Translating the Biology of Aging into New Therapeutics for Alzheimer's Disease: Senolytics.

The recent FDA-approval for amyloid lowering therapies reflects an unwavering commitment from the Alzheimer's disease (AD) research community to identify treatments for this leading cause of dementia. The clinical benefits achieved by reducing amyloid, though modest, provide evidence that disease modification is possible. Expanding the same tenacity to interventions targeting upstream drivers of AD pathogenesis could significantly impact the disease course. Advanced age is the greatest risk factor for developing AD. Interventions targeting biological aging offer the possibility of disrupting a foundational cause of AD. Senescent cells accumulate with age and contribute to inflammation and age-related diseases like AD. Senolytic drugs that clear senescent cells improve healthy aging, halt AD disease progression in animal models and are undergoing clinical testing. This review explores the biology of aging, the role of senescent cells in AD pathology, and various senotherapeutic approaches such as senolytics, dampening the SASP (senescence associated secretory phenotype), senescence pathway inhibition, vaccines, and prodrugs. We highlight ongoing clinical trials evaluating the safety and efficacy of the most advanced senolytic approach, dasatinib and quercetin (D+Q), including an ongoing Phase II senolytic trial supported by the Alzheimer's Drug Discovery Foundation (ADDF). Challenges in the field of senotherapy for AD, including target engagement and biomarker development, are addressed. Ultimately, this research pursuit may lead to an effective treatment for AD and provide the field with another disease-modifying therapy to be used, alone or in combination, with other emerging treatment options.

An online survey to understand the needs of caregivers of family members with 22q11 deletion syndrome.

BACKGROUND: Most individuals with 22q11.2 deletion syndrome (22q11DS) have multi-system and lifelong needs requiring substantial support. Their primary caregivers are usually family members who dedicate lifelong time and effort to their role. The pressures of their roles can negatively impact caregivers' psychosocial well-being, suggesting a need for additional support for this community who currently have no specialised interventions available. METHOD: This online study surveyed 103 caregivers of family members with 22q11DS to determine the barriers to accessing support that they faced, the kind of support they would value and whether an online intervention could meet their needs. RESULTS: The caregivers indicated that a brief online intervention focused on teaching practical skills and connecting them with a peer network of support would be most valuable. CONCLUSIONS: Future studies are planned that will build on these results by designing and testing online interventions tailored to this community.

Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD): A Pilot Clinical Trial.

Preclinical studies indicate an age-associated accumulation of senescent cells across multiple organ systems. Emerging evidence suggests that tau protein accumulation, which closely correlates with cognitive decline in Alzheimer's disease and other tauopathies, drives cellular senescence in the brain. Pharmacologically clearing senescent cells in mouse models of tauopathy reduced brain pathogenesis. Compared to vehicle treated mice, intermittent senolytic administration reduced tau accumulation and neuroinflammation, preserved neuronal and synaptic density, restored aberrant cerebral blood flow, and reduced ventricular enlargement. Intermittent dosing of the senolytics, dasatinib plus quercetin, has shown an acceptable safety profile in clinical studies for other senescence-associated conditions. With these data, we proposed and herein describe the objectives and methods for a clinical vanguard study. This initial open-label clinical trial pilots an intermittent senolytic combination therapy of dasatinib plus quercetin in five older adults with early-stage Alzheimer's disease. The primary objective is to evaluate the central nervous system penetration of dasatinib and quercetin through analysis of cerebrospinal fluid collected at baseline and after 12 weeks of treatment. Further, through a series of secondary outcome measures to assess target engagement of the senolytic compounds and Alzheimer's disease-relevant cognitive, functional, and physical outcomes, we will collect preliminary data on safety, feasibility, and efficacy. The results of this study will be used to inform the development of a randomized, double-blind, placebo-controlled multicenter phase II trial to further explore of the safety, feasibility, and efficacy of senolytics for modulating the progression of Alzheimer's disease. Clinicaltrials.gov registration number and date: NCT04063124 (08/21/2019).

Validity and Responsiveness of the Generic Health-Related Quality of Life Instrument (VetMetrica™) in Cats With Osteoarthritis. Comparison of Vet and Owner Impressions of Quality of Life Impact.

