admitted to an ICU in Australia, 1 January 2002 - 31 December 2013. Indigenous children were defined as those identified as Aboriginal and/or Torres Strait Islander in a mandatory admissions dataset. MAIN OUTCOMES: Population-based ICU mortality and admission rates. RESULTS: Invasive infections accounted for 23.0% of non-elective ICU admissions of Indigenous children (726 of 3150), resulting in an admission rate of 47.6 per 100 000 children per year. Staphylococcus aureus was the leading pathogen identified in children with sepsis/septic shock (incidence, 4.42 per 100 000 Indigenous children per year; 0.57 per 100 000 non-Indigenous children per year; incidence rate ratio 7.7; 95% CI, 5.8-10.1; P < 0.001). While crude and risk-adjusted ICU mortality related to invasive infections was not significantly different for Indigenous and non-Indigenous children (odds ratio, 0.75; 95% CI, 0.53-1.07; P = 0.12), the estimated population-based age-standardised mortality rate for invasive infections was significantly higher for Indigenous children (2.67 per 100 000 per year v 1.04 per 100 000 per year; crude incidence rate ratio, 2.65; 95% CI, 1.88-3.64; P < 0.001). CONCLUSIONS: The ICU admission rate for severe infections was several times higher for Indigenous than for non-Indigenous children, particularly for S. aureus infections. While ICU case fatality rates were similar, the population-based mortality was more than twice as high for Indigenous children. Our study highlights an important area of inequality in health care for Indigenous children in a high income country that needs urgent attention.

Effect of oral niacin on central retinal vein occlusion.

PURPOSE: Niacin, a treatment for dyslipidemia, is known to induce vasodilation as a secondary effect. Previous instances of patients with chronic central retinal vein occlusion (CRVO) and cystoid macular edema (CME) have been observed to spontaneously improve when placed on systemic niacin for hypercholesterolemia. The purpose of this study was to evaluate the effects of niacin on CRVO and associated ocular complications. METHODS: A prospective, single-center, non-randomized, interventional case series of niacin for CRVO was conducted. Best-correct visual acuity (BCVA), central macular thickness (CMT), and ocular complications were analyzed in 50 patients over 1 year. Eight patients were controls. RESULTS: The mean initial logMAR BCVA was 0.915, and improved with niacin to 0.745 (P = 0.12), 0.665 (P = 0.02) and 0.658 (P = 0.03) after 3, 6, and 12 months of follow-up, respectively. At baseline, mean CMT was 678.9 µm, and improved to 478.1 µm (P = 0.001), 388.6 µm (P < 0.001), and 317.4 µm (P < 0.001) for the same time points. The control group had a mean initial logMAR BCVA of 1.023, which gradually deteriorated to 1.162 (P = 0.36) after 12 months, and baseline CMT of 700.0 µm at baseline, which gradually improved to 490.9 µm (P = 0.06) after 12 months. Panretinal photocoagulation for neovascularization was required in 5 patients (13.2%) receiving niacin and 3 (37.5%) controls. CONCLUSIONS: These data suggest that niacin may be associated with functional and anatomic improvements in eyes with CRVO. Future investigations will help ascertain whether there is a role for niacin as an adjunct therapy to intravitreal injections in the management of CRVO.