Clinical Evaluation of Artificial Intelligence-Enabled Interventions.

Artificial intelligence (AI) health technologies are increasingly available for use in real-world care. This emerging opportunity is accompanied by a need for decision makers and practitioners across healthcare systems to evaluate the safety and effectiveness of these interventions against the needs of their own setting. To meet this need, high-quality evidence regarding AI-enabled interventions must be made available, and decision makers in varying roles and settings must be empowered to evaluate that evidence within the context in which they work. This article summarizes good practices across four stages of evidence generation for AI health technologies: study design, study conduct, study reporting, and study appraisal.

Development and Integration of Machine Learning Algorithm to Identify Peripheral Arterial Disease: Multistakeholder Qualitative Study.

BACKGROUND: Machine learning (ML)-driven clinical decision support (CDS) continues to draw wide interest and investment as a means of improving care quality and value, despite mixed real-world implementation outcomes. OBJECTIVE: This study aimed to explore the factors that influence the integration of a peripheral arterial disease (PAD) identification algorithm to implement timely guideline-based care. METHODS: A total of 12 semistructured interviews were conducted with individuals from 3 stakeholder groups during the first 4 weeks of integration of an ML-driven CDS. The stakeholder groups included technical, administrative, and clinical members of the team interacting with the ML-driven CDS. The ML-driven CDS identified patients with a high probability of having PAD, and these patients were then reviewed by an interdisciplinary team that developed a recommended action plan and sent recommendations to the patient's primary care provider. Pseudonymized transcripts were coded, and thematic analysis was conducted by a multidisciplinary research team. RESULTS: Three themes were identified: positive factors translating in silico performance to real-world efficacy, organizational factors and data structure factors affecting clinical impact, and potential challenges to advancing equity. Our study found that the factors that led to successful translation of in silico algorithm performance to real-world impact were largely nontechnical, given adequate efficacy in retrospective validation, including strong clinical leadership, trustworthy workflows, early consideration of end-user needs, and ensuring that the CDS addresses an actionable problem. Negative factors of integration included failure to incorporate the on-the-ground context, the lack of feedback loops, and data silos limiting the ML-driven CDS. The success criteria for each stakeholder group were also characterized to better understand how teams work together to integrate ML-driven CDS and to understand the varying needs across stakeholder groups. CONCLUSIONS: Longitudinal and multidisciplinary stakeholder engagement in the development and integration of ML-driven CDS underpins its effective translation into real-world care. Although previous studies have focused on the technical elements of ML-driven CDS, our study demonstrates the importance of including administrative and operational leaders as well as an early consideration of clinicians' needs. Seeing how different stakeholder groups have this more holistic perspective also permits more effective detection of context-driven health care inequities, which are uncovered or exacerbated via ML-driven CDS integration through structural and organizational challenges. Many of the solutions to these inequities lie outside the scope of ML and require coordinated systematic solutions for mitigation to help reduce disparities in the care of patients with PAD.

Evaluating the translation of implementation science to clinical artificial intelligence: a bibliometric study of qualitative research.

Introduction: Whilst a theoretical basis for implementation research is seen as advantageous, there is little clarity over if and how the application of theories, models or frameworks (TMF) impact implementation outcomes. Clinical artificial intelligence (AI) continues to receive multi-stakeholder interest and investment, yet a significant implementation gap remains. This bibliometric study aims to measure and characterize TMF application in qualitative clinical AI research to identify opportunities to improve research practice and its impact on clinical AI implementation. Methods: Qualitative research of stakeholder perspectives on clinical AI published between January 2014 and October 2022 was systematically identified. Eligible studies were characterized by their publication type, clinical and geographical context, type of clinical AI studied, data collection method, participants and application of any TMF. Each TMF applied by eligible studies, its justification and mode of application was characterized. Results: Of 202 eligible studies, 70 (34.7%) applied a TMF. There was an 8-fold increase in the number of publications between 2014 and 2022 but no significant increase in the proportion applying TMFs. Of the 50 TMFs applied, 40 (80%) were only applied once, with the Technology Acceptance Model applied most frequently (n = 9). Seven TMFs were novel contributions embedded within an eligible study. A minority of studies justified TMF application (n = 51,58.6%) and it was uncommon to discuss an alternative TMF or the limitations of the one selected (n = 11,12.6%). The most common way in which a TMF was applied in eligible studies was data analysis (n = 44,50.6%). Implementation guidelines or tools were explicitly referenced by 2 reports (1.0%). Conclusion: TMFs have not been commonly applied in qualitative research of clinical AI. When TMFs have been applied there has been (i) little consensus on TMF selection (ii) limited description of selection rationale and (iii) lack of clarity over how TMFs inform research. We consider this to represent an opportunity to improve implementation science's translation to clinical AI research and clinical AI into practice by promoting the rigor and frequency of TMF application. We recommend that the finite resources of the implementation science community are diverted toward increasing accessibility and engagement with theory informed practices. The considered application of theories, models and frameworks (TMF) are thought to contribute to the impact of implementation science on the translation of innovations into real-world care. The frequency and nature of TMF use are yet to be described within digital health innovations, including the prominent field of clinical AI. A well-known implementation gap, coined as the "AI chasm" continues to limit the impact of clinical AI on real-world care. From this bibliometric study of the frequency and quality of TMF use within qualitative clinical AI research, we found that TMFs are usually not applied, their selection is highly varied between studies and there is not often a convincing rationale for their selection. Promoting the rigor and frequency of TMF use appears to present an opportunity to improve the translation of clinical AI into practice.