Validity is not an inherent property of a measurement scale and so evidence for validity relating to its use for particular purposes, with defined populations and in specified contexts must be accumulated. We have published the development of a web-based, generic health-related quality of life instrument (VetMetrica™) to measure the affective impact of chronic disease in cats and provided evidence for its validity in a mixed population of cats, some of which, according to veterinary judgement, were healthy and others of which were suffering from chronic conditions likely to affect their quality of life, often with multiple co-morbidities present. The first aim of the current study was to demonstrate the construct validity of the VetMetrica™ generic instrument when used with cats suffering from osteoarthritis, by testing the hypothesis that the health-related quality of life profile of cats with different severities of osteoarthritis would differ and by demonstrating convergent validity between the health-related quality of life profile scores and independently quantified vet-assessed pain and quality of life impact scores. The latter involved simple correlation analysis and investigation of the relationship between health-related quality of life domain scores and vet-assessed scores, when adjusted for other potential explanatory variables including number of comorbidities and age. Responsiveness-the ability to detect clinically relevant change-is an essential quality for an evaluative instrument and it also provides evidence for "longitudinal validity". Therefore, a second aim of this study was to demonstrate that changes in health-related quality of life domain scores concurred with the clinician's impression of change over time in the health status of cats with osteoarthritis, thus providing evidence for the instrument's responsiveness. Previously, we have reported disagreement between owner and vet impression as to health status in cats in general, but not in relation to any specific disease. Accordingly, the third study aim was to investigate the extent of agreement or disagreement between owner impression of the impact of osteoarthritis on their cats' quality of life and vet impression of such impact. Fifty one percentage of cat owners believed their cats to be perfectly healthy despite a clinician diagnosis of osteoarthritis.

Corrigendum: Development of an Early Warning System for Owners Using a Validated Health-Related Quality of Life (HRQL) Instrument for Companion Animals and Its Use in a Large Cohort of Dogs.

[This corrects the article DOI: 10.3389/fvets.2020.575795.].

Development of an Early Warning System for Owners Using a Validated Health-Related Quality of Life (HRQL) Instrument for Companion Animals and Its Use in a Large Cohort of Dogs.

Preventive measures in human healthcare are recognized as a means of providing early detection of disease, however, the veterinary profession has not been as effective in communicating the benefits of preventive measures to pet owners. Readily available pet healthcare information on the internet, owners not understanding that regular health evaluations can ensure the well-being of their pets and owners confusing the signs of chronic disease with normal aging have contributed to declining numbers of veterinary visits. The use of web-based generic health-related quality of life (HRQL) measures to evaluate health status (wellness) remotely could facilitate veterinary preventive medicine. This publication describes the development and practical application of an integrated alert system for an online generic HRQL measurement instrument (VetMetrica™) which generates scores in four domains of HRQL-Energetic/Enthusiastic (E/E), Happy/Content (H/C), Active/Comfortable (A/C), and Calm/Relaxed (C/R)-for 2 age groups (young/middle-aged, ≤7 years and old, ≥8 years). The alert provides an early warning, via email to owners, that a potentially significant deterioration in health status has occurred. The model accurately predicted the health status of 93 and 83% of sick young/middle aged and old dogs respectively, with healthy dogs predicted with 83% accuracy. HRQL data, collected via a white-labeled veterinary clinic branded app designed to facilitate connected care between owner and veterinarian, were analyzed for 6,108 dogs, aged between 6 weeks and 16 years. Of these 5,002 were deemed to be in perfect health by their owners, yet the alert was triggered for 1,343 (27%) of these, 75% of which were young/middle-aged and 25% were old, indicating that acute injuries notwithstanding, many middle aged dogs may have been suffering from undetected chronic disease such as osteoarthritis. This work has demonstrated that the use of VetMetrica™ delivered via the PetDialog™ app, which supports 24/7 remote health monitoring is an efficient way for vets to provide all their owners with the opportunity to monitor their animal's wellness throughout their lifetime, providing the vet with a mechanism to identify health problems early while stimulating owners to be more proactive in seeking veterinary attention.

Simulated versus traditional therapeutic radiography placements: A randomised controlled trial.

INTRODUCTION: Clinical placements provide rich learning environments for health professional pre-registration education but add significant workload pressure to clinical departments. Advances in simulation approaches mean that many aspects of students' clinical learning can be undertaken in the academic environment. There is, however, little data identifying specific pedagogical gains afforded by simulation compared to clinical placement. This study measured the impact of a comprehensive integrated simulation placement on student clinical skill acquisition. METHODS: A virtual department was developed using a range of simulation equipment and software, with actors and service users providing a range of patients for students to engage with. A cohort of 29 first-year undergraduate therapeutic radiography students were randomly assigned to either simulated or conventional clinical placement. Clinical skills assessment scores provided by a blinded assessor were then compared. RESULTS: Mean overall assessment scores for each cohort were within 3% of each other. The simulation cohort had over 10% higher "communication" scores than the traditional group (p = 0.028). The ability to gain both technical and interpersonal skills simultaneously improved learning compared to clinical placement. Students valued the structured approach of the simulated placement and the opportunity to practice techniques in a safe unpressured environment. CONCLUSION: An integrated simulated placement can help students to achieve clinical learning outcomes and lead to improved interpersonal skills. IMPLICATIONS FOR PRACTICE: Use of blended simulation resources can enable students to acquire technical, procedural and interpersonal skills which in turn may enable reduction of overall clinical placement time and departmental training burden.

