Therapeutic continuity in Alzheimer's disease: switching patients to galantamine. Panel discussion: recommendations for prescribers.
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Biomedical subjects
Publications and source records attributed to D Wilkinson.
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Patients with dementia with Lewy bodies (DLB) have progressive deficits in cognition, parkinsonism, and neuropsychiatric symptoms. Cholinesterase inhibitors have been used to ameliorate cognitive decline and neuropsychiatric symptoms in short-term trials. In this study, patients with DLB were treated with rivastigmine up to 96 weeks. Improvement from baseline was seen in cognitive function as measured by the Mini-Mental State Examination (MMSE), and neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI) over the first 24 weeks of treatment. By 96 weeks, neither the MMSE scores nor the NPI scores were significantly worse than at baseline.
In a double-blind randomised study, we investigated the influence of positive intra-operative suggestions, presented to anaesthetised patients undergoing total abdominal hysterectomy, on postoperative pain, nausea and vomiting. One hundred and forty patients were randomly allocated to listen to one of four tapes containing either white noise or positive suggestions. The positive suggestions related to pain, postoperative nausea and vomiting, or both. We found that the positive intra-operative suggestions had no beneficial effects in reducing postoperative pain or nausea scores, nor was the consumption of morphine or anti-emetics reduced.
BACKGROUND: Studies relating to the ethnic origin of patients with an abdominal aortic aneurysm (AAA) are few and are mainly concerned with the differences between black and white Americans. The purpose of this study was to determine whether the incidence of AAA among the Asian population of Bradford is different from that in the Caucasian population. METHODS: A retrospective study of patients with an AAA was carried out between 1990 and 1997 using data collected by the Patient Administrative Service, personal databases of the vascular consultants and theatre records. Information about the ethnic composition of the population of Bradford was obtained from the 1991 national census. Demographic data, including ethnic origin and clinical details, were obtained from patient notes. RESULTS: Two hundred and thirty-three patients with an AAA were identified during the study interval. The Asian population comprised 14.0 per cent of the total population of Bradford. Twenty-eight AAAs would be expected per year. All of the aneurysms identified occurred in the Caucasian population and none in the Asian community. CONCLUSION: These early results suggest that AAA is rare among the Asian population.
Non-communicable diseases (NCDs) are becoming increasingly common and important in developing countries, yet their enumeration is problematic. We have attempted to enumerate NCD patients in a rural district of KwazuluNatal, South Africa, using the techniques of electronic data linkage and capture-recapture (CR). We examined four major NCDs (hypertension, diabetes, asthma and epilepsy). Basic patient details were recorded onto EpiInfo software over a 6-week period, from the main hospital clinic at Hlabisa, as well as the 10 outlying peripheral health clinics. Using electronic data linkage of lists from the main hospital, the peripheral clinics, and repeat prescription cards, a district NCD register was produced of 2455 patients. The mean age was 51 +/- 16 years (1 SD) and 76% were female. Of the total NCD patients, 62% had hypertension (age 57 +/- 12 years, 82% female), 16% epilepsy (age 35 +/- 17 years, 49% female), 13% asthma (age 45 +/- 19 years, 60% female) and 12% diabetes (age 54 +/- 13 years, 61% female). Estimated population crude prevalence rates for known NCD cases on the register were 7.4% for hypertension, epilepsy 0.2%, asthma 0.2% and diabetes 0.2%. We also attempted a CR analysis to assess completeness of data, by comparing overlap between patients attending peripheral clinics, and the central Hlabisa Hospital clinic. Matching by name, age, and diagnosis proved feasible, but there was little overlap, and CR calculations were invalid because of the relative independence of sources. We conclude that NCDs are common in rural Africa, and that a simple NCD district register is a potentially feasible and inexpensive option. Capture-recapture analysis is feasible, but requires suitable lists with acceptable overlap of patients.
