Cg Swift

Prevention of falls in the elderly trial (PROFET): a randomised controlled trial

BACKGROUND Falls in elderly people are a common presenting complaint to accident and emergency departments. Current practice commonly focuses on the injury, with little systematic assessment of the underlying cause, functional consequences, and possibilities for future prevention. We undertook a randomised controlled study to assess the benefit of a structured inderdisciplinary assessment of people who have fallen in terms of further falls. METHODS Eligible patients were aged 65 years and older, lived in the community, and presented to an accident and emergency department with a fall. Patients assigned to the intervention group (n=184) underwent a detailed medical and occupational-therapy assessment with referral to relevant services if indicated; those assigned to the control group (n=213) received usual care only. The analyses were by intention to treat. Follow-up data were collected every 4 months for 1 year. FINDINGS At 12-month follow-up, 77% of both groups remained in the study. The total reported number of falls during this period was 183 in the intervention group compared with 510 in the control group (p=0.0002). The risk of falling was significantly reduced in the intervention group (odds ratio 0.39 [95% CI 0.23-0.66]) as was the risk of recurrent falls (0.33 [0.16-0.68]). In addition, the odds of admission to hospital were lower in the intervention group (0.61 [0.35-1.05]) whereas the decline in Barthel score with time was greater in the control group (p<0.00001). INTERPRETATION The study shows that an interdisciplinary approach to this high-risk population can significantly decrease the risk of further falls and limit functional impairment.

Neuromuscular and psychomotor function in elderly subjects who fall and the relationship with vitamin D status

Vitamin D and calcium supplementation significantly reduces the incidence of fractures. Evidence suggests vitamin D deficiency impairs neuromuscular function, causing an increase in falls and thereby fractures. The relationship between vitamin D, functional performance, and psychomotor function in elderly people who fall was examined in a prospective cross‐sectional study. Patients were recruited from a falls clinic and stratified according to serum 25‐hydroxyvitamin‐D levels (25OHD): group 1, 25OHD < 12 μg/liter; group 2 25OHD, 12‐17 μg/liter; and group 3, 25OHD > 17 μg/liter. Healthy elderly volunteers with 25OHD > 17 μg/liter comprised group 4 (n = 20/group). Measures included aggregate functional performance time (AFPT, seconds), isometric quadriceps strength (Newtons), postural sway (degrees), and choice reaction time (CRT, seconds). Serum bone biochemistry, 25OHD, and parathyroid hormone levels were measured. Patients who fell had significantly impaired functional performance, psychomotor function, and quadriceps strength compared with healthy subjects (AFPT: 51.0 s vs. 32.8 s, p < 0.05; CRT: 1.66 s vs. 0.98 s, p < 0.05; strength: 223N vs. 271N, t = 2.35, p = 0.02). Group 1 had significantly slower AFPT (66.0 s vs. 44.8 s, t = 4.15, p < 0.05) and CRT (2.37 s vs. 0.98 s, t = 3.59, p < 0.05) than groups 2 and 3. Group 1 had the greatest degree of postural sway and the weakest quadriceps strength, although this did not reach significance. Multivariate analysis revealed 25OHD as an independent variable for AFPT, CRT, and postural sway. PTH was an independent variable for muscle strength. Older people who fall have impaired functional performance, psychomotor function, and muscle strength. Within this group, those with 25OHD < 12 μg/liter are the most significantly affected.

Alternative strategies for stroke care: a prospective randomised controlled trial