Optimising outputs from a validated online instrument to measure health-related quality of life (HRQL) in dogs.

Measurement of health-related quality of life (HRQL) is becoming increasingly valuable within veterinary preventative health care and chronic disease management, as well as in outcomes research. Initial reliability and validation of a 22 item shortened version of VetMetrica (VM), structured questionnaire instrument to measure HRQL in dogs via a mobile application was reported previously. Meaningful interpretation and presentation of the 4 domain scores comprising the HRQL profile generated by VM is key to its successful use in clinical practice and research. Study one describes transformation of domain scores from 0-6 to 0-100 and normalisation of these based on the healthy canine population in two age ranges, such that a score of 50 on a 0-100 scale represents the score for the age-related average healthy dog, and establishment of a threshold to assess domain-specific health status for individual dogs. This provides the clinician with a simple method of ascertaining the health status of an individual dog relative to the average healthy population in the same age group (norm-based scoring). Study two determines the minimum important difference (MID) in domain scores which represents the smallest improvement in score that is meaningful to the dog owner, thus providing the clinician with a means of recognising what is likely to be a significant improvement in scores for an individual dog over time. Visual representation of these guidelines for the purpose of interpreting VM profile scores is presented using case studies.

The burden of healthcare-associated Clostridium difficile infection in a non-metropolitan setting.

OBJECTIVE: Healthcare-associated Clostridium difficile infection (HCA-CDI) remains a major cause of morbidity and mortality in industrialized countries. However, few data exist on the burden of HCA-CDI in multi-site non-metropolitan settings. This study examined the introduction of an antimicrobial stewardship programme (ASP) in relation to HCA-CDI rates, and the effect of HCA-CDI on length of stay (LOS) and hospital costs. METHODS: A comparative before-and-after intervention study of patients aged ≥16 years with HCA-CDI from December 2010 to April 2016 across the nine hospitals of a non-metropolitan health district in New South Wales, Australia was undertaken. The intervention comprised a multi-site ASP supported by a clinical decision support system, with subsequent introduction of email feedback of HCA-CDI cases to admitting medical officers. MAIN OUTCOME MEASURES: HCA-CDI rates, comparative LOS and hospital costs, prior use of antimicrobials and proton pump inhibitors, and appropriateness of CDI treatment. RESULTS: HCA-CDI rates rose from 3.07 to 4.60 cases per 10,000 occupied bed-days pre-intervention, and remained stable at 4 cases per 10,000 occupied bed-days post-intervention (P=0.24). Median LOS (17 vs six days; P<0.01) and hospital costs (AU$19,222 vs $7861; P<0.01) were significantly greater for HCA-CDI cases (N=91) than for matched controls (N=172). Half of the patients with severe HCA-CDI (4/8) did not receive initial appropriate treatment (oral vancomycin). CONCLUSIONS: HCA-CDI placed a significant burden on the regional and rural health service through increased LOS and hospital costs. Interventions targeting HCA-CDI could be employed to consolidate the effects of ASPs.

Change in attitudes and knowledge of problem drug use and harm reduction among a community cohort in Kabul, Afghanistan.

This pre-post evaluation aimed to measure changes in knowledge and attitudes towards drug users among community representatives in Kabul, Afghanistan, over a period of expansion of harm reduction and drug dependence programming. A convenience sample of 160 professionals aged 18+ years completed interview questionnaires in 2007 and 2009. Views endorsing programme quality and the provision of condoms, infection counselling/testing and needle/syringe distribution increased significantly over the 2-year period. In 13 of 38 statements, there was a substantial (> 10%) change in agreement level, most commonly among men and medical professionals. Attitudes concerning support of drug users remained largely positive, with substantial attitude changes in some subgroups of the population. Further community education through the media and a more cohesive government drug policy may be needed to strengthen community support for harm reduction/drug treatment in Afghanistan.

