Clinically relevant doses of tiludronate do not affect bone remodelling in pasture-exercised horses.

BACKGROUND: Bisphosphonates are widely used in equine athletes to reduce lameness associated with skeletal disorders. Widespread off-label use has led to concern regarding potential negative effects on bone healing, but little evidence exists to support or refute this. OBJECTIVES: To investigate the influence of clinically relevant doses of tiludronate on bone remodelling and bone healing. STUDY DESIGN: Randomised, controlled in vivo experiments. METHODS: Each horse had a single tuber coxae biopsied (Day 0), then were divided into a treatment (IV tiludronate) or control (IV saline) group. Treatments were administered 30 and 90 days following initial biopsy. Biopsy of the tuber coxae was repeated on Day 60 to evaluate bone healing following a single treatment. Oxytetracycline was administered on Days 137 and 147 to label bone formation. The contralateral tuber coxae was biopsied on Day 150 to evaluate effects of repeated treatment. Bone biopsies were evaluated with micro-computed tomography and/or dynamic histomorphometry using standard techniques. RESULTS: Nineteen horses completed the study, with no complications following the biopsies and treatments. No significant differences in the trabecular bone parameters or bone formation rate were observed between treatment groups. MAIN LIMITATIONS: The use of a first-generation bisphosphonate may mean some effects of these drugs are underrepresented using this model. The results pertain to the tuber coxae and may not reflect injury or the healing response that occurs in long bones in training or racing. CONCLUSIONS: In this model, tiludronate did not affect normal bone remodelling in the horse, despite repeat dosages.

A multicentre cross-sectional observational study to determine the effect of living with frailty on digital exclusion from video consultations: (Access-VIGIL).

OBJECTIVES: Many older people regularly access digital services, but many others are totally excluded. Age alone may not explain these discrepancies. As health care services offer more video consultations, we aimed to determine if living with frailty is a significant risk factor for digital exclusion in accessing video consultations, and if this changes if a person has a support network to help with access. DESIGN: We undertook a muticenter cross-sectional survey across South West England. SETTING AND PARTICIPANTS: Patients in primary care, hospital at home, and secondary care services were enrolled between February 21 and April 12, 2022. METHODS: The primary outcome was complete digital exclusion defined as no individual access or network support access to video consultations. Secondary analysis looked at the person's digital exclusion when ignoring any network support. The association between frailty and outcomes was analyzed with logistic regression. In addition, older people's digital skills, motivation, and confidence were examined. RESULTS: 255 patients were included in the analysis. The median age was 63 years (interquartile range 43-77) with 148 (57%) women. Complete digital exclusion was rare (5.1%). Only 1 of 155 who were not frail (Clinical Frailty Scale 1-3) experienced complete digital exclusion compared with 12 of 99 (10.7%) who were living with frailty (Clinical Frailty Scale 4-8). There was no association between frailty and complete digital exclusion. Frailty was associated with individual digital exclusion when no network support was available to assist. CONCLUSIONS AND IMPLICATIONS: When taking into account a person's support network, complete digital exclusion from video consultation was rare. When no support network was available, frailty was associated with individual digital exclusion. Health care services should ask about a person's support network to help people living with frailty access video consultations.

Ethical and legal implications of implementing risk algorithms for early detection and screening for oesophageal cancer, now and in the future.

BACKGROUND: Oesophageal cancer has significant morbidity and mortality but late diagnosis is common since early signs of disease are frequently misinterpreted. Project DELTA aims to enable earlier detection and treatment through targeted screening using a novel risk prediction algorithm for oesophageal cancer (incorporating risk factors of Barrett's oesophagus including prescriptions for acid-reducing medications (CanPredict)), together with a non-invasive, low-cost sampling device (CytospongeTM). However, there are many barriers to implementation, and this paper identifies key ethical and legal challenges to implementing these personalised prevention strategies for Barrett's oesophagus/oesophageal cancer. METHODS: To identify ethical and legal issues relevant to the deployment of a risk prediction tool for oesophageal cancer into primary care, we adopted an interdisciplinary approach, incorporating targeted informal literature reviews, interviews with expert collaborators, a multidisciplinary workshop and ethical and legal analysis. RESULTS: Successful implementation raises many issues including ensuring transparency and effective risk communication; addressing bias and inequity; managing resources appropriately and avoiding exceptionalism. Clinicians will need support and training to use cancer risk prediction algorithms, ensuring that they understand how risk algorithms supplement rather than replace medical decision-making. Workshop participants had concerns about liability for harms arising from risk algorithms, including from potential bias and inequitable implementation. Determining strategies for risk communication enabling transparency but avoiding exceptionalist approaches are a significant challenge. Future challenges include using artificial intelligence to bolster risk assessment, incorporating genomics into risk tools, and deployment by non-health professional users. However, these strategies could improve detection and outcomes. CONCLUSIONS: Novel pathways incorporating risk prediction algorithms hold considerable promise, especially when combined with low-cost sampling. However immediate priorities should be to develop risk communication strategies that take account of using validated risk algorithms, and to ensure equitable implementation. Resolving questions about liability for harms arising should be a longer-term objective.

