Publications by authors named "Robert Hyde"

47 Publications

Treatment Switching and Discontinuation Over 20 Years in the Big Multiple Sclerosis Data Network.

Front Neurol 2021 17;12:647811. Epub 2021 Mar 17.

Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.

Although over a dozen disease modifying treatments (DMTs) are available for relapsing forms of multiple sclerosis (MS), treatment interruption, switching and discontinuation are common challenges. The objective of this study was to describe treatment interruption and discontinuation in the Big MS data network. We merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2016 from five clinical registries in this cohort study. Treatment stop was defined as a clinician recorded DMT end for any reason and included treatment interruptions, switching to alternate DMTs and long-term or permanent discontinuations. The incidence of DMT stopping cross the full observation period was lowest in FTY (19.7 per 100 person-years (PY) of treatment; 95% CI 19.2-20.1), followed by NAT (22.6/100 PY; 95% CI 22.2-23.0), IFNβ (23.3/100 PY; 95% CI 23.2-23.5). Of the 184,013 observed DMT stops, 159,309 (86.6%) switched to an alternate DMT within 6 months. Reasons for stopping a drug were stable during the observation period with lack of efficacy being the most common reason followed by lack of tolerance and side effects. The proportion of patients continuing on most DMTs were similarly stable until 2014 and 2015 when drop from 83 to 75% was noted. DMT stopping reasons and rates were mostly stable over time with a slight increase in recent years, with the availability of more DMTs. The overall results suggest that discontinuation of MS DMTs is mostly due to DMT properties and to a lesser extent to risk management and a competitive market.
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http://dx.doi.org/10.3389/fneur.2021.647811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010264PMC
March 2021

Factors associated with daily weight gain in preweaned calves on dairy farms.

Prev Vet Med 2021 Mar 6;190:105320. Epub 2021 Mar 6.

School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, LE12 5RD, United Kingdom.

The preweaning period is vital in the development of calves on dairy farms and improving daily liveweight gain (DLWG) is important to both financial and carbon efficiency; minimising rearing costs and improving first lactation milk yields. In order to improve DLWG, veterinary advisors should provide advice that has both a large effect size as well as being consistently important on the majority of farms. Whilst a variety of factors have previously been identified as influencing the DLWG of preweaned calves, it can be challenging to determine their relative importance, which is essential for optimal on-farm management decisions. Regularised regression methods such as ridge or lasso regression provide a solution by penalising variable coefficients unless there is a proportional improvement in model performance. Elastic net regression incorporates both lasso and ridge penalties and was used in this research to provide a sparse model to accommodate strongly correlated predictors and provide robust coefficient estimates. Sixty randomly selected British dairy farms were enrolled to collect weigh tape data from preweaned calves at birth and weaning, resulting in data being available for 1014 calves from 30 farms after filtering to remove poor quality data, with a mean DLWG of 0.79 kg/d (range 0.49-1.06 kg/d, SD 0.13). Farm management practices (e.g. colostrum, feeding, hygiene protocols), building dimensions, temperature/humidity and colostrum quality/bacteriology data were collected, resulting in 293 potential variables affecting farm level DLWG. Bootstrapped elastic net regression models identified 17 variables as having both a large effect size and high stability. Increasing the maximum preweaned age within the first housing group (0.001 kg/d per 1d increase, 90 % bootstrap confidence interval (BCI): 0.000-0.002), increased mean environmental temperature within the first month of life (0.012 kg/d per 1 °C increase, 90 % BCI: 0.002-0.037) and increased mean volume of milk feeding (0.012 kg/d per 1 L increase, 90 % BCI: 0.001-0.024) were associated with increased DLWG. An increase in the number of days between the cleaning out of calving pen (-0.001 kg/d per 1d increase, 90 % BCI: -0.001-0.000) and group housing pens (-0.001 kg/d per 1d increase, 90 % BCI: -0.002-0.000) were both associated with decreased DLWG. Through bootstrapped elastic net regression, a small number of stable variables have been identified as most likely to have the largest effect size on DLWG in preweaned calves. Many of these variables represent practical aspects of management with a focus around stocking demographics, milk/colostrum feeding, environmental hygiene and environmental temperature; these variables should now be tested in a randomised controlled trial to elucidate causality.
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http://dx.doi.org/10.1016/j.prevetmed.2021.105320DOI Listing
March 2021

Understanding patients' end-of-life goals of care in the emergency department.

J Am Coll Emerg Physicians Open 2021 Apr 2;2(2):e12388. Epub 2021 Mar 2.

Department of Emergency Medicine Mayo Clinic Alix School of Medicine Rochester Minnesota USA.

Background: Emergency departments (ED) are frequently the entryway to the health system for older, more ill patients. Because decisions made in the ED often influence escalation of care both in the ED and after admission, it is important for emergency physicians to understand their patients' goals of care.

Study Objectives: To determine how well emergency physicians understand their patients' goals of care.

Methods: This was a prospective survey study of a convenience sample of ED patients 65 years and older presenting between February 18 and March 1, 2019 to an academic center with 77,000 annual visits. If a patient did not have decision-making capacity, a surrogate decision-maker was interviewed when possible. Two sets of surveys were designed, one for patients and one for physicians. The patient survey included questions regarding their goals of care and end-of-life care preferences. The physician survey asked physicians to select which goals of care were important to their patients and to identify which was the most important. Patient-physician agreement on patients' most important goal of care was analyzed with Cohen's kappa.

Results: A total of 111 patient participants were invited to complete the survey, of whom 80 (72%) agreed to participate. The patients consisted of 43 women and 37 men with an age range from 65 to 98 years. Additionally, 16 attending and 14 resident physicians participated in the study for a total of 49 attending responses and 41 resident responses. A total of 88% of patients believed it was either very important or important to discuss goals of care with their physicians. Both patients and physicians most frequently chose "Improve or maintain function, quality of life, or independence" as the most important goal; however, there was wide variation in patient responses. Patients and attending physicians selected the same most important goal of care in 20% of cases (kappa 0.03) and patients and resident physicians selected the same goal in 27% of cases (kappa 0.11).