Impact of the COVID-19 pandemic on the research activities of UK ophthalmologists.

BACKGROUND: The COVID-19 pandemic has impacted negatively on many areas of biomedical research and there is concern that academic recovery will take several years. This survey aimed to define the impact of the COVID-19 pandemic on UK ophthalmologists' research activities and understand the implications for recovery. METHODS: An online survey comprising multiple choice and free-text questions was designed, piloted and then distributed to Royal College of Ophthalmologists (RCOphth) members in January 2021. Respondent characteristics, research expectations and experiences through the pandemic were captured. Descriptive and comparative statistics were applied to quantitative data alongside content analysis of qualitative data. RESULTS: In total, 148 respondents (3.7% of RCOphth membership) comprised 46 trainees (31.1%), 97 consultants (65.5%) and 5 SAS doctors (3.4%); 54 had clinical-academic roles (36.5%) and 65/94 (69.1%) ophthalmologists with fully clinical posts identified as research-active. Of 114 research-active respondents, 104 (91.2%) reported an impact on their research from COVID-19; negative impacts included loss of research time (n = 69), research delays (n = 96) and funding shortfalls (n = 63). Content analysis identified five common themes; type of research activity, clinical demands, institutional challenges, COVID-19 alignment and work-life balance. CONCLUSIONS: UK ophthalmology research has been adversely impacted by the pandemic. A substantial proportion of UK ophthalmologists are research active, but 20.4% of those surveyed felt that the pandemic had made research less attractive. Strategic steps must be taken to nurture UK ophthalmologists' engagement with research, especially for those who currently do no research, if the profession is to align itself with the Government vision of 'Research for All'.

Stakeholder Perspectives on Clinical Decision Support Tools to Inform Clinical Artificial Intelligence Implementation: Protocol for a Framework Synthesis for Qualitative Evidence.

BACKGROUND: Quantitative systematic reviews have identified clinical artificial intelligence (AI)-enabled tools with adequate performance for real-world implementation. To our knowledge, no published report or protocol synthesizes the full breadth of stakeholder perspectives. The absence of such a rigorous foundation perpetuates the "AI chasm," which continues to delay patient benefit. OBJECTIVE: The aim of this research is to synthesize stakeholder perspectives of computerized clinical decision support tools in any health care setting. Synthesized findings will inform future research and the implementation of AI into health care services. METHODS: The search strategy will use MEDLINE (Ovid), Scopus, CINAHL (EBSCO), ACM Digital Library, and Science Citation Index (Web of Science). Following deduplication, title, abstract, and full text screening will be performed by 2 independent reviewers with a third topic expert arbitrating. The quality of included studies will be appraised to support interpretation. Best-fit framework synthesis will be performed, with line-by-line coding completed by 2 independent reviewers. Where appropriate, these findings will be assigned to 1 of 22 a priori themes defined by the Nonadoption, Abandonment, Scale-up, Spread, and Sustainability framework. New domains will be inductively generated for outlying findings. The placement of findings within themes will be reviewed iteratively by a study advisory group including patient and lay representatives. RESULTS: Study registration was obtained from PROSPERO (CRD42021256005) in May 2021. Final searches were executed in April, and screening is ongoing at the time of writing. Full text data analysis is due to be completed in October 2021. We anticipate that the study will be submitted for open-access publication in late 2021. CONCLUSIONS: This paper describes the protocol for a qualitative evidence synthesis aiming to define barriers and facilitators to the implementation of computerized clinical decision support tools from all relevant stakeholders. The results of this study are intended to expedite the delivery of patient benefit from AI-enabled clinical tools. TRIAL REGISTRATION: PROSPERO CRD42021256005; https://tinyurl.com/r4x3thvp. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/33145.