Ethical and legal considerations influencing human involvement in the implementation of artificial intelligence in a clinical pathway: A multi-stakeholder perspective.

Introduction: Ethical and legal factors will have an important bearing on when and whether automation is appropriate in healthcare. There is a developing literature on the ethics of artificial intelligence (AI) in health, including specific legal or regulatory questions such as whether there is a right to an explanation of AI decision-making. However, there has been limited consideration of the specific ethical and legal factors that influence when, and in what form, human involvement may be required in the implementation of AI in a clinical pathway, and the views of the wide range of stakeholders involved. To address this question, we chose the exemplar of the pathway for the early detection of Barrett's Oesophagus (BE) and oesophageal adenocarcinoma, where Gehrung and colleagues have developed a "semi-automated", deep-learning system to analyse samples from the CytospongeTM TFF3 test (a minimally invasive alternative to endoscopy), where AI promises to mitigate increasing demands for pathologists' time and input. Methods: We gathered a multidisciplinary group of stakeholders, including developers, patients, healthcare professionals and regulators, to obtain their perspectives on the ethical and legal issues that may arise using this exemplar. Results: The findings are grouped under six general themes: risk and potential harms; impacts on human experts; equity and bias; transparency and oversight; patient information and choice; accountability, moral responsibility and liability for error. Within these themes, a range of subtle and context-specific elements emerged, highlighting the importance of pre-implementation, interdisciplinary discussions and appreciation of pathway specific considerations. Discussion: To evaluate these findings, we draw on the well-established principles of biomedical ethics identified by Beauchamp and Childress as a lens through which to view these results and their implications for personalised medicine. Our findings are not only relevant to this context but have implications for AI in digital pathology and healthcare more broadly.

Dupilumab Efficacy in Steroid-Dependent Severe Asthma by Baseline Oral Corticosteroid Dose.

BACKGROUND: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4/-13, key and central drivers of type 2 inflammation in multiple diseases. In the phase 3 LIBERTY ASTHMA VENTURE (VENTURE) study (NCT02528214), dupilumab versus placebo reduced oral corticosteroid (OCS) dose and improved clinical outcomes in patients with OCS-dependent severe asthma. Dupilumab efficacy in patients with varying disease burden (defined by baseline OCS dose) has not been assessed. OBJECTIVE: This post hoc analysis of VENTURE evaluated dupilumab efficacy across subgroups defined by baseline OCS dose. METHODS: The OCS dose, proportion no longer needing OCS at week 24, annualized severe exacerbation rate, and least squares mean change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 second at week 24 were evaluated in VENTURE patients with OCS-dependent severe asthma receiving dupilumab 300 mg every 2 weeks versus placebo, categorized by a baseline OCS dose of less than 10 mg/d or 10 or more mg/d. RESULTS: Dupilumab reduced daily OCS dose from baseline at week 24 in both dose groups. In dupilumab-/placebo-treated patients with a baseline OCS dose of less than 10 mg/d and 10 or more mg/d, 72%/42% and 37%/23% stopped OCS by week 24 (P < .01/P < .05), respectively. Dupilumab significantly reduced the annualized severe exacerbation rate by 71% and 48% (P < .01/P < .05). At week 24, dupilumab improved pre- and post-bronchodilator forced expiratory volume in 1 second in patients in both dose groups. CONCLUSIONS: In patients with OCS-dependent severe asthma receiving lower or higher baseline OCS doses, dupilumab significantly reduced the OCS dose and improved the likelihood of no longer requiring OCS while also reducing exacerbations and improving lung function.

Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing-remitting MS.

BACKGROUND: Alemtuzumab efficacy and safety was demonstrated in CARE-MS I and extension studies (CAMMS03409; TOPAZ). OBJECTIVE: Evaluate serum neurofilament light chain (sNfL) in CARE-MS I patients and highly active disease (HAD) subgroup, over 7 and 2 years for alemtuzumab and subcutaneous interferon beta-1a (SC IFNB-1a), respectively. METHODS: Patients received SC IFNB-1a 44 µg 3×/week or alemtuzumab 12 mg/day at baseline and month 12, with further as-needed 3-day courses. sNfL was measured using single-molecule array (Simoa™). HAD definition was ⩾2 relapses in year before randomization and ⩾1 baseline gadolinium-enhancing lesion. RESULTS: Baseline median sNfL levels were similar in alemtuzumab (n = 354) and SC IFNB-1a-treated (n = 159) patients (31.7 vs 31.4 pg/mL), but decreased with alemtuzumab versus SC IFNB-1a until year 2 (Y2; 13.2 vs 18.7 pg/mL; p < 0.0001); 12.7 pg/mL for alemtuzumab at Y7. Alemtuzumab-treated patients had sNfL at/below healthy control median at Y2 (72% vs 47%; p < 0.0001); 73% for alemtuzumab at Y7. HAD patients (n = 102) had higher baseline sNfL (49.4 pg/mL) versus overall population; alemtuzumab HAD patients attained similar levels (Y2, 12.8 pg/mL; Y7, 12.7 pg/mL; 75% were at/below control median at Y7). CONCLUSION: Alemtuzumab was superior to SC IFNB-1a in reducing sNfL, with levels in alemtuzumab patients remaining stable through Y7. CLINICALTRIALS.GOV IDENTIFIER: NCT00530348, NCT00930553, NCT02255656.

Association between intrahospital transfer and hospital-acquired infection in the elderly: a retrospective case-control study in a UK hospital network.

BACKGROUND: Intrahospital transfers have become more common as hospital staff balance patient needs with bed availability. However, this may leave patients more vulnerable to potential pathogen transmission routes via increased exposure to contaminated surfaces and contacts with individuals. OBJECTIVE: This study aimed to quantify the association between the number of intrahospital transfers undergone during a hospital spell and the development of a hospital-acquired infection (HAI). METHODS: A retrospective case-control study was conducted using data extracted from electronic health records and microbiology cultures of non-elective, medical admissions to a large urban hospital network which consists of three hospital sites between 2015 and 2018 (n=24 240). As elderly patients comprise a large proportion of hospital users and are a high-risk population for HAIs, the analysis focused on those aged 65 years or over. Logistic regression was conducted to obtain the OR for developing an HAI as a function of intrahospital transfers until onset of HAI for cases, or hospital discharge for controls, while controlling for age, gender, time at risk, Elixhauser comorbidities, hospital site of admission, specialty of the dominant healthcare professional providing care, intensive care admission, total number of procedures and discharge destination. RESULTS: Of the 24 240 spells, 2877 cases were included in the analysis. 72.2% of spells contained at least one intrahospital transfer. On multivariable analysis, each additional intrahospital transfer increased the odds of acquiring an HAI by 9% (OR=1.09; 95% CI 1.05 to 1.13). CONCLUSION: Intrahospital transfers are associated with increased odds of developing an HAI. Strategies for minimising intrahospital transfers should be considered, and further research is needed to identify unnecessary transfers. Their reduction may diminish spread of contagious pathogens in the hospital environment.

Effect of Multiple Sclerosis on Daily Activities, Emotional Well-being, and Relationships: The Global vsMS Survey.

