A 6-month open-label study of the effectiveness and tolerability of galantamine in patients with Alzheimer's disease.

The objective of this study was to assess the effectiveness and tolerability of galantamine in patients with mild-to-moderate Alzheimer's disease (AD) in everyday clinical practice. Patient selection was made on 36 sequential patients attending Belfast City Hospital Memory Clinic between December 2000 and June 2001. Patients were treated with galantamine for 6 months, starting from 4 mg twice daily increasing to 8 mg twice daily and then to 12 mg twice daily at 4-weekly intervals. Patients (25 females, 11 males), mean age 78 years (59-90), were diagnosed with probable AD and had a mini-mental state examination (MMSE) score of 10-26. Efficacy was assessed using the MMSE, neuropsychiatric inventory (NPI), neuropsychiatric inventory caregiver distress (NPI-D) scale and the Bristol activities of daily living (B-ADL) scale at baseline and after 3 and 6 months of treatment. Mean improvements were noted on all four measures of efficacy at 3 and 6 months; improvements were significant on the MMSE, NPI and NPI-D at 3 months and on the NPI-D at 6 months. Galantamine was overall well tolerated. The most common adverse events were gastrointestinal, particularly nausea. Four patients stopped treatment due to adverse events, and seven were stabilised on 8 mg twice daily as they were unable to tolerate the target dose. This naturalistic study confirms clinical trial data, which shows galantamine improves cognition and behavioural symptoms and is overall well tolerated.

How reliable is a radiological report in osteoporosis in diagnosing low bone density?

Patients are often referred to osteoporosis clinics with a radiological diagnosis of osteoporosis. Previous studies attempting to ascertain risk of osteoporosis from radiographs have been conflicting. The aim of our study was to determine how reliable spinal radiographs were at detecting low bone density compared with Dual Energy X ray Absorptiometry (DXA). We retrospectively measured the Bone Mineral Density (BMD) at the spine in 130 patients with a radiological diagnosis of osteopenia or osteoporosis in the absence of vertebral fractures. They were compared with a group of 119 age and sex matched patients with one or more low trauma vertebral fractures. There was a statistically significant difference in the mean BMD between these two groups. 12.7%, of the x-ray group with osteopenia reported, had a normal bone density, 49.2% had osteopenia (T-score -1 to -2.5) and 38.1% had osteoporosis (T-score <-2.5). Of those with a radiological report of osteoporosis, 12.8% had a normal bone density, 44.7% had osteopenia and 42.6% had osteoporosis. We conclude that a radiological report of low bone density is a strong predictor of osteopenia or osteoporosis by BMD measurement.

Changes in seasonal deaths from myocardial infarction.

BACKGROUND: Cardiovascular disease is the major contributor to excess morbidity and mortality in winter. With the rise in temperatures through global warming, and the use of central heating and air conditioning, this seasonal variation may be declining. AIM: To study possible changes in seasonal variation in case-fatality rates of myocardial infarction (MI), in men and women, over a 20-year period and compare this with possible environmental influences. DESIGN: Retrospective analysis of death certificate and climatological data. METHODS: We analysed all monthly death certificate data from Northern Ireland, for death caused by MI from 1979 through 1998 (n=68 683). Mortality data were standardized to a single reference group for the whole period. Seasonal variation in mortality and in environmental variables was described using the cosinor model. RESULTS: A total of 29 875 women and 38 808 men died from MI during the 20-year period. A significant decrease in mortality from MI was observed in both sexes, accompanied by a non-significant decline in the amplitude of the seasonal rhythm over the study period. Low temperature was associated with higher mortality rates from MI. DISCUSSION: We have documented an overall decline in cardiovascular mortality from 1979 to 1998, together with a small but non-significant decrease in seasonal variation. While improvements in medical care, lifestyle, housing and diet may have contributed to the observed decline in mortality rate, seasonal fluctuations remain a significant problem.

Preparing tomorrow's doctors: the impact of a special study module in medical informatics.