Conclusions: We found poor agreement between patients and physicians in the ED regarding patients' most important goal of care. Additionally, we found that most patients visiting the ED believe it is important to discuss goals of care with their physicians. Future work may focus on interventions to facilitate goals of care discussions in the ED.
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http://dx.doi.org/10.1002/emp2.12388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925851PMC
April 2021

Model selection for inferential models with high dimensional data: synthesis and graphical representation of multiple techniques.

Sci Rep 2021 Jan 11;11(1):412. Epub 2021 Jan 11.

School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, LE12 5RD, UK.

Inferential research commonly involves identification of causal factors from within high dimensional data but selection of the 'correct' variables can be problematic. One specific problem is that results vary depending on statistical method employed and it has been argued that triangulation of multiple methods is advantageous to safely identify the correct, important variables. To date, no formal method of triangulation has been reported that incorporates both model stability and coefficient estimates; in this paper we develop an adaptable, straightforward method to achieve this. Six methods of variable selection were evaluated using simulated datasets of different dimensions with known underlying relationships. We used a bootstrap methodology to combine stability matrices across methods and estimate aggregated coefficient distributions. Novel graphical approaches provided a transparent route to visualise and compare results between methods. The proposed aggregated method provides a flexible route to formally triangulate results across any chosen number of variable selection methods and provides a combined result that incorporates uncertainty arising from between-method variability. In these simulated datasets, the combined method generally performed as well or better than the individual methods, with low error rates and clearer demarcation of the true causal variables than for the individual methods.
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http://dx.doi.org/10.1038/s41598-020-79317-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801732PMC
January 2021

Quantitative Analysis of Colostrum Bacteriology on British Dairy Farms.

Front Vet Sci 2020 7;7:601227. Epub 2020 Dec 7.

School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, United Kingdom.

Total bacterial counts (TBC) and coliform counts (CC) were estimated for 328 colostrum samples from 56 British dairy farms. Samples collected directly from cows' teats had lower mean TBC (32,079) and CC (21) than those collected from both colostrum collection buckets (TBC: 327,879, CC: 13,294) and feeding equipment (TBC: 439,438, CC: 17,859). Mixed effects models were built using an automated backwards stepwise process in conjunction with repeated bootstrap sampling to provide robust estimates of both effect size and 95% bootstrap confidence intervals (BCI) as well as an estimate of the reproducibility of a variable effect within a target population (stability). Colostrum collected using parlor (2.06 log cfu/ml, 95% BCI: 0.35-3.71) or robot (3.38 log cfu/ml, 95% BCI: 1.29-5.80) milking systems, and samples collected from feeding equipment (2.36 log cfu/ml, 95% BCI: 0.77-5.45) were associated with higher TBC than those collected from the teat, suggesting interventions to reduce bacterial contamination should focus on the hygiene of collection and feeding equipment. The use of hot water to clean feeding equipment (-2.54 log cfu/ml, 95% BCI: -3.76 to -1.74) was associated with reductions in TBC, and the use of peracetic acid (-2.04 log cfu/ml, 95% BCI: -3.49 to -0.56) or hypochlorite (-1.60 log cfu/ml, 95% BCI: -3.01 to 0.27) to clean collection equipment was associated with reductions in TBC compared with water. Cleaning collection equipment less frequently than every use (1.75 log cfu/ml, 95% BCI: 1.30-2.49) was associated with increased TBC, the use of pre-milking teat disinfection prior to colostrum collection (-1.85 log cfu/ml, 95% BCI: -3.39 to 2.23) and the pasteurization of colostrum (-3.79 log cfu/ml, 95% BCI: -5.87 to -2.93) were associated with reduced TBC. Colostrum collection protocols should include the cleaning of colostrum collection and feeding equipment after every use with hot water as opposed to cold water, and hypochlorite or peracetic acid as opposed to water or parlor wash. Cows' teats should be prepared with a pre-milking teat disinfectant and wiped with a clean, dry paper towel prior to colostrum collection, and colostrum should be pasteurized where possible.
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http://dx.doi.org/10.3389/fvets.2020.601227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750185PMC
December 2020

Long-term effectiveness of natalizumab on MRI outcomes and no evidence of disease activity in relapsing-remitting multiple sclerosis patients treated in a Czech Republic real-world setting: A longitudinal, retrospective study.

Mult Scler Relat Disord 2020 Nov 28;46:102543. Epub 2020 Sep 28.

Department of Radiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

Background: Magnetic resonance imaging (MRI) data from multiple sclerosis (MS) patients treated in real-world settings are important for understanding disease-modifying therapy effects, including no evidence of disease activity (NEDA) assessment. This longitudinal, retrospective, single-cohort analysis assessed MRI and clinical disease outcomes in patients with relapsing-remitting MS treated with natalizumab for up to 5 years in Prague, the Czech Republic.

Methods: The primary study endpoint was the proportion of patients free of new or enlarging fluid-attenuated inversion recovery (FLAIR) lesions after at least 2 years of natalizumab treatment. Secondary endpoints included percentage brain volume change over time, the number of new T1-hypointense lesions that persisted for ≥6 months, FLAIR and T1-hypointense lesion volume change over time, and the proportion of patients with NEDA-3 (defined as no relapses, no confirmed disability worsening, and no new or enlarging FLAIR lesions).

Results: A total of 193 patients were included in the study. During year 1 of natalizumab treatment, 78.9% of patients had no new or enlarging FLAIR lesions and 79.5% had no new T1 lesions. These proportions increased in years 2-5, with ≥98.0% of patients free of new or enlarging FLAIR lesions and ≥98.8% free of new T1 lesions. During year 1 on natalizumab, 52.2% of patients achieved NEDA-3; this proportion increased to ≥69.2% in years 2-5.

Conclusion: This study provides additional evidence that long-term MS disease activity, as measured by both MRI activity and NEDA-3, is well-controlled in patients treated with natalizumab in real-world settings.
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http://dx.doi.org/10.1016/j.msard.2020.102543DOI Listing
November 2020

A Systematic Review and Mixed Treatment Comparison of Pharmaceutical Interventions for Multiple Sclerosis.

Neurol Ther 2020 Dec 28;9(2):359-374. Epub 2020 Sep 28.

School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands.