BACKGROUND Organised specialist care for stroke improves outcome, but the merits of different methods of organisation are in doubt. This study compares the efficacy of stroke unit with stroke team or domiciliary care. METHODS A single-blind, randomised, controlled trial was undertaken in 457 acute-stroke patients (average age 76 years, 48% women) randomly assigned to stroke unit, general wards with stroke team support, or domiciliary stroke care, within 72 h of stroke onset. Outcome was assessed at 3, 6, and 12 months. The primary outcome measure was death or institutionalisation at 12 months. Analyses were by intention to treat. FINDINGS 152 patients were allocated to the stroke unit, 152 to stroke team, and 153 to domiciliary stroke care. 51 (34%) patients in the domiciliary group were admitted to hospital after randomisation. Mortality or institutionalisation at 1 year were lower in patients on a stroke unit than for those receiving care from a stroke team (21/152 [14%] vs 45/149 [30%]; p<0.001) or domiciliary care (21/152 [14%] vs 34/144 [24%]; p=0.03), mainly as a result of reduction in mortality. The proportion of patients alive without severe disability at 1 year was also significantly higher on the stroke unit compared with stroke team (129/152 [85%] vs 99/149 [66%]; p<0.001) or domiciliary care (129/152 [85%] vs 102/144 [71%]; p=0.002). These differences were present at 3 and 6 months after stroke. INTERPRETATION Stroke units are more effective than a specialist stroke team or specialist domiciliary care in reducing mortality, institutionalisation, and dependence after stroke.

The Hypertension in the Very Elderly Trial (HYVET). Rationale, methodology and comparison with previous trials

SummaryThe Hypertension in the Very Elderly Trial (HYVET) is a multicentre, open, randomised, controlled trial. The aim of this trial is to investigate the effect of active treatment on stroke incidence in hypertensive patients over the age of 80 years. Secondary end-points include total cardiovascular mortality and morbidity.Entry criteria include a sustained sitting systolic blood pressure of 160 to 219mm Hg plus a sustained sitting diastolic pressure of 95 to 109mm Hg. Also required is a standing systolic blood pressure of at least 140mm Hg. Patients must give their informed consent, and be free of congestive heart failure requiring treatment, gout, renal failure or a recent cerebral haemorrhage. Patients are to be randomised to 3 groups — (i) no treatment; (ii) treatment with a diuretic [bendroflumethiazide (bendrofluazide)]; or (iii) treatment with an angiotensin converting enzyme (ACE) inhibitor (lisinopril).Starting dosage for bendroflumethiazide and lisinopril is 2.5 mg/day. In order to achieve goal sitting systolic and diastolic blood pressures (< 150/80mm Hg), a doubling of the dosage is allowed. Furthermore, slow release diltiazem (120 mg/day increasing to 240 mg/day if required) may be added to the medication of the actively treated groups. These drugs have been chosen as inexpensive and appropriate representatives of their therapeutic classes.700 patients in each group (a total of 2100) will be sufficient to detect a 40% difference in cerebrovascular events between no treatment and active treatment (α = 0.01, 1−β = 0.90). These numbers will also detect a difference in total mortality of 25% and in cardiovascular mortality of 35%.The pilot phase of the trial has been started with support from the British Heart Foundation. Centres which are interested in taking part should contact C. J. Bulpitt or any of the other authors.

Effects of folic acid supplementation on inflammatory and thrombogenic markers in chronic smokers. A randomised controlled trial