Impact of canine overweight and obesity on health-related quality of life.

Canine obesity is increasing in prevalence in the UK and raises concerns about dog welfare. This study compares the health-related quality of life (HRQL) of dogs of varying body condition: overweight and obese (BCS 4 and 5) versus non-overweight dogs (BCS 2 and 3), obese (BCS 5) versus non-overweight (BCS 2 and 3) and an overall comparison between all four BCS (BCS 2, 3, 4 and 5) using a novel, validated HRQL instrument which is both web and mobile tablet/phone app based. Of 271 dog owners who were approached, 174 completed a web-based instrument (2013) or a mobile tablet app instrument (2014) during the summers of 2013 and 2014. Automatically generated scores in four domains of HRQL (energetic/enthusiastic, happy/content, active/comfortable, calm/relaxed) were compared for dogs with each of the body condition scores (BCS 2-5). For all body condition scores a statistically significant difference was found between the HRQL scores in two of the domains: energetic/enthusiastic (p=0.02) and active comfortable (p=0.004). When BCS 2 and 3 were compared to BCS 4 and 5, statistical significance was found in the same two domains - energetic/enthusiastic (p=0.01) and active comfortable (p=0.001) - as it was in comparison of non-overweight (BCS 2 and 3) compared to obese dogs (BCS 5): energetic/enthusiastic (p=0.012) and active comfortable (p=0.004). These results suggest that overweight and obese dogs have a reduced HRQL in two of the domains compared to non-overweight dogs, and that differences in HRQL are detectable between BCS scores 2, 3, 4 and 5.

Change in attitudes and knowledge of problem drug use and harm reduction among a community cohort in Kabul, Afghanistan

هذا التقييم لما قبل ومابعد تطبيق البرنامج يهدف الى قياس التغيرات التي طرأت على المعارف والاتجاهات تجاه متعاطي المخدرات لدي ممثلين عن المجتمع في كابول بافغانستان خلال فتره من فترات التوسع في تطبيق برنامج لمعالجه ادمان المخدرات والحد من اضرارها فقد قامت عينه ملائمه تضم 160 مهنيا اعمارهم 18 سنه فما فوق بملء استبيانات مقابله في عامي 2007 و 2009 فتبين ان الآراء المؤيدة لجودة البرنامج ولتوفير الواقي الذكري وتقديم المشورة والاختبارات الخاصة بالعدوي وتوزيع الابر والمحاقن قد ازدادت زيادة ملحوظة خلال هذين العامين وكان هناك تغير جوهري في مستوي القبول ( اكثر من 10%)في 13 بيانا من اصل 38 لاسيما لدي الرجال واصحاب المهن الطبيه المتعلقه بدعم متعاطي المخدرات ايجابيه الى حد كبير مع تغيرات كبيره في مواقف بعض المجموعات السكانيه الفرعيه ربما تكون هناك حاجة الى مزيد من تثقيف المجتمع عن طريق وسائل الاعلام والى سياسه حكوميه اكثر تماسكا بشأن المخدرات تعزز دعم المجتمع لمعالجة تعاطي المخدرات والحد من اضرارها في افغانستان

La presente evaluation pre-post visait a mesurer ['acquisition de connaissances et les changements d'attitudes a I'egard des toxicomanes parmi les representants d'une communaute a Kaboul [Afghanistan]au cours d'une periode d'elargissement des programmes de reduction des effets nocifs et de traitement de la clependance aux drogues.Un echantillon de commodite de 160 professionnels ages de plus de 18 ans a rempli des questionnaires dans le cadre d'entretiens en 2007 et en 2009.Les opinions au sujet de ['application de programmes de qualite et de la fourniture de preservatifs,du conseil et du depistage en matiere defections,ainsi que de la distribution d/aiguilles/de seringues se sont considerablement ameliorees au cours de ces deux annees.Dans 13 des 38 declarations,on a pu noter un changement notable [>10 %]dans le niveau d'acceptation,le plus souvent parmi les hommes et les professionnels de sante.Les attitudes concernant le soutien a apporter aux toxicomanes sont restees positives dans une large mesure,avec des changements d'attitude notables dans certains sous-groupes de la population.Une education plus poussee des communautes par le biais des medias et des politiques gouvernementales de lutte contre la drogue plus coherentes sont necessaires pour renforcer le soutien communautaire a la reduction des effets nocifs/au traitement des toxicomanies en Afghanistan

This pre-post evaluation aimed to measure changes in knowledge and attitudes towards drug users among community representatives in Kabul,Afghanistan,over a period of expansion of harm reduction and drug dependence programming.A convenience sample of 160 professionals aged 18+ years completed interview questionnaires in 2007 and 2009.Views endorsing programme quality and the provision of condoms,infection counselling/testing and needle/syringe distribution increased significantly over the 2-year period.In 13 of 38 statements,there was a substantial [>10%]change in agreement level,most commonly among men and medical professionals.Attitudes concerning support of drug users remained largely positive,with substantial attitude changes in some subgroups of the population.further community education through the media and a more cohesive government drug policy may be needed to strengthen community support for harm reduction/drug treatment in Afghanistan

Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer.