Difficulty recruiting and retaining doctors in rural and remote Australia is well recognised. Here, we describe the positive impact on recruitment and retention of general practitioners of a network of university-linked rural family practices in South Australia. Between August 1995 and October 1999, 17 doctors were recruited; eight (47%) were female and six (35%) worked part time. Four doctors left the practices after an average of 20 months service (annual turnover of 6%). Of the two general practice registrars placed in the single accredited practice, one has since joined the practice and the other will do so in 2000. Five doctors are overseas-trained (24%) and four are expected to stay permanently. Rural academic family practices have successfully recruited and retained medical staff in this setting over the past few years. This model of practice may be a useful recruitment and retention strategy for other parts of Australia.
The GP Links program aims to promote the amalgamation of smaller general practices into larger group practices and is one of several strategies being used to modernise Australian family practice. GP Links provides financial incentives to practices willing to amalgamate. The focus of the program has been on urban practices to date and indeed some of the requirements of the program mean that rural practices are less likely to access the scheme. We report our positive and negative experiences of practice amalgamation through the GP Links program in a regional setting of South Australia. From our experience we suggest that for rural practices, a staged approach of increasing collaboration that may lead to amalgamation, which focuses on rural practices developing a supportive network and alliances with others such as Divisions and University Departments of Rural Health might be a positive way ahead.
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The purpose of this report was to investigate the efficacy of hyperbaric oxygen treatment in the management of a persisting radiation induced ulcer following standard breast irradiation. A 57-year-old Caucasian patient was referred following partial mastectomy and axillary node clearance for a T2N0 grade 3 infiltrating ductal carcinoma of the left breast. She received 45 Gy in 25 fractions at 1.8 Gy per fraction to the isocentre to the whole breast using tangential fields and 4 MV photons, in conjunction with intravenous chemotherapy (cyclophosphamide, methotrexate and 5 fluorouracil). Treatment was interrupted for 3.5 weeks because of a grade 4 skin and subcutaneous reaction. Treatment resumed to the tumour bed alone. Chemotherapy was abandoned. The tumour bed received 14 Gy in 7 fractions at 2 Gy per fraction prescribed to the 100% using 10 MeV electrons and a direct field, completing treatment on 7 July 1998. The radiation induced a painful 8x4 cm ulcer which persisted in spite of rigorous treatment including Gentian Violet, Silvazine Cream, Duoderm and antibiotics. The patient received 30 hyperbaric treatments, six times a week, completing treatment on 15 December 1998. The patient required insertion of bilateral ear grommets under local anaesthetic. The breast ulcer showed a response to treatment with early healing after 7-8 days and clinical evidence of re-epithelization. At completion of 30 treatments the patient was left with a small shallow faintly discharging multilocular 3-4 cm ulcer. The ulcer had completely healed by 14 January 1999. The patient has been symptom free since completion of treatment. This report highlights the efficacy of hyperbaric oxygen therapy in the management of persisting radiation-induced ulcers.
Aboriginal Community Controlled Health Services face particular management issues as they adjust to the dominant Western paradigm of managerialism and the market model of health service provision. Their cultural orientation leads to distinctive organisational features which both advantage and disadvantages them in this environment. The holistic model of health used and community control enable the delivery of integrated, culturally appropriate health care. However, effective community control is difficult to achieve. Services may benefit from partnerships with collaborators such as hospitals, regional health services and university departments of rural health if the partnerships are based on mutual respect and ensure that community control is retained.
We present a descriptive analysis of a mechanism to coordinate and implement human immunodeficiency virus (HIV) prevention and care in the occupational setting. The mechanism we describe is a multidisciplinary committee composed of stakeholders in the occupational health environment including unions, management, medical researchers, and medical personnel. The site chosen for the analysis was a South African sugar mill in rural KwaZulu-Natal. The factory is situated in an area of high HIV seroprevalence and has a workforce of 400 employees. The committee was initiated to coordinate a combined prevention-care initiative. The issues that were important in the formation of the committee included confidentiality, trust, and the traditional roles of the stakeholder relationships. When these points were addressed through the focus on a common goal, the committee was able to function in its role as a coordinating body. Central to this success was the inclusion of all stakeholders in the process, including those with traditionally opposing interests and legitimacy conferred by the stakeholders. This committee was functionally effective and demonstrated the benefit of a freestanding committee dedicated to addressing HIV/acquired immune deficiency syndrome (AIDS) issues. We describe the implementation and feasibility of a multisectoral committee in directing HIV/AIDS initiatives in the occupational setting in rural South Africa.