BACKGROUND: In response to the call for more informatics teaching in the medical curriculum, an elective special study module has been offered to first-year students at Queen's University since 1997. OBJECTIVES: To assess the impact of a medical informatics course in terms of the use of skills acquired and attitudes held about information technology (IT) in medicine. METHODS: A postal structured questionnaire was sent to all 30 students who took the medical informatics special study module in 1997 and to all 29 students who took the module in 1998, plus an age and sex-matched group of controls in each year. Main outcome measures included attitudes to the role of IT in medicine and declared frequency of use of various software packages. RESULTS: Compared with the control group, those taking the module felt less confident initially with computers. There was a high level of positive attitude to computers in medicine following the course, in both study and control groups. There was a significantly greater use of word-processing (P=0.001) and presentation packages (P=0.0005) amongst third-year students compared with second-year students, but there was no significant difference in this regard between those taking the module and controls. CONCLUSIONS: Students' use of computer technology and IT skills, is more influenced by the demands of the overall curriculum than by undertaking a single module in medical informatics. A special study module may, however, provide valuable support by performing a 'remedial function'. The authors found the module a useful first step in the process of introducing medical informatics to the core curriculum.

Common guidelines and equitable service: variation between adjacent districts regarding admissions to elderly care institutions.

With the increasing number of older people, the cost of providing institutional care has become a major issue. In 1993 the introduction of care management and a needs-led approach aimed to remove the existing 'perverse incentive' to institutional care and to ensure equality in the dependency levels of those who were admitted to care. To test this consistency, we examined the dependency levels of all persons aged > or = 65 years admitted to residential and nursing homes in two adjacent Health and Social Services (HSS) Community Trusts in Belfast, Northern Ireland, in the year following the introduction of care management. We measured differences between the Trusts with respect to number of admissions, levels of dependency as determined by several standard scoring systems, financial support, source of admission and demographic information. A total of 389 people were surveyed. Trust A had significantly higher levels of physical dependency and mental impairment in both residential and nursing homes than Trust B. We also identified differences in dependency with respect to funding status, with those who were self-funding in Trust B having lower physical dependency in residential and nursing homes and less mental impairment in nursing homes than supplemented residents. This study reports the existence of variations between adjacent Community Trusts operating under the same policy guidelines with respect to the dependency levels of admissions to residential and nursing care. These differences may relate to number of places available, the economic status of the population, and the assessment procedures of the two Community Trusts. The need for standard assessment and eligibility criteria is highlighted.

The relationship between elevated fibrinogen and markers of infection: a comparison of seasonal cycles.

To test the hypothesis that higher levels of fibrinogen in winter are related to infections via the acute phase response, we assessed seasonal variation in fibrinogen and C-reactive protein, together with three other responses to infection: white cell count, human herpesvirus-6 IgG antibody and interleukin-6. Monthly blood samples from 24 subjects aged 75+ years were assessed for fibrinogen, C-reactive protein, white cell count, and human herpesvirus-6 IgG antibody. Interleukin-6 was measured in seven. Seasonal variation of these measures was determined by the population-mean cosinor procedure. Fibrinogen had a significant seasonal variation with a winter peak (mid-February) 1.26 g/l above the corresponding summer trough. C-reactive protein had a late-February peak, 3.71 mg/l above the summer trough. No seasonal rhythm was found in any other response to infection investigated. This study provides no evidence that winter infections are responsible for the seasonal variation in fibrinogen or C-reactive protein. The explanation for the seasonal changes in these proteins remains unknown.

