Mutation screening of patients with Alzheimer disease identifies APP locus duplication in a Swedish patient

BACKGROUND: Missense mutations in three different genes encoding amyloid-β precursor protein, presenilin 1 and presenilin 2 are recognized to cause familial early-onset Alzheimer disease. Also duplications of the amyloid precursor protein gene have been shown to cause the disease. At the Dept. of Geriatric Medicine, Karolinska University Hospital, Sweden, patients are referred for mutation screening for the identification of nucleotide variations and for determining copy-number of the APP locus. METHODS: We combined the method of microsatellite marker genotyping with a quantitative real-time PCR analysis to detect duplications in patients with Alzheimer disease. RESULTS: In 22 DNA samples from individuals diagnosed with clinical Alzheimer disease, we identified one patient carrying a duplication on chromosome 21 which included the APP locus. Further mapping of the chromosomal region by array-comparative genome hybridization showed that the duplication spanned a maximal region of 1.09 Mb. CONCLUSIONS: This is the first report of an APP duplication in a Swedish Alzheimer patient and describes the use of quantitative real-time PCR as a tool for determining copy-number of the APP locus

Patients’ willingness to attend the NHS cardiovascular health checks in primary care: A qualitative interview study

Background: The NHS Cardiovascular Health Check (NHSHC) programme was introduced in England in 2009 to reduce cardiovascular disease mortality and morbidity for all patients aged 40 to 74 years old. Programme cost-effectiveness was based on an assumed uptake of 75% but current estimates of uptake in primary care are less than 50%. The purpose of this study was to identify factors influencing patients’ willingness to attend an NHSHC. For those who attended, their views, experiences and their future willingness to engage in the programme were explored. Method: Telephone or face-to-face interviews were conducted with patients who had recently been invited for an NHSHC by a letter from four general practices in Torbay, England. Patients were purposefully sampled (by gender, age, attendance status). Interviews were audio recorded, transcribed verbatim and analysed thematically. Results: 17 attendees and 10 non-attendees were interviewed. Patients who attended an NHSHC viewed it as worthwhile. Proactive attitudes towards their health, a desire to prevent disease before they developed symptoms, and a willingness to accept screening and health check invitations motivated many individuals to attend. Non-attendees cited not seeing the NHSHC as a priority, or how it differed from regular monitoring already received for other conditions as barriers to attendance. Some non-attendees actively avoided GP practices when feeling well, while others did not want to waste health professionals’ time. Misunderstandings of what the NHSHC involved and negative views of what the likely outcome might be were common. Conclusion: While a minority of non-attendees simply had made an informed choice not to have an NHSHC, improving the clarity and brevity of invitational materials, better advertising, and simple administrative interventions such as sending reminder letters, have considerable potential to improve NHSHC uptake

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Clinician's Gaze Behaviour in Simulated Paediatric Emergencies

AimDifferences in the gaze behaviour of experts and novices are described in aviation and surgery. This study sought to describe the gaze behaviour of clinicians from different training backgrounds during a simulated paediatric emergency.MethodsClinicians from four clinical areas undertook a simulated emergency. Participants wore SMI (SensoMotoric Instruments) eye tracking glasses. We measured the fixation count and dwell time on predefined areas of interest and the time taken to key clinical interventions.ResultsPaediatric intensive care unit (PICU) consultants performed best and focused longer on the chest and airway. Paediatric consultants and trainees spent longer looking at the defibrillator and algorithm (51 180 ms and 50 551 ms, respectively) than the PICU and paediatric emergency medicine consultants.ConclusionsThis study is the first to describe differences in the gaze behaviour between experts and novices in a resuscitation. They mirror those described in aviation and surgery. Further research is needed to evaluate the potential use of eye tracking as an educational tool.</jats:sec