Background: Since 2010, 27 mixed-treatment comparisons (MTCs) of disease-modifying therapies (DMTs) for multiple sclerosis have been published. However, there has been continued evolution in the field of MTCs. Additionally, limitations in methodological approach and reporting transparency, even in the most recent publications, makes interpretation and comparison of existing studies difficult.

Objectives: The objectives of this study are twofold: (1) to estimate the efficacy and safety of DMTs at European Commission-approved doses compared with placebo in adults with relapsing-remitting multiple sclerosis (RRMS) using MTC, and (2) to identify and address methodological challenges when performing MTC in RRMS, thereby creating a baseline for comparisons with future treatments.

Methods: Searches were completed in 14 databases, including MEDLINE, Embase, CENTRAL, CDSR and DARE, from inception to June 2018 to identify published or unpublished prospective, randomised controlled trials of all European Union-approved DMTs or DMTs expected to be approved in the near future in RRMS or rapidly-evolving severe RRMS. No language or date restrictions were applied. Studies were included in the MTC if they were judged to have sufficiently similar characteristics, based on the following: patient age; proportion of male participants; Expanded Disability Status Scale (EDSS) score; duration of disease; number of relapses prior to enrolment and proportion of previously treated patients. Background information from the included studies, as well as effect size and confidence intervals (where relevant) of defined outcomes were extracted. Reporting of the MTC was consistent with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) network meta-analysis guidelines.

Results: In total, 33 studies were included in the MTC. Annualised relapse rate (ARR 28 trials) was significantly reduced in all treatments compared with placebo. Alemtuzumab had the highest probability (63%) of being the most effective treatment in terms of ARR compared with placebo (rate ratio [RR] 0.28, 95% credible interval [CrI] 0.21-0.38), followed by natalizumab (30% probability; RR 0.32, 95% CrI 0.23-0.43). The risk of 3- and 6-month confirmed disability progression (CDP3M, 13 trials; CDP6M, 14 trials) were similar; CDP6M was significantly reduced for alemtuzumab (hazard ratio [HR] 0.365; 95% CrI 0.165-0.725), ocrelizumab (HR 0.405, 95% CrI 0.188-0.853) and natalizumab (HR 0.459, 95% CrI 0.252-0.840) relative to placebo. There were no significant differences in the odds of serious adverse events (SAEs, 6 trials) between any treatment and placebo. The results of the MTC were limited by the lack of studies reporting direct comparisons between the included treatments and by heterogeneous reporting of key outcome data.

Conclusions: Meta-analyses confirmed the benefit of all DMTs in terms of relapse rate compared with placebo with a comparable rate of SAEs for the DMTs that could be included in the network. The rigor and transparency of reporting in this study provide a benchmark for comparisons with future new agents.
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http://dx.doi.org/10.1007/s40120-020-00212-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606402PMC
December 2020

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

J Clin Ultrasound 2021 May 27;49(4):328-333. Epub 2020 Sep 27.

Department of Emergency Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.

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.
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http://dx.doi.org/10.1002/jcu.22929DOI Listing
May 2021

Overview of Differences and Similarities of Published Mixed Treatment Comparisons on Pharmaceutical Interventions for Multiple Sclerosis.

Neurol Ther 2020 Dec 25;9(2):335-358. Epub 2020 Sep 25.

School for Public Health and Primary Care, Maastricht University, Maastricht, The Netherlands.

Introduction: Mixed treatment comparisons (MTCs) are increasingly important in the assessment of the benefit-risk profile of pharmaceutical treatments for relapsing-remitting multiple sclerosis (RRMS). Interpretation of MTCs requires a clear understanding of the methods of analysis and population studied. The objectives of this work were to compare MTCs of pharmaceutical treatments for RRMS, including a detailed description of differences in populations, treatments assessed, methods used and findings; and to discuss key considerations when conducting an MTC.

Methods: Fourteen databases were searched until July 2019 to identify MTCs (published during or after 2010) in adults (at least 18 years of age) with RRMS or rapidly evolving severe RRMS treated with any form of pharmaceutical treatment. No language restriction was imposed.

Results: Twenty-seven MTCs assessing 21 treatments were identified. Comparison highlighted many differences in conduct and reporting between MTCs relating to the patient populations or treatments included, duration of follow-up and outcomes of interest measured. The lack of similarity between the MTCs leads to questions about variability in the robustness of analyses and makes comparisons between studies challenging.

Conclusion: Given the importance of MTCs for healthcare decision-making, it is imperative that reporting of methods, results and assumptions is clear and transparent to allow accurate interpretation of findings. For MTCs to be relevant, the choice of outcome measures should reflect clinical practice. Combination of treatments or of outcomes measured at different points of time should be avoided, as should imputation without justification. Furthermore, all approved treatment options should be included and updates of MTCs should be conducted when data for new treatments are published.
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http://dx.doi.org/10.1007/s40120-020-00213-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606374PMC
December 2020

Automated prediction of mastitis infection patterns in dairy herds using machine learning.

Sci Rep 2020 03 9;10(1):4289. Epub 2020 Mar 9.

School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, LE12 5RD, United Kingdom.

Mastitis in dairy cattle is extremely costly both in economic and welfare terms and is one of the most significant drivers of antimicrobial usage in dairy cattle. A critical step in the prevention of mastitis is the diagnosis of the predominant route of transmission of pathogens into either contagious (CONT) or environmental (ENV), with environmental being further subdivided as transmission during either the nonlactating "dry" period (EDP) or lactating period (EL). Using data from 1000 farms, random forest algorithms were able to replicate the complex herd level diagnoses made by specialist veterinary clinicians with a high degree of accuracy. An accuracy of 98%, positive predictive value (PPV) of 86% and negative predictive value (NPV) of 99% was achieved for the diagnosis of CONT vs ENV (with CONT as a "positive" diagnosis), and an accuracy of 78%, PPV of 76% and NPV of 81% for the diagnosis of EDP vs EL (with EDP as a "positive" diagnosis). An accurate, automated mastitis diagnosis tool has great potential to aid non-specialist veterinary clinicians to make a rapid herd level diagnosis and promptly implement appropriate control measures for an extremely damaging disease in terms of animal health, productivity, welfare and antimicrobial use.
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http://dx.doi.org/10.1038/s41598-020-61126-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062853PMC
March 2020

SEROLOGY NEGATIVE BARTONELLA NEURORETINITIS IN AN IMMUNOCOMPROMISED PATIENT.

