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1.
Heart Fail Clin ; 19(4): 531-543, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37714592

ABSTRACT

Artificial intelligence (AI) applications are expanding in cardiac imaging. AI research has shown promise in workflow optimization, disease diagnosis, and integration of clinical and imaging data to predict patient outcomes. The diagnostic and prognostic paradigm of heart failure is heavily reliant on cardiac imaging. As AI becomes increasingly validated and integrated into clinical practice, AI influence on heart failure management will grow. This review discusses areas of current research and potential clinical applications in AI as applied to heart failure cardiac imaging.


Subject(s)
Artificial Intelligence , Heart Failure , Humans , Diagnostic Imaging , Cardiac Imaging Techniques , Heart Failure/diagnostic imaging
2.
Psychol Med ; 52(3): 467-475, 2022 02.
Article in English | MEDLINE | ID: mdl-32597742

ABSTRACT

BACKGROUND: Cognitive deficits affect a significant proportion of patients with bipolar disorder (BD). Problems with sustained attention have been found independent of mood state and the causes are unclear. We aimed to investigate whether physical parameters such as activity levels, sleep, and body mass index (BMI) may be contributing factors. METHODS: Forty-six patients with BD and 42 controls completed a battery of neuropsychological tests and wore a triaxial accelerometer for 21 days which collected information on physical activity, sleep, and circadian rhythm. Ex-Gaussian analyses were used to characterise reaction time distributions. We used hierarchical regression analyses to examine whether physical activity, BMI, circadian rhythm, and sleep predicted variance in the performance of cognitive tasks. RESULTS: Neither physical activity, BMI, nor circadian rhythm predicted significant variance on any of the cognitive tasks. However, the presence of a sleep abnormality significantly predicted a higher intra-individual variability of the reaction time distributions on the Attention Network Task. CONCLUSIONS: This study suggests that there is an association between sleep abnormalities and cognition in BD, with little or no relationship with physical activity, BMI, and circadian rhythm.


Subject(s)
Bipolar Disorder , Bipolar Disorder/complications , Bipolar Disorder/psychology , Body Mass Index , Circadian Rhythm , Cognition , Exercise , Humans , Sleep
3.
PLoS Comput Biol ; 17(6): e1009108, 2021 06.
Article in English | MEDLINE | ID: mdl-34115749

ABSTRACT

Staphylococcus aureus is a serious human and animal pathogen threat exhibiting extraordinary capacity for acquiring new antibiotic resistance traits in the pathogen population worldwide. The development of fast, affordable and effective diagnostic solutions capable of discriminating between antibiotic-resistant and susceptible S. aureus strains would be of huge benefit for effective disease detection and treatment. Here we develop a diagnostics solution that uses Matrix-Assisted Laser Desorption/Ionisation-Time of Flight Mass Spectrometry (MALDI-TOF) and machine learning, to identify signature profiles of antibiotic resistance to either multidrug or benzylpenicillin in S. aureus isolates. Using ten different supervised learning techniques, we have analysed a set of 82 S. aureus isolates collected from 67 cows diagnosed with bovine mastitis across 24 farms. For the multidrug phenotyping analysis, LDA, linear SVM, RBF SVM, logistic regression, naïve Bayes, MLP neural network and QDA had Cohen's kappa values over 85.00%. For the benzylpenicillin phenotyping analysis, RBF SVM, MLP neural network, naïve Bayes, logistic regression, linear SVM, QDA, LDA, and random forests had Cohen's kappa values over 85.00%. For the benzylpenicillin the diagnostic systems achieved up to (mean result ± standard deviation over 30 runs on the test set): accuracy = 97.54% ± 1.91%, sensitivity = 99.93% ± 0.25%, specificity = 95.04% ± 3.83%, and Cohen's kappa = 95.04% ± 3.83%. Moreover, the diagnostic platform complemented by a protein-protein network and 3D structural protein information framework allowed the identification of five molecular determinants underlying the susceptible and resistant profiles. Four proteins were able to classify multidrug-resistant and susceptible strains with 96.81% ± 0.43% accuracy. Five proteins, including the previous four, were able to classify benzylpenicillin resistant and susceptible strains with 97.54% ± 1.91% accuracy. Our approach may open up new avenues for the development of a fast, affordable and effective day-to-day diagnostic solution, which would offer new opportunities for targeting resistant bacteria.