Evaluation of a low-resource screening strategy for ophthalmic pathologies and associated neurological morbidity in an older Tanzanian HIV-positive population.

Globally, 43 million people are living with HIV, 90% in developing countries. Increasing life expectancy with combination antiretroviral therapy (cART) results in chronic complications, including HIV-associated neurocognitive disorders (HAND) and eye diseases. HAND screening is currently challenging. Our aim was to evaluate clinical utility of retinopathy as a screening measure of HAND in older cART-treated individuals in Tanzania and feasibility of smartphone-based retinal screening in this low-resource setting. A cross-sectional systematic sample aged ≥ 50-years attending routine HIV follow-up in Tanzania were comprehensively assessed for HAND by American Academy of Neurology criteria and received ophthalmic assessment including smartphone-based retinal imaging. HAND and ophthalmic assessments were independent and blinded. Diagnostic accuracy was evaluated by AUROC curves. Of 129 individuals assessed, 69.8% were visually impaired. Thirteen had retinopathy. HAND prevalence was 66.7%. Retinopathy was significantly associated with HAND but HIV-disease factors (CD4, viral load) were not. Diagnostic accuracy of retinopathy for HAND was poor (AUROC 0.545-0.617) but specificity and positive predictive value were high. We conclude that ocular pathology and HAND appear highly prevalent in this low-resource setting. Although retinal screening cannot be used alone identify HAND, prioritization of individuals with abnormal retinal screening is a potential strategy in low-resource settings.

An observational clinical study of the influence of phacoemulsification on choroidal neovascular membrane activity in age related macular degeneration.

BACKGROUND: Thousands of phacoemulsification surgeries are performed on eyes with age-related macular degeneration (AMD) complicated by choroidal neovascular membrane (CNV) in the United Kingdom each year. As populations age this number is expected to rise. Controversy over phacoemulsification's influence on CNV activity limits the information which clinicians and these patients use to decide on surgery. This observational study aims to resolve this controversy by reporting on intravitreal injection (IVI) frequency as a pragmatic marker of CNV activity in a large cohort. METHODS: A cohort of eyes with AMD complicated by CNV (n = 327) that underwent cataract surgery at a single tertiary centre from 2014 to 2019 were identified. These cases were matched by interval since CNV diagnosis at a specified 'time zero' within the follow-up of pseudophakic eyes with AMD (n = 327). Data concerning demographics, visual acuity (VA) and intravitreal injection frequency before and after 'time zero'/phacoemulsification were collected. RESULTS: Following 'time zero'/phacoemulsification' the mean reduction in annual IVI frequency was 0.6 injections/year (95% CI 0.4,0.9) and 0.4 injections/year (95% CI 0.1,0.7) in the comparison and phacoemulsification cohorts respectively. The mean VA gain 12 months after phacoemulsification in the intervention cohort was 11.3 (95% CI 9.2,13.4) early treatment of diabetic retinopathy study (ETDRS) letters, with 214 eyes (65.4%) having gained ≥5 ETDRS letters after surgery. CONCLUSIONS: Phacoemulsification has no clinically significant impact on the activity of pre-existent CNV secondary to AMD. Phacoemulsification should be offered to patients with AMD and cataract that limits vision, regardless of CNV activity.

Real-World Visual and Neovascularisation Outcomes from anti-VEGF in Central Retinal Vein Occlusion.