Retin Cases Brief Rep 2020 Mar 3. Epub 2020 Mar 3.

Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, Ann Arbor, Michigan.

Background/purpose: To report a case of serology-negative severe disseminated Bartonella neuroretinitis in an immunocompromised patient in which diagnosis was made by detection of B. henselae DNA by universal polymerase chain reaction of brain tissue.

Methods: Case report.

Results: A 57-year-old man with immunoglobulin A vasculitis on immunosuppressive therapy presented with lethargy, weight loss, and bilateral decreased vision. Fundus examination revealed bilateral mild vitritis, marked optic disc edema, vascular sheathing, and numerous white inner retinal and preretinal lesions. Brain magnetic resonance imaging revealed multiple foci of restricted diffusion and a ring-enhancing focus in the left parietal lobe. Serologies, cerebrospinal fluid, and vitreous biopsies were all negative for Bartonella. A brain biopsy was performed and B. henselae DNA was detected by universal polymerase chain reaction of the specimen. The patient demonstrated resolution of fundus findings with antibiotic treatment. Repeat serological testing demonstrated seroconversion.

Conclusion: In immunocompromised patients, infection by Bartonella henselae can present as severe disseminated disease. Establishing the diagnosis can be challenging as serologic testing is often unrevealing in the setting of a blunted immune response. Polymerase chain reaction has been used in select cases to establish the diagnosis.
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http://dx.doi.org/10.1097/ICB.0000000000000995DOI Listing
March 2020

Quantitative analysis of calf mortality in Great Britain.

J Dairy Sci 2020 Mar 15;103(3):2615-2623. Epub 2020 Jan 15.

School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, United Kingdom LE12 5RD.

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.
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http://dx.doi.org/10.3168/jds.2019-17383DOI Listing
March 2020

Evaluation of the underlying causes of papilledema in children.

Can J Ophthalmol 2019 12 4;54(6):653-658. Epub 2019 Apr 4.

Department of Ophthalmology, Illinois Eye and Ear Infirmary, University of Illinois-Chicago, Chicago, Ill.

Objective: The purpose of this retrospective study was to identify the types and relative frequencies of intracranial disorders in pediatric patients who present with papilledema.

Design: Retrospective case series.

Participants And Methods: This study was conducted in 2 pediatric ophthalmology clinics, both providing community-based care in a large inner-city urban center in the U.S. Pediatric patients aged between 0 and 16 years diagnosed with papilledema and who had an underlying etiology identified were included in the study. Patient demographic data, ophthalmologic examination findings, and diagnostic work-up results were identified from clinical records.

Results: The mean age of 38 study patients (19 female, 19 male) was 8.6 ± 4.8 years. Of the 38 patients, 16 (42.1%) had idiopathic intracranial hypertension (IIH) as the underlying cause of the papilledema, 7 (18.4%) had a craniosynostosis disorder, 6 (15.8%) had intracranial tumours, 2 (5.3%) had primary hydrocephalus, and 1 (2.6%) patient each had transverse sinus thrombosis related to sinusitis, hypertensive crisis, subdural hematoma, intracranial abscess, Lyme disease, presumed neurosarcoidosis, and acute disseminated encephalomyelitis. Of the 6 intracranial tumours, 2 (33.3%) presented in the sellar/parasellar region, 2 (33.3%) in the posterior fossa, and 2 (33.3%) were in cortical locations.

Conclusion: Clinicians should have a high index of suspicion for IIH and brain tumours in children presenting with papilledema. Patients with craniosynostosis should have routine eye examinations to monitor for asymptomatic papilledema. Understanding the relative incidence of etiologies for papilledema highlights the urgency of appropriate work-up and the need to consider low-frequency etiologies.
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http://dx.doi.org/10.1016/j.jcjo.2019.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931261PMC
December 2019

Increased Clinical and Economic Burden Associated With Peripheral Intravenous Catheter-Related Complications: Analysis of a US Hospital Discharge Database.

Inquiry 2019 Jan-Dec;56:46958019875562

Ethicon, Inc., Somerville, NJ, USA.

The burden of complications associated with peripheral intravenous use is underevaluated, in part, due to the broad use, inconsistent coding, and lack of mandatory reporting of these devices. This study aimed to analyze the clinical and economic impact of peripheral intravenous-related complications on hospitalized patients. This analysis of Premier Perspective Database US hospital discharge records included admissions occurring between July 1, 2013 and June 30, 2015 for pneumonia, chronic obstructive pulmonary disease, myocardial infarction, congestive heart failure, chronic kidney disease, diabetes with complications, and major trauma (hip, spinal, cranial fractures). Admissions were assumed to include a peripheral intravenous. Admissions involving surgery, dialysis, or central venous lines were excluded. Multivariable analyses compared inpatient length of stay, cost, admission to intensive care unit, and discharge status of patients with versus without peripheral intravenous-related complications (bloodstream infection, cellulitis, thrombophlebitis, other infection, or extravasation). Models were conducted separately for congestive heart failure, chronic obstructive pulmonary disease, diabetes with complications, and overall (all 7 diagnoses) and adjusted for demographics, comorbidities, and hospital characteristics. We identified 588 375 qualifying admissions: mean (SD), age 66.1 (20.6) years; 52.4% female; and 95.2% urgent/emergent admissions. Overall, 1.76% of patients (n = 10 354) had peripheral intravenous-related complications. In adjusted analyses between patients with versus without peripheral intravenous complications, the mean (95% confidence interval) inpatient length of stay was 5.9 (5.8-6.0) days versus 3.9 (3.9-3.9) days; mean hospitalization cost was $10 895 ($10 738-$11 052) versus $7009 ($6988-$7031). Patients with complications were less likely to be discharged home versus those without (62.4% [58.6%-66.1%] vs 77.6% [74.6%-80.5%]) and were more likely to have died (3.6% [2.9%-4.2%] vs 0.7% [0.6%-0.9%]). Models restricted to single admitting diagnosis were consistent with overall results. Patients with peripheral intravenous-related complications have longer length of stay, higher costs, and greater risk of death than patients without such complications; this is true across diagnosis groups of interest. Future research should focus on reducing these complications to improve clinical and economic outcomes.
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http://dx.doi.org/10.1177/0046958019875562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747868PMC
March 2020

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

Mult Scler 2020 08 30;26(9):1064-1073. Epub 2019 May 30.

Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

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  = 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  = 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.
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http://dx.doi.org/10.1177/1352458519849513DOI Listing
August 2020

Late detachment of Descemet's membrane after penetrating keratoplasty for pellucid marginal degeneration.

Am J Ophthalmol Case Rep 2019 Mar 18;13:151-153. Epub 2018 Dec 18.

Department of Ophthalmology & Visual Sciences, University of Illinois College of Medicine, 1855 W Taylor Street, Chicago, IL 60612, USA.

Purpose: we report a case of late spontaneous large detachment of Descemet's membrane in recurrent pellucid marginal degeneration after penetrating keratoplasty.

Observations: a 73-year-old man presented to clinic with spontaneous detachment of his Descemet's membrane 30 years after penetrating keratoplasty for pellucid marginal degeneration. Efforts were made to bubble the membrane back into place without success. The patient then underwent endothelial keratoplasty with successful restoration of cornea clarity.

Conclusions And Importance: this condition may cause diagnostic and treatment dilemmas if not properly identified and managed. In addition this case has information for both the use of scleral contact lens and the success of endothelial keratoplasty in an extremely steep cornea.
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http://dx.doi.org/10.1016/j.ajoc.2018.12.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350212PMC
March 2019

Incidence of pregnancy and disease-modifying therapy exposure trends in women with multiple sclerosis: A contemporary cohort study.

Mult Scler Relat Disord 2019 Feb 3;28:235-243. Epub 2019 Jan 3.

Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Department of Neurology, Alfred Hospital, Melbourne, Australia; Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Melbourne, Australia. Electronic address:

Background: Exposure to disease-modifying therapy (DMT) during early pregnancy in women with relapsing-remitting MS (RRMS) may be increasing.

Objective: To retrospectively determine incidence of pregnancy, DMT exposure and pregnancy outcomes in women with RRMS.

Methods: We identified all women with RRMS aged 15-45 years in the MSBase Registry between 2005-2016. Annualised pregnancy incidence rates were calculated using Poisson regression models. DMT exposures and pregnancy outcomes were assessed.

Results: Of 9,098 women meeting inclusion criteria, 1,178 (13%) women recorded 1,521 pregnancies. The annualised incidence rate of pregnancy was 0.042 (95% CI 0.040, 0.045). A total of 635 (42%) reported pregnancies were conceived on DMT, increasing from 27% in 2006 to 62% in 2016. The median duration of DMT exposure during pregnancy was 30 days (IQR: 9, 50). There were a higher number of induced abortions on FDA pregnancy class C/D drugs compared with pregnancy class B and no DMT (p = 0.010); but no differences in spontaneous abortions, term or preterm births.

Conclusions: We report low pregnancy incidence rates, with increasing number of pregnancies conceived on DMT over the past 12-years. The median duration of DMT exposure in pregnancy was relatively short at one month.
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http://dx.doi.org/10.1016/j.msard.2019.01.003DOI Listing
February 2019

Removal of copper from cattle footbath wastewater with layered double hydroxide adsorbents as a route to antimicrobial resistance mitigation on dairy farms.

Sci Total Environ 2019 Mar 22;655:1139-1149. Epub 2018 Nov 22.

Faculty of Engineering, University of Nottingham, University Park, Nottingham NG7 2RD, UK.

Copper and zinc are routinely used in livestock antimicrobial footbaths in commercial farming. The footbath mix is a cost to farmers, and the disposal of spent footbath into slurry tanks leads to soil contamination, as well as the potential for antimicrobial metal resistance and co-selection. This study assesses the potential to mitigate a source of antimicrobial metal resistance in slurry tanks while recovering copper and zinc from spent cattle footbaths. This is the first study in literature to investigate the potential of recovering copper from cattle footbath solutions via any method. The sorbent, CaAl-EDTA Layered Double Hydroxides (LDH), were used to remove Cu from a CuSO·5H0 solution at different temperatures. The maximum Cu uptake from the CuSO·5H0 solution was 568 ± 88 mg g. Faster and higher equilibrium uptake was achieved by increasing the temperature of the solution. The sorbent was found to be effective in removing copper and zinc from a commercially available cattle footbath solution (filtered footbath solution Cu uptake 283 ± 11.05 mg g, Zn uptake 60 ± 0.05 mg g). Thus, this study demonstrates the opportunity for a completely novel and potentially economically beneficial method of mitigating antimicrobial resistance in agriculture and the environment, while also providing a new valuable copper and zinc waste stream for secondary metal production.
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http://dx.doi.org/10.1016/j.scitotenv.2018.11.330DOI Listing
March 2019

Comparative effectiveness of delayed-release dimethyl fumarate versus interferon, glatiramer acetate, teriflunomide, or fingolimod: results from the German NeuroTransData registry.

J Neurol 2018 Dec 16;265(12):2980-2992. Epub 2018 Oct 16.

NeuroTransData, Bahnhofstraße 103B, 86633, Neuburg an der Donau, Germany.

Background: Comparative effectiveness (CE) research allows real-world treatment comparisons using outcome measurements important to physicians/patients. This German NeuroTransData registry-based analysis compared delayed-release dimethyl fumarate (DMF) effectiveness with interferons (IFN), glatiramer acetate (GA), teriflunomide (TERI), or fingolimod (FTY) in patients with relapsing-remitting multiple sclerosis (RRMS) using propensity score matching (PSM).

