Personalising medicine : feasibility and future implications from a payers' perspective

There are considerable differences in how patients respond to treatments due to a number of factors calling for personalised approaches to care, which is happening. However, the early promise of personalised medicine has not always translated into improved care for patients. Payers have concerns that current tests can be costly, requests for funding specific tests have subsequently been reversed as more information becomes available, and there is currently fragmentation in the funding of diagnostic tests. Payers also have concerns that pharmaceutical companies are exploiting the situation by seeking orphan status for their new targeted medicines driving up requested prices. It is also not clear who should fund biomarkers that accompany new expensive medicines. This is changing as the cost of tests come down, and payers develop new models to optimise the managed entry of new medicines as well as evaluate potential prices for new medicines for orphan diseases. There are also developments with ‘big data’ offering new understanding of disease complexity to enhance pipeline productivity and diagnosis as well as ongoing developments with drug resistance testing and research into the role of microbiomes to improve future health. Current challenges and concerns are being addressed. This will continue to improve patient care

Population receptive field estimates for motion-defined stimuli

The processing of motion changes throughout the visual hierarchy, from spatially restricted ‘local motion’ in early visual cortex to more complex large-field ‘global motion’ at later stages. Here we used functional magnetic resonance imaging (fMRI) to examine spatially selective responses in these areas related to the processing of random-dot stimuli defined by differences in motion. We used population receptive field (pRF) analyses to map retinotopic cortex using bar stimuli comprising coherently moving dots. In the first experiment, we used three separate background conditions: no background dots (dot-defined bar-only), dots moving coherently in the opposite direction to the bar (kinetic boundary) and dots moving incoherently in random directions (global motion). Clear retinotopic maps were obtained for the bar-only and kinetic-boundary conditions across visual areas V1-V3 and in higher dorsal areas. For the global-motion condition, retinotopic maps were much weaker in early areas and became clear only in higher areas, consistent with the emergence of global-motion processing throughout the visual hierarchy. However, in a second experiment we demonstrate that this pattern is not specific to motion-defined stimuli, with very similar results for a transparent-motion stimulus and a bar defined by a static low-level property (dot size) that should have driven responses particularly in V1. We further exclude explanations based on stimulus visibility by demonstrating that the observed differences in pRF properties do not follow the ability of observers to localise or attend to these bar elements. Rather, our findings indicate that dorsal extrastriate retinotopic maps may primarily be determined by the visibility of the neural responses to the bar relative to the background response (i.e. neural signal-to-noise ratios) and suggests that claims about stimulus selectivity from pRF experiments must be interpreted with caution

Crystal sedimentation and stone formation

Mechanisms of crystal collision being the first step of aggregation (AGN) were analyzed for calcium oxalate monohydrate (COM) directly produced in urine. COM was produced by oxalate titration in urine of seven healthy men, in solutions of urinary macromolecules and in buffered distilled water (control). Crystal formation and sedimentation were followed by a spectrophotometer and analyzed by scanning electron microscopy. Viscosity of urine was measured at 37°C. From results, sedimentation rate (vS), particle diffusion (D) and incidences of collision of particles in suspension by sedimentation (IS) and by diffusion (ID) were calculated. Calculations were related to average volume and urinary transit time of renal collecting ducts (CD) and of renal pelvis. vS was in urine 0.026 ± 0.012, in UMS 0.022 ± 0.01 and in control 0.091 ± 0.02 cm min−1 (mean ± SD). For urine, a D of 9.53 ± 0.97 μm within 1 min can be calculated. At maximal crystal concentration, IS was only 0.12 and ID was 0.48 min−1 cm−3 which, even at an unrealistic permanent and maximal crystalluria, would only correspond to less than one crystal collision/week/CD, whereas to the same tubular wall being in horizontal position 1.3 crystals/min and to a renal stone 624 crystals/cm2 min could drop by sedimentation. Sedimentation to renal tubular or pelvic wall, where crystals can accumulate and meet with a tissue calcification or a stone, is probably essential for stone formation. Since vS mainly depends on particle size, reducing urinary supersaturation and crystal growth by dietary oxalate restriction seems to be an important measure to prevent aggregation

Anesthetic consideration for patients with severe tracheal obstruction caused by thyroid cancer -A report of 2 cases-