PURPOSE: Central retinal vein occlusion (CRVO) can be complicated by macular oedema, requiring intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF). CRVO can cause neovascularisation, potentially causing persistent pain if not identified early. Whilst clinical trial data describe visual and anti-neovascular benefit from anti-VEGF there are limited real-world data. METHODS: A retrospective cohort study of a consecutive series of patients found from a review of the electronic medical record at a single UK centre. Visual acuity, macula status, number of IVIs and neovascular status were extracted at standardised timepoints. RESULTS: In total, 231 eyes from 231 patients were identified with 6-48 months of follow up. Twenty-four months after treatment initiation, 81 eyes (53.3%) had no remaining macula oedema and mean visual acuity gained was 8.9 (SD 19.0) Early Treatment of Diabetic Retinopathy Study (ETDRS) letters following a mean of 10.1 (3.9) IVIs. Of 222 eyes that had no initial neovascularisation, 11 went on to develop it, with iris involvement in 10 eyes. Median time from treatment initiation to neovascularisation was 17.2 (range 5.0-44.1) months, and the median time from latest IVI to neovascularisation was 9.6 (2.9-27.6) months after a median of 4 (3-10) IVIs. CONCLUSIONS: Visual acuity in CRVO complicated by macular oedema improves following anti-VEGF treatment but real-world gains are more modest than those from clinical trials. Neovascularisation following CRVO can be substantially delayed by anti-VEGF treatment and so if individuals who have received IVIs are to be effectively screened for neovascularisation long-term surveillance is necessary.

A non-randomised trial of video and written educational adjuncts in undergraduate ophthalmology.

BACKGROUND: Provision of relevant pre-learning materials has been shown to increase student engagement and improve outcomes in medical education. This non-randomised study attempts to quantify the educational gains, and relative efficacy of video and written pre-learning materials, in ophthalmology undergraduate teaching. METHODS: Ninety-eight final year medical students were contacted prior to their three-day ophthalmology placements at a British tertiary ophthalmology unit. All participants were sent welcome packs prior to arrival requesting they undertake 90 min of work focusing on a list of specified ophthalmic conditions. One cohort (N = 33) were sent written materials, another (N = 32) was provided with video materials and a third cohort (N = 33) were not sent any materials. On arrival participants completed a simple knowledge test, a questionnaire estimating the time they spent preparing for the placement and a self-reported knowledge score. The teaching on placement was the same for all cohorts. At the conclusion of each placement participants completed a challenging knowledge test, a clinical skills test and repeated self-reported knowledge scores. RESULTS: Eighty seven percent of students receiving specified materials claimed to complete pre-placement work compared to 70% of those receiving learning outcomes alone (p = 0.05). Students receiving learning materials scored higher in the post-placement tests of knowledge (p < 0.001), 74.8% (72.4-77.2%) vs 63.6% (95%CI 59.3-67.9%) and skills (p = 0.04), 86.9% (83.9-89.9%) vs 81.3% (77.2-85.4%). Students using video resources outperformed students using written materials in their visual acuity assessment test (p = 0.03), 90.4% (86.6-94.2%) vs 83.6% (80.1-87.1%) whilst those receiving written rather than video material performed better in the end of placement knowledge test (p = 0.03), 77.7% (74.3-81.1%) vs 72.0% (68.9-75.1%). CONCLUSION: This study showed that providing pre-placement learning materials improves undergraduates' commitment and achievement. Written materials better facilitate knowledge acquisition while video materials preferentially promote skill acquisition. This is a novel demonstration within ophthalmology and can help address the imbalance between the expectations placed on undergraduates and the resources committed to ensuring they are met.

10-year trends in English primary care glaucoma prescribing.

BACKGROUND: In 2018 NHS prescriptions in England cost £8.83 billion. Within ophthalmic prescribing, glaucoma is the most costly indication. The 2017 glaucoma NICE guideline shows there is little evidence for clinical preference of particular molecules within a therapeutic class, yet the cost of these products varies greatly. We aim to describe trends in glaucoma prescribing and its relation to recent NICE Guidance. METHODS: Prescription cost analyses for England from 2009 to 2018 were reviewed and data concerning items for the treatment of glaucoma were extracted. Costs and prescription frequencies were normalised for inflation and population. RESULTS: The 2018 cost of glaucoma prescribing was £114.2 million. This cost is 18.1% lower than in 2009 but the annual number of items prescribed per 10,000 people has increased from 1382 to 1668 (20.7%). This is despite an increased prescription of combination drops from 265 to 478 per 10,000 (80.4%). Preservative free item prescriptions rose from 1.7% of total spend in 2009, at £3.4 million in 2009, to 13.9%, in 2018, at £22.5 million. Generic items represented 11.7% of prescriptions in 2009 and 55.2% in 2018. Around half of glaucoma spending is accounted for by the use of preservative free or branded items in the place of the cheapest item in each therapeutic class. CONCLUSIONS: Glaucoma prescribing costs the NHS a great deal. There is a broad trend to generic prescribing as per recent NICE guidance, but significant further costs could be saved with no robustly evidenced clinical consequence.