BACKGROUND: The aim of this study was to study ecological correlations between age-adjusted all-cause mortality rates in Australian statistical divisions and (1) the proportion of residents that self-identify as Indigenous, (2) remoteness, and (3) socio-economic deprivation. METHODS: All-cause mortality rates for 57 statistical divisions were calculated and directly standardized to the 1997 Australian population in 5-year age groups using Australian Bureau of Statistics (ABS) data. The proportion of residents who self-identified as Indigenous was obtained from the 1996 Census. Remoteness was measured using ARIA (Accessibility and Remoteness Index for Australia) values. Socioeconomic deprivation was measured using SEIFA (Socio-Economic Index for Australia) values from the ABS. RESULTS: Age-standardized all-cause mortality varies two-fold from 5.7 to 11.3 per 1,000 across Australian statistical divisions. Strongest correlation was between Indigenous status and mortality (r = 0.69, p < 0.001). Correlation between remoteness and mortality was modest (r = 0.39, p = 0.002) as was correlation between socio-economic deprivation and mortality (r = -0.42, p = 0.001). Excluding the three divisions with the highest mortality, a multiple regression model using the logarithm of the adjusted mortality rate as the dependent variable showed that the partial correlation (and hence proportion of the variance explained) for Indigenous status was 0.03 (9 per cent; p = 0.03), for SEIFA score was -0.17 (3 per cent; p = 0.22); and for remoteness was -0.22 (5 per cent; p = 0.13). Collectively, the three variables studied explain 13 per cent of the variability in mortality. CONCLUSIONS: Ecological correlation exists between all-cause mortality, Indigenous status, remoteness and disadvantage across Australia. The strongest correlation is with Indigenous status, and correlation with all three characteristics is weak when the three statistical divisions with the highest mortality rates are excluded. Intervention targeted at these three statistical divisions could reduce much of the variability in mortality in Australia.
OBJECTIVE: To document trends in the distribution of general practitioners (GPs) in Australia between 1986 and 1996, adjusted for community need. METHODS: Data on the location of GPs, population size and crude mortality in statistical divisions (SD) were obtained from the Australian Bureau of Statistics Census of Population and Housing in 1986 and 1996. From these data, we calculated measures of distribution equality (number of people sharing each GP in each SD) and distribution equity (number of people sharing each GP divided by the crude mortality rate; the Robin Hood Index), and analysed temporal changes in the distribution of GPs. RESULTS: Nationally, the number of people sharing each GP fell 11% from 1,038 in 1986 to 921 in 1996. However, in 41 of 57 SDs (72%, p=0.01) the number of people sharing a GP actually increased over this time, and the average Robin Hood Index across SDs fell from 0.943 to 0.783 (p=0.004), indicating increasingly inequitable distribution. Comparing the Robin Hood Index values of all SDs ranked in pairs, the value fell in 53 of 57 (93%, p<0.001) paired SDs over the decade. These patterns demonstrate increasing inequity over the decade. The number of people sharing each GP was consistently and substantially lower in the capital city SDs and the Robin Hood Index values were consistently and substantially higher (overserved) compared with country SDs. CONCLUSIONS: Despite there being more GPs per capita in Australia, their distribution became increasingly unequal and inequitable between 1986 and 1996, such that rural and remote areas became increasingly poorly served.
