The Patient-Determined Disease Steps scale is not interchangeable with the Expanded Disease Status Scale in mild to moderate multiple sclerosis.

BACKGROUND AND PURPOSE: The validity, reliability, and longitudinal performance of the Patient-Determined Disease Steps (PDDS) scale is unknown in people with multiple sclerosis (MS) with mild to moderate disability. We aimed to examine the psychometric properties and longitudinal performance of the PDDS. METHODS: We included relapsing-remitting MS patients with an Expanded Disability Status Scale (EDSS) score of less than 4. Validity and test-retest reliability was examined. Longitudinal data were analysed with mixed-effect modelling and Cohen's kappa for concordance in confirmed disability progression (CDP). RESULTS: We recruited a total of 1093 participants, of whom 904 had complete baseline data. The baseline correlation between PDDS and EDSS was weak (ρ = 0.45, p < 0.001). PDDS had stronger correlations with patient-reported outcomes (PROs). Conversely, EDSS had stronger correlations with age, disease duration, Kurtzke's functional systems and processing speed test. PDDS test-retest reliability was good to excellent (concordance correlation coefficient = 0.73-0.89). Longitudinally, PDDS was associated with EDSS, age and depression. A higher EDSS score was associated with greater PDSS progression. The magnitude of these associations was small. There was no concordance in CDP as assessed by PDDS and EDSS. CONCLUSION: The PDDS has greater correlation with other PROs but less correlation with other MS-related outcome measures compared to the EDSS. There was little correlation between PDDS and EDSS longitudinally. Our findings suggest that the PDDS scale is not interchangeable with the EDSS.

Quantification of the effect of in utero events on lifetime resilience in dairy cows.

Currently, the dairy industry is facing many challenges that could affect its sustainability, including climate change and public perception of the industry. As a result, interest is increasing in the concept of identifying resilient animals, those with a long productive lifespan, as well as good reproductive performance and milk yield. There is much evidence that events in utero, that is, the developmental origins of health and disease hypothesis, alter the life-course health of offspring and we hypothesized that these could alter resilience in calves, where resilience is identified using lifetime data. The aim of this study was to quantify lifetime resilience scores (LRS) using an existing scoring system, based on longevity with secondary corrections for age at first calving and calving interval, and to quantify the effects of in utero events on the LRS using 2 datasets. The first was a large dataset of cattle on 83 farms in Great Britain born from 2006 to 2015 and the second was a smaller, more granular dataset of cattle born between 2003 and 2015 in the Langhill research herd at Scotland's Rural College. Events during dam's pregnancy included health events (lameness, mastitis, use of an antibiotic or anti-inflammatory medication), the effect of heat stress as measured by temperature-humidity index, and perturbations in milk yield and quality (somatic cell count, percentage fat, percentage protein and fat:protein ratio). Daughters born to dams that experienced higher temperature-humidity indexes while they were in utero during the first and third trimesters of pregnancy had lower LRS. Daughter LRS were also lower where milk yields or median fat percentages in the first trimester were low, and when milk yields were high in the third trimester. Dam LRS was positively associated with LRS of their offspring; however, as parity of the dam increased, LRS of their calves decreased. Similarly, in the Langhill herd, dams of a higher parity produced calves with lower LRS. Additionally, dams that recorded a high maximum locomotion score in the third trimester of pregnancy were negatively associated with lower calf LRS in the Langhill herd. Our results suggest that events that occur during pregnancy have lifelong consequences for the calf's lifetime performance. However, experience of higher temperature-humidity indexes, higher dam LRS, and mothers in higher parities explained a relatively small proportion of variation in offspring LRS, which suggests that other factors play a substantial role in determining calf LRS. Although "big data" can contain a considerable amount of noise, similar findings between the 2 datasets indicate it is likely these findings are real.

Comparison of multiple international metrics for benchmarking antibiotic usage (ABU) using UK beef and sheep data.