Microbial keratitis in corneal grafts: predisposing factors and outcomes.

PurposeTo identify the nature of microbial keratitis in corneal grafts and the clinical outcomes at a tertiary hospital in the United Kingdom.Patients and methodsA retrospective case series of microbial keratitis in corneal grafts at the Royal Victoria Infirmary, Newcastle upon Tyne over a 17-year period (1997-2014).ResultsA total of 759 consecutive corneal grafts were identified from the Cornea Transplantation database. Of these, 59 episodes of microbial keratitis occurred in 41 eyes of 41 patients (5.4%; 19 male, 46.3%). Median patient age was 73 years (SD=19.4 years). The most common indication for corneal transplantation was bullous keratopathy (11/41, 26.8%). There were 34/59 (57.6%) episodes of culture-positive graft keratitis; Streptococcus pneumoniae and Staphylococcus aureus were each isolated in 5/34 (14.7%) culture-positive episodes. In all, 35/59 (59.3%) episodes of microbial keratitis occurred in 22 previously failed grafts and 3 de novo graft failures. Gram-negative keratitis was more likely to cause reduced BCVA after (χ2-test, P=0.02). Median graft duration was 49.5 months (SD=43.7 months). Failed grafts were significantly older (median 69 vs 27 months, P=0.009).ConclusionThis represents the longest published follow-up data on microbial keratitis and is the only of its kind in the United Kingdom. The incidence of 5.4% is comparable to that within the developed world. Graft age was significantly associated with graft failure in microbial keratitis; the ongoing risk of microbial keratitis warrants providing patients with long-term open access to hospital eye services.

An 8-year longitudinal analysis of UK ophthalmic publication rates.

Purpose44.5% of abstracts presented at biomedical conferences are published. 26.5% of abstracts presented are basic science. The 2005 Walport Report reformed clinical academic training in the United Kingdom (UK) to promote trainee research. This study aims to analyse UK Ophthalmology research output following the reconstruction of clinical academic training.Patients and Methods1862 abstracts presented at The Royal College of Ophthalmologists' (RCOphth) Annual Congress from May 2005-May 2012 were examined using PubMed. Publication trends were analysed using SPSS v22 (IBM), using Spearman's rank coefficient and Mann-Whitney U test.Results44 (2.4%) abstracts were randomized controlled trials (RCTs), 88 (4.7%) basic science, and 231 (12.4%) oral presentations. 486 (26.6%) abstracts were published to a mean impact factor (IF) of 2.39 (95% CI 2.21-2.57). Mean time to publication from presentation was 15.17 (13.88-16.48) months, negatively correlating with IF (r=-0.149, P<0.003). Oral presentation (P<0.0001), RCTs (P=0.002), and basic science (P<0.0001) abstracts all made publication significantly more likely, with hazard ratios of 2.63 (2.13-2.24), 2.07 (1.3-3.2), and 1.92 (1.41-2.59), respectively. Higher IF was associated with oral presentation (3.4 vs 2.16, P<0.0001), basic science (3.57 vs 2.35, P<0.0001), and RCTs (4.78 vs 2.38, P=0.002). No significant change in publication rate was seen across the 8 years (P=0.61).ConclusionThe proportion of basic science and total abstracts published that are presented at the RCOphth is lower than that in other biomedical conferences. RCTs, basic science abstracts, and oral presentations are more likely to be published. There was no improvement in publication rates following the 2005 Walport Report.

Surgical outcome and patterns of recurrence for retroperitoneal sarcoma at a single centre.