Butyrylcholinesterase K variant is genetically associated with late onset Alzheimer's disease in Northern Ireland.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has been associated, sometimes controversially, with polymorphisms in a number of genes. Recently the butyrylcholinesterase K variant (BCHE K) allele has been shown to act in synergy with the apolipoprotein E epsilon4 (APOE epsilon4) allele to promote risk for AD. Most subsequent replicative studies have been unable to confirm these findings. We have conducted a case-control association study using a clinically well defined group of late onset AD patients (n=175) and age and sex matched control subjects (n=187) from the relatively genetically homogeneous Northern Ireland population to test this association. The BCHE genotypes of patients were found to be significantly different from controls (chi(2)=23.68, df=2, p<<0.001). The frequency of the K variant allele was also found to differ significantly in cases compared to controls (chi(2)=16.39, df=1, p<<0.001) leading to an increased risk of AD in subjects with this allele (OR=3.50, 95% CI 2. 20-6.07). This risk increased in subjects 75 years and older (OR=5. 50, 95% CI 2.56-11.87). At the same time the APOE epsilon4 associated risk was found to decrease from 6.70 (95% CI 2.40-19.04) in 65-74 year olds to 3.05 (95% CI 1.34-6.95) in those subjects 75 years and older. However, we detected no evidence of synergy between BCHE K and APOE epsilon4. The results from this study suggest that possession of the BCHE K allele constitutes a significant risk for AD in the Northern Ireland population and, furthermore, this risk increases with increasing age.

Effect of tourniquet pressure and intra-individual variability on plasma fibrinogen, platelet P-selectin and monocyte tissue factor.

Small differences in levels of certain haemostatic components may be clinically significant. It is important therefore to eliminate potential sources of confounding variability. This study investigated the effect of removing tourniquet pressure prior to sample collection on plasma fibrinogen levels, platelet P-selectin and monocyte tissue factor expression. Blood was collected from the right arm under maintained tourniquet pressure and from the left arm following the release of pressure once the vein was sufficiently inflated for insertion of a needle. Whole blood was labelled within one hour of venepuncture to allow analysis of platelet P-selectin and monocyte tissue factor by flow cytometry. Plasma fibrinogen levels were analysed in samples stored at -70 degrees C, for all individuals at the end of the study using a method based on the Clauss technique. Intra-individual variability for each of the components was assessed by collecting samples under tourniquet pressure from four individuals on the same day on three consecutive weeks. Intra-individual variations were greater than assay CVs for all three components. There were no significant differences between the two tourniquet methods of collection for fibrinogen, P-selectin or tissue factor. In conclusion, there is no reason not to use a tourniquet during collection of blood for analysis of plasma fibrinogen, platelet P-selectin or monocyte tissue factor.

The winter bed crisis--quantifying seasonal effects on hospital bed usage.

Winter bed crises are a common feature in NHS hospitals, and have given rise to great concern. We set out to determine the relative contribution of seasonal effects and other factors to bed occupancy in a large teaching hospital over one year. There were 190,804 occupied bed-days, which we analysed by specialty groupings. There was considerable variability in bed occupancy in each specialty. A significant winter peak occurred for general medicine and orthopaedics together with a significant increase on 'take-in' days. Virtually all specialties showed a significant variation in occupancy between weekdays. Geriatric Medicine had a high and fairly constant occupancy, with some seasonal effect. We conclude that seasonal trends in bed occupancy occur in 'front door' specialties and are predictable. In these specialties, admission policies also make a contribution to bed usage and are amenable to modification. There is no surge in occupancy in the immediate post-Christmas period, except that attributable to the seasonal trend. In the 'elective' specialties, bed occupancy fluctuates widely, with reduced occupancy at weekends and at Christmas. These differences are entirely amenable to modification. More effective bed management would make a very significant contribution to avoiding winter bed crises.

Measurement of fibrinogen in frozen plasma.

Several large studies have compared fibrinogen measurements determined over a particular time interval. These assays are subject to difficulties encountered by all laboratories on tests carried out over a period of time such as assay drift. To avoid this problem, plasma can be stored frozen and fibrinogen determined in a large number of samples simultaneously. However, a thorough comparison of measurements carried out in fresh and frozen plasma has not yet been performed. Fibrinogen concentration was therefore determined in fresh plasma samples and then at a later date in the same samples after storage at -70 degrees C. A good correlation was observed between the two measurements, however, bias increased at the higher fibrinogen levels which are most critical in the determination of thrombotic risk. An increase in measurement error as a result of freezing was also observed. These effects may, therefore, be important considerations in future studies of this nature.

