Developing evidence on the primary case presentation and assessment of acute abdominal pain (colic) in the horse

Abdominal pain (colic) in the horse is one of the most common emergency problems in the horse, but there are major gaps in the current evidence. Five original studies were undertaken to build evidence on the primary assessment of abdominal pain in the horse. The first study was a systematic review of risk factors for abdominal pain. This identified 83 publications on risk factors for colic; 47 met inclusion criteria and were reviewed and categorised. Twenty four studies were evaluated using the JBI-Mastari critical appraisal tool. Evidence from the ten publications with least susceptibility to bias was collated. There was consensus of evidence for increasing age, recent change in diet and previous history of abdominal pain are risk factors for colic. This evidence should inform veterinary practitioner’s clinical decision making and approach to disease prevention. The second study was a systematic review of diagnostic tests for abdominal pain. This identified 190 publications; 46 publications met inclusion criteria and were reviewed and categorised. Thirty studies were evaluated using the QUADAS critical appraisal tool. None of the studies used a suitable methodology to assess the value of a diagnostic test to differentiate critical cases. The outcomes of this systematic review were a description of the current evidence and recommendations for future research using appropriate study designs. Both systematic reviews highlighted a lack of evidence from primary practice. The third study was a prospective survey of the primary assessment of horses with abdominal pain by veterinary practitioners. Data was collected from 1016 cases, including clinical history, presenting signs, diagnostic and treatment approaches and case outcome. Cases were categorised as critical or non-critical. Multivariate logistic regression was used to identify clinical features associated with critical cases. Five variables remained in the final model: pain, heart rate, capillary refill time, pulse character and gastrointestinal borborygmi. These should be considered essential components of the initial assessment and triage of horses presenting with colic. The fourth study was an online survey of veterinary practitioner’s opinions of diagnostic tests for colic. Responses from 228 participants were analysed. The most frequently used tests were ‘response to analgesia’, ‘rectal examination’ and ‘nasogastric intubation’, but there was a wide variation in practitioners’ approaches. The main reasons for not using tests were that practitioners considered they were not required, or had concerns around personal safety, lack of facilities or financial constraints. The final phase was two multi-disciplinary workshops to review current evidence and generate recommendations. Fifty participants attended the first workshop and generated 84 statements on the recognition of colic. Forty one participants attended the second workshop and generated 160 statements on the assessment of horses with colic. These statements form the first phase of a multi-disciplinary Delphi process to develop best practice guidelines on the recognition and primary assessment of horses with abdominal pain. This research makes significant contributions to the current evidence on abdominal pain in the horse. It has consolidated existing information, made recommendations for future research, and worked with practitioners to address evidence gaps, and involved different stakeholders in deciding how this evidence should be applied

Prospective survey of veterinary practitioners’ primary assessment of equine colic: clinical features, diagnoses, and treatment of 120 cases of large colon impaction

Background Large colon impactions are a common cause of colic in the horse. There are no scientific reports on the clinical presentation, diagnostic tests and treatments used in first opinion practice for large colon impaction cases. The aim of this study was to describe the presentation, diagnostic approach and treatment at the primary assessment of horses with large colon impactions. Methods Data were collected prospectively from veterinary practitioners on the primary assessment of equine colic cases over a 12 month period. Inclusion criteria were a diagnosis of primary large colon impaction and positive findings on rectal examination. Data recorded for each case included history, signalment, clinical and diagnostic findings, treatment on primary assessment and final case outcome. Case outcomes were categorised into three groups: simple medical (resolved with single treatment), complicated medical (resolved with multiple medical treatments) and critical (required surgery, were euthanased or died). Univariable analysis using one-way ANOVA and Tukey’s post-hoc test, Kruskal Wallis with Dunn’s post-hoc test and Chi squared analysis were used to compare between different outcome categories. Results 1032 colic cases were submitted by veterinary practitioners: 120 cases met the inclusion criteria for large colon impaction. Fifty three percent of cases were categorised as simple medical, 36.6% as complicated medical, and 9.2% as critical. Most cases (42.1%) occurred during the winter. Fifty nine percent of horses had had a recent change in management, 43% of horses were not ridden, and 12.5% had a recent / current musculoskeletal injury. Mean heart rate was 43bpm (range 26-88) and most cases showed mild signs of pain (67.5%) and reduced gut sounds (76%). Heart rate was significantly increased and gut sounds significantly decreased in critical compared to simple medical cases (p<0.05). Fifty different treatment combinations were used, with NSAIDs (93%) and oral fluids (71%) being administered most often. Conclusions Large colon impactions typically presented with mild signs of colic; heart rate and gut sounds were the most useful parameters to distinguish between simple and critical cases at the primary assessment. The findings of seasonal incidence and associated management factors are consistent with other studies. Veterinary practitioners currently use a wide range of different treatment combinations for large colon impactions

Risk factors for acute abdominal pain (colic) in the adult horse: A scoping review of risk factors, and a systematic review of the effect of management-related changes