BACKGROUND: Accurate surveillance of livestock antibiotic usage (ABU) at the farm level is an increasingly important part of national antibiotic stewardship initiatives. Numerous ABU indicators or metrics have been developed in Europe and North America but the comparability of these metrics is poorly understood. For policymakers, understanding the relationship between metrics is important when considering the risks posed by ABU and how to regulate them, at the national level, and regulate international trade access in livestock products between countries who use different ABU metrics. OBJECTIVES: To quantify the patterns of ABU among beef (cattle) and lamb (sheep) production systems. To explore ABU variation between farm types across seven ABU metrics developed in Europe and North America using a common dataset of sheep and beef farms' antibiotic purchases from the UK. METHODS: A dataset of >16 200 antibiotic sales events to 686 farm enterprises of different types underwent quantitative analysis. Correlation matrixes were generated for seven international ABU metrics. RESULTS: ABU was significantly higher among calf-rearers. Across all farm types, tetracyclines and ß-lactams were the predominant groups by mass, but represent a similar dose equivalent to macrolides across most farm types. Good agreement (>0.9) was observed between metrics. CONCLUSIONS: Reliable metrics to accurately benchmark farms are crucial for maintaining confidence of farmers in the fairness of any surveillance system, especially when the ranking of any given system may be linked to financial subsidies or penalties and also when negotiating import and export access for livestock products between countries.

Heterogeneity on long-term disability trajectories in patients with secondary progressive MS: a latent class analysis from Big MS Data network.

BACKGROUND: Over the decades, several natural history studies on patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS) were reported from international registries. In PPMS, a consistent heterogeneity on long-term disability trajectories was demonstrated. The aim of this study was to identify subgroups of patients with SPMS with similar longitudinal trajectories of disability over time. METHODS: All patients with MS collected within Big MS registries who received an SPMS diagnosis from physicians (cohort 1) or satisfied the Lorscheider criteria (cohort 2) were considered. Longitudinal Expanded Disability Status Scale (EDSS) scores were modelled by a latent class growth analysis (LCGA), using a non-linear function of time from the first EDSS visit in the range 3-4. RESULTS: A total of 3613 patients with SPMS were included in the cohort 1. LCGA detected three different subgroups of patients with a mild (n=1297; 35.9%), a moderate (n=1936; 53.6%) and a severe (n=380; 10.5%) disability trajectory. Median time to EDSS 6 was 12.1, 5.0 and 1.7 years, for the three groups, respectively; the probability to reach EDSS 6 at 8 years was 14.4%, 78.4% and 98.3%, respectively. Similar results were found among 7613 patients satisfying the Lorscheider criteria. CONCLUSIONS: Contrary to previous interpretations, patients with SPMS progress at greatly different rates. Our identification of distinct trajectories can guide better patient selection in future phase 3 SPMS clinical trials. Additionally, distinct trajectories could reflect heterogeneous pathological mechanisms of progression.

Occult retinopathy following treatment of Hepatitis C with glecaprevir/pibrentasvir (Mavyret).

BACKGROUND/PURPOSE: Medication-induced ocular toxicity is an important consideration in the differential diagnosis of unexplained visual disturbance. We present a case of visual disturbance after starting treatment with glecaprevir/pibrentasvir (Mavyret), a therapy for Hepatitis C virus approved by the FDA in 2017. METHODS: A 50-year-old male with no significant ocular history experienced bilateral visual disturbance, including visual field and acuity loss, shortly after initiating treatment with Mavyret for Hepatitis C. Examination of the anterior and posterior segments was unremarkable, and no abnormalities could be identified on multimodal imaging of the eye and brain, including MRI, SD-OCT, and fundus autofluorescence. Extensive testing for inflammatory, infectious, nutritional, and genetic etiologies for optic neuropathy and retinopathy was negative. RESULTS: Electrophysiology testing was pursued to narrow the broad differential diagnosis. Full-field electroretinography and multi-focal electroretinography detected deficiencies in the rod and cone visual pathways and attenuated electrophysiologic responses in the fovea. Pattern electroretinography and visually-evoked potentials demonstrated macula dysfunction. Taken together, electrophysiologic data suggested diffuse retinal dysfunction, which was most pronounced in the macula. CONCLUSIONS: Given the temporal relationship between Mavyret administration and vision loss in our patient, and the absence of an underlying cause after extensive evaluation, we propose that Mavyret may be associated with a toxic occult retinopathy characterized by panretinal dysfunction without clinically apparent structural findings.

Serum 1H nuclear magnetic resonance-based metabolomics of sole lesion development in Holstein cows.