Audit of surgical delay in relationship to outcome after proximal femoral fracture.

To ascertain the influence of surgical delay on outcome after proximal femoral fracture in elderly females, a cohort study of patients presenting in 1987 was compared to 1989/90. Organisational changes in the intervening period were introduced to reduce delay to surgical intervention. Two hundred and eighty females aged 65 years and over presenting from the local catchment area of an acute inner-city teaching hospital were enrolled in the study. Seventy-nine patients received surgery in 1987 and 186 in 1989/90. The one year mortality was 34% and 26% respectively. The proportion receiving surgery within 24 hours rose from 34% in 1987 to 57% in 1989/90. The relative hazard of the group receiving surgery on day 2 in comparison to day 1 was 1.7 (95% CI 1.0 to 2.9) when adjusted for co-variance of age and mental score. Medically fit elderly patients presenting with proximal femoral fracture have improved survival with early surgery within 24 hours of admission. Improvements in the organisation of hospital care will result in important benefits for the increasing number of elderly females presenting with proximal femoral fracture.

Seasonal changes in haemostatic factors in young and elderly subjects.

Morbidity and mortality from cardiovascular disease are more common in colder seasons, especially in elderly people. Previous studies have shown higher fibrinogen levels in old people in the winter months. The present studies of haemostatic factors in relation to age and season have shown that fibrinogen, tissue plasminogen activator (tPA), protein S and protein C levels are higher in old (aged 75 years and over) than young (aged 25-30 years) subjects while antiplasmin levels are lower in old people. Antiplasmin and protein C levels are lower in winter in both young and old while plasminogen activator inhibitor (PAI) is higher, and tPA higher in old people only. This study illustrates the complex interrelationships of the haemostatic system and may suggest that in 'successful' elderly people the fibrinolytic system may alter to maintain the delicate balance between thrombogenic and fibrinolytic activity. Nevertheless, the results presented here suggest that both old age and cold weather may increase the risk of atherothrombotic disease.

Diagnostic regimes for urinary tract infection--are research results applied to practice?

A clinical audit of ward practice for diagnosing and treating urinary tract infection was carried out to assess the impact on clinical practice four years after publication of a working protocol. Data were collected from all medical, surgical, gynaecology and geriatric wards in 25 hospitals in Northern Ireland. All wards made use of urinary dipsticks for ward testing, as recommended by the protocol. However many negative samples were still forwarded for laboratory analysis. The potential financial savings which would result from effective ward screening were not being realised and the publication appeared to have minimal impact on clinical practice. Advice on an improved diagnostic protocol for urinary tract infection may not have been disseminated to the nursing staff whose role was pivotal in the screening process.

Comparison of nursing home residents admitted from home or hospital.

A growing elderly population coupled with a reduction in hospital long term care has led to an increase in the independent nursing home sector. This is an expensive resource. Proper placement is therefore essential to ensure its efficient use. Prior to the introduction of care management there was no standard assessment procedure for admission to nursing home care from different sources. A nursing home population (n = 624) in North and West Belfast was studied and mental scores, levels of disability, and the source of admission to the nursing home recorded. Residents admitted from geriatric medical units (n = 132) were compared with those from general medical and surgical wards (n = 168) and those from home (n = 243). Residents who were admitted from a geriatric unit were the most disabled, those admitted from home were the least and those from general wards had intermediate levels of disability (p < 0.005). This is likely to be the result of different assessment procedures for prospective nursing home residents. With the introduction of care management, it is hoped that standardised assessment will follow. The roles of different medical specialists in this process is not yet clear. Further study is needed to assess the appropriateness of placement in nursing homes under care management.

Conservative podiatric medicine and disability in elderly people.

A survey was conducted of 248 noninstitutionalized people aged 75 years and older, residing in a designated geographical area. The effect of dependency and physical disability on the receipt of conservative podiatric medicine was examined, and, in addition, the prevalence of medical and podiatric conditions was determined.