Subject(s)
Diagnosis, Computer-Assisted/veterinary , Mastitis, Bovine/diagnosis , Penicillin G/pharmacology , Staphylococcal Infections/veterinary , Staphylococcus aureus , Animals , Bacterial Proteins/chemistry , Cattle , Computational Biology , Diagnosis, Computer-Assisted/methods , Diagnosis, Computer-Assisted/statistics & numerical data , Drug Resistance, Multiple, Bacterial , Female , Humans , Mastitis, Bovine/drug therapy , Mastitis, Bovine/microbiology , Methicillin-Resistant Staphylococcus aureus/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Microbial Sensitivity Tests , Models, Molecular , Protein Interaction Maps , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Staphylococcus aureus/chemistry , Staphylococcus aureus/drug effects , Staphylococcus aureus/isolation & purification , Supervised Machine Learning , United Kingdom
4.
Nephrol Dial Transplant ; 32(5): 890-900, 2017 May 01.
Article in English | MEDLINE | ID: mdl-28379431

ABSTRACT

BACKGROUND: Living donor kidney transplantation (LDKT) provides more timely access to transplantation and better clinical outcomes than deceased donor kidney transplantation (DDKT). This study investigated disparities in the utilization of LDKT in the UK. METHODS: A total of 2055 adults undergoing kidney transplantation between November 2011 and March 2013 were prospectively recruited from all 23 UK transplant centres as part of the Access to Transplantation and Transplant Outcome Measures (ATTOM) study. Recipient variables independently associated with receipt of LDKT versus DDKT were identified. RESULTS: Of the 2055 patients, 807 (39.3%) received LDKT and 1248 (60.7%) received DDKT. Multivariable modelling demonstrated a significant reduction in the likelihood of LDKT for older age {odds ratio [OR] 0.11 [95% confidence interval (CI) 0.08-0.17], P < 0.0001 for 65-75 years versus 18-34 years}; Asian ethnicity [OR 0.55 (95% CI 0.39-0.77), P = 0.0006 versus White]; Black ethnicity [OR 0.64 (95% CI 0.42-0.99), P = 0.047 versus White]; divorced, separated or widowed [OR 0.63 (95% CI 0.46-0.88), P = 0.030 versus married]; no qualifications [OR 0.55 (95% CI 0.42-0.74), P < 0.0001 versus higher education qualifications]; no car ownership [OR 0.51 (95% CI 0.37-0.72), P = 0.0001] and no home ownership [OR 0.65 (95% CI 0.85-0.79), P = 0.002]. The odds of LDKT varied significantly between countries in the UK. CONCLUSIONS: Among patients undergoing kidney transplantation in the UK, there are significant age, ethnic, socio-economic and geographic disparities in the utilization of LDKT. Further work is needed to explore the potential for targeted interventions to improve equity in living donor transplantation.


Subject(s)
Donor Selection , Health Knowledge, Attitudes, Practice , Kidney Transplantation , Living Donors , Tissue and Organ Procurement , Adolescent , Adult , Black or African American , Aged , Communication Barriers , Female , Humans , Male , Middle Aged , Prospective Studies , United Kingdom , White People , Young Adult
5.
Hum Psychopharmacol ; 29(3): 295-8, 2014 May.
Article in English | MEDLINE | ID: mdl-24911579

ABSTRACT

OBJECTIVE: The association between hypothalamic-pituitary-adrenal (HPA)-axis function and cognition has long been investigated. An inverted U-shaped relationship has been described between various measures of HPA-axis function and neuropsychological performance in animals and man. Work with glucocorticoid receptor manipulation has corroborated these findings, with particular effects observed in relation to spatial working memory (SWM). As HPA-axis dysfunction is frequently found in patients with psychiatric illness, research in this area has potential implications for the treatment of the commonly observed cognitive impairment in such disorders. Here, we present the results of a pilot study examining the relationship between cortisol awakening response (CAR) and cognitive functions known to be susceptible to HPA-axis manipulation. METHODS: Nineteen healthy male volunteers were recruited, and their CAR and performance in a task of SWM were assessed. RESULTS: A highly significant quadratic relationship was observed between the CAR and SWM error rate (R(2)=0.63, p=0.001). CONCLUSION: We provide novel evidence supporting the existence of an inverted U-shaped relationship between corticosteroid levels and cognitive function in humans.