Sole hemorrhage and sole ulcers, referred to as sole lesions, are important causes of lameness in dairy cattle. We aimed to compare the serum metabolome of dairy cows that developed sole lesions in early lactation with that of cows that remained unaffected. We prospectively enrolled a cohort of 1,169 Holstein dairy cows from a single dairy herd and assessed animals at 4 time points: before calving, immediately after calving, early lactation, and late lactation. Sole lesions were recorded by veterinary surgeons at each time point, and serum samples were collected at the first 3 time points. Cases were defined by the presence of sole lesions in early lactation and further subdivided by whether sole lesions had been previously recorded; unaffected controls were randomly selected to match cases. Serum samples from a case-control subset of 228 animals were analyzed with proton nuclear magnetic resonance spectroscopy. Spectral signals, corresponding to 34 provisionally annotated metabolites and 51 unlabeled metabolites, were analyzed in subsets relating to time point, parity cohort, and sole lesion outcome. We used 3 analytic methods (partial least squares discriminant analysis, least absolute shrinkage and selection operator regression, and random forest) to determine the predictive capacity of the serum metabolome and identify informative metabolites. We applied bootstrapped selection stability, triangulation, and permutation to support the inference of variable selection. The average balanced accuracy of class prediction ranged from 50 to 62% depending on the subset. Across all 17 subsets, 20 variables had a high probability of being informative; those with the strongest evidence of being associated with sole lesions corresponded to phenylalanine and 4 unlabeled metabolites. We conclude that the serum metabolome, as characterized by proton nuclear magnetic resonance spectroscopy, does not appear able to predict sole lesion presence or future development of lesions. A small number of metabolites may be associated with sole lesions although, given the poor prediction accuracies, these metabolites are likely to explain only a small proportion of the differences between affected and unaffected animals. Future metabolomic studies may reveal underlying metabolic mechanisms of sole lesion etiopathogenesis in dairy cows; however, the experimental design and analysis need to effectively control for interanimal and extraneous sources of spectral variation.

Predicting lameness in dairy cattle using untargeted liquid chromatography-mass spectrometry-based metabolomics and machine learning.

Lameness in dairy cattle is a highly prevalent condition that impacts on the health and welfare of dairy cows. Prompt detection and implementation of effective treatment is important for managing lameness. However, major limitations are associated with visual assessment of lameness, which is the most commonly used method to detect lameness. The aims of this study were to investigate the use of metabolomics and machine learning to develop novel methods to detect lameness. Untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) alongside machine learning models and a stability selection method were utilized to evaluate the predictive accuracy of differences in the metabolomics profile of first-lactation dairy cows before (during the transition period) and at the time of lameness (based on visual assessment using the 0-3 scale of the Agriculture and Horticulture Development Board). Urine samples were collected from 2 cohorts of dairy heifers and stored at -86°C before analysis using LC-MS. Cohort 1 (n = 90) cows were recruited as current first-lactation cows with weekly mobility scores recorded over a 4-mo timeframe, from which newly lame and nonlame cows were identified. Cohort 2 (n = 30) cows were recruited within 3 wk before calving, and lameness events (based on mobility score) were recorded through lactation until a minimum of 70 d in milk (DIM). All cows were matched paired by DIM ± 14 d. The median DIM at lameness identification was 187.5 and 28.5 for cohort 1 and 2, respectively. The best performing machine learning models predicted lameness at the time of lameness with an accuracy of between 81 and 82%. Using stability selection, the prediction accuracy at the time of lameness was 80 to 81%. For samples collected before and after calving, the best performing machine learning model predicted lameness with an accuracy of 71 and 75%, respectively. The findings from this study demonstrate that untargeted LC-MS profiling combined with machine learning methods can be used to predict lameness as early as before calving and before observable changes in gait in first-lactation dairy cows. The methods also provide accuracies for detecting lameness at the time of observable changes in gait of up to 82%. The findings demonstrate that these methods could provide substantial advancements in the early prediction and prevention of lameness risk. Further external validation work is required to confirm these findings are generalizable; however, this study provides the basis from which future work can be conducted.

Charting a global research strategy for progressive MS-An international progressive MS Alliance proposal.