Acute abdominal pain (colic) is the most common reason for emergency veterinary treatment in the horse. Consolidation of data through a systematic review is important to inform evidence-based medicine and clinical guidelines, but there are currently no published systematic reviews on colic in the horse. The aim of this study was to identify, categorize and appraise the evidence on factors associated with increased risk of developing abdominal pain (colic) due to gastrointestinal disease in the adult horse. A scoping review was performed to identify and categorize evidence on all risk factors for colic. A systematic review of management-related risk factors was then performed following PRISMA guidelines. Both searches were conducted in Medline, CAB Abstracts and Web of Science databases, and publications were assessed against inclusion and exclusion criteria. For the scoping review, study and participant characteristics of included publications and key results were extracted and tabulated. For the systematic review, cohort, case-control or cross-sectional studies investigating acute abdominal pain in horses within two weeks of management changes were assessed. Study characteristics, participant characteristics and study results of included publications for the systematic review were extracted and tabulated. Included publications were appraised using the Joanna Briggs Institute Critical Appraisal Tools for cohort, case-control and cross-sectional studies. The scoping review search identified 3,756 publications. Fifty eight studies met final inclusion criteria, and 22 categories of risk factors were identified. These were grouped into three broad areas: horse-related factors, management-related factors and environment-related factors. The largest body of evidence related to management change. The systematic review of management change identified 410 publications: 14 met inclusion criteria for analysis. These consisted of one cohort, eight case-control and five cross-sectional studies. The studies were conducted between 1990–2008, and the majority of studies were located in the USA (8/14) or UK (3/14). The risk factors related to management change that were assessed were feed, carer, exercise, pasture, water and housing. The largest bodies of evidence for increased risk of colic associated with management change were changes in feed (5/14 publications) and recent change in housing (3/14). Most studies (8/14) did not meet the JBI criterion on confounding factors. There was marked heterogeneity of study methodologies and measures. This is the first study to use a combined scoping and systematic review to analyse evidence for modifiable risk factors for a common condition in the horse. It provides a comprehensive review that will be a key resource for researchers, veterinary practitioners and horse owners. It identified modifiable risk factors associated with an increased risk of colic which should be a key target for preventative health programmes. The findings from the critical appraisal were used to develop recommendations for future research to improve the quality of evidence-based veterinary medicine

Quantum Holographic Encoding in a Two-dimensional Electron Gas

The advent of bottom-up atomic manipulation heralded a new horizon for attainable information density, as it allowed a bit of information to be represented by a single atom. The discrete spacing between atoms in condensed matter has thus set a rigid limit on the maximum possible information density. While modern technologies are still far from this scale, all theoretical downscaling of devices terminates at this spatial limit. Here, however, we break this barrier with electronic quantum encoding scaled to subatomic densities. We use atomic manipulation to first construct open nanostructures--"molecular holograms"--which in turn concentrate information into a medium free of lattice constraints: the quantum states of a two-dimensional degenerate Fermi gas of electrons. The information embedded in the holograms is transcoded at even smaller length scales into an atomically uniform area of a copper surface, where it is densely projected into both two spatial degrees of freedom and a third holographic dimension mapped to energy. In analogy to optical volume holography, this requires precise amplitude and phase engineering of electron wavefunctions to assemble pages of information volumetrically. This data is read out by mapping the energy-resolved electron density of states with a scanning tunnelling microscope. As the projection and readout are both extremely near-field, and because we use native quantum states rather than an external beam, we are not limited by lensing or collimation and can create electronically projected objects with features as small as ~0.3 nm. These techniques reach unprecedented densities exceeding 20 bits/nm2 and place tens of bits into a single fermionic state.Comment: Published online 25 January 2009 in Nature Nanotechnology; 12 page manuscript (including 4 figures) + 2 page supplement (including 1 figure); supplementary movie available at http://mota.stanford.ed

The direct medical costs of epilepsy in children and young people: a population-based study of health resource utilisation

We described the health resource utilisation (HRU) and associated direct medical costs of managing epilepsy in children and young people (CYP) using population-level data from the United Kingdom. The study cohort were CYP born between 1988 and 2004 who were newly diagnosed with epilepsy and identified using a nationally representative primary care database from the United Kingdom. Reference unit costs were applied to each element of HRU to calculate annual direct medical costs per child. We assessed whether HRU and costs differed by time from diagnosis, age, sex and socioeconomic deprivation. Of 798 CYP newly diagnosed with epilepsy, 56% were male and the mean age at diagnosis was 5.6 years. The highest burden of HRU was in the first year following diagnosis with a mean annual cost of £930 (95% confidence interval (CI) £839–1022) per child in this first year. This decreased to £461 (95%CI 368–551) in the second year which remained fairly constant each subsequent year (£413 (95% CI 282–540) in the 8th year). The highest contribution to the annual medical costs was from inpatient hospital admissions followed by the costs of AEDs. Mean annual medical costs were significantly higher in children under 6 years of age compared with older children (p &lt; 0.01), but were similar across socioeconomic groups (p = 0.62). The direct medical costs of HRU in CYP with epilepsy are higher in the first year after diagnosis compared to subsequent years, reflecting HRU related to the diagnostic process in the first year. Medical costs did not vary substantially by sex or socioeconomic deprivation indicating a similar level of consultation and care across these groups