Methods: Data from registry patients aged ≥ 18 years with RRMS, ≥ 1 relapse, and Expanded Disability Status Scale (EDSS) assessment(s) after index therapy initiation underwent 1:1 PSM to match DMF with comparator populations baseline characteristics. Primary outcome measurement was time to first relapse (TTFR). Secondary outcome measurements included annualised relapse rate (ARR), proportion of patients relapse free at 12 and 24 months, time to index therapy discontinuation (TTD), and reasons for discontinuation. Exploratory analyses included time to 3- and 6-month EDSS confirmed disability progression (CDP). Non-pairwise censoring was the primary analysis method; pairwise censoring was the main sensitivity analysis method.

Findings: Post-matched cohorts were well-balanced. By non-pairwise censoring, TTFR and ARR were significantly lower in DMF populations versus matched IFN, GA, and TERI, but there was no evidence of difference between DMF and FTY. TTD was similar between DMF and IFN, GA, and TERI, but significantly shorter versus FTY. Time to CDP generally showed no evidence of difference between DMF and comparator populations. Pairwise censored analysis results confirmed the non-pairwise censoring results.

Interpretation: These results support previous CE studies in demonstrating relative improvement in real-world effectiveness with DMF versus first-line agents IFN, GA, and TERI, and similar effectiveness versus FTY.
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http://dx.doi.org/10.1007/s00415-018-9083-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244642PMC
December 2018

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

Orbit 2019 Jun 21;38(3):256-258. Epub 2018 May 21.

a Department of Ophthalmology and Visual Sciences , University of Illinois Chicago , Chicago , IL , USA.

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.
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http://dx.doi.org/10.1080/01676830.2018.1474930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249116PMC
June 2019

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

Retina 2018 09;38 Suppl 1:S125-S133

Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, Illinois.

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.
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http://dx.doi.org/10.1097/IAE.0000000000002036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056324PMC
September 2018

Quantitative analysis of antimicrobial use on British dairy farms.

Vet Rec 2017 12 20;181(25):683. Epub 2017 Dec 20.

School of Veterinary Medicine and Science, University of Nottingham, Nottingham, UK.

Antimicrobial resistance has been reported to represent a growing threat to both human and animal health, and concerns have been raised around levels of antimicrobial usage (AMU) within the livestock industry. To provide a benchmark for dairy cattle AMU and identify factors associated with high AMU, data from a convenience sample of 358 dairy farms were analysed using both mass-based and dose-based metrics following standard methodologies proposed by the European Surveillance of Veterinary Antimicrobial Consumption project. Metrics calculated were mass (mg) of antimicrobial active ingredient per population correction unit (mg/PCU), defined daily doses (DDDvet) and defined course doses (DCDvet). AMU on dairy farms ranged from 0.36 to 97.79 mg/PCU, with a median and mean of 15.97 and 20.62 mg/PCU, respectively. Dose-based analysis ranged from 0.05 to 20.29 DDDvet, with a median and mean of 4.03 and 4.60 DDDvet, respectively. Multivariable analysis highlighted that usage of antibiotics via oral and footbath routes increased the odds of a farm being in the top quartile (>27.9 mg/PCU) of antimicrobial users. While dairy cattle farm AMU appeared to be lower than UK livestock average, there were a selection of outlying farms with extremely high AMU, with the top 25 per cent of farms contributing greater than 50 per cent of AMU by mass. Identification of these high use farms may enable targeted AMU reduction strategies and facilitate a significant reduction in overall dairy cattle AMU.
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http://dx.doi.org/10.1136/vr.104614DOI Listing
December 2017

Quantitative analysis of antibiotic usage in British sheep flocks.

Vet Rec 2017 Nov 19;181(19):511. Epub 2017 Oct 19.

Dairy Herd Health and Productivity Service, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Midlothian, UK.

The aim of this study was to examine the variation in antibiotic usage between 207 commercial sheep flocks using their veterinary practice prescribing records. Mean and median prescribed mass per population corrected unit (mg/PCU) was 11.38 and 5.95, respectively and closely correlated with animal defined daily dose (ADDD) 1.47 (mean), 0.74 (median) (R=0.84, P<0.001). This is low in comparison with the suggested target (an average across all the UK livestock sectors) of 50 mg/PCU. In total, 80 per cent of all antibiotic usage occurred in the 39 per cent of flocks where per animal usage was greater than 9.0 mg/PCU. Parenteral antibiotics, principally oxytetracycline, represented 82 per cent of the total prescribed mass, 65.5 per cent of antibiotics (mg/PCU) were prescribed for the treatment of lameness. Oral antibiotics were prescribed to 49 per cent of flocks, 64 per cent of predicted lamb crop/farm. Lowland flocks were prescribed significantly more antibiotics than hill flocks. Variance partitioning apportioned 79 per cent of variation in total antibiotic usage (mg/PCU) to the farm level and 21 per cent to the veterinary practice indicating that veterinary practices have a substantial impact on overall antimicrobial usage. Reducing antibiotic usage in the sheep sector should be possible with better understanding of the drivers of high usage in individual flocks and of veterinary prescribing practices.
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http://dx.doi.org/10.1136/vr.104501DOI Listing
November 2017

Photopolymerization-based synthesis of iron oxide nanoparticle embedded PNIPAM nanogels for biomedical applications.

Drug Deliv 2017 Nov;24(1):1317-1324

a Department of Physics , University of South Florida , Tampa , FL , USA.

Conventional therapeutic techniques treat patients by delivering biotherapeutics to the entire body. With targeted delivery, biotherapeutics are transported to the afflicted tissue reducing exposure to healthy tissue. Targeted delivery devices are minimally composed of a stimuli responsive polymer allowing triggered release and magnetic nanoparticles enabling targeting as well as alternating magnetic field (AMF) heating. Although more traditional methods, like emulsion polymerization, have been used to realize such devices, the synthesis is problematic. For example, surfactants preventing agglomeration must be removed from the product increasing time and cost. Ultraviolet (UV) photopolymerization is more efficient and ensures safety by using biocompatible substances. Reactants selected for nanogel fabrication were N-isopropylacrylamide (monomer), methylene bis-acrylamide (crosslinker), and Irgacure 2959 (photoinitiator). The 10 nm superparamagnetic nanoparticles for encapsulation were composed of iron oxide. Herein, a low-cost, scalable, and rapid, custom-built UV photoreactor with in situ, spectroscopic monitoring system is used to observe synthesis. This method also allows in situ encapsulation of the magnetic nanoparticles simplifying the process. Nanogel characterization, performed by transmission electron microscopy, reveals size-tunable nanogel spheres between 40 and 800 nm in diameter. Samples of nanogels encapsulating magnetic nanoparticles were subjected to an AMF and temperature increase was observed indicating triggered release is possible. Results presented here will have a wide range of applications in medical sciences like oncology, gene delivery, cardiology, and endocrinology.
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http://dx.doi.org/10.1080/10717544.2017.1373164DOI Listing
November 2017

Is multiple sclerosis a length-dependent central axonopathy? The case for therapeutic lag and the asynchronous progressive MS hypotheses.