Subject(s)
Circadian Rhythm/physiology , Hydrocortisone/metabolism , Memory, Short-Term/physiology , Saliva/metabolism , Spatial Memory/physiology , Wakefulness/physiology , Adult , Area Under Curve , Attention/physiology , Humans , Male , Middle Aged , Neuropsychological Tests , Pilot Projects , Radioimmunoassay , Regression Analysis
6.
J Dairy Sci ; 97(10): 6594-607, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25129497

ABSTRACT

Dry cow therapy is an important part of mastitis control. This therapy typically consists of an antibiotic or antibiotics administered at a single dose by intramammary infusion at dry off to treat or prevent infection by prevalent mastitis pathogens. A combination dry cow therapy consisting of the active components penicillin and framycetin is currently used in several countries. Despite its use, standardized methods for the susceptibility testing of this combination against mastitis pathogens have not been established. In this study, which used Clinical and Laboratory Standards Institute methodology, preliminary interpretive criteria for the broth microdilution minimum inhibitory concentration (MIC) testing of mastitis pathogens to penicillin combined with framycetin (2:1 wt/wt) were established based on the amount of drug achieved and maintained postadministration in the udder. Based on resulting MIC distributions of recent veterinary field isolates and a subset of isolates preselected for resistance to ß-lactams or aminoglycosides and concentrations achieved postadministration, criteria for broth microdilution testing of the combination (susceptible, intermediate, resistant in micrograms per milliliter) were set as follows: Escherichia coli ≤8/4, 16/8, ≥32/16; Staphylococcus spp. ≤2/1, 4/2-8/4, >16/8; Streptococcus uberis and Streptococcus dysgalactiae <0.25/0.12, 0.5/0.25-2/1, >4/2. A disk diffusion test using disks containing 100 µg of framycetin and 10 IU of penicillin was also developed, and preliminary interpretive criteria (susceptible, intermediate, resistant in millimeters) were set based on correlation to broth MIC values and the minimization of interpretive errors between isolates tested concurrently by broth microdilution and disk diffusion as follows: E. coli ≥18, 16-17, ≤15; Staphylococcus spp. ≥21, 18-20, ≤17; Strep. uberis and Strep. dysgalactiae ≥21, 19-20, ≤18. In addition, ranges for the quality control of the testing of this combination by both broth microdilution and disk diffusion are provided. Based on these criteria and recent veterinary mastitis isolates, 96.0/96.8% of E. coli, 93.7/89.1% of Staph. aureus, 94.6/96.4% coagulase-negative staphylococci, 94.5/97.0% of Strep. uberis, and 96.7/100.0% Strep. dysgalactiae were susceptible to the combination by broth microdilution or disk diffusion, respectively. The availability of these methods will allow for the susceptibility testing of clinical isolates in the field and will also provide a way to monitor for resistance development as this combination is used going forward.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Framycetin/pharmacology , Mastitis, Bovine/microbiology , Penicillins/pharmacology , Animals , Cattle , Escherichia coli/drug effects , Female , Mammary Glands, Animal/metabolism , Mastitis, Bovine/drug therapy , Microbial Sensitivity Tests/veterinary , Staphylococcus/drug effects , Staphylococcus aureus/drug effects , Streptococcal Infections/drug therapy , Streptococcal Infections/veterinary , Streptococcus/drug effects
7.
Vet Rec ; 194(4): e3605, 2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38012022

ABSTRACT

BACKGROUND: Achieving a reduction in mastitis in dairy cows is a common industry goal, but there is no recent peer-reviewed record of progress in the UK. METHODS: A convenience sample of 125 herds in England and Scotland was recruited based on the quality of records in 2016, willingness to participate and representative geographical distribution. Individual cow somatic cell counts and clinical mastitis data from 2012 to 2021 were summarised annually, and temporal changes were analysed. Eighty-one herds had sufficient data for comparison between 2012 and 2021, for one or more parameters. RESULTS: Over this period, the median incidence rate of clinical mastitis decreased from 40.0 to 21.0 cases per 100 cows per year (p < 0.001), with improvement in both lactation and dry period indicators. Lactation new infection rate calculated from individual cow somatic cell counts fell from 8.75% to 5.95% (p < 0.001), dry period new infection rate fell from 16.8% to 14.1% (p < 0.05) and proportion of cows over 200,000 cells/mL fell from 20.0% to 14.3% (p < 0.001). LIMITATIONS: Data were necessarily from herds with good records and do not provide absolute values for the industry. CONCLUSION: The findings reflect good progress over a 10-year period in a cohort of well-recorded herds and align with other national datasets.