BACKGROUND: Selumetinib (AZD6244, ARRY-142886)+docetaxel increases median overall survival (OS) and significantly improves progression-free survival (PFS) and objective response rate (ORR) compared with docetaxel alone in patients with KRAS mutant, stage IIIB/IV non-small-cell lung cancer (NSCLC; NCT00890825). METHODS: Retrospective analysis of OS, PFS, ORR and change in tumour size at week 6 for different sub-populations of KRAS codon mutations. RESULTS: In patients receiving selumetinib+docetaxel and harbouring KRAS G12C or G12V mutations there were trends towards greater improvement in OS, PFS and ORR compared with other KRAS mutations. CONCLUSION: Different KRAS mutations in NSCLC may influence selumetinib/docetaxel sensitivity.

Development, validation and reliability of a web-based questionnaire to measure health-related quality of life in dogs.

OBJECTIVES: To describe the development, preliminary validation and reliability testing of a shortened web-based form of GUVQuest, a structured questionnaire to measure health-related quality of life in dogs. METHODS: The original 109 items were reduced using expert judgement and factor analysis. Validity was established by factor analysis and in a subsequent field trial using a "known groups" approach and classical test theory. Test-retest reliability was assessed using intraclass correlation coefficients. RESULTS: The instrument comprises 46 items each of which is rated by dog owners using a 7-point Likert scale. Factor analysis revealed a sensible structure containing four health-related quality of life domains (vitality, pain, distress and anxiety) accounting for 64·1% of the variability in the data. The field test involving 125 dogs demonstrated very good discriminative properties and intraclass correlation coefficient values of greater than 0·6. CLINICAL SIGNIFICANCE: This is the first report of a valid and reliable companion animal health-related quality of life instrument, the contemporary approach to animal welfare measurement, which is presented in a web-based format, with automated production of a health-related quality of life profile. It offers major advantages to dog owners, practitioners and researchers.

Quality of life is reduced in obese dogs but improves after successful weight loss.

Obesity is thought to affect quality of life, but limited objective data exist to support this supposition. The current study aim was to use a questionnaire to determine health-related quality of life (HRQOL) both before and after weight loss, in obese client-owned dogs. Fifty obese dogs were included, and represented a variety of breeds and genders. Prior to weight loss, owners were asked to complete a validated standardised questionnaire to determine HRQOL. Thirty of the dogs successfully completed their weight loss programme and reached target, and owners then completed a follow-up questionnaire. The completed questionnaire responses were transformed to scores corresponding to each of four factors (vitality, emotional disturbance, anxiety and pain), and scored on a scale of 0-6. Changes in the scores were used to explore the sensitivity of the questionnaire, and scores were correlated with responses to direct questions about quality of life and pain, as well as weight loss. Dogs that failed to complete their weight loss programme had lower vitality and higher emotional disturbance scores than those successfully losing weight (P=0.03 for both). In the 30 dogs that completed, weight loss led to an increased vitality score (P<0.001), and decreased scores for both emotional disturbance (P<0.001) and pain (P<0.001). However, there was no change in anxiety (P=0.09). The change in vitality score was positively associated with percentage weight loss (r(P)=0.43, P=0.02) and percentage body fat loss (r(P)=0.39, P=0.03). These results indicate demonstrable improvement in HRQOL for obese dogs that successfully lose weight.

Predator detection enables juvenile Lymnaea to form long-term memory.