Mult Scler Relat Disord 2017 Feb 17;12:70-78. Epub 2017 Jan 17.

Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK. Electronic address:

Trials of anti-inflammatory therapies in non-relapsing progressive multiple sclerosis (MS) have been stubbornly negative except recently for an anti-CD20 therapy in primary progressive MS and a S1P modulator siponimod in secondary progressive MS. We argue that this might be because trials have been too short and have focused on assessing neuronal pathways, with insufficient reserve capacity, as the core component of the primary outcome. Delayed neuroaxonal degeneration primed by prior inflammation is not expected to respond to disease-modifying therapies targeting MS-specific mechanisms. However, anti-inflammatory therapies may modify these damaged pathways, but with a therapeutic lag that may take years to manifest. Based on these observations we propose that clinically apparent neurodegenerative components of progressive MS may occur in a length-dependent manner and asynchronously. If this hypothesis is confirmed it may have major implications for the future design of progressive MS trials.
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http://dx.doi.org/10.1016/j.msard.2017.01.007DOI Listing
February 2017

Tool to measure antimicrobial use on farms.

Vet Rec 2017 Feb;180(7):183

Nottingham Dairy Herd Health Group, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington LE12 5RD; e-mail:

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http://dx.doi.org/10.1136/vr.j823DOI Listing
February 2017

Emergency Medicine Resident Assessment of the Emergency Ultrasound Milestones and Current Training Recommendations.

Acad Emerg Med 2017 03 18;24(3):353-361. Epub 2017 Feb 18.

Department of Emergency Medicine, University of Arizona, Tucson, AZ.

Objectives: Emergency ultrasound (EUS) has been recognized as integral to the training and practice of emergency medicine (EM). The Council of Emergency Medicine Residency-Academy of Emergency Ultrasound (CORD-AEUS) consensus document provides guidelines for resident assessment and progression. The Accredited Council for Graduate Medical Education (ACGME) has adopted the EM Milestones for assessment of residents' progress during their residency training, which includes demonstration of procedural competency in bedside ultrasound. The objective of this study was to assess EM residents' use of ultrasound and perceptions of the proposed ultrasound milestones and guidelines for assessment.

Methods: This study is a prospective stratified cluster sample survey of all U.S. EM residency programs. Programs were stratified based on their geographic location (Northeast, South, Midwest, West), presence/absence of ultrasound fellowship program, and size of residency with programs sampled randomly from each stratum. The survey was reviewed by experts in the field and pilot tested on EM residents. Summary statistics and 95% confidence intervals account for the survey design, with sampling weights equal to the inverse of the probability of selection, and represent national estimates of all EM residents.

Results: There were 539 participants from 18 residency programs with an overall survey response rate of 85.1%. EM residents considered several applications to be core applications that were not considered core applications by CORD-AEUS (quantitative bladder volume, diagnosis of joint effusion, interstitial lung fluid, peritonsillar abscess, fetal presentation, and gestational age estimation). Of several core and advanced applications, the Focused Assessment with Sonography in Trauma examination, vascular access, diagnosis of pericardial effusion, and cardiac standstill were considered the most likely to be used in future clinical practice. Residents responded that procedural guidance would be more crucial to their future clinical practice than resuscitative or diagnostic ultrasound. They felt that an average of 325 (301-350) ultrasound examinations would be required to be proficient, but felt that number of examinations poorly represented their competency. They reported high levels of concern about medicolegal liability while using EUS. Eighty-nine percent of residents agreed that EUS is necessary for the practice of EM.

Conclusions: EM resident physicians' opinion of what basic and advanced skills they are likely to utilize in their future clinical practice differs from what has been set forth by various groups of experts. Their opinion of how many ultrasound examinations should be required for competency is higher than what is currently expected during training.
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http://dx.doi.org/10.1111/acem.13113DOI Listing
March 2017

Primary Baerveldt Shunt Implantation: Outcomes and Complications.

Ophthalmol Ther 2016 Dec 25;5(2):253-262. Epub 2016 Jul 25.

Illinois Eye and Ear Infirmary, University of Illinois at Chicago College of Medicine, Chicago, IL, USA.

Introduction: This study is a retrospective case series to evaluate the outcomes and complications of Baerveldt glaucoma implant surgery (BGI) in patients without prior cataract or incisional glaucoma surgery.

Methods: Patients who underwent 350-mm BGI through the Glaucoma Service of the University of Illinois at Chicago between 2010 and 2015 were included in this study. Outcome measures included age, sex, ethnicity, operated eye, preoperative diagnosis, preoperative, and sequential postoperative intraocular pressure (IOP), visual acuity, glaucoma medications, and postoperative complication and interventions. Statistical analyses were performed using the two-sided Student t test for continuous variables.

Results: Thirty-seven patients were studied. IOP was consistently and statistically significantly lower at 3 months (17.4 ± 6.4, p = 3 × 10), 6 months (13.9 ± 5.1, p = 2 × 10), 1 year (12.2 ± 4.0, p = 9 × 10), and 2 years (14.6 ± 3.3, p = 0.0004) postoperatively compared to IOP at baseline (27.5 ± 8.1). Fewer glaucoma medications were used at 3 months (2.8 ± 1.3, p = 0.04), 6 months (2.6 ± 1.2, p = 0.02), 1 year (2.7 ± 1.7, p = 0.04), and 2 years (2.0 ± 1.2, p = 0.03) postoperatively compared to baseline (3.4 ± 1.1). A total of six cases (16%) had failure. A total of five patients (15%) had postoperative complications. Mean Snellen visual acuity was not statistically different at 6 months (0.5 ± 0.6, p = 0.88) or 1 year (0.4 ± 0.4, p = 0.57) postoperatively from baseline (0.5 ± 0.6).

