A three-year follow-up on the efficacy of psychosocial interventions for patients with mild dementia and their caregivers: the multicentre, rater-blinded, randomised Danish Alzheimer Intervention Study (DAISY).

OBJECTIVES: To examine the long-term efficacy at the 36-month follow-up of an early psychosocial counselling and support programme lasting 8-12 months for community-dwelling patients with mild Alzheimer's disease and their caregivers. DESIGN: Multicentre, randomised, controlled, rater-blinded trial. SETTING: Primary care and memory clinics in five Danish districts. PARTICIPANTS: 330 home-dwelling patients with mild Alzheimer's disease and their primary caregivers (dyads). INTERVENTIONS: Dyads were randomised to receive intervention during the first year after diagnosis. Both intervention and control groups had follow-up visits at 3, 6, 12 and 36 months. MAIN OUTCOME MEASURES: Primary outcomes for the patients assessed at 36-month follow-up were changes from baseline in global cognitive function (Mini-Mental State Examination), depressive symptoms (Cornell Depression Scale) and proxy-rated EuroQoL quality of life on visual analogue scale. The primary outcomes for the caregivers were changes from baseline in depressive symptoms (Geriatric Depression Scale) and self-rated EuroQoL quality of life on a visual analogue scale. The secondary outcome measures for the patient were proxy-rated Quality of Life Scale for Alzheimer's disease (QoL-AD), Neuropsychiatric Inventory-Questionnaire, Alzheimer's disease Cooperative Study Activities of Daily Living Scale, all-cause mortality and nursing home placement. RESULTS: At a 36-month follow-up, 2 years after the completion of the Danish Alzheimer Intervention Study (DAISY), the unadjusted positive effects previously detected at the 12-month follow-up in one patient primary outcome (Cornell depression score) and one patient secondary outcome (proxy-rated QoL-AD) disappeared (Cornell depression score, p=0.93; proxy-rated QoL-AD, p=0.81). No long-term effect of DAISY intervention on any other primary and secondary outcomes was found at the 36-month follow-up. CONCLUSIONS: For patients with very mild Alzheimer's disease and their caregivers, an intensive, multi-component, semitailored psychosocial intervention programme with counselling, education and support during the first year after diagnosis did not show any positive long-term effect on primary and secondary outcomes. TRIAL REGISTRATION: The study was registered in the Clinical Trial Database (http://www.controlled-trials.com/ISRCTN74848736).

Efficacy of psychosocial intervention in patients with mild Alzheimer's disease: the multicentre, rater blinded, randomised Danish Alzheimer Intervention Study (DAISY).

OBJECTIVE: To assess the efficacy at 12 months of an early psychosocial counselling and support programme for outpatients with mild Alzheimer's disease and their primary care givers. DESIGN: Multicentre, randomised, controlled, rater blinded trial. SETTING: Primary care and memory clinics in five Danish districts. PARTICIPANTS: 330 outpatients with mild Alzheimer's disease and their 330 primary care givers. INTERVENTIONS: Participating dyads (patient and primary care giver) were randomised to control support during follow-up or to control support plus DAISY intervention (multifaceted and semi-tailored counselling, education, and support). MAIN OUTCOME MEASURES: Primary outcomes at 12 months for patients were change from baseline in mini mental state examination (MMSE) score, Cornell depression scale score, and proxy rated European quality of life visual analogue scale (EQ-VAS) score. For care givers, outcomes were change from baseline in geriatric depression scale (GDS 30 items) score and EQ-VAS score. RESULTS: Because of multiple testing, statistical significance was set at an adjusted P limit of <0.0005. At 12 months there were no significant differences between the two allocation groups in changes from baseline in the primary and secondary outcomes. However, although non-significant with the adjusted P limit, a small difference was observed for one of the primary patient outcomes (Cornell depression scale score) in patients in favour of the DAISY intervention group before and after adjusting for attrition (P = 0.0146 and P = 0.0103 respectively). CONCLUSIONS: The multifaceted, semi-tailored intervention with counselling, education, and support for patients with mild Alzheimer's disease and their care givers did not have any significant effect beyond that with well structured follow-up support at 12 months after adjustment for multiple comparisons. The small positive effect found in the unadjusted primary outcome addressing depressive symptoms in patients may call for further research focusing on patients with Alzheimer's disease and comorbid depression. TRIAL REGISTRATION: ISRCTN74848736.

The Danish Alzheimer intervention study: rationale, study design and baseline characteristics of the cohort.

BACKGROUND: There is a lack of appropriately designed trials investigating the efficacy of psychosocial interventions for patients with mild dementia and their family caregivers. This paper reports the rationale and design of the Danish Alzheimer Disease Intervention Study and baseline characteristics of the cohort. METHODS: The study was a 1-year multicentre randomized controlled rater-blinded trial with randomization to follow-up and a multifaceted semitailored intervention programme or to follow-up only (with extension of follow-up to 3 years). The intervention included a counselling programme, teaching courses, written information and logbooks. The outcomes included clinical efficacy parameters, patient satisfaction and health economic consequences. RESULTS: A total of 330 patients and their 330 caregivers were included during a period of 18 months. The majority (65.2 %) of the caregivers were spouses. At inclusion the mean age of the patients and caregivers was 76.2 and 66.0 years, respectively. CONCLUSION: The study will explore the added value of a multifaceted intervention programme and contribute to the design of future interventions for patients with mild dementia and their caregivers.

Syntheses of Ru-S clusters with kinetically labile ligands via the photolysis of [(cymene)3RuS2](PF6)2.