Subject(s)
Cattle Diseases , Mammary Glands, Human , Mastitis, Bovine , Female , Animals , Cattle , Humans , Milk , Mastitis, Bovine/epidemiology , Mastitis, Bovine/prevention & control , Dairying , Mammary Glands, Animal , Lactation , England/epidemiology , Scotland/epidemiology , Cell Count/veterinary
8.
Front Vet Sci ; 10: 1297750, 2023.
Article in English | MEDLINE | ID: mdl-38144465

ABSTRACT

Udder health remains a priority for the global dairy industry to reduce pain, economic losses, and antibiotic usage. The dry period is a critical time for the prevention of new intra-mammary infections and it provides a point for curing existing intra-mammary infections. Given the wealth of udder health data commonly generated through routine milk recording and the importance of udder health to the productivity and longevity of individual cows, an opportunity exists to extract greater value from cow-level data to undertake risk-based decision-making. The aim of this research was to construct a machine learning model, using routinely collected farm data, to make probabilistic predictions at drying off for an individual cow's risk of a raised somatic cell count (hence intra-mammary infection) post-calving. Anonymized data were obtained as a large convenience sample from 108 UK dairy herds that undertook regular milk recording. The outcome measure evaluated was the presence of a raised somatic cell count in the 30 days post-calving in this observational study. Using a 56-farm training dataset, machine learning analysis was performed using the extreme gradient boosting decision tree algorithm, XGBoost. External validation was undertaken on a separate 28-farm test dataset. Statistical assessment to evaluate model performance using the external dataset returned calibration plots, a Scaled Brier Score of 0.095, and a Mean Absolute Calibration Error of 0.009. Test dataset model calibration performance indicated that the probability of a raised somatic cell count post-calving was well differentiated across probabilities to allow an end user to apply group-level risk decisions. Herd-level new intra-mammary infection rate during the dry period was a key driver of the probability that a cow had a raised SCC post-calving, highlighting the importance of optimizing environmental hygiene conditions. In conclusion, this research has determined that probabilistic classification of the risk of a raised SCC in the 30 days post-calving is achievable with a high degree of certainty, using routinely collected data. These predicted probabilities provide the opportunity for farmers to undertake risk decision-making by grouping cows based on their probabilities and optimizing management strategies for individual cows immediately after calving, according to their likelihood of intra-mammary infection.

9.
Ann Clin Transl Neurol ; 10(8): 1442-1455, 2023 08.
Article in English | MEDLINE | ID: mdl-37483011

ABSTRACT

OBJECTIVE: FHL1-related reducing body myopathy is an ultra-rare, X-linked dominant myopathy. In this cross-sectional study, we characterize skeletal muscle ultrasound, muscle MRI, and cardiac MRI findings in FHL1-related reducing body myopathy patients. METHODS: Seventeen patients (11 male, mean age 35.4, range 12-76 years) from nine independent families with FHL1-related reducing body myopathy underwent clinical evaluation, muscle ultrasound (n = 11/17), and lower extremity muscle MRI (n = 14/17), including Dixon MRI (n = 6/17). Muscle ultrasound echogenicity was graded using a modified Heckmatt scale. T1 and STIR axial images of the lower extremity muscles were evaluated for pattern and distribution of abnormalities. Quantitative analysis of intramuscular fat fraction was performed using the Dixon MRI images. Cardiac studies included electrocardiogram (n = 15/17), echocardiogram (n = 17/17), and cardiac MRI (n = 6/17). Cardiac muscle function, T1 maps, T2-weighted black blood images, and late gadolinium enhancement patterns were analyzed. RESULTS: Muscle ultrasound showed a distinct pattern of increased echointensity in skeletal muscles with a nonuniform, multifocal, and "geographical" distribution, selectively involving the deeper fascicles of muscles such as biceps and tibialis anterior. Lower extremity muscle MRI showed relative sparing of gluteus maximus, rectus femoris, gracilis, and lateral gastrocnemius muscles and an asymmetric and multifocal, "geographical" pattern of T1 hyperintensity within affected muscles. Cardiac studies revealed mild and nonspecific abnormalities on electrocardiogram and echocardiogram with unremarkable cardiac MRI studies. INTERPRETATION: Skeletal muscle ultrasound and muscle MRI reflect the multifocal aggregate formation in muscle in FHL1-related reducing body myopathy and are practical and informative tools that can aid in diagnosis and monitoring of disease progression.