BACKGROUND: The vsMS survey was conducted to better understand the negative effects of fatigue, cognitive impairment, emotional burden, and decreased physical functioning on the personal, professional, and social lives of individuals with multiple sclerosis (MS). METHODS: The vsMS survey was an online survey conducted in Australia, Canada, France, Italy, Spain, the United Kingdom, and the United States that assessed the impact of MS on individuals' daily activities, emotional well-being, relationships, and employment. RESULTS: The survey included 1075 participants with relapsing-remitting MS. Almost 42% of participants reported that their ability to perform and manage daily activities had worsened during the previous 2 years. More than 50% reported limitations in daily activities due to fatigue, physical weakness, problems with balance/coordination, heat/cold sensitivity, memory problems, numbness/tingling, trouble concentrating, impaired movement/muscle stiffness, and impaired sleeping. Participants also reported a negative effect on emotional and social factors, including self-esteem, general outlook, well-being, maintaining/starting relationships, ability to progress in their career/keep their job, and ability to cope with life roles. CONCLUSIONS: These data highlight the importance of addressing the impact of MS and the social and emotional disease burdens on daily activities when planning the care of patients with MS.

Pregnancy outcomes and postpartum relapse rates in women with RRMS treated with alemtuzumab in the phase 2 and 3 clinical development program over 16 years.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) is frequently diagnosed in women of reproductive age. Because the use of disease-modifying therapies (DMTs) early in the disease course is increasing, it is important to evaluate the safety of DMTs in pregnant women and their developing fetuses. Alemtuzumab, approved for the treatment of relapsing forms of MS, is administered as 2 courses of 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Alemtuzumab is eliminated from the body within approximately 30 days after administration; it is recommended that women of childbearing potential use effective contraception during and for 4 months after treatment. Here, we report pregnancy outcomes in alemtuzumab-treated women from the phase 2 and 3 clinical development program over 16 years. METHODS: We followed 972 women who had alemtuzumab in phase 2 (CAMMS223 [NCT00050778]) and phase 3 (CARE-MS I [NCT00530348], CARE-MS II [NCT00548405]) studies, and/or in 2 consecutive extension studies (NCT00930553; NCT02255656 [TOPAZ]). In the extension studies, patients could receive additional alemtuzumab (12 mg/day on 3 days; ≥12 months apart) as needed for disease activity. All women who received alemtuzumab in the clinical development program were included. Pregnant or lactating patients were followed up for safety. RESULTS: As of November 26, 2018, 264 pregnancies occurred in 160 alemtuzumab-treated women, with a mean age at conception of 32.6 years, and mean time from last alemtuzumab dose to conception of 35.9 months. Of the 264 pregnancies, 233 (88%) were completed, 11 (4%) were ongoing, and 20 (8%) had unknown outcomes; 16 (6%) conceptions occurred within 4 months, and 5 conceptions within 1 month of the last alemtuzumab dose. Of the 233 completed pregnancies with known outcomes, there were 155 (67%) live births with no congenital abnormalities or birth defects, 52 (22%) spontaneous abortions, 25 (11%) elective abortions, and 1 (0.4%) stillbirth. Maternal age was associated with an increased risk of spontaneous abortion in alemtuzumab-treated patients (<35 years: 15%; ≥35 years: 37%; relative risk [RR], 2.46 [95% CI: 1.53-3.95], p=0.0002). Risk of spontaneous abortion was not increased in patients becoming pregnant ≤4 months versus >4 months since alemtuzumab exposure (19% vs 23%; RR, 1.08 [95% CI: 0.41-2.85], p=0.88). Autoimmune thyroid adverse events did not increase risk for spontaneous abortion (patients with vs without thyroid adverse events, 23.7% vs 21.3%; RR, 1.11 [95% CI: 0.69-1.80], p=0.75). Annualized relapse rate was 0.10 and 0.12 in the 2 years prior to pregnancy (post alemtuzumab), and was 0.22, 0.12, and 0.12 in each of the first 3 years postpartum, respectively. CONCLUSION: Normal live births were the most common outcome in women exposed to alemtuzumab 12 mg or 24 mg in clinical studies. Spontaneous abortion rate in alemtuzumab-treated patients was comparable with rates in the general population and treatment-naive MS patients, and was not increased in women with pregnancy onset within 4 months of alemtuzumab exposure. There was a minimal increase in postpartum relapses.

Pharmacokinetics and pharmacodynamics of clodronate disodium evaluated in plasma, synovial fluid and urine.

