Vishnu Madhok

Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in human subjects

BACKGROUND Atopic dermatitis (AD) is a major inflammatory condition of the skin caused by inherited skin barrier deficiency, with mutations in the filaggrin gene predisposing to development of AD. Support for barrier deficiency initiating AD came from flaky tail mice, which have a frameshift mutation in Flg and also carry an unknown gene, matted, causing a matted hair phenotype. OBJECTIVE We sought to identify the matted mutant gene in mice and further define whether mutations in the human gene were associated with AD. METHODS A mouse genetics approach was used to separate the matted and Flg mutations to produce congenic single-mutant strains for genetic and immunologic analysis. Next-generation sequencing was used to identify the matted gene. Five independently recruited AD case collections were analyzed to define associations between single nucleotide polymorphisms (SNPs) in the human gene and AD. RESULTS The matted phenotype in flaky tail mice is due to a mutation in the Tmem79/Matt gene, with no expression of the encoded protein mattrin in the skin of mutant mice. Matt(ft) mice spontaneously have dermatitis and atopy caused by a defective skin barrier, with mutant mice having systemic sensitization after cutaneous challenge with house dust mite allergens. Meta-analysis of 4,245 AD cases and 10,558 population-matched control subjects showed that a missense SNP, rs6684514, [corrected] in the human MATT gene has a small but significant association with AD. CONCLUSION In mice mutations in Matt cause a defective skin barrier and spontaneous dermatitis and atopy. A common SNP in MATT has an association with AD in human subjects.

Greater number of group identifications is associated with healthier behaviour: Evidence from a Scottish community sample

OBJECTIVES This paper investigates the interplay between group identification (i.e., the extent to which one has a sense of belonging to a social group, coupled with a sense of commonality with in-group members) and four types of health behaviour, namely physical exercise, smoking, drinking, and diet. Specifically, we propose a positive relationship between ones number of group identifications and healthy behaviour. DESIGN This study is based on the Scottish portion of the data obtained for Wave 1 of the two-wave cross-national Health in Groups project. Totally 1,824 patients from five Scottish general practitioner (GP) surgeries completed the Wave 1 questionnaire in their homes. METHODS Participants completed measures of group identification, group contact, health behaviours, and demographic variables. RESULTS Results demonstrate that the greater the number of social groups with which one identifies, the healthier ones behaviour on any of the four health dimensions considered. CONCLUSIONS We believe our results are due to the fact that group identification will generally (1) enhance ones sense of meaning in life, thereby leading one to take more care of oneself, (2) increase ones sense of responsibility towards other in-group members, thereby enhancing ones motivation to be healthy in order to fulfil those responsibilities, and (3) increase compliance with healthy group behavioural norms. Taken together, these processes amply overcompensate for the fact that some groups with which people may identify can actually prescribe unhealthy behaviours.

Prescribe prednisolone alone for Bell's palsy diagnosed within 72 hours of symptom onset.

The authors explain their reasons for the need for a new change in treatment for early Bell’s palsy

Use of oral anticoagulants in atrial fibrillation is highly variable and only weakly associated with estimated stroke risk: Cross-sectional population database study

Abstract Background: Current international guidelines promote the use of stroke risk stratification tools to inform decision making about oral anticoagulant (OAC) use in atrial fibrillation (AF). Objectives: To examine (a) differences between CHADS2 and CHA2DS2VASc in classifying stroke risk in a primary care population of AF patients; (b) patterns of use of antithrombotics by stroke risk; and (c) patient and practice characteristics associated with use of oral anticoagulants in patients with AF. Methods: Cross-sectional multilevel modelling study of all patients with AF and without rheumatic heart disease or valve replacement (n = 21 564) from 315 Scottish General Practices. Results: (a) CHADS2 characterized 30.3% in the intermediate and 53.8% in the high-risk category, compared to CHA2DS2VASC only 9.7% intermediate and 85.1% high-risk. (b) Of included patients, 17.8% were currently not prescribed any antithrombotic and 43.3% were on OAC. OAC use was only weakly related to stroke risk. (c) Patients with paroxysmal AF and those with dementia and previous peptic ulcer (adjusted ORs 0.26, 0.25 and 0.79) were less likely to be prescribed OAC. OAC use varied over five-fold between practices after adjustment for patient case mix, with remote and non-training practices and those with high levels of high-risk prescribing being more likely to prescribe OAC. Conclusion: Evidence was found of both underuse and overuse of OAC in patients with AF. Promoting instruments for stroke risk assessment in AF is a plausible but untested strategy to improve decision making in AF, and its impact on OAC prescribing and patient outcomes should be evaluated in pragmatic trials.

The pain of low status: the relationship between subjective socio-economic status and analgesic prescriptions in a Scottish community sample.

There is a strong positive relationship between objective measures of socio-economic status (OSS) and general health. However, there is an increasing interest in the relationship between health and subjective socio-economic status (SSS), which describes one’s perceived rank in relation to the rest of the society, based on factors such as income, occupation and education. While the relationship between SSS and general health is well established, the relationship between SSS and pain has received little attention. Gathering both self-report questionnaire data and General Practitioner medical data from a large representative community sample in Scotland between 2012 and 2013 (N = 1824), we investigated the relationship between SSS and prescriptions for analgesic drugs. We found that higher levels of SSS significantly predicted lower odds of participants having been prescribed at least one analgesic drug in the previous six months. We obtained this result even after controlling for OSS-related variables (education, occupational status and geographical location) and demographic variables (age and gender). This suggests that, just like the relationship between SSS and general health, SSS has important effects on pain that go beyond the influence of OSS.

A young woman with acute one-sided facial paralysis

A 24-year-old woman presents in the emergency department with weakness on the left side of her face that started two hours previously. She reports a sudden onset of an uncomfortable sensation in the affected region with difficulty closing her left eye, a crooked smile and increased sensitivity to

The GP as an investigator

Andrew McGregor,* a 71-year-old man with a past history of hypertension and myocardial infarction, has recently been discharged from hospital after having an intracerebral haemorrhage (ICH). He wonders if he should restart aspirin, and asks for your advice. Patient-centred care and shared decision making underpinned by rigorous evidence-based medicine provide an ideal combination to answer areas of clinical equipoise such as the question asked by Mr McGregor. Research within primary care is able to help tailor treatment for patients, given the many daily consultations that GPs have with their patients, and whose multiple conditions require an integrated approach.1 Primary care research can also help to improve the application of health policy and its implementation, an increasingly bigger task that is likely to become more common in the future workload of all doctors.2 Considering the time …