Subject(s)
Contrast Media , Muscular Diseases , Humans , Male , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Cross-Sectional Studies , Muscle Proteins , Gadolinium , Muscle, Skeletal/diagnostic imaging , Muscular Diseases/diagnostic imaging , Muscular Diseases/genetics , Intracellular Signaling Peptides and Proteins , LIM Domain Proteins/genetics
10.
Clin Cardiol ; 46(5): 477-483, 2023 May.
Article in English | MEDLINE | ID: mdl-36847047

ABSTRACT

AIMS: We compared diagnostic performance, costs, and association with major adverse cardiovascular events (MACE) of clinical coronary computed tomography angiography (CCTA) interpretation versus semiautomated approach that use artificial intelligence and machine learning for atherosclerosis imaging-quantitative computed tomography (AI-QCT) for patients being referred for nonemergent invasive coronary angiography (ICA). METHODS: CCTA data from individuals enrolled into the randomized controlled Computed Tomographic Angiography for Selective Cardiac Catheterization trial for an American College of Cardiology (ACC)/American Heart Association (AHA) guideline indication for ICA were analyzed. Site interpretation of CCTAs were compared to those analyzed by a cloud-based software (Cleerly, Inc.) that performs AI-QCT for stenosis determination, coronary vascular measurements and quantification and characterization of atherosclerotic plaque. CCTA interpretation and AI-QCT guided findings were related to MACE at 1-year follow-up. RESULTS: Seven hundred forty-seven stable patients (60 ± 12.2 years, 49% women) were included. Using AI-QCT, 9% of patients had no CAD compared with 34% for clinical CCTA interpretation. Application of AI-QCT to identify obstructive coronary stenosis at the ≥50% and ≥70% threshold would have reduced ICA by 87% and 95%, respectively. Clinical outcomes for patients without AI-QCT-identified obstructive stenosis was excellent; for 78% of patients with maximum stenosis < 50%, no cardiovascular death or acute myocardial infarction occurred. When applying an AI-QCT referral management approach to avoid ICA in patients with <50% or <70% stenosis, overall costs were reduced by 26% and 34%, respectively. CONCLUSIONS: In stable patients referred for ACC/AHA guideline-indicated nonemergent ICA, application of artificial intelligence and machine learning for AI-QCT can significantly reduce ICA rates and costs with no change in 1-year MACE.


Subject(s)
Atherosclerosis , Coronary Artery Disease , Coronary Stenosis , Fractional Flow Reserve, Myocardial , Humans , Female , Male , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/complications , Coronary Angiography/methods , Constriction, Pathologic/complications , Artificial Intelligence , Tomography, X-Ray Computed , Coronary Stenosis/complications , Computed Tomography Angiography/methods , Atherosclerosis/complications , Referral and Consultation , Predictive Value of Tests
11.
Front Cardiovasc Med ; 9: 834738, 2022.
Article in English | MEDLINE | ID: mdl-35990938

ABSTRACT

Pregnancy is associated with profound hemodynamic changes that are particularly impactful in patients with underlying cardiovascular disease. Management of pregnant women with cardiovascular disease requires careful evaluation that considers the well-being of both the woman and the developing fetus. Clinical assessment begins before pregnancy and continues throughout gestation into the post-partum period and is supplemented by cardiac imaging. This review discusses the role of imaging, specifically echocardiography, cardiac MRI, and cardiac CT, in pregnant women with valvular diseases, hypertrophic cardiomyopathy, and aortic pathology.