INTRODUCTION: Retroperitoneal sarcoma is a surgically managed condition that can recur locally following macroscopically complete resection. Owing to the low incidence of the condition, advances in treatment are reported infrequently but complete compartmental resection and adjuvant or neoadjuvant radiotherapy are areas under investigation. Given the practical difficulty of randomised trials, observational data can highlight advantages from progressive treatment approaches. METHODS: A retrospective database of consecutive retroperitoneal sarcoma resections performed at a single referral centre between March 1997 and March 2013 was interrogated. Histological, radiological and clinical data were collected. Univariate and multivariate analyses for disease free and overall survival were performed to establish independent predictors of disease recurrence and patient survival. RESULTS: A total of 79 patients underwent 90 resections (63 primary). The mean five-year overall and disease free survival rates were 55.3% and 24.8% respectively. Higher patient age, high tumour grade, presence of extraretroperitoneal disease and invasive tumour phenotype were found to significantly predict survival following multivariate analysis. Half (50%) of the tumours displayed invasive behaviour on histopathology and 42% of locoregional recurrence was intraperitoneal. CONCLUSIONS: Retroperitoneal sarcoma is commonly an infiltrative tumour and often recurs outside of the retroperitoneum. These features limit the therapeutic impact of interventions that focus on gaining local control such as complete compartmental resection and radiotherapy. It seems likely that future advances in the management of this cancer will involve new systemic agents to treat this frequently systemic disease.

Velocity-dependent changes of time, force and spatial parameters in Warmblood horses walking and trotting on a treadmill.

REASONS FOR PERFORMING STUDY: Gait analysis parameters are sensitive to alterations in velocity. For comparison of nonspeed-matched data, the velocity dependency needs to be known. OBJECTIVES: To describe the changes in gait pattern and determine the relationships between stride duration, vertical impulse, contact time and peak vertical force within a range of walking and trotting speeds. METHODS: Thirty-eight nonlame Warmblood horses were subjected to an incremental speed test. The spans of speed were adjusted individually to each horse and ranged from 1.1-2.1 m/s at walk and from 2.5-5.8 m/s at trot. Time, force and spatial parameters of each limb were measured with an instrumented treadmill and analysed with regression analysis using velocity as the independent variable. RESULTS: At a slow walk the shape of the force curve was generally single-peaked in the fore- and trapezoidal in the hindlimbs. With increasing speed, the curves turned into the typical double-peaked shape with a higher second peak in the fore- and a higher first peak in the hindlimbs. With increasing velocity, stride duration, stance durations and limb impulses of the fore- and hindlimbs decreased in both gaits (r2 > 0.92). Increasing speed caused a weight shift to the forehand (walk: from 56 to 59%; trot: from 55 to 57%). Despite decreasing limb impulses, peak vertical forces increased in both gaits (r2 > 0.83). The suspension duration of the trot increased with faster velocities and reached a plateau of around 90 ms at the highest speeds. At a slow trot, the forelimbs impacted first and followed the hindlimbs at lift-off; with increasing speed, the horses tended to impact earlier with the hindlimbs. Contralateral symmetry indices of all parameters remained unchanged. CONCLUSIONS: Subject velocity affects time, force and spatial parameters. Knowing the mathematical function of these interdependencies enables correction of nonspeed-matched data.

Compensatory load redistribution of horses with induced weightbearing hindlimb lameness trotting on a treadmill.

REASONS FOR PERFORMING STUDY: The compensatory mechanisms of horses with weightbearing hindlimb lameness are still not fully understood. HYPOTHESIS: That weightbearing, unilateral hindlimb lameness would not only alter stride characteristics to diminish structural stress in the affected limb but also induce compensatory load adjustments in the other supporting limbs. OBJECTIVE: To document the load and time shifting mechanisms of horses with unilateral weightbearing hindlimb lameness. METHODS: Reversible lameness was induced in 8 clinically sound horses by applying a solar pressure model. Three degrees of lameness (subtle, mild and moderate) were induced and compared with the nonlame (sound) control measurement. Vertical ground reaction forces were recorded for all 4 limbs simultaneously on an instrumented treadmill. RESULTS: Compared to the sound situation, moderate hindlimb hoof lameness induced a decrease in stride duration (-3.3%) and stride impulse (-3.1%). Diagonal impulse decreased selectively in the lame diagonal stance (-7.7%). Within the diagonal limb pair, vertical impulse was shifted to the forelimb during the lame diagonal stance (+6.5%) and to the hindlimb during the sound diagonal stance (+3.2%). Peak vertical force and vertical impulse decreased in the lame limb (-15%), but only vertical impulse increased in the contralateral hindlimb (+5.7%). Stance duration was prolonged in both hindlimbs (+2.5%). Suspension duration was reduced to a greater extent after push-off of the lame diagonal limb pair (-21%) than after the sound diagonal limb pair (-9.2%). CONCLUSIONS: Four compensatory mechanisms could be identified that served to reduce structural stress, i.e. peak vertical force on the affected limb: 1) reduction of the total vertical impulse per stride; 2) diagonal impulse decreased selectively in the lame diagonal; 3) impulse was shifted within the lame diagonal to the forelimb and in the sound diagonal to the hindlimb; and 4) the rate of loading and peak forces were reduced by prolonging the stance duration. POTENTIAL RELEVANCE: Load shifting mechanisms are not only effective in diminishing peak forces in the affected limb, but also suppress compensatory overload in other limbs. Selected force and time parameters allow the unequivocal identification of the lame limb. Future studies have to examine how far these compensatory mechanisms may be generalised for other defined orthopaedic problems in the hindlimb.