OBJECTIVE: To assess the efficacy and safety of galantamine in Alzheimer's disease at 3 months using flexible dose escalation. METHODS: A randomised, double blind, placebo controlled trial in 43 centres in the United States, Canada, Great Britain, South Africa, Australia, and New Zealand. Patients with probable Alzheimer's disease (n=386; 171 women) with a score of 11-24 on the mini mental state examination, and a score> or =12 on the cognitive subscale of the Alzheimer's disease assessment scale (ADAS-cog) were randomised to placebo, or galantamine escalated over 4 weeks to a maintenance dose of 24 or 32 mg/day. The primary outcome measures were the change in ADAS-cog score and the clinician's interview based impression of change plus caregiver input (CIBIC-plus) score. Activities of daily living (ADL) and behavioural symptoms were secondary outcomes. To compare the effects of highest levels of dosing, an observed cases (OC) analysis was undertaken, with classic intention to treat (ITT) and ITT with last observation carried forward (LOCF) as confirmatory analyses. RESULTS: At 3 months, galantamine (24-32 mg/day) produced a significantly better outcome on cognitive function than placebo (treatment difference=1.9 points on ADAS-cog, p=0.002) and a significantly better global response than placebo, as measured by CIBIC-plus (deterioration in 21% of patients on galantamine v 37% on placebo; p<0.001). Galantamine produced significant benefits on basic and instrumental ADL. Behavioural symptoms did not change significantly from baseline levels in either group. Adverse events (primarily gastrointestinal) were of mild to moderate intensity. There were no important differences between the OC, ITT, and ITT/LOCF analyses. Most patients (82%) who were maintained on the higher dose of galantamine completed the study. CONCLUSIONS: Patients on galantamine, compared with those on placebo, experienced benefits in cognitive function and instrumental and basic activities of daily living. Flexible dose escalation of galantamine was well tolerated.
An increasing proportion of the population perceive complementary medicine as a safer alternative for non-life threatening conditions such as genital herpes. The extract of the plant Echinacea purpurea (Echinaforce) has been shown to have immunomodulating properties and has been advocated in the lay press for the treatment of genital herpes. This study, a single centre, prospective, double blind, placebo-controlled cross-over trial set out to assess whether an extract of the plant and root of E. purpurea can prevent or decrease the frequency and severity of genital herpes recurrences. These were assessed using a detailed history and clinical review of symptoms. Visual analogue scales were used for documentation and haematological and immunological parameters were measured. Over a one-year period, 50 patients took part in the study receiving 6 months' placebo and 6 months' Echinaforce each. No statistically significant benefit could be detected in this study comparing placebo versus Echinaforce in the treatment of frequently recurrent genital herpes.
This evaluation examined the effectiveness of the K-Four (Parema) high compression bandage system on 50 patients with recalcitrant 'hard-to-heal' venous leg ulcers and relates the outcome to an earlier randomised study which compared three other four-layer bandage systems. Twelve-week healing rates were 53.2% in the current series, which included patients with poor mobility, large ulcers and long pretreatment ulcer duration, rising to 69.5% at 20 weeks. When account was taken of known risk factors for delayed ulcer healing, no significant difference could be identified between between either K-Four or the earlier evaluated bandages, which included the original Charing Cross system, where the overall healing rates were 64.5% and 80%, respectively, at 12 and 20 weeks. It would seem more likely that treatment outcome is related to patient risk factors for delayed healing and bandaging expertise than to the bandage system employed.
Individual differences in response to radiation are well known, but the molecular basis for these differences is not well understood, and molecular indicators that are useful in assessing individual variation are lacking. Cells from patients developing unexpected radiation responses have occasionally been analyzed for rare genetic anomalies (such as alleles of the ATM gene), but few data exist on the long-term effects of genetic variation on radiation response. We hypothesize that much of the variation in the response to radiation is due to differences in the genes that respond to radiation exposure, and that changes in gene expression may serve as surrogate markers of individual response. As a first step in developing a selection of suitable markers of gene expression, we used cDNA microarrays to identify genes that were altered in expression in lymphoblastoid cells 4 h after exposure to 1 Gy X rays. We found changes in gene expression ranging from a 10-fold repression to a 12-fold induction. Some of the responsive genes have been noted previously in other cell types, whereas others are reported for the first time. Using these data, we are beginning to characterize the range of structural, temporal and functional variations in the responsive genes. The results of this work will assist in developing response markers both for prescreening for sensitive individuals and for risk assessment.
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