BACKGROUND: Progressive forms of multiple sclerosis (MS) affect more than 1 million individuals globally. Recent approvals of ocrelizumab for primary progressive MS and siponimod for active secondary progressive MS have opened the therapeutic door, though results from early trials of neuroprotective agents have been mixed. The recent introduction of the term 'active' secondary progressive MS into the therapeutic lexicon has introduced potential confusion to disease description and thereby clinical management. OBJECTIVE: This paper reviews recent progress, highlights continued knowledge and proposes, on behalf of the International Progressive MS Alliance, a global research strategy for progressive MS. METHODS: Literature searches of PubMed between 2015 and May, 2021 were conducted using the search terms "progressive multiple sclerosis", "primary progressive multiple sclerosis", "secondary progressive MS". Proposed strategies were developed through a series of in-person and virtual meetings of the International Progressive MS Alliance Scientific Steering Committee. RESULTS: Sustaining and accelerating progress will require greater understanding of underlying mechanisms, identification of potential therapeutic targets, biomarker discovery and validation, and conduct of clinical trials with improved trial design. Encouraging developments in symptomatic and rehabilitative interventions are starting to address ongoing challenges experienced by people with progressive MS. CONCLUSION: We need to manage these challenges and realise the opportunities in the context of a global research strategy, which will improve quality of life for people with progressive MS.

Metabolic alterations in dairy cattle with lameness revealed by untargeted metabolomics of dried milk spots using direct infusion-tandem mass spectrometry and the triangulation of multiple machine learning models.

Lameness is a major challenge in the dairy cattle industry in terms of animal welfare and economic implications. Better understanding of metabolic alteration associated with lameness could lead to early diagnosis and effective treatment, there-fore reducing its prevalence. To determine whether metabolic signatures associated with lameness could be discovered with untargeted metabolomics, we developed a novel workflow using direct infusion-tandem mass spectrometry to rapidly analyse (2 min per sample) dried milk spots (DMS) that were stored on commercially available Whatman® FTA® DMPK cards for a prolonged period (8 and 16 days). An orthogonal partial least squares-discriminant analysis (OPLS-DA) method validated by triangulation of multiple machine learning (ML) models and stability selection was employed to reliably identify important discriminative metabolites. With this approach, we were able to differentiate between lame and healthy cows based on a set of lipid molecules and several small metabolites. Among the discriminative molecules, we identified phosphatidylglycerol (PG 35:4) as the strongest and most sensitive lameness indicator based on stability selection. Overall, this untargeted metabolomics workflow is found to be a fast, robust, and discriminating method for determining lameness in DMS samples. The DMS cards can be potentially used as a convenient and cost-effective sample matrix for larger scale research and future routine screening for lameness.

Inpatient Management of Pulmonary Embolism: Clinical Characteristics and Mortality in a High-Volume Tertiary Care Center.

The optimal management strategy for submassive or intermediate risk pulmonary embolism (IRPE)-anticoagulation alone versus anticoagulation plus advanced therapies-remains in equipoise leading many institutions to create multidisciplinary PE response teams (PERTs) to guide therapy. Cause-specific mortality of IRPE has not been thoroughly examined, which is a meaningful outcome when examining the effect of specific interventions for PE. In this retrospective study, we reviewed all adult inpatient admissions between 8/1/2018 and 8/1/2019 with an encounter diagnosis of PE to study all cause and PE cause specific mortality as the primary outcomes and bleeding complications from therapies as a secondary outcome. There were 429 total inpatient admissions, of which 59.7% were IRPE. The IRPE 30-day all-cause mortality was 8.7% and PE cause-specific mortality was 0.79%. Treatment consisted of anticoagulation alone in 93.4% of cases. Advanced therapies-systemic thrombolysis, catheter directed thrombolysis, or mechanical thrombectomy, were performed in only six IRPE cases (2.3%). Decompensation of IRPE cases requiring higher level of care and/or rescue advanced therapy occurred in only five cases (2%). In-hospital major bleeding and clinically relevant non-major bleeding were more common in those receiving systemic thrombolysis (61.5%) compared to anticoagulation combined with other advanced therapies (11.7%). Despite the high overall acuity of PE cases at our institution, in-hospital all-cause mortality was low and cause-specific mortality for IRPE was rare. These data suggest the need to target other clinically meaningful outcomes when examining advanced therapies for IRPE.

The effect of environmental temperature on average daily gain in preweaned calves: A randomized controlled trial and Bayesian analysis.