12.
Vet Rec ; 190(7): e1066, 2022 04.
Article in English | MEDLINE | ID: mdl-34802151

ABSTRACT

BACKGROUND: The nature and depth of bedding material have an important influence on cow lying behaviour and comfort. Increasing use of recycled manure solids (RMS) as bedding led to an investigation of the influence of this material on cow lying behaviour. METHODS: Leg mounted accelerometers were used to estimate daily lying time and number and duration of lying bouts in four groups of 40 cows. Each group spent two 2-week periods on each of four bedding systems: deep sand, deep RMS, sawdust on mattresses and RMS on mattresses. RESULTS: Total daily lying times were significantly shorter on both RMS treatments than on sawdust. Number of lying bouts per day was greater on sawdust than any other treatment, while lying bouts were 2.6 min longer on deep RMS and 9.3 min longer on sand, than on sawdust. CONCLUSIONS: Greater depth and apparent softness of bedding material does not necessarily result in longer total daily lying times. RMS may have some characteristics that reduce its attraction as a bedding material for cows. The influence of bedding system on number and duration of lying bouts and the resulting total lying time appear complex.


Subject(s)
Dairying , Housing, Animal , Animals , Bedding and Linens/veterinary , Beds , Behavior, Animal , Cattle , Dairying/methods , Female
13.
Front Cardiovasc Med ; 9: 839400, 2022.
Article in English | MEDLINE | ID: mdl-35387447

ABSTRACT

Coronary artery disease is a leading cause of death worldwide. There has been a myriad of advancements in the field of cardiovascular imaging to aid in diagnosis, treatment, and prevention of coronary artery disease. The application of artificial intelligence in medicine, particularly in cardiovascular medicine has erupted in the past decade. This article serves to highlight the highest yield articles within cardiovascular imaging with an emphasis on coronary CT angiography methods for % stenosis evaluation and atherosclerosis quantification for the general cardiologist. The paper finally discusses the evolving paradigm of implementation of artificial intelligence in real world practice.

14.
Rheumatol Ther ; 9(1): 109-125, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34709605

ABSTRACT

INTRODUCTION: Ixekizumab, a selective interleukin-17A antagonist, was compared with adalimumab in the SPIRIT-H2H study (NCT03151551) in patients with psoriatic arthritis (PsA) and concomitant psoriasis. This post hoc analysis reports outcomes to week 52 in patients from SPIRIT-H2H, stratified by baseline psoriasis severity. METHODS: SPIRIT-H2H was a 52-week, multicenter, randomized, open-label, rater-blinded, parallel-group study of biologic disease-modifying antirheumatic drug (DMARD)-naïve patients (N = 566) with PsA and active psoriasis (≥ 3% body surface area involvement). Patients were randomized to ixekizumab or adalimumab (1:1) with stratification by baseline concomitant use of conventional synthetic DMARDs and psoriasis severity (with/without moderate-to-severe psoriasis). Patients received on-label dosing according to psoriasis severity. The primary endpoint was the proportion of patients simultaneously achieving ≥ 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100) at week 24. Secondary endpoints included musculoskeletal, disease activity (defined by composite indices), skin and nail, quality of life and safety outcomes. In this post hoc analysis, primary and secondary endpoints of SPIRIT-H2H were analyzed by baseline psoriasis severity. RESULTS: A greater proportion of patients achieved the combined endpoint of ACR50 + PASI100 and PASI100 with ixekizumab compared with adalimumab at weeks 24 and 52, regardless of baseline psoriasis severity. ACR response rates were similar for ixekizumab and adalimumab across both patient subgroups. For musculoskeletal outcomes, similar efficacy was seen for ixekizumab and adalimumab, but ixekizumab showed greater responses for skin outcomes regardless of psoriasis severity. The safety profiles of ixekizumab and adalimumab were consistent between subgroups. CONCLUSIONS: Regardless of baseline psoriasis severity, ixekizumab demonstrated greater efficacy than adalimumab with respect to simultaneous achievement of ACR50 + PASI100, and showed consistent and sustained efficacy across PsA-related domains. It also demonstrated higher response rates for skin outcomes. These subgroup analyses highlight the efficacy of ixekizumab in patients with PsA irrespective of the severity of concomitant psoriasis.