BACKGROUND: Clodronate is a non-nitrogenated bisphosphonate approved for use in horses. There are no peer-reviewed published reports describing the pharmacokinetics or evaluating renal health indices and urinary excretion patterns in conjunction with plasma and synovial fluid concentration following the systemic administration of clodronate to horses. OBJECTIVES: Describe clodronate concentrations in plasma, urine and synovial fluid and evaluate the effects on renal indices after intramuscular administration to healthy horses. STUDY DESIGN: Experimental study with repeated measures. METHODS: Six healthy adult horses received a single intramuscular dose of clodronate (1.8 mg/kg). Blood, synovial fluid and urine were collected prior to and after administration of clodronate up to 72, 48 and 168 hours respectively. Drug concentrations were measured using LC-MS/MS and noncompartmental pharmacokinetic analysis was performed. Renal function indices were also evaluated. RESULTS: Clodronate was quantifiable for up to 24 hours in plasma and 48 hours in synovial fluid and detected at all time points in urine. Maximum plasma concentration of clodronate 210 ± 68.2 ng/mL occurred at approximately 34.8 ± 0.2 minutes after administration, while peak synovial concentration (57.7 ± 32.8 ng/mL) occurred at 2.67 ± 2.32 hours after administration and peak urine concentration (88 358.2 ± 79 521.4 ng/mL) occurred at 2.67 ± 2.58 hours post administration. Terminal half-life in plasma was 3.32 ± 1.25 and was 4.8 ± 3.05 hours in synovial fluid. Creatinine concentrations rose significantly after treatment but remained within normal adult reference ranges at all times. MAIN LIMITATIONS: Limited number of animals and sampling times and the absence of urine collection for determination of concentration beyond 7 days. CONCLUSIONS: Clodronate is rapidly cleared from the blood and synovial fluid. It has variable and biphasic urinary excretion. While significant increase in blood creatinine concentrations was present after a single intramuscular dose of clodronate, values were never above the normal reference range. Further studies are warranted in horses undergoing exercise and those undergoing multiple dosing schemes.

Experts reflecting on the duty to recontact patients and research participants; why professionals should take the lead in developing guidelines.

Sequencing technology is increasing the scale of information that could benefit patients who have been tested in the past. This raises the question whether professionals have a duty to recontact such patients or their families. There is currently no clear basis for a legal duty to recontact, and professional guidelines are limited. We conducted interviews with 14 senior professionals from the Netherlands and UK to obtain a range of opinions on what obligations are estimated to be possible or desirable. There was (near) consensus that a lack of resources currently inhibits recontacting in clinical practice, that recontacting is less desirable in research, that information on recontacting should be part of informed consent, and that a legal duty should follow professional standards. There was a diversity of opinions on the desirability of a more systematic approach, potential obligations in hybrid clinical-research projects, and who should bear responsibility for seeking updates. Based on the literature, legal framework and these interviews, we conclude that a general duty to recontact is unlikely, but that in specific circumstances a limited duty may apply if the benefit to the individual is significant and the burden on professionals not too extensive. The variation in opinion demonstrates that further deliberations are desirable. The development of guidelines-a process the European Society of Human Genetics has begun-is important to ensure that the courts, in deciding a recontacting case, can take into account what professionals consider responsible standards in this field.

Evaluation of peer teaching and deliberate practice to teach veterinary surgery.

OBJECTIVE: To assess the impact of peer teaching and deliberate practice on surgical skills acquisition and retention in first- and second-year veterinary students. STUDY DESIGN: Randomized, prospective, comparative study. SAMPLE POPULATION: Eighteen first-year and 25 second-year students from 1 college of veterinary medicine who had previously demonstrated proficiency in basic surgical skills. METHODS: Forty-three participants were divided into 3 groups: the test group (group A, n = 15), who participated in a structured peer-assisted learning program using deliberate practice; the time-practice control group (group B, n = 15), who participated in an unstructured peer-supported environment; and the assessment-only control group (group C, n = 13), who participated in the assessments. Participants performed a subcutaneous mass removal on a cadaver model and were assessed via a global rating system. Three assessment points were evaluated: pretraining, immediate posttraining, and retention. RESULTS: The number of participants who achieved acceptable or excellent grand total scores in group A increased after training. Among all participants, 22% in group A, 35% in group B, and 38% in group C did not achieve an acceptable total score at the retention assessment. CONCLUSION: The study population improved in skill level and retention through the use of standardized video and peer instruction with attention to effective learning strategies, particularly deliberate practice. CLINICAL SIGNIFICANCE: Use and enhancement of the format introduced in this study could augment veterinary surgical education.

Feltman: evaluating the utilisation of an Aboriginal diabetes education tool by health professionals.