Neonatal calves are relatively susceptible to heat loss, and previous research suggests that reduced environmental temperatures are associated with reduced average daily gain (ADG) during the preweaning phase. Current methods of mitigating negative effects of colder environmental conditions include the use of calf jackets and the provision of supplementary heat sources; however, previous research is limited. The aim of this study was to evaluate the effect of calf jackets and 1-kW heat lamps on the growth rates of preweaning calves and evaluate associations between environmental temperature and ADG using a Bayesian approach to incorporate both current and previous data. Seventy-nine calves from a single British dairy farm were randomly allocated at birth to 1 of the following 4 groups: no jacket and no heat lamp, heat lamp but no jacket, jacket but no heat lamp, or both heat lamp and jacket between January and April of 2021. Calves were weighed at both birth and at approximately 21 d of age. Temperature was recorded both inside and outside of the calf building, and in pens both with and without heat lamps using data loggers. To explore the effect of treatment group and environmental temperature on ADG, a fixed effects model was fitted over 1,000 bootstrap samples. The effect of environmental temperature on ADG was further explored within a Bayesian framework that used temperature and ADG data for 484 calves from 16 farms available from a previous trial as prior information. Calves housed under a 1-kW heat lamp had an increased ADG of 0.09 kg/d (95% bootstrap confidence interval: -0.02 to 0.20 kg/d), and no effect of jacket or interactions between jacket and heat lamp were found. A significant positive association was identified between the mean environmental temperature of the calf building and ADG, with a 1°C increase in temperature being associated with a 0.03 kg/d increase in ADG (95% bootstrap confidence interval: 0.01 to 0.04 kg/d). Associations between environmental temperature and ADG were further evaluated within a Bayesian framework, and posterior estimates were 0.014 kg/d of ADG per 1°C increase (95% credible interval: 0.009 to 0.021 kg/d). This study demonstrated that a 1-kW heat lamp was effective in increasing ADG in calves, and no significant effect of calf jacket on ADG was found. A significant, positive effect of increased pen temperature on calf ADG was identified in this study and was reinforced when including prior information from previous research within a Bayesian framework.

Improving growth rates in preweaning calves on dairy farms: A randomized controlled trial.

Previous research has identified key factors associated with improved average daily gain (ADG) in preweaning dairy calves and these factors have been combined to create a web app-based calf health plan (www.nottingham.ac.uk/herdhealthtoolkit). A randomized controlled trial was conducted to determine the effect of implementing this evidence-based calf health plan on both productivity and health outcomes for calves reared on British dairy farms. Sixty dairy farms were randomized by location (North, South, and Midlands) to either receive the plan at the beginning (INT) or after the end of the trial (CON) and recorded birth and weaning weights by weigh tape, and cases of morbidity and mortality. Calf records were returned for 3,593 calves from 45 farms (21 CON, 24 INT), with 1,760 calves from 43 farms having 2 weights recorded >40 d apart for ADG calculations, with 1,871 calves from 43 farms born >90 d before the end of the trial for morbidity and mortality calculations. Associations between both intervention group and the number of interventions in place with ADG were analyzed using linear regression models. Morbidity and mortality rates were analyzed using beta regression models. Mean ADG was 0.78 kg/d, ranging from 0.33 to 1.13 kg/d, with mean rates of 20.12% (0-96.55%), 16.40% (0-95.24%), and 4.28% (0-18.75%) for diarrhea, pneumonia, and mortality. The INT farms were undertaking a greater number of interventions (9.9) by the end of the trial than CON farms (7.6). Mean farm ADG was higher for calves on INT farms than CON farms for both male beef (MB, +0.22 kg/d) and dairy heifer (DH, +0.03 kg/d) calves. The MB calves on INT farms had significantly increased mean ADG (0.12 kg/d, 95% confidence interval: 0.02-0.22) compared with CON farms. No significant differences were observed between intervention groups for morbidity or mortality. Implementing one additional intervention from the plan, regardless of intervention group, was associated with improvements in mean ADG for DH calves of 0.01 kg/d (0.01, 0-0.03) and MB calves of 0.02 kg/d (0.00-0.04). Model predictions suggest that a farm with the highest number of interventions in place (15) compared with farms with the lowest number of interventions in place (4) would expect an improvement in growth rates from 0.65 to 0.81 kg/d for MB, from 0.73 to 0.88 kg/d for DH, a decrease in mortality rates from 10.9% to 2.8% in MB, and a decrease in diarrhea rates from 42.1% to 15.1% in DH. The calf health plan tested in this study represents a useful tool to aid veterinarians and farmers in the implementation of effective management interventions likely to improve the growth rates, health, and welfare of preweaning calves on dairy farms.

Early treatment delays long-term disability accrual in RRMS: Results from the BMSD network.