INTRODUCTION Cigarette smoking may induce pro-inflammatory and pro-thrombotic changes. It is not known whether these abnormalities are caused at least partly by increased homocysteine levels. We investigated whether lowering homocysteine by folic acid supplementation might reduce the plasma concentration of inflammatory and thrombogenic markers in chronic smokers. MATERIAL AND METHODS Twenty-four healthy cigarette smokers (age 37.8+/-2.5 years, mean+/-SEM) were randomly assigned to 4 weeks of folic acid 5 mg/day or placebo. The following parameters were measured before and after treatment: (1) markers of inflammation (C-reactive protein, CRP, and white cell count, WCC); (2) blood coagulation screen (Activated Partial Thromboplastin time Ratio, APTR, and International Normalized Ratio, INR); (3) pro-thrombotic markers (fibrinogen, factor VIII coagulant activity, VIII:C, von Willebrand factor, vWF, and D-dimer). RESULTS Folic acid induced a significant reduction in homocysteine (10.8+/-0.6 vs. 8.2+/-0.5 micromol/l, p<0.001), plasma fibrinogen (3.15+/-0.14 vs. 2.87+/-0.14 g/l, p<0.05), and D-dimer (102+/-44 vs. 80+/-26 microg/l, p<0.05) concentrations. By contrast, no significant changes were observed in CRP (2.2+/-0.7 vs. 1.7+/-0.7 mg/l), WCC (7.2+/-0.5 vs. 6.8+/-0.5 10(9) cells/l), APTR (0.91+/-0.02 vs. 0.93+/-0.02), INR (0.92+/-0.01 vs. 0.91+/-0.01), vWF (103+/-8 vs. 102+/-9 U/dl), and VIII:C (120+/-8 vs. 107+/-8 U/dl) levels. Changes in folic acid plasma concentrations were significantly and negatively correlated with changes in fibrinogen (r=-0.48, p=0.01) but not with changes in D-dimer (r=-0.15, p=0.5) levels. Changes in plasma homocysteine concentrations did not correlate with changes in either fibrinogen or D-dimer. No significant changes in homocysteine, inflammatory and thrombogenic markers were observed in the placebo group. CONCLUSIONS Short-term folic acid supplementation had no significant effects on inflammatory markers but induced a significant reduction in plasma fibrinogen and D-dimer concentrations in healthy chronic smokers. Thus, folic acid might have an anti-thrombotic effect in this high-risk group independent of the homocysteine lowering effect.

ACE inhibition : Postsynaptic adrenergic sympatholytic action in men

BACKGROUND The mechanisms by which ACE inhibitors produce a sustained clinical benefit are not entirely clear but may involve the sympathetic nervous system. We compared the effect of local brachial artery infusions of an ACE inhibitor (perindoprilat) with the effect of placebo (0.9% NaCl) on endogenously mediated (lower body negative pressure [LBNP]) and exogenously mediated (brachial artery infusions of norepinephrine) sympathetic vasoconstriction. METHODS AND RESULTS Eight healthy, normotensive male volunteers (20 to 32 years) were studied on one occasion. Forearm blood flow (FABF; mL x dL forearm(-1) x min(-1)) responses to LBNP (-20 cm H2O) and increasing increments of norepinephrine (60, 120, and 240 pmol/min) were compared when coinfused with placebo and perindoprilat (5 nmol/mL). FABF was measured simultaneously in both arms by venous occlusion plethysmography with mercury-in-Silastic strain gauges with drugs infused locally at the left brachial artery. The right arm served as a control. Baseline FABFs did not differ between the infused and control arms (3.04+/-0.52 versus 3.05+/-0.42 mL x dL forearm(-1) x min(-1); P=.98). Perindoprilat did not alter FABF when infused alone, but the FABF response to LBNP in the infused arm was attenuated during the perindoprilat infusion compared with placebo (-17.8+/-4.3% versus -33.8+/-3.1%, respectively; P=.015). The FABF response to the maximum dose of norepinephrine was also attenuated during the perindoprilat infusion compared with placebo (-28.3+/-1.4% versus -36.9+/-2.8%, respectively; P=.015). The mean slope of the FABF (log transformed) versus norepinephrine dose-response curve was significantly attenuated by perindoprilat compared with placebo (-0.11+/-0.019 versus -0.02+/-0.02; P=.001). CONCLUSIONS We conclude that ACE inhibition has a significant postsynaptic sympatholytic effect in the forearm circulation of men.

Psychomotor performance: investigating the dose-response relationship for caffeine and theophylline in elderly volunteers