Diabetes contributes considerably to the health disparities in the Aboriginal population. To address the lack of Aboriginal-specific diabetes education tools, Feltman was designed for health professionals to deliver diabetes prevention and management information. This qualitative study aims to explore how this resource was used and its perceived effect on diabetes prevention and management in Victorian Aboriginal communities. Convenience sampling was used to recruit 18 participants (n=6 were Aboriginal) who had attended Feltman training between 2010 and 2016. Semi-structured interviews conducted via telephone or face-to-face were audio-recorded, transcribed and analysed via content analysis. Content analysis identified three main categories regarding Feltman: (1) utilisation in Aboriginal and mainstream health services; (2) as a comprehensive, engaging tool that supports understanding of diabetes; and (3) the barriers and challenges to Feltman's use. Overall, Feltman was regarded as a culturally appropriate diabetes education tool that is visual, tactile, engaging, supportive of health literacy and perceived to enhance Community members' understanding of diabetes prevention and management. This is the first study to provide insight into Feltman's implementation; adding to the evidence-base for Aboriginal-specific diabetes education tools.

Tiludronate and clodronate do not affect bone structure or remodeling kinetics over a 60 day randomized trial.

BACKGROUND: Tiludronate and clodronate are FDA-approved bisphosphonate drug therapies for navicular disease in horses. Although clinical studies have determined their ability to reduce lameness associated with skeletal disorders in horses, data regarding the effect on bone structure and remodeling is lacking. Additionally, due to off-label use of these drugs in young performance horses, effects on bone in young horses need to be investigated. Therefore, the purpose of this randomized, experimental pilot study was to determine the effect of tiludronate and clodronate on normal bone cells, structure and remodeling after 60 days in clinically normal, young horses. Additionally, the effect of clodronate on bone healing 60 days after an induced defect was investigated. RESULTS: All horses tolerated surgery well, with no post-surgery lameness and all acquired biopsies being adequate for analyses. Overall, tiludronate and clodronate did not significantly alter any bone structure or remodeling parameters, as evaluated by microCT and dynamic histomorphometry. Tiludronate did not extensively impact bone formation or resorption parameters as evaluated by static histomorphometry. Similarly, clodronate did not affect bone formation or resorption after 60 days. Sixty days post-defect, healing was minimally affected by clodronate. CONCLUSIONS: Tiludronate and clodronate do not appear to significantly impact bone tissue on a structural or cellular level using standard dose and administration schedules.

Legal challenges for the implementation of advanced clinical digital decision support systems in Europe.

Systems based on artificial intelligence and machine learning that facilitate decision making in health care are promising new tools in the era of 'personalized' or 'precision' medicine. As the volume of patient data and scientific evidence grows, these computerised decision support systems (DSS) have great potential to help healthcare professionals improve diagnosis and care for individual patients. However, the implementation of these tools in clinical care raises some foreseeable legal challenges for healthcare providers and DSS-suppliers in Europe: How does the use of complex and novel DSS relate to professional standards to provide a reasonable standard of care? What should be done in terms of testing before DSS can be used in regular practice? What are the potential liabilities of health care providers and DSS companies if a DSS fails to function well? How do legal requirements for the protection of patient data and general privacy rights apply to likely DSS scenarios? In this article, we provide an overview of the current law and its general implications for the use of DSS, from a European perspective. We conclude that healthcare providers and DSS-suppliers will have the best chance of meeting legal challenges if: they are first tested in translational research with the patients' explicit, informed consent; DSS-suppliers and healthcare providers are able to clarify and agree on their individual legal responsibilities, and; patients are properly informed about privacy risks and able to decide themselves whether their data can be used for other purposes, or are stored and processed outside the EU. DSS developers and healthcare providers will need to work together closely to ensure compliance with national and European regulations and standards required for reasonable and safe patient care. RELEVANCE FOR PATIENTS: Advanced digital decision support systems have the potential to improve patient diagnosis and care. In this article we discuss key legal issues to support translational research using DSS and ensure that they meet the high standards for protection of patient safety and privacy in Europe.

Exploring the potential duty of care in clinical genomics under UK law.