15.
RMD Open ; 8(2)2022 09.
Article in English | MEDLINE | ID: mdl-36171019

ABSTRACT

BACKGROUND/OBJECTIVE: The aim of this study was to evaluate relative performance of composite measures in psoriatic arthritis and assess the impact of structural damage and functional disability on outcomes during ixekizumab treatment. METHODS: Data from SPIRIT-P1 and SPIRIT-P2 were analysed to evaluate the effect of ixekizumab on achievement of low disease activity (LDA) and remission with the minimal disease activity (MDA) and very low disease activity (VLDA) composite, Disease Activity index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score, GRAppa Composite ScorE and modified Composite Psoriatic Disease Activity Index (mCPDAI). Performance was compared by quantifying residual symptom burden and the impact of structural damage and functional disability. RESULTS: Significantly more ixekizumab-treated patients achieved treatment targets at week 24 versus placebo assessed with all composites. More patients achieved targets assessed by mCPDAI and DAPSA than other composites. Residual disease activity was similar between composites, but residual high patient-reported outcomes (PROs) and functional disability were more frequent when assessed with mCPDAI and DAPSA. Achievement of treatment targets was reduced by high baseline levels of structural damage and functional disability. CONCLUSION: Residual disease activity was similar in patients achieving treatment targets assessed with all composites, but residual high PROs and functional disability were more common when assessed with mCPDAI and DAPSA, most likely due to the absence/attenuated functional assessment in these composites. High baseline levels of structural damage and functional disability attenuated response rates with all composites, affecting MDA/VLDA most prominently; LDA may be the most appropriate target in these patients. TRIAL REGISTRATION NUMBER: NCT01695239.


Subject(s)
Antirheumatic Agents , Arthritis, Psoriatic , Antibodies, Monoclonal, Humanized , Antirheumatic Agents/therapeutic use , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/drug therapy , Disease Progression , Humans , Severity of Illness Index , Treatment Outcome
16.
Sci Rep ; 12(1): 15083, 2022 09 05.
Article in English | MEDLINE | ID: mdl-36065056

ABSTRACT

Selection and spread of Extended Spectrum Beta-Lactamase (ESBL) -producing Enterobacteriaceae within animal production systems and potential spillover to humans is a major concern. Intramammary treatment of dairy cows with first-generation cephalosporins is a common practice and potentially selects for ESBL-producing Enterobacteriaceae, although it is unknown whether this really occurs in the bovine fecal environment. We aimed to study the potential effects of intramammary application of cephapirin (CP) and cefalonium (CL) to select for ESBL-producing Escherichia coli in the intestinal content of treated dairy cows and in manure slurry, using in vitro competition experiments with ESBL and non-ESBL E. coli isolates. No selection of ESBL-producing E. coli was observed at or below concentrations of 0.8 µg/ml and 4.0 µg/ml in bovine feces for CP and CL, respectively, and at or below 8.0 µg/ml and 4.0 µg/ml, respectively, in manure slurry. We calculated that the maximum concentration of CP and CL after intramammary treatment with commercial products will not exceed 0.29 µg/ml in feces and 0.03 µg/ml in manure slurry. Therefore, the results of this study did not find evidence supporting the selection of ESBL-producing E. coli in bovine feces or in manure slurry after intramammary use of commercial CP or CL-containing products.


Subject(s)
Escherichia coli Infections , Escherichia coli , Animals , Anti-Bacterial Agents/pharmacology , Cattle , Cephalosporins/pharmacology , Enterobacteriaceae , Escherichia coli Infections/drug therapy , Escherichia coli Infections/veterinary , Feces , Female , Humans , Manure , Microbial Sensitivity Tests , beta-Lactamases
17.
Sci Rep ; 11(1): 7736, 2021 04 08.
Article in English | MEDLINE | ID: mdl-33833319

ABSTRACT

Streptococcus uberis is one of the leading pathogens causing mastitis worldwide. Identification of S. uberis strains that fail to respond to treatment with antibiotics is essential for better decision making and treatment selection. We demonstrate that the combination of supervised machine learning and matrix-assisted laser desorption ionization/time of flight (MALDI-TOF) mass spectrometry can discriminate strains of S. uberis causing clinical mastitis that are likely to be responsive or unresponsive to treatment. Diagnostics prediction systems trained on 90 individuals from 26 different farms achieved up to 86.2% and 71.5% in terms of accuracy and Cohen's kappa. The performance was further increased by adding metadata (parity, somatic cell count of previous lactation and count of positive mastitis cases) to encoded MALDI-TOF spectra, which increased accuracy and Cohen's kappa to 92.2% and 84.1% respectively. A computational framework integrating protein-protein networks and structural protein information to the machine learning results unveiled the molecular determinants underlying the responsive and unresponsive phenotypes.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Dairying , Machine Learning , Mastitis, Bovine/drug therapy , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Streptococcal Infections/veterinary , Streptococcus/pathogenicity , Animals , Cattle , Female , Mastitis, Bovine/microbiology , Pregnancy , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology , Streptococcus/isolation & purification
18.
Sci Rep ; 11(1): 6577, 2021 03 22.
Article in English | MEDLINE | ID: mdl-33753828

