Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability

Mutations in several classes of embryonically-expressed transcription factor genes are associated with behavioral disorders and epilepsies. However, there is little known about how such genetic and neurodevelopmental defects lead to brain dysfunction. Here we present the characterization of an epilepsy syndrome caused by the absence of the transcription factor SOX1 in mice. In vivo electroencephalographic recordings from SOX1 mutants established a correlation between behavioral changes and cortical output that was consistent with a seizure origin in the limbic forebrain. In vitro intracellular recordings from three major forebrain regions, neocortex, hippocampus and olfactory (piriform) cortex (OC) showed that only the OC exhibits abnormal enhanced synaptic excitability and spontaneous epileptiform discharges. Furthermore, the hyperexcitability of the OC neurons was present in mutants prior to the onset of seizures but was completely absent from both the hippocampus and neocortex of the same animals. The local inhibitory GABAergic neurotransmission remained normal in the OC of SOX1-deficient brains, but there was a severe developmental deficit of OC postsynaptic target neurons, mainly GABAergic projection neurons within the olfactory tubercle and the nucleus accumbens shell. Our data show that SOX1 is essential for ventral telencephalic development and suggest that the neurodevelopmental defect disrupts local neuronal circuits leading to epilepsy in the SOX1-deficient mice

Coronary heart disease risk screening: the community pharmacy Healthy Heart Assessment Service

Objectives We examined the characteristics and CHD risks of people who accessed the free Healthy Heart Assessment (HHA) service operated by a large UK pharmacy chain from August 2004 to April 2006. Methods Associations between participants’ gender, age, and socioeconomics were explored in relation to calculated 10-year CHD risks by cross-tabulation of the data. Specific associations were tested by forming contingency tables and using Pearson chi-square (χ2). Results Data from 8,287 records were analysable; 5,377 were at low and 2,910 at moderate-to-high CHD risk. The likelihood of moderate-to-high risk for a male versus female participant was significantly higher with a relative risk ratio (RRR) 1.72 (P < 0.001). A higher percentage of those in socioeconomic categories ‘constrained by circumstances’ (RRR 1.15; P < 0.05) and ‘blue collar communities’ (RRR 1.13; P < 0.05) were assessed with moderate-to-high risk compared to those in ‘prospering suburbs’. Conclusions People from ‘hard-to-reach’ sectors of the population, men and people from less advantaged communities, accessed the HHA service and were more likely to return moderate-to-high CHD risk. Pharmacists prioritised provision of lifestyle information above the sale of a product. Our study supports the notion that pharmacies can serve as suitable environments for the delivery of similar screening services.

Uptake of a free coronary heart disease risk screening programme in community pharmacy: the Healthy Heart Assessment service

Introduction Health promotion (HP) aims to enhance good health while preventing ill-health at three levels of activity; primary (preventative), secondary (diagnostic) and tertiary (management).1 It can range from simple provision of health education to ongoing support, but the effectiveness of HP is ultimately dependent on its ability to influence change. HP as part of the Community Pharmacy Contract (CPC) aims to increase public knowledge and target ‘hard-to-reach’ individuals by focusing mainly on primary and tertiary HP. The CPC does not include screening programmes (secondary HP) as a service. Coronary heart disease (CHD) is a significant cause of morbidity and mortality in the UK. While there is evidence to support the effectiveness of some community pharmacy HP strategies in CHD, there is paucity of research in relation to screening services.2 Against this background, Alliance Pharmacy introduced a free CHD risk screening programme to provide tailored HP advice as part of a participant–pharmacist consultation. The aim of this study is to report on the CHD risk levels of participants and to provide a qualitative indication of consultation outcomes. Methods Case records for 12 733 people who accessed a free CHD risk screening service between August 2004 and April 2006 offered at 217 community pharmacies were obtained. The service involved initial self-completion of the Healthy Heart Assessment (HHA) form and measurement of height, weight, body mass index, blood pressure, total cholesterol and highdensity lipoprotein levels by pharmacists to calculate CHD risk.3 Action taken by pharmacists (lifestyle advice, statin recommendation or general practitioner (GP) referral) and qualitative statements of advice were recorded, and a copy provided to the participants. The service did not include follow-up of participants. All participants consented to taking part in evaluations of the service. Ethical committee scrutiny was not required for this service development evaluation. Results Case records for 10 035 participants (3658 male) were evaluable; 5730 (57%) were at low CHD risk (<15%); 3636 (36%) at moderate-to-high CHD risk (≥15%); and 669 (7%) had existing heart disease. A significantly higher proportion of male (48% versus 30% female) participants were at moderate- to-high risk of CHD (chi-square test; P < 0.005). A range of outcomes resulted from consultations. Lifestyle advice was provided irrespective of participants’ CHD risk or existing disease. In the moderate-to-high-risk group, of which 52% received prescribed medication, lifestyle advice was recorded for 62%, 16% were referred and 34% were advised to have a re-assessment. Statin recommendations were made in 1% of all cases. There was evidence of supportive and motivational statements in the advice recorded. Discussion Pharmacists were able to identify individuals’ level of CHD risk and provide them with bespoke advice. Identification of at-risk participants did not automatically result in referrals or statin recommendation. One-third of those accessing the screening service had moderate-to-high risk of CHD, a significantly higher proportion of whom were men. It is not known whether these individuals had been previously exposed to HP but presumably by accessing this service they may have contemplated change. As effectiveness of HP advice will depend among other factors on ability to influence change, future consultations may need to explore patients’ attitude towards change in relation to the Trans Theoretical Model4 to better tailor HP advice. The high uptake of the service by those at moderate-to-high CHD risk indicates a need for this type of screening programme in community pharmacy, perhaps specifically to reach men who access medical services less.

Under-investigation of older people with abnormal chest radiographs

Background: Whilst many authors have previously suggested that older people are under-represented in the investigation and management of lung cancer, few data are available as to the effect of age on the subsequent investigation and management of a patient with an abnormal chest radiograph. Methods: During a 3-month period in a university teaching hospital, all abnormal chest radiographs suggestive of a possible diagnosis of lung cancer were identified, and patients subsequently followed to determine investigation, management and date of death over a 5-year period. Results: Thirty-seven younger (less than or equal to69 years, median age 62 years) and 43 older patients ( 670 years, median age 80 years) were identified. Of the 80 patients with a possible bronchial carcinoma only 59% had a further chest radiograph performed. Bronchoscopy was performed in 34% of patients, but a biopsy of the lesion was undertaken in only 24% of patients. Sixteen of the 80 patients, irrespective of what investigations had been undertaken, were referred for an oncological or surgical opinion. During the study period ( 3 months), 24% of the patients died. At 6, 24 and 60 months, respectively, the total deaths were 40, 78 and 88%. Conclusion: Older patients compared with those aged less than 70 years were less likely to be investigated, further, were more likely to be managed differently (i.e., less aggressively) and more likely to die within each time interval. In more of the older group a presumed death certificate diagnosis of pneumonia was made. When an abnormal chest radiograph raises the possibility of an underlying bronchial carcinoma, the finding of this study suggests that an ageist attitude influences the subsequent management of some patients. Copyright (C) 2005 S. Karger AG, Basel.