Prospective study of the primary evaluation of 1016 horses with clinical signs of abdominal pain by veterinary practitioners, and the differentiation of critical and non‑critical cases

Background: The majority of research on the evaluation of horses with colic is focused on referral hospital populations. Early identification of critical cases is important to optimise outcome and welfare. The aim of this prospective study was to survey the primary evaluation of horses with clinical signs of abdominal pain by veterinary practitioners, and compare the initial presentation of critical and non-critical cases. Results: Data from 1016 primary evaluations of horses presenting with clinical signs of colic were submitted by 167 veterinary practitioners across the United Kingdom over a 13 month period. The mean age of the study population was 13.5 years (median 12.0, range 0–42). Mean heart rate on primary presentation was 47 beats/min (median 44, range 18–125), mean respiratory rate was 20 breaths/min (median 16, range 6–100), and median gastrointestinal auscultation score (0–12, minimum–maximum) was 5 (range 0–12). Clinical signs assessed using a behavioural severity score (0–17, minimum–maximum), were between 0 and 6 in 70.4 % of cases, and 7 12 for 29.6 % of cases. Rectal examination was performed in 73.8 % of cases. Cases that responded positively to simple medical treatment were categorised retrospectively as ‘non-critical’; cases that required intensive medical treatment, surgical intervention, died or were euthanased were categorised as ‘critical’. Eight-hundred-and-twenty- two cases met these criteria; 76.4 % were ‘non-critical’ and 23.6 % were ‘critical’. Multivariable logistic regression was used to identify features of the clinical presentation associated with critical cases. Five variables were retained in the final multivariable model: combined pain score: (OR 1.19, P 2.5 s (OR 3.21, P = 0.046, 95 % CI 1.023–10.09), weak pulse character (OR 2.90, P = 0.004, 95 % CI 1.39–5.99) and absence of gut sounds in ≥1 quadrant (OR 3.65, P < 0.001, 95 % CI 2.08–6.41). Conclusions: This is the first study comparing the primary presentation of critical and non-critical cases of abdominal pain. Pain, heart rate, gastrointestinal borborygmi and simple indicators of hypovolaemia were significant indicators of critical cases, even at the primary veterinary examination, and should be considered essential components of the initial assessment and triage of horses presenting with colic

A mixed methods inquiry into the validity of data

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Developing evidence on the primary case presentation and assessment of acute abdominal pain (colic) in the horse

Abdominal pain (colic) in the horse is one of the most common emergency problems in the horse, but there are major gaps in the current evidence. Five original studies were undertaken to build evidence on the primary assessment of abdominal pain in the horse. The first study was a systematic review of risk factors for abdominal pain. This identified 83 publications on risk factors for colic; 47 met inclusion criteria and were reviewed and categorised. Twenty four studies were evaluated using the JBI-Mastari critical appraisal tool. Evidence from the ten publications with least susceptibility to bias was collated. There was consensus of evidence for increasing age, recent change in diet and previous history of abdominal pain are risk factors for colic. This evidence should inform veterinary practitioner’s clinical decision making and approach to disease prevention. The second study was a systematic review of diagnostic tests for abdominal pain. This identified 190 publications; 46 publications met inclusion criteria and were reviewed and categorised. Thirty studies were evaluated using the QUADAS critical appraisal tool. None of the studies used a suitable methodology to assess the value of a diagnostic test to differentiate critical cases. The outcomes of this systematic review were a description of the current evidence and recommendations for future research using appropriate study designs. Both systematic reviews highlighted a lack of evidence from primary practice. The third study was a prospective survey of the primary assessment of horses with abdominal pain by veterinary practitioners. Data was collected from 1016 cases, including clinical history, presenting signs, diagnostic and treatment approaches and case outcome. Cases were categorised as critical or non-critical. Multivariate logistic regression was used to identify clinical features associated with critical cases. Five variables remained in the final model: pain, heart rate, capillary refill time, pulse character and gastrointestinal borborygmi. These should be considered essential components of the initial assessment and triage of horses presenting with colic. The fourth study was an online survey of veterinary practitioner’s opinions of diagnostic tests for colic. Responses from 228 participants were analysed. The most frequently used tests were ‘response to analgesia’, ‘rectal examination’ and ‘nasogastric intubation’, but there was a wide variation in practitioners’ approaches. The main reasons for not using tests were that practitioners considered they were not required, or had concerns around personal safety, lack of facilities or financial constraints. The final phase was two multi-disciplinary workshops to review current evidence and generate recommendations. Fifty participants attended the first workshop and generated 84 statements on the recognition of colic. Forty one participants attended the second workshop and generated 160 statements on the assessment of horses with colic. These statements form the first phase of a multi-disciplinary Delphi process to develop best practice guidelines on the recognition and primary assessment of horses with abdominal pain. This research makes significant contributions to the current evidence on abdominal pain in the horse. It has consolidated existing information, made recommendations for future research, and worked with practitioners to address evidence gaps, and involved different stakeholders in deciding how this evidence should be applied