ABSTRACT

In this work, we sought to delineate the prevalence of cardiothoracic imaging findings of Proteus syndrome in a large cohort at our institution. Of 53 individuals with a confirmed diagnosis of Proteus syndrome at our institution from 10/2001 to 10/2019, 38 individuals (men, n = 23; average age = 24 years) underwent cardiothoracic imaging (routine chest CT, CT pulmonary angiography and/or cardiac MRI). All studies were retrospectively and independently reviewed by two fellowship-trained cardiothoracic readers. Disagreements were resolved by consensus. Differences between variables were analyzed via parametric and nonparametric tests based on the normality of the distribution. The cardiothoracic findings of Proteus syndrome were diverse, but several were much more common and included: scoliosis from bony overgrowth (94%), pulmonary venous dilation (62%), band-like areas of lung scarring (56%), and hyperlucent lung parenchyma (50%). In addition, of 20 individuals who underwent cardiac MRI, 9/20 (45%) had intramyocardial fat, mostly involving the endocardial surface of the left ventricular septal wall. There was no statistically significant difference among the functional cardiac parameters between individuals with and without intramyocardial fat. Only one individual with intramyocardial fat had mildly decreased function (LVEF = 53%), while all others had normal ejection fraction.


Subject(s)
Diagnostic Imaging , Proteus Syndrome/diagnosis , Thorax/abnormalities , Thorax/diagnostic imaging , Adolescent , Adult , Child , Diagnostic Imaging/methods , Female , Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/genetics , Humans , Lung/abnormalities , Lung/diagnostic imaging , Magnetic Resonance Imaging , Male , Mediastinum/abnormalities , Mediastinum/diagnostic imaging , Middle Aged , Thoracic Wall/abnormalities , Thoracic Wall/diagnostic imaging , Tomography, X-Ray Computed , Young Adult
19.
Sci Rep ; 10(1): 4289, 2020 03 09.
Article in English | MEDLINE | ID: mdl-32152401

ABSTRACT

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.


Subject(s)
Animal Husbandry , Dairying/methods , Infections/diagnosis , Machine Learning , Mastitis, Bovine/microbiology , Models, Statistical , Animals , Cattle , Female , Infections/microbiology
20.
Heart ; 104(17): 1469-1470, 2018 09.
Article in English | MEDLINE | ID: mdl-29934369

ABSTRACT

CLINICAL INTRODUCTION: A 63-year-old man with HIV presented with 1 month of dyspnoea and productive cough without orthopnoea. He was afebrile with normal blood pressure, borderline tachycardia and mild pulmonary wheezing. He had exertional hypoxia requiring 4 L per minute of oxygen. No murmurs, jugular venous distention or lower extremity oedema was noted. Clinical evaluation included transthoracic echocardiography (TTE), which showed mild left ventricular hypertrophy with normal size and systolic function. The right ventricle was normal. There was mild aortic insufficiency; other valves were normal. An abnormality was incidentally seen at the aortic root.The patient was treated for bronchitis and chronic obstructive pulmonary disease exacerbation, while further evaluation of the incidental aortic root finding was performed with transoesophageal echocardiography (TEE) and cardiac MRI (CMR). QUESTION: What is the most likely diagnosis for this finding?Sinus of Valsalva aneurysm.Chronic aortic dissection.Left ventricular outflow tract (LVOT) pseudoaneurysm.Right coronary artery aneurysm.Aortic root abscess.


Subject(s)
Aneurysm, False/diagnostic imaging , Aorta/diagnostic imaging , Aortic Valve/diagnostic imaging , Bronchitis , Echocardiography/methods , Heart Ventricles/diagnostic imaging , Magnetic Resonance Imaging, Cine/methods , Bronchitis/complications , Bronchitis/diagnosis , Bronchitis/physiopathology , HIV Infections/complications , Humans , Incidental Findings , Male , Middle Aged , Ventricular Outflow Obstruction/diagnosis , Ventricular Outflow Obstruction/etiology
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