BACKGROUND: The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined. OBJECTIVE: The aim of this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network. METHODS: Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference. RESULTS: A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower (p < 0.0004) for the first quintile patients' group. CONCLUSION: Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.

Awake intubations in the emergency department: A report from the National Emergency Airway Registry.

OBJECTIVE: To describe awake intubation practices in the emergency department (ED) and report success, complications, devices used, and rescue techniques using multicenter surveillance. METHODS: We analyzed data from the National Emergency Airway Registry (NEAR). Patients with an awake intubation attempt between January 1, 2016 and December 31, 2018 were included. We report univariate descriptive data as proportions with cluster-adjusted 95% confidence intervals (CIs). RESULTS: Of 19,071 discrete patient encounters, an awake technique was used on the first attempt in 82 (0.4%) patients. The majority (91%) of first attempts were performed by emergency medicine physicians. Angioedema (32%) and non-angioedema airway obstruction (31%) were the most common indications for an awake intubation attempt. The most common initial device used was a flexible endoscope (78%). Among all awake intubations first-attempt success was achieved in 85% (95% CI [76%-95%]), and peri-intubation complications occurred in 16% (95% CI [9%-26%]). CONCLUSION: Awake intubation in this multicenter cohort of emergency department patients was rare and was performed most often in patients with airway edema or obstruction. Emergency physicians performed the majority of first intubation attempts with high first-attempt success. Further studies are needed to determine optimal emergency airway management in this patient population.

Increased body mass index is associated with decreased imaging quality of point-of-care abdominal aortic ultrasonography.

BACKGROUND: Given that abdominal aorta is a retroperitoneal structure, increased body mass index (BMI) may have an adverse effect upon the quality of aortic ultrasonographic imaging. PURPOSE: To assess the hypothesis that increased BMI is associated with worsening point-of-care abdominal aortic ultrasonographic image quality. METHODS: This is a retrospective single-center study of point-of-care abdominal aortic ultrasound examinations performed in an academic emergency department (ED) with fellowship-trained emergency ultrasonography faculty performing quality assurance review. RESULTS: Mean ± SD BMI was 27.4 ± 6.2, among the 221 included records. The overall quality rating decreased as BMI increased (correlation coefficient - 0.24; P < .001) and this persisted after adjustment for age and sex (P < .001). Although BMI was higher on average in the records that were of insufficient quality for clinical decisions when compared with those of sufficient quality (mean BMI 28.7 vs 27.0), this did not reach statistical significance in a univariable setting (P = .11) or after adjusting for age and sex (P = .14). CONCLUSION: This study data shows a decrease in point-of-care abdominal aorta ultrasound imaging quality as BMI increases, though this difference did not result in a statistically significant impairment in achieving the minimum quality for clinical decisions. This finding may help ameliorate some clinician concerns about ultrasonography for patients with high BMI.

A proof-of-concept application of a novel scoring approach for personalized medicine in multiple sclerosis.

BACKGROUND: Stratified medicine methodologies based on subgroup analyses are often insufficiently powered. More powerful personalized medicine approaches are based on continuous scores. OBJECTIVE: We deployed a patient-specific continuous score predicting treatment response in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Data from two independent randomized controlled trials (RCTs) were used to build and validate an individual treatment response (ITR) score, regressing annualized relapse rates (ARRs) on a set of baseline predictors. RESULTS: The ITR score for the combined treatment groups versus placebo detected differential clinical response in both RCTs. High responders in one RCT had a cross-validated ARR ratio of 0.29 (95% confidence interval (CI) = 0.13-0.55) versus 0.62 (95% CI = 0.47-0.83) for all other responders (heterogeneity p = 0.038) and were validated in the other RCT, with the corresponding ARR ratios of 0.31 (95% CI = 0.18-0.56) and 0.61 (95% CI = 0.47-0.79; heterogeneity p = 0.036). The strongest treatment effect modifiers were the Short Form-36 Physical Component Summary, age, Visual Function Test 2.5%, prior MS treatment and Expanded Disability Status Scale. CONCLUSION: Our modelling strategy detects and validates an ITR score and opens up avenues for building treatment response calculators that are also applicable in routine clinical practice.

Quantitative analysis of calf mortality in Great Britain.