Genome-wide sequencing technologies are beginning to be used in projects that have both clinical diagnostic and research components. The clinical application of this technology, which generates a huge amount of information of varying diagnostic certainty, involves addressing a number of challenges to establish appropriate standards. In this article, we explore the way that UK law may respond to three of these key challenges and could establish new legal duties in relation to feedback of findings that are unrelated to the presenting condition (secondary, additional or incidental findings); duties towards genetic relatives as well as the patient and duties on the part of researchers and professionals who do not have direct contact with patients. When considering these issues, the courts will take account of European and international comparisons, developing guidance and relevant ethical, social and policy factors. The UK courts will also be strongly influenced by precedent set in case law.

Could It Be Snowing Microbes on Enceladus? Assessing Conditions in Its Plume and Implications for Future Missions.

We analyzed Cassini Imaging Science Subsystem (ISS) images of the plume of Enceladus to derive particle number densities for the purpose of comparing our results with those obtained from other Cassini instrument investigations. Initial discrepancies in the results from different instruments, as large as factors of 10-20, can be reduced to ∼2 to 3 by accounting for the different times and geometries at which measurements were taken. We estimate the average daily ice production rate, between 2006 and 2010, to be 29 ± 7 kg/s, and a solid-to-vapor ratio, S/V > 0.06. At 50 km altitude, the plume's peak optical depth during the same time period was τ ∼ 10-3; by 2015, it was ∼10-4. Our inferred differential size distribution at 50 km altitude has an exponent q = 3. We estimate the average geothermal flux into the sea beneath Enceladus' south polar terrain to be comparable to that of the average Atlantic, of order 0.1 W/m2. Should microbes be present on Enceladus, concentrations at hydrothermal vents on Enceladus could be comparable to those on Earth, ∼105 cells/mL. We suggest the well-known process of bubble scrubbing as a means by which oceanic organic matter and microbes may be found in the plume in significantly enhanced concentrations: for the latter, as high as 107 cells/mL, yielding as many as 103 cells on a 0.04 m2 collector in a single 50 km altitude transect of the plume. Mission design can increase these numbers considerably. A lander mission, for example, catching falling plume particles on the same collector, could net, over 100 Enceladus days without bubble scrubbing, at least 105 cells; and, if bubble scrubbing is at work, up to 108 cells. Key Words: Enceladus-Microbe-Organic matter-Life detection. Astrobiology 17, 876-901.

Assessment of tuber coxae bone biopsy in the standing horse.

OBJECTIVE: To describe a biopsy technique in standing horses with minimal morbidity that consistently provides a substantial bone biopsy with intact, undamaged architecture. STUDY DESIGN: Experimental, prospective study. ANIMALS: Ten Thoroughbred horses. METHODS: Biopsies were obtained from the tuber coxae of 10 sedated, standing horses using an oscillating saw. Bilateral biopsies, separated by 60 days, were evaluated with micro-computed tomography (microCT). The first biopsy was prepared for decalcified histology; the second for undecalcified histology. Both biopsies were evaluated qualitatively for histologic quality. RESULTS: The biopsy technique did not result in any significant complications, was well tolerated and all biopsies were of good histologic quality. CONCLUSION: Cortical and trabecular bone biopsies can be successfully collected from the tuber coxa using a simple technique that creates minimal morbidity and allows sequential samples to be collected. The biopsies were larger than those described previously, provided adequate bone for multiple histologic sections, and had intact, undamaged architecture on examination with microCT and light microscopy.

Training in general internal medicine: what do trainees want and what can we deliver?

General internal medicine (GIM) training, usually as part of a dual accreditation programme, is increasingly challenging to deliver as a result of increased numbers of acute admissions, changes to consultant input into medical 'on call' and the reduction in the numbers of units taking unselected medical patients. GIM has become synonymous with acute medical take, reducing the scope of programmes to deliver a true general medical experience. The role of the 'medical registrar' is reported to be increasingly unpopular with trainees. Differing models of the delivery of training are in place. We have carried out a two-stage questionnaire in order to determine the views of both trainees and trainers on different models of training and their deliverability. The first stage defined the key areas of concern for trainees and the second focused on these areas and the ability of local education providers to deliver an expanded GIM programme. Our data suggest that trainees would value a face-to-face annual review of competence progression (ARCP) for GIM, separate from their specialty ARCP, and would support more structured blocks of GIM training in order to allow later specialty-focused training. However, -significant concerns were raised about the ability of many units to deliver such training beyond the acute medical 'take'.