To achieve safe airway management, it is essential first to predict whether there will be difficulties in intubating or ventilating the patient's airway. An enlarged thyroid mass can produce a tracheal obstruction by compression or intraluminal invasion or both. We report two patients with thyroid cancer that obstructed the trachea by compression or invasion. There was no difficulty in endotracheal intubation of the patients with marked thyroid enlargement or in securing passage of the endotracheal tube through the compressed or narrowed portion of the trachea

Walk well:a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

Background - Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design - This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion - Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities

Assessment of Objectively Measured Physical Activity Levels in Individuals with Intellectual Disabilities with and without Down's Syndrome

Objective: To investigate, using accelerometers, the levels of physical activity being undertaken by individuals with intellectual disabilities with and without Down’s syndrome. Methods: One hundred and fifty two individuals with intellectual disabilities aged 12–70 years from East and South-East England. Physical activity levels in counts per minute (counts/min), steps per day (steps/day), and minutes of sedentary, light, moderate, vigorous, and moderate to vigorous physical activity (MVPA) measured with a uni-axial accelerometer (Actigraph GT1M) for seven days. Results: No individuals with intellectual disabilities met current physical activity recommendations. Males were more active than females. There was a trend for physical activity to decline and sedentary behaviour to increase with age, and for those with more severe levels of intellectual disability to be more sedentary and less physically active, however any relationship was not significant when adjusted for confounding variables. Participants with Down’s syndrome engaged in significantly less physical activity than those with intellectual disabilities without Down’s syndrome and levels of activity declined significantly with age. Conclusions: Individuals with intellectual disabilities, especially those with Down’s syndrome may be at risk of developing diseases associated with physical inactivity. There is a need for well-designed, accessible, preventive health promotio

Pathways to emotional closeness in neonatal units – a cross-national qualitative study

Background: Research shows evidence for the importance of physical and emotional closeness for the infant, the parent and the infant-parent dyad. Less is known about how, when and why parents experience emotional closeness to their infants in a neonatal unit (NU), which was the aim of this study. Methods: A qualitative study using a salutogenic approach to focus on positive health and wellbeing was undertaken in three NUs: one in Sweden, England and Finland. An ‘emotional closeness’ form was devised, which asked parents to describe moments/situations when, how and why they had felt emotionally close to their infant. Data for 23 parents of preterm infants were analyzed using thematic networks analysis. Results: A global theme of ‘pathways for emotional closeness’ emerged from the data set. This concept related to how emotional, physical, cognitive and social influences led to feelings of emotional closeness between parents and their infants. The five underpinning organising themes relate to the: Embodied recognition through the power of physical closeness; Reassurance of, and contributing to, infant wellness; Understanding the present and the past; Feeling engaged in the day to day and Spending time and bonding as a family. Conclusion: These findings generate important insights into why, how and when parents feel emotionally close. This knowledge contributes to an increased awareness of how to support parents of premature infants to form positive and loving relationships with their infants. Health care staff should create a climate where parents’ emotions and their emotional journey are individually supported

Contextual and individual factors associated with dental services utilisation by Brazilian adults: A multilevel analysis

BACKGROUND: Inequalities in the utilisation of dental services in Brazil are remarkable. The aim of this study was to evaluate the association of contextual and individual factors with the utilisation of dental services by Brazilian adults using the Andersen's behavioural model. METHODS: Individual-level data from 27,017 adults residents in the State capitals who were interviewed in the 2013 Brazilian National Health Survey were pooled with contextual city-level data. The outcomes were non-utilisation of dental services and last dental visit over 12 months ago. Individual predisposing variables were age, sex, race/skin colour, schooling and social network. Individual enabling variables included income, health insurance and registration in primary health care. Individual need variables were self-perceived dental health and self-reported missing teeth. Multilevel logistic regression models were performed to estimate odds ratio (OR) and 95% confidence intervals (95% CIs) of the association of contextual and individual predisposing, enabling and need-related variables with dental services outcomes. RESULTS: Predisposing (OR = 0.89; 95% CI 0.81-0.97) and enabling (OR = 0.90; 95% CI 0.85-0.96) contextual factors were associated with non-utilisation of dental services. Individual predisposing (sex, race/skin colour, schooling), enabling (income, health insurance) and need (self-perceived oral health, missing teeth) were associated with non-utilisation of dental services and last dental visit over 12 months ago. The latter was also associated with other individual predisposing (age, social network) and need (eating difficulties due to oral problems) characteristics. CONCLUSIONS: Individual and contextual determinants influenced dental services utilisation in Brazilian adults. These factors should be on the policy agenda and considered in the organisation of health services aiming to reduce oral health inequalities related to access and utilisation of dental services