Conclusions: Primary BGI is effective at reducing IOP and the medication burden in patients suffering glaucomatous optic neuropathy. Further randomized prospective studies are needed to compare various procedures in the primary surgical management of patients with uncontrolled glaucoma.

Funding: This study was funded by an unrestricted grant from Research to Prevent Blindness.
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http://dx.doi.org/10.1007/s40123-016-0056-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125118PMC
December 2016

Comparative efficacy of first-line natalizumab vs IFN-β or glatiramer acetate in relapsing MS.

Neurol Clin Pract 2016 Apr;6(2):102-115

Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital (TS, TK, VJ, HB), University of Melbourne, Australia; Biogen Idec Inc. (AZ, FP, SB, RH), Cambridge, MA; Department of Neurology (HW), University of Münster, Germany; Groene Hart Ziekenhuis (FV), Gouda, the Netherlands; MS Center, Department of Neuroscience, Imaging and Clinical Sciences (AL), University "G. d'Annunzio," Chieti, Italy; MS Center, Department of Neurology, First Medical Faculty (EH, DH), Charles University, Prague, Czech Republic; Center de Réadaptation Déficience Physique Chaudière-Appalache (PG), Levis; Hôpital Notre Dame (PD, AP), Montreal, Canada; Ospedali Riuniti di Salerno (G. Iuliano), Salerno, Italy; 19 Mayis University (M. Terzi), Medical Faculty, Turkey; Hospital Universitario Virgen Macarena (G. Izquierdo), Sevilla, Spain; Orbis Medical Centre (RMMH), Sittard-Geleen, the Netherlands; KTU Medical Faculty Farabi Hospital (CB), Trabzon, Turkey; Neurology Unit (EP, GG), ASUR Marche-AV3, Macerata; Nuovo Ospedale Civile S. Agostino (PS), Modena; AORN San Giuseppe Moscati (DLAS), Avellino, Italy; John Hunter Hospital (JL-S), Newcastle, Australia; Neurological Institute IRCCS Mondino (RB), Pavia, Italy; Neuro Rive-Sud (F. Grand'Maison), Hôpital Charles LeMoyne, Quebec, Canada; University of Parma (F. Granella), Italy; Department of Neurology (LK), University Hospital Basel, Switzerland; Department of Basic Medical Sciences, Neuroscience and Sense Organs (M. Trojano), University of Bari, Italy; and Department of Neurology (HB), Eastern Health, Monash University, Australia.

Background: We compared efficacy and treatment persistence in treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS) initiating natalizumab compared with interferon-β (IFN-β)/glatiramer acetate (GA) therapies, using propensity score-matched cohorts from observational multiple sclerosis registries.

Methods: The study population initiated IFN-β/GA in the MSBase Registry or natalizumab in the Tysabri Observational Program, had ≥3 months of on-treatment follow-up, and had active RRMS, defined as ≥1 gadolinium-enhancing lesion on cerebral MRI at baseline or ≥1 relapse within the 12 months prior to baseline. Baseline demographics and disease characteristics were balanced between propensity-matched groups. Annualized relapse rate (ARR), time to first relapse, treatment persistence, and disability outcomes were compared between matched treatment arms in the total population (n = 366/group) and subgroups with higher baseline disease activity.

Results: First-line natalizumab was associated with a 68% relative reduction in ARR from a mean (SD) of 0.63 (0.92) on IFN-β/GA to 0.20 (0.63) ( [signed-rank] < 0.0001), a 64% reduction in the rate of first relapse (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.28-0.47; < 0.001), and a 27% reduction in the rate of discontinuation (HR 0.73, 95% CI 0.58-0.93; = 0.01), compared with first-line IFN-β/GA therapy. Confirmed disability progression and area under the Expanded Disability Status Scale-time curve analyses were not significant. Similar relapse and treatment persistence results were observed in each of the higher disease activity subgroups.

Conclusions: This study provides Class IV evidence that first-line natalizumab for RRMS improves relapse and treatment persistence outcomes compared to first-line IFN-β/GA. This needs to be balanced against the risk of progressive multifocal leukoencephalopathy in natalizumab-treated patients.

Classification Of Evidence: This study provides Class IV evidence that first-line natalizumab for RRMS improves relapse rates and treatment persistence outcomes compared to first-line IFN-β/GA.
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http://dx.doi.org/10.1212/CPJ.0000000000000227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828679PMC
April 2016

Dynamics of robust pattern separability in the hippocampal dentate gyrus.

Hippocampus 2016 May 5;26(5):623-32. Epub 2015 Nov 5.

Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio.

The dentate gyrus (DG) is thought to perform pattern separation on inputs received from the entorhinal cortex, such that the DG forms distinct representations of different input patterns. Neuronal responses, however, are known to be variable, and that variability has the potential to confuse the representations of different inputs, thereby hindering the pattern separation function. This variability can be especially problematic for tissues such as the DG, in which the responses can persist for tens of seconds following stimulation: the long response duration allows for variability from many different sources to accumulate. To understand how the DG can robustly encode different input patterns, we investigated a recently developed in vitro hippocampal DG preparation that generates persistent responses to transient electrical stimulation. For 10-20 s after stimulation, the responses are indicative of the pattern of stimulation that was applied, even though the responses exhibit significant trial-to-trial variability. Analyzing the dynamical trajectories of the evoked responses, we found that, following stimulation, the neural responses follow distinct paths through the space of possible neural activations, with a different path associated with each stimulation pattern. The neural responses' trial-to-trial variability shifts the responses along these paths rather than between them, maintaining the separability of the input patterns. Manipulations that redistributed the variability more isotropically over the space of possible neural activations impeded the pattern separation function. Consequently, we conclude that the confinement of neuronal variability to these one-dimensional paths mitigates the impacts of variability on pattern encoding and, thus, may be an important aspect of the DG's ability to robustly encode input patterns.
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http://dx.doi.org/10.1002/hipo.22546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546763PMC
May 2016