National bodies in Great Britain (GB) have expressed concern over young stock health and welfare and identified calf survival as a priority; however, no national data have been available to quantify mortality rates. The aim of this study was to quantify the temporal incidence rate, distributional features, and factors affecting variation in mortality rates in calves in GB since 2011. The purpose was to provide information to national stakeholder groups to inform resource allocation both for knowledge exchange and future research. Cattle birth and death registrations from the national British Cattle Movement Service were analyzed to determine rates of both slaughter and on-farm mortality. The number of births and deaths registered between 2011 and 2018 within GB were 21.2 and 21.6 million, respectively. Of the 3.3 million on-farm deaths, 1.8 million occurred before 24 mo of age (54%) and 818,845 (25%) happened within the first 3 mo of age. The on-farm mortality rate was 3.87% by 3 mo of age, remained relatively stable over time, and was higher for male calves (4.32%) than female calves (3.45%). Dairy calves experience higher on farm mortality rates than nondairy (beef) calves in the first 3 mo of life, with 6.00 and 2.86% mortality rates, respectively. The 0- to 3-mo death rate at slaughterhouse for male dairy calves has increased from 17.40% in 2011 to 26.16% in 2018, and has remained low (<0.5%) for female dairy calves and beef calves of both sexes. Multivariate adaptive regression spline models were able to explain a large degree of the variation in mortality rates (coefficient of determination = 96%). Mean monthly environmental temperature and month of birth appeared to play an important role in neonatal on-farm mortality rates, with increased temperatures significantly reducing mortality rates. Taking the optimal month of birth and environmental temperature as indicators of the best possible environmental conditions, maintaining these conditions throughout the year would be expected to result in a reduction in annual 0- to 3-mo mortality of 37,571 deaths per year, with an estimated economic saving of around £11.6 million (USD $15.3 million) per annum. National cattle registers have great potential for monitoring trends in calf mortality and can provide valuable insights to the cattle industry. Environmental conditions play a significant role in calf mortality rates and further research is needed to explore how to optimize conditions to reduce calf mortality rates in GB.

Solitary fibrous tumor of the orbit with growth during pregnancy: a case report.

We report the case of an anterior orbital tumor in a young woman that enlarged during pregnancy. The mass was excised and found to be a spindle cell tumor with immunohistochemical reactivity consistent with a solitary fibrous tumor, a rare entity in the spectrum of fibroblastic mesenchymal tumors. The tumor was strongly positive for the progesterone receptor, consistent with its clinical growth during the antenatal and postnatal periods. To our knowledge, a primary orbital tumor with these characteristics has rarely been reported in the literature.

COMPARISON OF VISUAL AND ANATOMICAL OUTCOMES OF EYES UNDERGOING TYPE I BOSTON KERATOPROSTHESIS WITH COMBINATION PARS PLANA VITRECTOMY WITH EYES WITHOUT COMBINATION VITRECTOMY.

PURPOSE: To determine whether 1-year visual and anatomical results after surgery combining pars plana vitrectomy, Boston keratoprosthesis, and a glaucoma drainage device as needed are similar, better, or worse than Boston keratoprosthesis initial implantation alone. METHODS: We performed a retrospective review of adult patients undergoing Boston keratoprosthesis at our institution. Visual acuity outcomes, anatomical results, and complication rates of patients undergoing combination surgery (including pars plana vitrectomy and a posterior glaucoma drainage device) were compared with those undergoing keratoprosthesis placement alone. RESULTS: There were 70 eyes in the keratoprosthesis alone group and 55 eyes in the keratoprosthesis with pars plana vitrectomy group. Mean follow-up durations were 54.67 months in the keratoprosthesis alone group and 48.41 months in the combination group. Baseline mean Snellen equivalent visual acuities were worse for the combination group compared with the keratoprosthesis alone group (P = 0.027). Visual acuities improved postoperatively by 1 month after keratoprosthesis implantation for both groups and improved three or more lines of Snellen acuity in the majority of eyes for both groups (≥72% by 12 months). Eyes undergoing pars plana vitrectomy had lower rates of de novo (P = 0.015) and significantly lower rates of secondary procedures (P = 0.002) at 1 year. One year complications rates for retroprosthetic membrane formation, retinal detachment, hypotony, cystoid macular edema, epiretinal membrane formation, endophthalmitis, and corneal melting were similar for both groups. CONCLUSION: Compared with keratoprosthesis alone, combining keratoprosthesis with pars plana vitrectomy and a glaucoma drainage device as needed, resulted in lower rates of de novo glaucoma, lower rates of additional surgical procedures, similar visual acuity outcomes at 1 year, and did not result in higher complication rates.