AbstractObjective: The aim of this study was to investigate the dose-response relationship for psychomotor performance, caffeine and theophylline in healthy elderly volunteers. Methods: In a randomized, double-blind, placebo-controlled, six-period cross-over study we compared the effect of three doses of theophylline (predicted peak concentrations of 3, 6 mg · l−1 and 12 mg · l−1), two doses of caffeine (predicted peak concentrations of 4.5 mg · l−1 and 9 mg · l−1) and placebo on ten healthy elderly volunteers. Psychomotor performance was measured using a continuous attention task, symbol digit substitution test and choice reaction time. Subjective effects were assessed using visual analogue scales. Following drug administration, subjects received the test battery at 30-min intervals, up to 150 min. Maximum and mean effects from baseline on each variable were included in the analysis. Results: Significant improvement on the continuous attention task was seen at the lowest concentration of caffeine and theophylline used, while at higher concentrations there was a non-significant trend towards placebo scores. There was little effect of either drug on the subjective effects measured by visual analogue scales. Conclusion: Caffeine and theophylline increase psychomotor performance measures of attention at low plasma concentrations in healthy elderly volunteers. This effect is not increased by higher drug concentrations and there is trend towards a return to placebo scores. The lack of effect of both caffeine and theophylline on subjective measures is consistent with previous studies of caffeine in the elderly.

The Role of Standardised Assessments in Comparing Stroke Unit Rehabilitation

Background: Comparisons of outcome between stroke units are important but difficult to undertake because of differences in patient composition and operational environments. This pro

Selective AT1 Receptor Antagonism Enhances Sympathetically Mediated Vasoconstriction in Man

The vasoconstrictive action of angiotensin II (AII) is partly, sympathetically mediated and angiotensin‐converting enzyme (ACE) inhibitors appear to exert a sympatholytic effect. We examine the effect of an orally administered, selective AT1 receptor antagonist (losartan 50 mg) on sympathetically mediated vasoconstriction in healthy volunteers in an observer blind crossover study. Seven healthy, normotensive volunteers (21–32 years), were studied on two occasions at the end of each 6‐week treatment period (losartan or placebo). Forearm blood flow (FABF) (ml/dl forearm/min) was measured by venous occlusion plethysmography during the application of lower body negative pressure (LBNP) (−20 cm H2O) and at the end of each incremental infusion of norepinephrine (60, 120, and 240 pmol/min). Comparison of blood flow changes was by repeated measures analysis of variance; P<0.05 was taken as statistically significant. Losartan did not alter blood pressure compared to placebo. It did significantly enhance LBNP‐induced vasoconstriction in both the left arm compared to placebo (−36.6±3.4 vs −23.5±3.3% P=0.017) and the right arm compared to placebo (−39.5±3.8 vs −21.0±3.6% P=0.005). The FABF response to all doses of infused norepinephrine (60, 120, and 240 pmol/min) was also enhanced by losartan compared to placebo (−35.0±2.7 vs −18.2±6.0% −43.6±4.3 vs −28.6±5.8%, and −53.9±3.2 vs −42.5±6.8% P=0.057, respectively. Losartan enhances locally mediated sympathetic vasoconstriction in the forearm circulation of man, probably through its effect on circulating AII concentrations and we postulate that the adrenergic sympathetic constrictor action of AII is not mediated by the AT1 receptor or is surmountable at this receptor.

Single dose pharmacodynamics of thioridazine and remoxipride in healthy younger and older volunteers

Phenothiazines are widely used in older patients, but little experimental work has been carried out in this age group. Two groups of healthy volunteers, a younger group (Y: six males and six females, aged 20-42 years) and an older group (0: six males and eight females, aged 65-77 years) took part in a randomized double-blind threeperiod crossover study in which they received by mouth single doses of thioridazine (Y: 50mg; 0: 25mg) remoxipride (Y: 100mg; 0: 50mg) or placebo. Measures of central nervous system (CNS) and haemodynamic function were carried out before drug administration and at 1.5-h intervals up to 9h post-dose, and blood samples were collected over a 24-h period. No significant differences in dose-corrected pharmacokinetic variables were found between the two groups. There was evidence of marked CNS depressant effects of thioridazine from both objective and subjective measures. The effects for remoxipride were similar, though generally less marked. After allowance was made for dose, there was little indication of any difference in degree of CNS depression between the two age groups. Haemodynamic measures showed orthostatic reductions in blood pressure with thioridazine which were particularly marked in the older group, who also showed lower compensatory increases in pulse rate. These results indicate potential problems with orthostatic hypotension with thioridazine in older patients. CNS depression may also be a problem, especially in patients with compromised cholinergic function.