Three ruthenium sulfide clusters with labile CH3CN ligands have been photochemically synthesized. Irradiation of [(cymene)3Ru3S2](PF6)2 ([1](PF6)2) in CH3CN gives [(cymene)2(CH3CN)3Ru3S2](PF6)2 ([2](PF6)2), which has been characterized by 1H NMR spectroscopy, ESI mass spectrometry, and chemical reactivity. Treatment of [2](PF6)2 with PPh3 gives [(cymene)2(CH3CN)2(PPh3)Ru3S2](PF6)2 ([3](PF6)2) and [(cymene)2(CH3CN)(PPh3)2Ru3S2](PF6)2 ([4](PF6)2), while treatment with 1,4,7-trithiacyclononane (9S3) gives [(cymene)2(9S3)Ru3S2](PF6)2 ([5](PF6)2). A crystallographic study demonstrated that the Ru3 core in [3](PF6)2, [4](PF6)2, and [5](PF6)2 is distorted with a pair of elongated Ru-Ru bonds. Cyclic voltammetry shows that [3](PF6)2 and [4](PF6)2 undergo two closely spaced reversible one-electron reductions whereas [5](PF6)2 undergoes one irreversible one-electron reduction and one reversible one-electron reduction. Prolonged irradiation of [1](PF6)2 in CH3CN causes decomposition, resulting in the pentanuclear cluster [(cymene)4Ru5S4](PF6)2 ([6](PF6)2).

Effect of calcium channel blockade on skin blood flow in diabetic hypertension: a comparison of isradipine and atenolol.

In previous studies, using laser Doppler techniques, the authors have demonstrated a duration-dependent reduction in skin blood flow reserve at sites of nutritive (NUTR) perfusion that occurs in diabetes and correlates with the presence of diabetic retinopathy and proteinuria. They speculated that it might be possible to reverse this decrease in blood flow by using agents with peripheral vasodilating properties. They chose the calcium channel blocking agent isradipine as a prototype. As a contrast agent, they chose atenolol, which has an equivalent antihypertensive effect but minimal peripheral vasodilating properties. They studied 24 diabetic hypertensive patients in a randomized, two-way crossover design. They assigned patients randomly to one or the other active drug and titrated to a maximum tolerated maintenance dose. Skin blood flow was measured at the end of the titration and maintenance phases. Patients then entered a four-week washout period, followed by crossover to the alternative drug, and measurements were repeated. At baseline, the twenty-four-hour mean ambulatory systolic blood pressure was 150 +/- 2 mm Hg with a twenty-four-hour mean diastolic blood pressure of 93 +/- 1 mm Hg. Thermally stimulated skin blood flow reserve was about 50% lower in these patients as compared with an age-, sex-, and weight-matched group of 28 nondiabetic, nonhypertensive patients. There was no difference in skin blood flow between the two groups at basal skin temperature or at a controlled temperature of 35 degrees C. Both atenolol and isradipine successfully lowered blood pressure in the study patients. There was a slightly greater decrease in systolic blood pressure with isradipine and a greater decrease in heart rate with atenolol. Neither isradipine nor atenolol treatment affected skin blood flow values at the maximal 44 degrees C temperature. However, at basal skin temperature and at 35 degrees C, isradipine-treated patients had substantial increases in skin blood flow at NUTR sites. For example, skin blood flow at the knee at 35 degrees C with isradipine treatment was 3.1 +/- 0.4 mL/min/100 g compared with 1.1 +/- 0.2 with atenolol, 1.3 +/- 0.1 with placebo, and 0.9 +/- 0.1 for the nondiabetic controls (all P < 0.01). The authors found a twofold to threefold increase in basal skin blood flow at NUTR sites with isradipine treatment. This degree of increase is substantially greater than that previously demonstrated by their group using pentoxifylline. Locally reduced skin blood flow is a factor in promoting skin breakdown and delayed healing. Further study is needed to explore the possibility that isradipine treatment may enhance healing of diabetic skin ulcers.

The effect of aging on skin blood flow in the Wistar-Kyoto rat.

Using laser Doppler techniques in man, we have previously demonstrated that skin blood flow decreases linearly with age. In previous work, we have shown similarities in skin blood flow properties between man and the rat. Our goal was to assess a possible aging effect of skin blood flow in the rat. We determined skin blood flow sequentially in 13 Wistar-Kyoto rats, beginning at 3 months of age, then at 6, 12, 15, and 18 months. We measured flow on the back, the base of the tail, the upper leg, all nutritively (NUTR) perfused sites, and on the plantar paw surface, which is perfused chiefly by arteriovenous anastomotic (AVA) capillaries. We measured flow, microvascular volume and red blood cell velocity at basal temperature and also heated the skin locally to 44 degrees C, to elicit maximal vasodilation. Skin blood flow declined in a linear fashion with increasing age. The decrease was in the order of 15% over 18 months and occurred at both NUTR sites and the paw. The decrease was due to reduced microvascular volume, presumably representing loss of skin capillaries. Red blood cell velocity was not reduced; in fact, it was significantly increased at several NUTR sites. The WKY rat provides an excellent model of aging of the skin microvasculature. The changes we have demonstrated, while not identical to those we have previously demonstrated in man, are sufficiently similar to permit further exploration of the mechanisms of these changes.

Strengthening the role of primary health care in health promotion by bridging cultures in aboriginal health.

This paper advocates strengthening the role of primary health care in health promotion by bridging cultures in Aboriginal health. It encourages health care providers to consider the need for cross-cultural awareness in order to provide more effective health promotion. It suggests a number of strategies for overcoming structural barriers and individual factors which may hinder positive personal and professional cross-cultural communications.