Predictive, pre-natal and diagnostic genetic testing for Huntington's disease: the experience in Canada from 1987 to 2000.

Predictive and pre-natal testing for Huntington's Disease (HD) has been available since 1987. Initially this was offered by linkage analysis, which was surpassed by the advent of the direct mutation test for HD in 1993. Direct mutation analysis provided an accurate test that not only enhanced predictive and pre-natal testing, but also permitted the diagnostic testing of symptomatic individuals. The objective of this study was to investigate the uptake, utilization, and outcome of predictive, pre-natal and diagnostic testing in Canada from 1987 to April 1, 2000. A retrospective design was used; all Canadian medical genetics centres and their affiliated laboratories offering genetic testing for HD were invited to participate. A total of 15 of 22 centres (68.2%), currently offering or ever having offered genetic testing for HD, responded, providing data on test results, demographics, and clinical history. A total of 1061 predictive tests, 15 pre-natal tests, and 626 diagnostic tests were performed. The uptake for predictive testing was approximately 18% of the estimated at-risk Canadian population, ranging from 12.5% in the Maritimes to 20.7% in British Columbia. There appears to have been a decline in the rate of testing in recent years. Of the predictive tests, 45.0% of individuals were found to have an increased risk, and a preponderance of females (60.2%) sought testing. A greater proportion of those at < or = 25% risk sought predictive testing once direct CAG mutation analysis had become available (10.9% after mutation analysis vs 4.7% before mutation analysis, p = 0.0077). Very few pre-natal tests were requested. Of the 15 pre-natal tests, 12 had an increased risk, resulting in termination of pregnancy in all but one. Diagnostic testing identified 68.5% of individuals to be positive by mutation analysis, while 31.5% of those with HD-like symptoms were not found to have the HD mutation. The positive diagnostic tests included 24.5% of individuals with no known prior family history of HD.

Assessment of gait irregularities in the horse: eye vs. gait analysis.

The purpose of this study was to verify the sensitivity of 2 gait analysis methods in detecting subtle lameness and to compare the results to the traditional orthopaedic evaluation. Twenty-two horses were evaluated (1) subjectively by 3 different experienced clinicians and (2) objectively with synchronised ground reaction force and accelerometric gait measurements on a treadmill. The horses were assigned for each of the 3 methods independently to one of 3 groups (GR): sound, lameness front limb, lameness hindlimb. Additionally, for each horse, the affected limb (AL) and degree of lameness (DL) were defined. The accordance between the 3 assessment methods for the categorical variables was tested with a Spearman correlation analysis. The relationship between vertical ground reaction forces and dorsoventral as well as mediolateral accelerations were studied using a Pearson correlation matrix. Significant correlation was found between the clinical GR and GR based on force (r = 0.51, P < 0.05) and acceleration data (r = 0.47, P < 0.05), respectively, and between AL based on clinical and ground reaction force (r = 0.65, P < 0.05) assessment. No significant correlation was found, neither for GR between the 2 measuring methods, nor for DL between the 3 assessment methods. The Pearson correlation matrix revealed significant correlations between peak vertical forces and dorsoventral acceleration in the hindlimbs. We conclude that the measurement of kinetic parameters represents a helpful complementary tool in the assessment of subtle gait alterations. However, this information needs to be interpreted carefully and always related to the clinical observation.