Learning and memory provide the flexibility an organism requires to respond to changing social and ecological conditions. Juvenile Lymnaea have previously been shown to have a diminished capacity to form long-term memory (LTM) following operant conditioning of aerial respiratory behavior. Juvenile Lymnaea, however, can form LTM following classical conditioning of appetitive behaviors. Here, we demonstrate that laboratory-reared juvenile Lymnaea have the ability to detect the presence of a sympatric predator (i.e. crayfish) and respond to the predator by altering their aerial respiratory behavior. In addition to increasing their total breathing time, predator detection confers on juvenile Lymnaea an enhanced capability to form LTM following operant conditioning of aerial respiratory behavior. That is, these juveniles now have the ability to form long-lasting memory. These data support the hypothesis that biologically relevant levels of stress associated with predator detection induce behavioral phenotypic alterations (i.e. enhanced LTM formation) in juveniles, which may increase their fitness. These data also support the notion that learning and memory formation in conjunction with predator detection is a form of inducible defense.

Differences in LTM-forming capability between geographically different strains of Alberta Lymnaea stagnalis are maintained whether they are trained in the lab or in the wild.

We found strain differences in the ability of wild Alberta Lymnaea stagnalis to form long-term memory (LTM) following operant conditioning when L. stagnalis were collected from the wild and trained in the laboratory. Lymnaea stagnalis obtained from the Belly River watershed had an enhanced ability to form LTM compared with those from an isolated pond (referred to as Jackson snails). We therefore asked whether the differences in cognitive ability were an epiphenomenon as a result of training in the laboratory. To answer this question we trained each specific strain (Belly and Jackson) in both the laboratory and the field (i.e. in their home pond and in the pond where the other strain resided - referred to as the visitor pond). We found that within each strain there was no difference in the LTM phenotype whether they were trained in the lab or in either their home or visitor pond. That is, the strain differences in the ability to form LTM were still present. Interestingly, we found no strain differences in the ability to learn or the ability to form intermediate-term memory (ITM).

Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study.

BACKGROUND: This study investigated the potential clinical utility of circulating free DNA (cfDNA) as a source of BRAF mutation detection in patients enrolled into a phase II study of AZD6244, a specific MEK1/2 inhibitor, in patients with advanced melanoma. METHODS: BRAF mutations were detected using Amplification Refractory Mutation System allele-specific PCR. BRAF mutation status was assessed in serum-derived cfDNA from 126 patients enrolled into the study and from 94 matched tumour samples. RESULTS: Of 94 tumour samples, 45 (47.9%) were found to be BRAF mutation positive (BRAF+). Serum-derived cfDNA was BRAF+ in 33 of 126 (26.2%) samples, including in five samples for which tumour data were unavailable. Of BRAF+ tumours, 25 of 45 (55.6%) were BRAF+ in cfDNA. In three cases in which the tumour was negative, cfDNA was BRAF+. Progression-free survival (PFS) of patients with BRAF+ tumour and cfDNA was not significantly different compared with tumour BRAF+ but cfDNA BRAF-negative patients, indicating that cfDNA BRAF detection is not associated with poorer prognosis on PFS in stage III/IV advanced melanoma. CONCLUSIONS: These data demonstrate the feasibility of BRAF mutation detection in cfDNA of patients with advanced melanoma. Future studies should aim to incorporate BRAF mutation testing in cfDNA to further validate this biomarker for patient selection.

Usability of a mobile electronic medical record prototype: a verbal protocol analysis.

BACKGROUND: Point of care access to electronic medical records may provide clinicians with the information they want when they need it and may in turn improve patient safety. Yet providing an electronic medical record on handheld devices presents many usability challenges, and it is unclear whether clinicians will use them. METHODS: An iterative design process for the development and evaluation of a prototype of a mobile electronic medical record was performed. Usability sessions were conducted in which physicians were asked to 'think aloud' while working through clinical scenarios using the prototype. Verbal protocol analysis, which consists of coding utterances, was conducted on the transcripts from the sessions and common themes were extracted. RESULTS: Usability sessions were held with five family physicians and four internists with varying levels of computer expertise. Physicians were able to use the device to complete 52 of 54 required tasks. Users commented that it was intuitive (9/9), would increase accessibility (5/9) but for them to use it, it would need the system to be fast and time-saving (5/9). Users had difficulty entering information (5/9) and reading the screen (4/9). In terms of functionality, users had concerns about completeness of information (6/9), details of ordering (5/9) and desired billing functionality (5/9) and integration with other systems (4/9). CONCLUSIONS: While physicians can use mobile electronic medical records in realistic scenarios, certain requirements likely need to be met including a fast system with easy data selection, easy data entry and improved display before widespread adoption occurs.

An unusual cause of locking after total knee replacement.

Locking after total knee replacement is uncommon and is generally caused by the formation of fibrous tissue around the patella. We report an unusual cause of locking resulting from intermittent occlusion of the popliteal artery, which was tethered to cement at the posterior aspect of the tibial component.